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Introduction: Septic shock, a life-threatening condition, can result in cerebral dysfunction and heightened mortality rates. In these patients, disturbances in cerebral hemodynamics, as reflected by impairment of myogenic cerebral autoregulation (CA), metabolic regulation, expressed by critical closing pressure (CrCP) and reductions in intracranial compliance (ICC), can adversely impact septic shock outcomes. The general recommendation is to maintain a target mean arterial pressure (MAP) of 65 mmHg but the effect of different MAP targets on cerebral hemodynamics in these patients is not clear and optimal targets might be dependent on the status of CA. This protocol aims to assess the cerebral hemodynamics profile at different pressure targets in septic shock patients., Methods: Prospective, non-randomized, single-center trial, which will study cerebral hemodynamics in patients with septic shock within 48 hours of its onset. Patients will be studied at their baseline MAP and at three MAP targets (T1: 65, T2: 75, T3: 85 mmHg). Cerebral hemodynamics will be assessed by transcranial Doppler (TCD) and a skull micro-deformation sensor (B4C). Dynamic CA will be expressed by the autoregulation index (ARI), calculated by transfer function analysis, using fluctuations of MAP as input and corresponding oscillations in cerebral blood velocity (CBv). The instantaneous relationship between arterial blood pressure and CBv will be used to estimate CrCP and resistance-area product (RAP) for each cardiac cycle using the first harmonic method. The B4C will access ICC by intracranial pressure waveforms (P2/P1). The primary aim is to assess cerebral hemodynamics (ARI, CrCP, RAP, and P2/P1) at different targets of MAP in septic shock patients. Our secondary objective is to assess cerebral hemodynamics at 65mmHg (target recommended by guidelines). In addition, we will assess the correlation between markers of organ dysfunction (such as lactate levels, vasoactive drugs usage, SOFA score, and delirium) and CA., Ethics and Dissemination: The results of this study may help to understand the effect of the recommended MAP and variations in blood pressure in patients with septic shock and impaired CA and ICC. Furthermore, the results can assist large trials in establishing new hypotheses about neurological management in this group of patients. Approval was obtained from the local Ethics Committee (28134720.1.0000.0048). It is anticipated that the results of this study will be presented at national and international conferences and will be published in peer-reviewed journals in 2024 and 2025., Trial Registration: Trial registration number: NCT05833607. https://clinicaltrials.gov/study/NCT05833607., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cury et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In critically ill patients, endotracheal intubation (ETI) is lifesaving but carries a high risk of adverse events, notably hypoxemia. Preoxygenation is performed before introducing the tube to increase the safe apnea time. Oxygenation is monitored by pulse oximeter measurement of peripheral oxygen saturation (SpO2). However, SpO2 is unreliable at the high oxygenation levels produced by preoxygenation and, in the event of desaturation, may not decrease sufficiently early to allow preventive measures. The oxygen reserve index (ORI) is a dimensionless parameter that can also be measured continuously by a fingertip monitor and reflects oxygenation in the moderate hyperoxia range. The ORI ranges from 0 to 1 when arterial oxygen saturation (PaO2) varies between 100 to 200 mmHg, as occurs during preoxygenation. No trial has assessed the potential effects of ORI monitoring to guide preoxygenation for ETI in unstable patients. We designed a multicenter, two-arm, parallel-group, randomized, superiority, open trial in 950 critically ill adults requiring ETI. The intervention consists in monitoring ORI values and using an ORI target for preoxygenation of at least 0.6 for at least 1 minute. In the control group, preoxygenation is guided by SpO2 values recorded by a standard pulse oximeter, according to the standard of care, the goal being to obtain 100% SpO2 during preoxygenation, which lasts at least 3 minutes. The standard-of-care ETI technique is used in both arms. Baseline parameters, rapid-sequence induction medications, ETI devices, and physiological data are recorded. The primary outcome is the lowest SpO2 value from laryngoscopy to 2 minutes after successful ETI. Secondary outcomes include cognitive function on day 28. Assuming a 10% standard deviation for the lowest SpO2 value in the control group, no missing data, and crossover of 5% of patients, with the bilateral alpha risk set at 0.05, including 950 patients will provide 85% power for detecting a 2% between-group absolute difference in the lowest SpO2 value. Should ORI monitoring with a target of ≥0.6 be found to increase the lowest SpO2 value during ETI, then this trial may change current practice regarding preoxygenation for ETI. Trial registration: Registered on ClinicalTrials.gov (NCT05867875) on April 27, 2023., Competing Interests: JBL has received lecturing fees from BD and Masimo. Alexis Ferré reports honoraria by Fisher & Paykel for a lecture during the 2022 SFMU Congress, which bears no relation to the submitted work. None of the other authors has any competing interests to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Hille et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Natural Language Processing (NLP) is a subset of artificial intelligence that enables machines to understand and respond to human language through Large Language Models (LLMs)‥ These models have diverse applications in fields such as medical research, scientific writing, and publishing, but concerns such as hallucination, ethical issues, bias, and cybersecurity need to be addressed. To understand the scientific community's understanding and perspective on the role of Artificial Intelligence (AI) in research and authorship, a survey was designed for corresponding authors in top medical journals. An online survey was conducted from July 13th, 2023, to September 1st, 2023, using the SurveyMonkey web instrument, and the population of interest were corresponding authors who published in 2022 in the 15 highest-impact medical journals, as ranked by the Journal Citation Report. The survey link has been sent to all the identified corresponding authors by mail. A total of 266 authors answered, and 236 entered the final analysis. Most of the researchers (40.6%) reported having moderate familiarity with artificial intelligence, while a minority (4.4%) had no associated knowledge. Furthermore, the vast majority (79.0%) believe that artificial intelligence will play a major role in the future of research. Of note, no correlation between academic metrics and artificial intelligence knowledge or confidence was found. The results indicate that although researchers have varying degrees of familiarity with artificial intelligence, its use in scientific research is still in its early phases. Despite lacking formal AI training, many scholars publishing in high-impact journals have started integrating such technologies into their projects, including rephrasing, translation, and proofreading tasks. Efforts should focus on providing training for their effective use, establishing guidelines by journal editors, and creating software applications that bundle multiple integrated tools into a single platform., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Salvagno et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Traumatic brain injury (TBI) is a leading cause of mortality and morbidity globally. This study aimed to measure the health-related quality of life (HRQOL) of TBI patients in Vietnam and evaluate the associated factors., Methods: A longitudinal study was conducted in Thai Binh, Vietnam, from February to September 2020. The EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) and EQ-Visual Analog Scale (EQ-VAS) were used to measure HRQOL. Socio-demographic characteristics, including age, gender, education level, employment status, marital status, and income, as well as clinical characteristics such as injury severity, cause of injury, comorbidities, and functional status, were collected through patient interviews and medical records. Multivariate Tobit regression analysis was performed to identify variables associated with HRQOL., Results: The study included 212 TBI patients. The mean scores of the VAS and EQ-5D-5L scales were 82.4/100 (SD = 14.49) and 0.9/1.0 (SD = 0.2), respectively, indicating a relatively high HRQOL. However, certain factors significantly impacted HRQOL. Unemployed patients and those with depression or higher injury severity, as measured by the Injury Severity Score (ISS), had notably lower HRQOL scores. Poor sleep quality and severe functional impairments also adversely affected HRQOL, whereas patients discharged for a longer period had slightly better HRQOL scores., Conclusion: This study highlights that while HRQOL is relatively high among TBI patients, mental health disorders, injury severity, and functional impairments are key factors negatively impacting their quality of life. High HRQOL was defined by mean scores on the VAS and EQ-5D-5L scales, with higher scores indicating better quality of life. Home-based interventions addressing these issues could improve HRQOL for TBI patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Vu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The relationship between molybdenum and kidney-related disease outcomes, including hyperuricemia, is not well investigated. This study aims to determine whether molybdenum and its antioxidative property are associated with systemic inflammation and kidney-related disease parameters including hyperuricemia. Urinary molybdenum's epidemiological relationship to hyperuricemia and kidney-disease related outcomes was evaluated in 15,370 adult participants in the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2016. Individuals' urinary molybdenum levels were corrected to their urinary creatinine concentrations. The association between urinary molybdenum-to-creatinine ratio and kidney-disease related outcomes were assessed by multivariable linear and logistic regression analyses, adjusting for covariates including age, sex, ethnicity, diabetes mellitus, hypertension, body mass index, and estimated glomerular filtration rate. Antimony and tungsten were used as control trace metals. Experimentally, HK-2 cell was used to assess molybdenum's antioxidative properties. HK-2 cells were challenged with H2O2-induced oxidative stress. Oxidative stress was measured using a fluorescent microplate assay for reactive oxygen species (ROS) and antioxidation levels were assessed by measuring the expression of manganese superoxide dismutase. In the adult NHANES population, urinary molybdenum-to-creatinine ratio was significantly associated with decreased serum uric acid (β, -0.119; 95% CI, -0.148 to -0.090) concentrations, and decreased prevalence of hyperuricemia (OR, 0.73; 95% CI, 0.64-0.83) and gout (OR, 0.71; 95% CI, 0.52-0.94). Higher urinary molybdenum levels were associated with lower levels of systemic oxidative stress (gamma-glutamyltransferase levels; β, -0.052; 95% CI, -0.067 to -0.037) and inflammation (C-reactive protein levels; β, -0.184; 95% CI, -0.220 to -0.148). In HK-2 cells under H2O2-induced oxidative stress, molybdenum upregulated manganese superoxide dismutase expression and decreased oxidative stress. Urinary molybdenum levels are associated with decreased prevalence of hyperuricemia and gout in adult population. Molybdenum's antioxidative properties might have acted as an important mechanism for the reduction of systemic inflammation, ROS, and uric acid levels., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Joun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Mechanical power of ventilation, a summary parameter reflecting the energy transferred from the ventilator to the respiratory system, has associations with outcomes. INTELLiVENT-Adaptive Support Ventilation is an automated ventilation mode that changes ventilator settings according to algorithms that target a low work-and force of breathing. The study aims to compare mechanical power between automated ventilation by means of INTELLiVENT-Adaptive Support Ventilation and conventional ventilation in critically ill patients., Materials and Methods: International, multicenter, randomized crossover clinical trial in patients that were expected to need invasive ventilation > 24 hours. Patients were randomly assigned to start with a 3-hour period of automated ventilation or conventional ventilation after which the alternate ventilation mode was selected. The primary outcome was mechanical power in passive and active patients; secondary outcomes included key ventilator settings and ventilatory parameters that affect mechanical power., Results: A total of 96 patients were randomized. Median mechanical power was not different between automated and conventional ventilation (15.8 [11.5-21.0] versus 16.1 [10.9-22.6] J/min; mean difference -0.44 (95%-CI -1.17 to 0.29) J/min; P = 0.24). Subgroup analyses showed that mechanical power was lower with automated ventilation in passive patients, 16.9 [12.5-22.1] versus 19.0 [14.1-25.0] J/min; mean difference -1.76 (95%-CI -2.47 to -10.34J/min; P < 0.01), and not in active patients (14.6 [11.0-20.3] vs 14.1 [10.1-21.3] J/min; mean difference 0.81 (95%-CI -2.13 to 0.49) J/min; P = 0.23)., Conclusions: In this cohort of unselected critically ill invasively ventilated patients, automated ventilation by means of INTELLiVENT-Adaptive Support Ventilation did not reduce mechanical power. A reduction in mechanical power was only seen in passive patients., Study Registration: Clinicaltrials.gov (study identifier NCT04827927), April 1, 2021., Url of Trial Registry Record: https://clinicaltrials.gov/study/NCT04827927?term=intellipower&rank=1., Competing Interests: LBK received fees from Hamilton Medical for lecturing. MJS was part-time employed as a team leader of Research and New Technologies at Hamilton Medical from January 2022 till January 2023. The other authors declare no conflicts of interest., (Copyright: © 2024 Buiteman-Kruizinga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Most of the current bacteriophages (phages) are mostly isolated from environments. However, phages isolated from feces might be more specific to the bacteria that are harmful to the host. Meanwhile, some phages from the environment might affect non-pathogenic bacteria for the host., Methods: Here, bacteriophages isolated from mouse feces were intratracheally (IT) or intravenously (IV) administered in pneumonia mice caused by Pseudomonas aeruginosa at 2 hours post-intratracheal bacterial administration. As such, the mice with phage treatment, using either IT or IV administration, demonstrated less severe pneumonia as indicated by mortality, serum cytokines, bacteremia, bacterial abundance in bronchoalveolar lavage fluid (BALF), and neutrophil extracellular traps (NETs) in lung tissue (immunofluorescence of neutrophil elastase and myeloperoxidase)., Results: Interestingly, the abundance of phages in BALF from the IT and IV injections was similar, supporting a flexible route of phage administration. With the incubation of bacteria with neutrophils, the presence of bacteriophages significantly improved bactericidal activity, but not NETs formation, with the elevated supernatant IL-6 and TNF-α, but not IL-1β. In conclusion, our findings suggest that bacteriophages against Pseudomonas aeruginosa can be discovered from feces of the host., Conclusions: The phages attenuate pneumonia partly through an enhanced neutrophil bactericidal activity, but not via inducing NETs formation. The isolation of phages from the infected hosts themselves might be practically useful for future treatment. More studies are warranted., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sutnu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Type 2 diabetes mellitus (T2DM) represents a significant worldwide health issue, experiencing an increasing incidence rate. Effective dietary strategies are vital for T2DM management, but the optimal dietary patterns remain debated due to inconsistent research outcomes and single-outcome reporting. Network Meta-Analysis (NMA) provides a powerful approach for integrating data from randomized controlled trials (RCTs), enabling a detailed evaluation of the impact of different dietary patterns. This document presents our strategy for a systematic review and network meta-analysis, aimed at assessing the influence of key dietary patterns on glycemic control, lipid profiles, and weight management in individuals with Type 2 Diabetes Mellitus (T2DM)., Materials and Methods: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and network meta-analyses guidelines, we conducted a comprehensive search of PubMed, EMBASE, and the Cochrane Library, without language or date restrictions. Our objective is to assess the efficacy of various dietary interventions in managing Type 2 Diabetes Mellitus (T2DM). We used standardized mean differences for pairwise comparisons and a Bayesian framework for ranking interventions via Surface Under the Cumulative Ranking Curve (SUCRA). Key analyses include heterogeneity, transitivity, and sensitivity assessments, along with quality and risk evaluations using the Cochrane Collaboration's tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system., Ethics and Dissemination: This systematic review and network meta-analysis involve aggregate data from previous trials, obviating the need for additional ethical approval. The search strategy will be executed starting October 2023, with all searches completed by December 2023, to encompass the most current studies available. Findings will be shared through academic conferences and peer-reviewed journals focused on diabetes care and nutrition., Trial Registration: PROSPERO registration number CRD42023465791., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Expert opinion is widely used in clinical guidelines. No research has ever been conducted investigating the use of expert opinion in international infectious disease guidelines. This study aimed to create an analytical map by describing the prevalence and utilization of expert opinion in infectious disease guidelines and analyzing the methodological aspects of these guidelines., Methods: In this meta-epidemiological study, systematic searches in PubMed and Trip Medical Database were performed to identify clinical guidelines on infectious diseases, published between January 2018 and May 2023 in English, by international organizations. Data extracted included guideline characteristics, expert opinion utilization, and methodological details. Prevalence and rationale of expert opinion use were analyzed descriptively. Methodological differences between groups were analyzed with Chi-square and Mann-Whitney U Test., Results: The analysis covered 66 guidelines with 2296 recommendations, published/endorsed by 136 organizations. Most guidelines (79%) used systematic literature searches, 42% provided search strategies, and 38% presented screening flow diagrams and conducted risk of bias assessments. 48.5% of the guidelines allowed expert opinion, most of which included expert opinion as part of the evidence hierarchy within the grading system. Guidelines allowing expert opinion, compared to those which do not, issued more recommendations per guideline (48.82 vs.19.13, p<0.001), and reported fewer screening flow diagrams (25% vs. 65%, p = 0.002), and less risk of bias assessments (19% vs.78%, p<0.001)., Conclusions: Expert opinion is utilized in half of assessed guidelines, often integrated into the evidence hierarchy within the grading system. Its utilization varies considerably in methodology, form, and terminology between guidelines. These findings highlight a pressing need for additional research and guidance, to improve and advance the standardization of infectious disease guidelines., Competing Interests: BN: consulting services in guideline methodology for the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), outside the submitted work. BN is a member of the GRADE working group, outside the submitted work. LS: Is a member of the GRADE working group, outside the submitted work. IML: lecture honoraria from Thermofisher, Gilead, MSD and advisory board Fresenius Kabi, MaaT Pharma, Gilead, Biotest, Accelerate, bioMérieux, outside the submitted work. BL: is the president of the Hungarian Society of Infectious Diseases and Clinical Microbiology and Head of the Guideline Committee Working Group, outside the submitted work., (Copyright: © 2024 Nagavci et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Sepsis is a major cause of morbidity and mortality worldwide. In the updated, 2016 Sepsis-3 criteria, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, where organ dysfunction can be represented by an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more. We sought to apply the Sepsis-3 criteria to characterise the septic cohort in the Amsterdam University Medical Centres database (Amsterdam UMCdb)., Methods: We examined adult intensive care unit (ICU) admissions in the Amsterdam UMCdb, which contains de-identified data for patients admitted to a mixed surgical-medical ICU at a tertiary academic medical centre in the Netherlands. We operationalised the Sepsis-3 criteria, defining organ dysfunction as an increase in the SOFA score of 2 points or more, while infection was defined as a new course of antibiotics or an escalation in antibiotic therapy, with at least one antibiotic given intravenously. Patients with sepsis were determined to be in septic shock if they additionally required the use of vasopressors and had a lactate level >2 mmol/L., Results: We identified 18,221 ICU admissions from 16,408 patients in our cohort. There were 6,312 unique sepsis episodes, of which 30.2% met the criteria for septic shock. A total of 4,911/6,312 sepsis (77.8%) episodes occurred on ICU admission. Forty-seven percent of emergency medical admissions and 36.7% of emergency surgical admissions were for sepsis. Overall, there was a 12.5% ICU mortality rate; patients with septic shock had a higher ICU mortality rate (38.4%) than those without shock (11.4%)., Conclusions: We successfully operationalised the Sepsis-3 criteria to the Amsterdam UMCdb, allowing the characterization and comparison of sepsis epidemiology across different centres., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Williams et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The impact of closed-loop control systems to titrate oxygen flow in critically ill patients, including their effectiveness, efficacy, workload and safety, remains unclear. This systematic review investigated the utilization of closed-loop oxygen systems for critically ill patients in comparison to manual oxygen titration systems focusing on these topics., Methods and Findings: A search was conducted across several databases including MEDLINE, CENTRAL, EMBASE, LILACS, CINAHL, LOVE, ClinicalTrials.gov, and the World Health Organization on March 3, 2022, with subsequent updates made on June 27, 2023. Evidence databases were searched for randomized clinical parallel or crossover studies investigating closed-loop oxygen control systems for critically ill patients. This systematic review and meta-analysis was performed following the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. The analysis was conducted using Review Manager software, adopting the mean difference or standardized mean difference with a 95% confidence interval (95% CI) for continuous variables or risk ratio with 95% CI for dichotomous outcomes. The main outcome of interest was the percentage of time spent in the peripheral arterial oxygen saturation target. Secondary outcomes included time for supplemental oxygen weaning, length of stay, mortality, costs, adverse events, and workload of healthcare professional. A total of 37 records from 21 studies were included in this review with a total of 1,577 participants. Compared with manual oxygen titration, closed-loop oxygen control systems increased the percentage of time in the prescribed SpO2 target, mean difference (MD) 25.47; 95% CI 19.7, 30.0], with moderate certainty of evidence. Current evidence also shows that closed-loop oxygen control systems have the potential to reduce the percentage of time with hypoxemia (MD -0.98; 95% CI -1.68, -0.27) and healthcare workload (MD -4.94; 95% CI -7.28, -2.61) with low certainty of evidence., Conclusion: Closed-loop oxygen control systems increase the percentage of time in the preferred SpO2 targets and may reduce healthcare workload., Trial Registration: PROSPERO: CRD42022306033., Competing Interests: MJS was the team leader of Research and New Technologies at Hamilton Medical AG, Bonaduz, Switzerland, from January 2022 until January 2023. The other authors declare no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Mól et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Describing mitochondrial oxygenation (mitoPO2) and its within- and between-subject variability over time after 5-aminolevulinic acid (ALA) plaster application in healthy volunteers., Design: Prospective cohort study., Setting: Measurements were performed in Leiden University Medical Center, the Netherlands., Participants: Healthy volunteers enrolled from July to September 2020., Interventions: Two ALA plasters were placed parasternal left and right, with a 3-hour time interval, to examine the influence of the calendar time on the value of mitoPO2. We measured mitoPO2 at 4, 5, 7, 10, 28, and 31 hours after ALA plaster 1 application, and at 4, 5, 7, 25, and 28 hours after ALA plaster 2 application., Primary and Secondary Outcome Measures: At each time point, five mitoPO2 measurements were performed. Within-subject variability was defined as the standard deviation (SD) of the mean of five measurements per timepoint of a study participant. The between-subject variability was the SD of the mean mitoPO2 value of the study population per timepoint., Results: In 16 completed inclusions, median mitoPO2 values and within-subject variability were relatively similar over time at all time points for both plasters. An increase in overall between-subject variability was seen after 25 hours ALA plaster time (19.6 mm Hg vs 23.9 mm Hg after respectively 10 and 25 hours ALA plaster time)., Conclusions: The mitoPO2 values and within-subject variability remained relatively stable over time in healthy volunteers. An increase in between-subject variability was seen after 25 hours ALA plaster time warranting replacement of the ALA plaster one day after its application., Trial Registration: ClinicalTrials.gov with trial number NCT04626661., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: E.G. Mik is a founder and shareholder of Photonics Healthcare B.V. (Utrecht, The Netherlands). Photonics Healthcare develops and commercializes the COMET measuring system for mitochondrial oxygen measurements. The other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Baysan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sepsis-Associated Liver Injury (SALI) is an independent risk factor for death from sepsis. The aim of this study was to develop an interpretable machine learning model for early prediction of 28-day mortality in patients with SALI. Data from the Medical Information Mart for Intensive Care (MIMIC-IV, v2.2, MIMIC-III, v1.4) were used in this study. The study cohort from MIMIC-IV was randomized to the training set (0.7) and the internal validation set (0.3), with MIMIC-III (2001 to 2008) as external validation. The features with more than 20% missing values were deleted and the remaining features were multiple interpolated. Lasso-CV that lasso linear model with iterative fitting along a regularization path in which the best model is selected by cross-validation was used to select important features for model development. Eight machine learning models including Random Forest (RF), Logistic Regression, Decision Tree, Extreme Gradient Boost (XGBoost), K Nearest Neighbor, Support Vector Machine, Generalized Linear Models in which the best model is selected by cross-validation (CV&#95;glmnet), and Linear Discriminant Analysis (LDA) were developed. Shapley additive interpretation (SHAP) was used to improve the interpretability of the optimal model. At last, a total of 1043 patients were included, of whom 710 were from MIMIC-IV and 333 from MIMIC-III. Twenty-four clinically relevant parameters were selected for model construction. For the prediction of 28-day mortality of SALI in the internal validation set, the area under the curve (AUC (95% CI)) of RF was 0.79 (95% CI: 0.73-0.86), and which performed the best. Compared with the traditional disease severity scores including Oxford Acute Severity of Illness Score (OASIS), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Systemic Inflammatory Response Syndrome (SIRS), and Acute Physiology Score III (APS III), RF also had the best performance. SHAP analysis found that Urine output, Charlson Comorbidity Index (CCI), minimal Glasgow Coma Scale (GCS&#95;min), blood urea nitrogen (BUN) and admission&#95;age were the five most important features affecting RF model. Therefore, RF has good predictive ability for 28-day mortality prediction in SALI. Urine output, CCI, GCS&#95;min, BUN and age at admission(admission&#95;age) within 24 h after intensive care unit(ICU) admission contribute significantly to model prediction., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Wen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The consequences of partial nephrectomy (PN) compared to radical nephrectomy (RN) are less documented in patients with pre-existing chronic kidney disease (CKD) or with solitary kidney (SK). We assessed renal outcomes, and their determinants, after PN or RN in a retrospective cohort of patients with moderate-to-severe CKD (RN-CKD and PN-CKD) or SK (PN-SK). All surgical procedures conducted between 2013 and 2018 in our institution in patients with pre-operative estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m2 or with SK were included. The primary outcome was a composite criterion including CKD progression or major adverse cardio-vascular events (MACE) or death, assessed one year after surgery. Predictors of the primary outcome were determined using multivariate analyses. A total of 173 procedures were included (67 RN, and 106 PN including 27 SK patients). Patients undergoing RN were older, with larger tumors. Preoperative eGFR was not significantly different between the groups. One year after surgery, PN-CKD was associated with lower rate of the primary outcome compared to RN-CKD (43% vs 71% p = 0.007). In multivariate analysis, independent risk factors for the primary outcome were postoperative AKI (stage 1 to stage 3 ranging from OR = 8.68, 95% CI 3.23-23.33, to OR = 28.87, 95% CI 4.77-167.61), larger tumor size (OR = 1.21 per cm, 95% CI 1.02-1.45), while preoperative eGFR, age, sex, diabetes mellitus, and hypertension were not. Postoperative AKI after PN or RN was the major independent determinant of worse outcomes (CKD progression, MACE, or death) one year after surgery., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Schleef et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To evaluate the association of a validated chest computed tomography (Chest-CT) severity score in COVID-19 patients with their respiratory outcome in the Intensive Care Unit., Methods: A single-center, prospective study evaluated patients with positive RT-PCR for COVID-19, who underwent Chest-CT and had a final COVID-19 clinical diagnosis needing invasive mechanical ventilation in the ICU. The admission chest-CT was evaluated according to a validated Chest-CT Severity Score in COVID-19 (Chest-CTSS) divided into low ≤50% (<14 points) and >50% high (≥14 points) lung parenchyma involvement. The association between the initial score and their pulmonary clinical outcomes was evaluated., Results: 121 patients were clustered into the > 50% lung involvement group and 105 patients into the ≤ 50% lung involvement group. Patients ≤ 50% lung involvement (<14 points) group presented lower PEEP levels and FiO2 values, respectively GEE P = 0.09 and P = 0.04. The adjusted COX model found higher hazard to stay longer on invasive mechanical ventilation HR: 1.69, 95% CI, 1.02-2.80, P = 0.042 and the adjusted logistic regression model showed increased risk ventilator-associated pneumonia OR = 1.85 95% CI 1.01-3.39 for COVID-19 patients with > 50% lung involvement (≥14 points) on Chest-CT at ICU admission., Conclusion: COVID-19 patients with >50% lung involvement on Chest-CT admission presented higher chances to stay longer on invasive mechanical ventilation and more chances to developed ventilator-associated pneumonia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Esper Treml et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The fluid balance is a critical parameter in intensive care units (ICU) as it provides information about the patient's volume status. However, the accuracy of fluid balance measurements is often compromised due to the complexity and repetition of actions involved. Additionally, the fluid balance could be recalculated for insensible fluid loss. Weighing is an alternative method to estimate the patient's volume status. Built-in scales in beds make patient weighing easier and less time-consuming, allowing clinicians to intervene more quickly on existing treatments., Aim: This study compares fluid balance, and body weight changes over time in ICU patients. Furthermore, it seeks to determine the degree of congruence between the fluid balance corrected for insensible fluid loss and daily body weight in ICU patients., Methods: A single-center observational study was conducted in an ICU of a university hospital. All consecutive patients admitted to a bed with an integrated weighing scale were eligible. Exclusion criteria were (1) body weight ≥254,4 kilograms; (2) oral nutrition; (3) a flush catheter or balance; (4) only a single weight measurement; (5) delta body weight change of ≥5kg in 12 hours. Weights and fluid balances were obtained every 12 hours., Results: We obtained 2282 measurements (n = 187 patients). The correlation between weight and fluid balance was weak (r = 0.274). After adjusting the fluid balance for insensible fluid loss, the correlation remained weak (r = 0,268). Bland Altman analysis revealed a wide confidence interval for both the fluid balance and corrected fluid balance versus weight., Conclusion and Implications of Key Findings: This study shows a weak correlation between weight and fluid balance. Therefore, when monitoring the volume status in the ICU, fluid balance and weight should both be taken into account. This two-pronged approach is crucial because it provides more control over erroneous fluid balance or weighing measurements., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mensink et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Intraventricular hemorrhage (IVH) is a severe condition with poor outcomes and high mortality. IRRAflow® (IRRAS AB) is a new technology introduced to accelerate IVH clearance by minimally invasive wash-out. The IRRAflow® system performs active and controlled intracranial irrigation and aspiration with physiological saline, while simultaneously monitoring and maintaining a stable intracranial pressure (ICP). We addressed important aspects of the device implementation and intracranial lavage., Method: To allow versatile investigation of multiple device parameters, we designed an ex vivo lab setup. We evaluated 1) compatibility between the IRRAflow® catheter and the Silverline f10 bolt (Spiegelberg), 2) the physiological and hydrodynamic effects of varying the IRRAflow® settings, 3) the accuracy of the IRRAflow® injection volumes, and 4) the reliability of the internal ICP monitor of the IRRAflow®., Results: The IRRAflow® catheter was not compatible with Silverline bolt fixation, which was associated with leakage and obstruction. Design space exploration of IRRAflow® settings revealed that appropriate settings included irrigation rate 20 ml/h with a drainage bag height at 0 cm, irrigation rate 90 ml/h with a drainage bag height at 19 cm and irrigation rate 180 ml/h with a drainage bag height at 29 cm. We found the injection volume performed by the IRRAflow® to be stable and reliable, while the internal ICP monitor was compromised in several ways. We observed a significant mean drift difference of 3.16 mmHg (variance 0.4, p = 0.05) over a 24-hour test period with a mean 24-hour drift of 3.66 mmHg (variance 0.28) in the pressures measured by the IRRAflow® compared to 0.5 mmHg (variance 1.12) in the Raumedic measured pressures., Conclusion: Bolting of the IRRAflow® catheter using the Medtronic Silverline® bolt is not recommendable. Increased irrigation rates are recommendable followed by a decrease in drainage bag level. ICP measurement using the IRRAflow® device was unreliable and should be accompanied by a control ICP monitor device in clinical settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Haldrup et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: An increasing amount of longitudinal health data is available on critically ill septic patients in the age of digital medicine, including daily sequential organ failure assessment (SOFA) score measurements. Thus, the assessment in sepsis focuses increasingly on the evaluation of the individual disease's trajectory. Machine learning (ML) algorithms may provide a promising approach here to improve the evaluation of daily SOFA score dynamics. We tested whether ML algorithms can outperform the conventional ΔSOFA score regarding the accuracy of 30-day mortality prediction., Methods: We used the multicentric SepsisDataNet.NRW study cohort that prospectively enrolled 252 sepsis patients between 03/2018 and 09/2019 for training ML algorithms, i.e. support vector machine (SVM) with polynomial kernel and artificial neural network (aNN). We used the Amsterdam UMC database covering 1,790 sepsis patients for external and independent validation., Results: Both SVM (AUC 0.84; 95% CI: 0.71-0.96) and aNN (AUC 0.82; 95% CI: 0.69-0.95) assessing the SOFA scores of the first seven days led to a more accurate prognosis of 30-day mortality compared to the ΔSOFA score between day 1 and 7 (AUC 0.73; 95% CI: 0.65-0.80; p = 0.02 and p = 0.05, respectively). These differences were even more prominent the shorter the time interval considered. Using the SOFA scores of day 1 to 3 SVM (AUC 0.82; 95% CI: 0.68 0.95) and aNN (AUC 0.80; 95% CI: 0.660.93) led to a more accurate prognosis of 30-day mortality compared to the ΔSOFA score (AUC 0.66; 95% CI: 0.58-0.74; p < 0.01 and p < 0.01, respectively). Strikingly, all these findings could be confirmed in the independent external validation cohort., Conclusions: The ML-based algorithms using daily SOFA scores markedly improved the accuracy of mortality compared to the conventional ΔSOFA score. Therefore, this approach could provide a promising and automated approach to assess the individual disease trajectory in sepsis. These findings reflect the potential of incorporating ML algorithms as robust and generalizable support tools on intensive care units., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Palmowski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: To synthesize the existing evidence on the association between obesity and rotator cuff repair outcomes such as pain, shoulder function, range of motion, and complications., Methods: We searched PubMed, EMBASE, and Scopus databases for relevant observational studies (cohort and case-control) and randomized controlled trials (RCTs). The target population in the included studies comprised adults who had undergone rotator cuff repair procedures. The outcomes of interest were functional outcomes (such as range of motion), pain scores, patient-reported outcome measures, and complication rates (such as re-repair and readmission rates). We applied random-effects models and calculated pooled effect sizes reported as standardized mean differences (SMDs) or relative risks (RRs) with 95% confidence intervals., Results: We analysed data from 11 studies. In most, the follow-up periods ranged from 12 to 60 months. Obese individuals experienced greater pain (SMD 0.30; 95% CI, 0.10, 0.50) and lower shoulder function (SMD -0.33; 95% CI, -0.54, -0.12) than other individuals in the long-term post-operative follow-up. Obese individuals also had higher risks of complications (RR 1.48; 95% CI, 1.11, 1.98) and readmission (RR 1.35; 95% CI, 1.27, 1.43), but a similar likelihood of re-repair (RR, 1.27; 95% CI, 0.82, 1.95) than non-obese/normal BMI individuals. While the forward flexion and external rotation functions were comparable, obese individuals displayed less internal rotation function than other individuals (SMD -0.59; 95% CI, -0.87, -0.30)., Conclusion: Obesity was associated with unfavourable outcomes after rotator cuff surgery, including increased pain, reduced shoulder function, high risks of complications, and readmission. These findings emphasize the importance of addressing obesity-related factors to improve post-operative outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: A positive work environment (WE) is paramount for healthcare employees to provide good quality care. To stimulate a positive work environment, employees' perceptions of the work environment need to be assessed. This study aimed to assess the reliability and validity of the Dutch version of the Culture of Care Barometer (CoCB-NL) survey in hospitals., Methods: This longitudinal validation study explored content validity, structural validity, internal consistency, hypothesis testing for construct validity, and responsiveness. The study was conducted at seven departments in two Dutch university hospitals. The departments were included based on their managers' motivation to better understand their employees' perception of their WE. All employees of participating departments were invited to complete the survey (n = 1,730)., Results: The response rate was 63.2%. The content of the CoCB-NL was considered relevant and accessible by the respondents. Two factor models were found. First, confirmative factor analysis of the original four-factor structure showed an acceptable fit (X2 2006.49; df 399; p = <0.001; comparative fit index [CFI] 0.82; Tucker-Lewis index [TLI] 0.80; root mean square error of approximation [RMSEA] 0.09). Second, explanatory factor analysis revealed a five-factor model including 'organizational support', 'leadership', 'collegiality and teamwork', 'relationship with manager', and 'employee influence and development'. This model was confirmed and showed a better fit (X2 1552.93; df 395; p = < 0.00; CFI 0.87; TLI 0.86; RMSEA 0.07). Twelve out of eighteen hypotheses were confirmed. Responsiveness was assumed between the measurements., Conclusions: The CoCB-NL is a valid and reliable instrument for identifying areas needing improvement in the WE. Furthermore, the CoCB-NL appears to be responsive and therefore useful for longitudinal evaluations of healthcare employees' work environments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Maassen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To determine whether the age at menarche (AAM) and the age at menopause (ANM) are causally related to the development of sepsis., Methods: We performed a two-sample Mendelian randomization (MR) analysis by utilizing summary statistics from genome-wide association study (GWAS) datasets for both the exposure and outcome variables. Single nucleotide polymorphisms (SNPs) that exhibited significant associations with AAM and ANM were chosen as instrumental variables to estimate the causal effects on sepsis. Our study employed a variety of methods, including MR-Egger regression, weighted median estimation, inverse variance weighting, a simple model, and a weighted model. Odds ratios (ORs) along with their corresponding 95% confidence intervals (CIs) were used as the primary indicators for assessing causality. Furthermore, we conducted sensitivity analyses to explore the presence of genetic heterogeneity and validate the robustness of the tools employed., Result: Our analysis revealed a significant negative causal relationship between AAM and the risk of sepsis (IVW: OR = 0.870, 95% CI = 0.793-0.955, P = 0.003). However, our Mendelian randomization (MR) analysis did not yield sufficient evidence to support a causal link between ANM and sepsis (IVW: OR = 0.987, 95% CI = 0.971-1.004, P = 0.129)., Conclusions: Our findings suggest that an earlier AAM may be associated with an increased risk of sepsis. However, we did not find sufficient evidence to support a causal relationship between ANM and sepsis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Platelets (PLTS) and fresh frozen plasma (FFP) are often transfused in cardiac surgery patients for perioperative bleeding. Their relative effectiveness is unknown., Methods: We conducted an entropy-weighted retrospective cohort study using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database. All adults undergoing cardiac surgery between 2005-2021 across 58 sites were included. The primary outcome was operative mortality., Results: Of 174,796 eligible patients, 15,360 (8.79%) received PLTS in the absence of FFP and 6,189 (3.54%) patients received FFP in the absence of PLTS. The median cumulative dose was 1 unit of pooled platelets (IQR 1 to 3) and 2 units of FFP (IQR 0 to 4) respectively. After entropy weighting to achieve balanced cohorts, FFP was associated with increased perioperative (Risk Ratio [RR], 1.63; 95% Confidence Interval [CI], 1.40 to 1.91; P<0.001) and 1-year (RR, 1.50; 95% CI, 1.32 to 1.71; P<0.001) mortality. FFP was associated with increased rates of 4-hour chest drain tube output (Adjusted mean difference in ml, 28.37; 95% CI, 19.35 to 37.38; P<0.001), AKI (RR, 1.13; 95% CI, 1.01 to 1.27; P = 0.033) and readmission to ICU (RR, 1.24; 95% CI, 1.09 to 1.42; P = 0.001)., Conclusion: In perioperative bleeding in cardiac surgery patient, platelets are associated with a relative mortality benefit over FFP. This information can be used by clinicians in their choice of procoagulant therapy in this setting., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hinton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although CO2 field-flooding was first used during cardiac surgery more than 60 years ago, its efficacy is still disputed. The invisible nature of the gas and the difficulty in determining the "safe" quantity to protect the patient are two of the main obstacles to overcome for its validation. Moreover, CO2 concentration in the chest cavity is highly sensitive to procedural aspects, such suction and hand movements. Based on our review of the existing literature, we identified four major factors that influence the intra-cavity CO2 concentration during open-heart surgery: type of delivery device (diffuser), delivery CO2 flow rate, diffuser position around the wound cavity, and its orientation inside the cavity. In this initial study, only steady state conditions were considered to establish a basic understanding on the effect of the four above-mentioned factors. Transient factors, such as suction or hand movements, will be reported separately., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Puthettu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to evaluate the therapeutic efficacy and effect of blood purification (BP) therapy on severe acute pancreatitis (SAP). Information on 305 patients (BP group 68, control group 237) diagnosed with SAP was retrieved from the Medical Information Mart for Intensive Care IV (MIMIC IV) database. Firstly, the influence of BP treatment was preliminarily evaluated by comparing the outcome indicators of the two groups. Secondly, multiple regression analysis was used to screen the mortality risk factors to verify the impact of BP on the survival outcome of patients. Then, the effect of BP treatment was re-validated with baseline data. Finally, cox regression was used to make the survival curve after matching to confirm whether BP could affect the death outcome. The results indicated that the BP group had a lower incidence of shock (p = 0.012), but a higher incidence of acute kidney injury (AKI) (p < 0.001), with no differences observed in other outcome indicators when compared to the control group. It was also found that the 28-day survival curve of patients between the two groups was significantly overlapped (p = 0.133), indicating that BP treatment had no significant effect on the survival outcome of patients with SAP. Although BP is beneficial in stabilizing hemodynamics, it has no effect on short- and long-term mortality of patients. The application of this technology in the treatment of SAP should be done with caution until appropriate BP treatment methods are developed, particularly for patients who are not able to adapt to renal replacement therapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: General practitioners (GPs) often assess patients with acute infections. It is challenging for GPs to recognize patients needing immediate hospital referral for sepsis while avoiding unnecessary referrals. This study aimed to predict adverse sepsis-related outcomes from telephone triage information of patients presenting to out-of-hours GP cooperatives., Methods: A retrospective cohort study using linked routine care databases from out-of-hours GP cooperatives, general practices, hospitals and mortality registration. We included adult patients with complaints possibly related to an acute infection, who were assessed (clinic consultation or home visit) by a GP from a GP cooperative between 2017-2019. We used telephone triage information to derive a risk prediction model for sepsis-related adverse outcome (infection-related ICU admission within seven days or infection-related death within 30 days) using logistic regression, random forest, and neural network machine learning techniques. Data from 2017 and 2018 were used for derivation and from 2019 for validation., Results: We included 155,486 patients (median age of 51 years; 59% females) in the analyses. The strongest predictors for sepsis-related adverse outcome were age, type of contact (home visit or clinic consultation), patients considered ABCD unstable during triage, and the entry complaints"general malaise", "shortness of breath" and "fever". The multivariable logistic regression model resulted in a C-statistic of 0.89 (95% CI 0.88-0.90) with good calibration. Machine learning models performed similarly to the logistic regression model. A "sepsis alert" based on a predicted probability >1% resulted in a sensitivity of 82% and a positive predictive value of 4.5%. However, most events occurred in patients receiving home visits, and model performance was substantially worse in this subgroup (C-statistic 0.70)., Conclusion: Several patient characteristics identified during telephone triage of patients presenting to out-of-hours GP cooperatives were associated with sepsis-related adverse outcomes. Still, on a patient level, predictions were not sufficiently accurate for clinical purposes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Loots et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Falls among the elderly are an important global health problem. This study assesses knowledge regarding risk factors of falls, as well as attitudes and practices towards fall prevention among older adults in the rural community. A cross-sectional study was performed in four rural communes in Thai Binh province, Vietnam. A total of 3038 older people were recruited. Knowledge was assessed by using Falls Risk Awareness Questionnaire. Questions about attitudes were based on the Health Belief Model. Other questions regarding attitudes and practices regarding fall prevention were also asked. Multivariate regression was performed to identify associated factors with knowledge, attitudes and practices. Results showed that the mean score of knowledge regarding risk factors of falls was low at 11.37/32. The highest scores were observed in terms of drug aspects, followed by medical condition and behavioural aspects. Older people mostly agreed with perceived severity, susceptibility, benefits and barriers, but their attitudes about cues to action, health motivation and actions were most neutral. Meanwhile, more than half of the participants practised recommended fall preventive measures. To conclude, health education interventions and fall prevention services that enhance community-based fall prevention knowledge, attitudes and practices for older adults should be performed to reduce the burden of falls in this population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Transfusion of red blood cells (RBCs) has been associated with adverse outcomes. Mechanisms may be related to donor sex and biological age of RBC. This study hypothesized that receipt of female blood is associated with decreased post-transfusion recovery (PTR) and a concomitant increased organ entrapment in rats, related to young age of donor RBCs. Donor rats underwent bloodletting to stimulate production of new, young RBCs, followed by Percoll fractionation for further enrichment of young RBCs based on their low density. Control donors did not undergo these procedures. Male rats received either a (biotinylated) standard RBC product or a product enriched for young RBCs, derived from either male or female donors. Controls received saline. Organs and blood samples were harvested after 24 hours. This study found no difference in PTR between groups, although only the group receiving young RBCs from females failed to reach a PTR of 75%. Receipt of both standard RBCs and young RBCs from females was associated with increased entrapment of donor RBCs in the lung, liver, and spleen compared to receiving blood from male donors. Soluble ICAM-1 and markers of hemolysis were higher in recipients of female blood compared to control. In conclusion, transfusing RBCs from female donors, but not from male donors, is associated with trapping of donor RBCs in organs, accompanied by endothelial activation and hemolysis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Alshalani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The access, watch, and reserve (AWaRe) classification of antibiotics was developed in 2019 by the WHO Expert Committee on the Selection and Use of Essential Medicines as a tool to support antibiotic stewardship efforts at local, national, and global levels. The objectives of this study were to assess the availability of antibiotics as per WHO AWaRe classification at community pharmacies located around a tertiary care hospital in Lalitpur and to compare these antibiotics with the national essential medicine list of Nepal., Method: The cross-sectional study was conducted at community pharmacies located within a two-kilometer radius of a teaching hospital from August to November 2022. A total of 82 community pharmacies registered with the Nepal Chemist and Druggists Association and the Department of Drug Administration were studied. Data was collected using a standard proforma containing the names of the antibiotics classified as per the WHO's AWaRe classification., Results: Access group of antibiotics, Ampicillin, (82;100%), Amoxycillin, (82;100%), Flucloxacillin, (82;100%), and Metronidazole, (82;100%) were available in all community pharmacies. Results from the watch group showed that Azithromycin, (80; 97.6%) was available in all pharmacies followed by Cefixime, (80; 97.6%), Ciprofloxacin, (73; 89%), Levofloxacin, (74; 90.2%)and Ofloxacin, (74; 90.2%). Linezolid, (24; 29.3%) was the most common antibiotics available from the reserve group of antibiotics. Colistin was the second commonly available antibiotic. The most available antibiotic from the not recommended group were Ampicillin/Cloxacillin (82; 100%), followed by Piperacillin/Sulbactam, (39; 47.6%). There were differences in the classification of antibiotics between the WHO AWaRe list and the Essential Medicines list of Nepal in terms of numbers of antibiotics listed., Conclusion: Antibiotics from the not recommended and reserve groups were commonly available in community pharmacies. The implementation of antibiotic guidelines should be emphasized along with strict monitoring of the sale of antibiotics without a prescription in community pharmacy settings., Competing Interests: One of the authors, Dr P Ravi Shankar is an academic editor for PLoS One., (Copyright: © 2023 Jha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The endothelial angiopoietin/Tie2 system is an important regulator of endothelial permeability and targeting Tie2 reduces hemorrhagic shock-induced organ edema in males. However, sexual dimorphism of the endothelium has not been taken into account. This study investigated whether there are sex-related differences in the endothelial angiopoietin/Tie2 system and edema formation., Methods: Adult male and female heterozygous Tie2 knockout mice (Tie2+/-) and wild-type controls (Tie2+/+) were included (n = 9 per group). Renal and pulmonary injury were determined by wet/dry weight ratio and H&E staining of tissue sections. Protein levels were studied in plasma by ELISA and pulmonary and renal mRNA expression levels by RT-qPCR., Results: In Tie2+/+ mice, females had higher circulating angiopoietin-2 (138%, p<0.05) compared to males. Gene expression of angiopoietin-1 (204%, p<0.01), angiopoietin-2 (542%, p<0.001) were higher in females compared to males in kidneys, but not in lungs. Gene expression of Tie2, Tie1 and VE-PTP were similar between males and females in both organs. Renal and pulmonary wet/dry weight ratio did not differ between Tie2+/+ females and males. Tie2+/+ females had lower circulating NGAL (41%, p<0.01) compared to males, whereas renal NGAL and KIM1 gene expression was unaffected. Interestingly, male Tie2+/- mice had 28% higher renal wet/dry weight ratio (p<0.05) compared to Tie2+/+ males, which was not observed in females nor in lungs. Partial deletion of Tie2 did not affect circulating angiopoietin-1 or angiopoietin-2, but soluble Tie2 was 44% and 53% lower in males and females, respectively, compared to Tie2+/+ mice of the same sex. Renal and pulmonary gene expression of angiopoietin-1, angiopoietin-2, estrogen receptors and other endothelial barrier regulators was comparable between Tie2+/- and Tie2+/+ mice in both sexes., Conclusion: Female sex seems to protect against renal, but not pulmonary edema in heterozygous Tie2 knock-out mice. This could not be explained by sex dimorphism in the endothelial angiopoietin/Tie2 system., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 van Leeuwen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In Belgium, antibiotic resistance leads to approximately 530 deaths with a €24 million financial burden annually. This study estimated the impact of procalcitonin-guided antibiotic stewardship programs to reduce antibiotic consumption versus standard of care in patients with suspected sepsis. A decision analytic tree modelled health and budget outcomes of procalcitonin-guided antibiotic stewardship programs for patients admitted to the intensive care unit (ICU). A literature search, a survey with local clinical experts, and national database searches were conducted to obtain model input parameters. The main outcomes were total budget impact per patient, reduction in number of antibiotic resistance cases, and cost per antibiotic day avoided. To evaluate the impact of parameter uncertainty on the source data, a deterministic sensitivity analysis was performed. A scenario analysis was conducted to investigate budget impact when including parameters for reduction in length of ICU stay and mechanical ventilation duration, in addition to base-case parameters. Based on model predictions, procalcitonin-guided antibiotic stewardship programs could reduce the number of antibiotic days by 66,868, resulting in €1.98 million savings towards antibiotic treatment in current clinical practice. Antibiotic resistance cases could decrease by 7.7% (6.1% vs 9.2%) in the procalcitonin-guided setting compared with standard of care. The base-case budget impact suggests an investment of €1.90 per patient. The sensitivity analysis showed uncertainty, as the main drivers can alter potential cost savings. The scenario analysis indicated a saving of €1,405 per patient, with a reduction of 1.5 days in the ICU (14.8 days vs 12.8 days), and a reduction of 22.7% (18.1-27.2%) in mechanical ventilation duration. The associated sensitivity analysis was shown to be robust in all parameters. Procalcitonin-guided antibiotic stewardship programs are associated with clinical benefits that positively influence antimicrobial resistance in Belgium. A small investment per patient to implement procalcitonin testing may lead to considerable cost savings., Competing Interests: VMG, LI, and AL are employees of, and commercially affiliated with, Roche Diagnostics Belgium. This does not alter our adherence to PLOS ONE policies on sharing data and materials. OUG is an employee of, and owns stocks in, Roche Diagnostics International Ltd; and J-LV, DG and SV declare no conflict of interests., (Copyright: © 2023 Garnfeldt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Streptococcal toxic shock syndrome (STSS) is a severe consequence of infections from Streptococcus pyogenes. The early identification and timely intervention with appropriate anti-infective agents are pivotal for managing pediatric STSS. This study evaluates the effectiveness of various treatment regimens for STSS in children., Methods: Clinical data of children with STSS resulting from β-hemolytic streptococcal infections in two hospitals were retrospectively analyzed from January 2009 to April 2023. Additionally, literature from the China National Knowledge Infrastructure on pediatric STSS was examined. Antimicrobial treatments were categorized into four groups based on their compositions, with an additional categorization for adjunct therapeutic drugs., Results: Of 32 confirmed STSS cases, all displayed sensitivity to ampicillin, β-lactam antibiotics, and vancomycin, but resistance to clindamycin, erythromycin, and tetracycline. From the literature, 23 studies with 50 cases were extracted, leading to a total of 82 patients for evaluation. The efficacy rates varied significantly among the four treatment groups. Notably, the standard penicillin-containing group exhibited the highest efficacy (86.4%), while the group with macrolides/unused antibiotics registered a 0% efficacy rate. The other two groups demonstrated efficacy rates of 32.1% and 42.3%., Conclusion: For pediatric STSS, Streptococcus pyogenes shows notable sensitivity to ampicillin. Implementing timely β-lactam antibiotics, specifically penicillin, in conjunction with clindamycin and intravenous immunoglobulins enhances the treatment success rate., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: With the emergence of new subvariants, the disease severity of Severe Acute Respiratory Syndrome Coronavirus-2 has attenuated. This study aimed to compare the disease severity in patients hospitalized with omicron variant infection to those with influenza infection., Methods: We compared data from the multicenter observational, prospective, epidemiological "CORONA Germany" (Clinical Outcome and Risk in hospitalized COVID-19 patients) study on patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 to retrospective data on influenza infection cases from November 2016 to August 2022. Severe Acute Respiratory Syndrome Coronavirus-2 cases were classified as wild-type/delta variant before January 2022, or omicron variant from January 2022 onward. The primary outcome was in-hospital mortality, adjusted for age, gender, and comorbidities., Results: The study included 35,806 patients from 53 hospitals in Germany, including 4,916 patients (13.7%) with influenza infection, 16,654 patients (46.5%) with wild-type/delta variant infection, and 14,236 patients (39.8%) with omicron variant infection. In-hospital mortality was highest in patients with wild-type/delta variant infection (16.8%), followed by patients with omicron variant infection (8.4%) and patients with influenza infection (4.7%). In the adjusted analysis, higher age was the strongest predictor for in-hospital mortality (age 80 years vs. age 50 years: OR 4.25, 95% CI 3.10-5.83). Both, patients with wild-type/delta variant infection (OR 3.54, 95% CI 3.02-4.15) and patients with omicron variant infection (OR 1.56, 95% CI 1.32-1.84) had a higher risk for in-hospital mortality than patients with influenza infection., Conclusion: After adjusting for age, gender and comorbidities, patients with wild-type/delta variant infection had the highest risk for in-hospital mortality compared to patients with influenza infection. Even for patients with omicron variant infection, the adjusted risk for in-hospital mortality was higher than for patients with influenza infection. The adjusted risk for in-hospital mortality showed a strong age dependency across all virus types and variants., Trial Registration Number: NCT04659187., Competing Interests: NG reports grants from Boston Scientific, grants from Medtronic and support from Bayer Vital outside the submitted work. MAG reports grants/speaker honoraria and consultation fees from Boston Scientific, Farapulse Inc., Biosense Webster, Abbott and Medtronic outside the submitted work. WG reports grants/speaker honoraria and consultation fees from AstraZeneca, Olympus and PulmonX outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors have nothing to disclose., (Copyright: © 2023 Dickow et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: There is little prospective data to guide effective dosing for antibiotic prophylaxis during surgery requiring cardiopulmonary bypass (CPB). We aim to describe the effects of CPB on the population pharmacokinetics (PK) of total and unbound concentrations of cefazolin and to recommend optimised dosing regimens., Methods: Patients undergoing CPB for elective cardiac valve replacement were included using convenience sampling. Intravenous cefazolin (2g) was administered pre-incision and re-dosed at 4 hours. Serial blood and urine samples were collected and analysed using validated chromatography. Population PK modelling and Monte-Carlo simulations were performed using Pmetrics® to determine the fractional target attainment (FTA) of achieving unbound concentrations exceeding pre-defined exposures against organisms known to cause surgical site infections for 100% of surgery (100% fT>MIC)., Results: From the 16 included patients, 195 total and 64 unbound concentrations of cefazolin were obtained. A three-compartment linear population PK model best described the data. We observed that cefazolin 2g 4-hourly was insufficient to achieve the FTA of 100% fT>MIC for Staphylococcus aureus and Escherichia coli at serum creatinine concentrations ≤ 50 μmol/L and for Staphylococcus epidermidis at any of our simulated doses and serum creatinine concentrations. A dose of cefazolin 3g 4-hourly demonstrated >93% FTA for S. aureus and E. coli., Conclusions: We found that cefazolin 2g 4-hourly was not able to maintain concentrations above the MIC for relevant pathogens in patients with low serum creatinine concentrations undergoing cardiac surgery with CPB. The simulations showed that optimised dosing is more likely with an increased dose and/or dosing frequency., Competing Interests: J.L. has received grants from Pfizer and MSD J.A.R. has received investigator-initiated grants from, or has consulted for, bioMérieux, Astellas, MSD, Accelerate Diagnostics and Cardeas Pharma. C.R. has received grants from Pfizer and MSD., (Copyright: © 2023 Alli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Using a large dataset, we evaluated prevalence and severity of alterations in liver enzymes in COVID-19 and association with patient-centred outcomes., Methods: We included hospitalized patients with confirmed or suspected SARS-CoV-2 infection from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) database. Key exposure was baseline liver enzymes (AST, ALT, bilirubin). Patients were assigned Liver Injury Classification score based on 3 components of enzymes at admission: Normal; Stage I) Liver injury: any component between 1-3x upper limit of normal (ULN); Stage II) Severe liver injury: any component ≥3x ULN. Outcomes were hospital mortality, utilization of selected resources, complications, and durations of hospital and ICU stay. Analyses used logistic regression with associations expressed as adjusted odds ratios (OR) with 95% confidence intervals (CI)., Results: Of 17,531 included patients, 46.2% (8099) and 8.2% (1430) of patients had stage 1 and 2 liver injury respectively. Compared to normal, stages 1 and 2 were associated with higher odds of mortality (OR 1.53 [1.37-1.71]; OR 2.50 [2.10-2.96]), ICU admission (OR 1.63 [1.48-1.79]; OR 1.90 [1.62-2.23]), and invasive mechanical ventilation (OR 1.43 [1.27-1.70]; OR 1.95 (1.55-2.45). Stages 1 and 2 were also associated with higher odds of developing sepsis (OR 1.38 [1.27-1.50]; OR 1.46 [1.25-1.70]), acute kidney injury (OR 1.13 [1.00-1.27]; OR 1.59 [1.32-1.91]), and acute respiratory distress syndrome (OR 1.38 [1.22-1.55]; OR 1.80 [1.49-2.17])., Conclusions: Liver enzyme abnormalities are common among COVID-19 patients and associated with worse outcomes., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2023 Vijayaraghavan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: A multitude of diagnostic and predictive algorithms have been designed for COVID-19. However, currently no score can accurately quantify and track day-to-day disease severity in hospitalised patients with COVID-19. We aimed to design such a score to improve pathophysiological insight in COVID-19., Methods: Development of the Severity of COronavirus Disease Assessment (SCODA) score was based on the 4C Mortality score but patient demographic variables that remain constant during admission were excluded. Instead, parameters associated with breathing and oxygenation were added to reflect the daily condition. The SCODA score was subsequently applied to the BEAT-COVID cohort to describe COVID-19 severity over time and to determine the timing of clinical recovery for each patient, an important marker in pathophysiological studies. The BEAT-COVID study included patients with PCR confirmed COVID-19 who were hospitalized between April 2020 and March 2021 in the Leiden University Medical Center, The Netherlands., Results: The SCODA score consists of 6 clinical and 2 routine lab parameters. 191 patients participated in the BEAT-COVID study. Median age was 66, and 74.4% was male. The modal timepoint at which recovery was clinically initiated occurred on days 8 and 24 since symptom onset for non-ICU and ICU-patients, respectively., Conclusions: We developed a daily score which can be used to track disease severity of patients admitted due to COVID-19. This score is useful for improving insight in COVID-19 pathophysiology, its clinical course and to evaluate interventions. In a future stage this score can also be used in other (emerging) infectious respiratory diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Joosten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The COVID-19 pandemic has prompted many countries to formulate guidelines on how to deal with a worst-case scenario in which the number of patients needing intensive care unit (ICU) care exceeds the number of available beds. This study aims to explore the experiences of triage teams when triaging fictitious patients with the Dutch triage guidelines. It provides an overview of the factors that influence decision-making when performing ICU triage with triage guidelines., Methods: Eight triage teams from four hospitals were given files of fictitious patients needing intensive care and instructed to triage these patients. Sessions were observed and audio-recorded. Four focus group interviews with triage team members were held to reflect on the sessions and the Dutch guidelines. The results were analyzed by inductive content analysis., Results: The Dutch triage guidelines were the main basis for making triage decisions. However, some teams also allowed their own considerations (outside of the guidelines) to play a role when making triage decisions, for example to help avoid using non-medical criteria such as prioritization based on age group. Group processes also played a role in decision-making: triage choices can be influenced by the triagists' opinion on the guidelines and the carefulness with which they are applied. Intensivists, being most experienced in prognostication of critical illness, often had the most decisive role during triage sessions., Conclusions: Using the Dutch triage guidelines is feasible, but there were some inconsistencies in prioritization between teams that may be undesirable. ICU triage guideline writers should consider which aspects of their criteria might, when applied in practice, lead to inconsistencies or ethically questionable prioritization of patients. Practical training of triage team members in applying the guidelines, including explanation of the rationale underlying the triage criteria, might improve the willingness and ability of triage teams to follow the guidelines closely., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Abma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: INTELLiVENT-Adaptive Support Ventilation (ASV) is a closed-loop ventilation mode that uses capnography to adjust tidal volume (VT) and respiratory rate according to a user-set end-tidal CO2 (etCO2) target range. We compared sidestream versus mainstream capnography with this ventilation mode with respect to the quality of breathing in patients after cardiac surgery., Methods: Single-center, single-blinded, non-inferiority, randomized clinical trial in adult patients scheduled for elective cardiac surgery that were expected to receive at least two hours of postoperative ventilation in the ICU. Patients were randomized 1:1 to closed-loop ventilation with sidestream or mainstream capnography. Each breath was classified into a zone based on the measured VT, maximum airway pressure, etCO2 and pulse oximetry. The primary outcome was the proportion of breaths spent in a predefined 'optimal' zone of ventilation during the first three hours of postoperative ventilation, with a non-inferiority margin for the difference in the proportions set at -20%. Secondary endpoints included the proportion of breaths in predefined 'acceptable' and 'critical' zones of ventilation, and the proportion of breaths with hypoxemia., Results: Of 80 randomized subjects, 78 were included in the intention-to-treat analysis. We could not confirm the non-inferiority of closed-loop ventilation using sidestream with respect to the proportion of breaths in the 'optimal' zone (mean ratio 0.87 [0.77 to ∞]; P = 0.116 for non-inferiority). The proportion of breaths with hypoxemia was higher in the sidestream capnography group versus the mainstream capnography group., Conclusions: We could not confirm that INTELLiVENT-ASV using sidestream capnography is non-inferior to INTELLiVENT-ASV using mainstream capnography with respect to the quality of breathing in subjects receiving postoperative ventilation after cardiac surgery., Trial Registration: NCT04599491 (clinicaltrials.gov)., Competing Interests: MJS was a part–time employee of Hamilton Medical AG, Bonaduz, Switzerland, where he was the team leader of the department of research and new technologies from January 2022 to January 2023. The other authors have no conflicts of interest., (Copyright: © 2023 Nijbroek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The impact of critical illness on patients is profound, resulting in physical, mental, and social consequences and poor health-related quality of life (HRQOL). Several studies investigated HRQOL among patients discharged from the intensive care unit (ICU). However, few systematic reviews cover studies conducted in the last decade or using valid instruments for measuring HRQOL in general ICU survivor populations. Herein, we conduct a systematic review of these studies that followed PRISMA guidelines. We will search PubMed, Web of Science, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane Library, and Open Grey for papers. We will search for articles reporting the HRQOL of ICU survivors that were written in English and published from 01 January 2012 onward from the date of this protocol's publication. We will also extract HRQOL data and analyze associate factors. The risk of bias will be measured with a standard quality assessment tool. The strength of the results will depend on the number of studies and the consistency of their results. Trial registration number: PROSPERO CRD 42022304279., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Elevations of plasma creatinine are common after major surgery, but their pathophysiology is poorly understood. To identify possible contributing mechanisms, we pooled data from eight prospective studies performed in four different countries to study circumstances during which elevation of plasma creatinine occurs. We included 642 patients undergoing mixed major surgeries, mostly open gastrointestinal. Plasma and urinary creatinine and a composite index for renal fluid conservation (Fluid Retention Index, FRI) were measured just before surgery and on the first postoperative morning. Urine flow was measured during the surgery. The results show that patients with a postoperative increase in plasma creatinine by >25% had a high urinary creatinine concentration (11.0±5.9 vs. 8.3±5.6 mmol/L; P< 0001) and higher FRI value (3.2±1.0 vs. 2.9±1.1; P< 0.04) already before surgery was initiated. Progressive increase of plasma creatinine was associated with a gradually lower urine flow and larger blood loss during the surgery (Kruskal-Wallis test, P< 0.001). The patients with an elevation > 25% also showed higher creatinine and a higher FRI value on the first postoperative morning (P< 0.001). Elevations to > 50% of baseline were associated with slightly lower mean arterial pressure (73 ± 10 vs. 80 ± 12 mmHg; P< 0.005). We conclude that elevation of plasma creatinine in the perioperative period was associated with low urine flow and greater blood loss during surgery and with concentrated urine both before and after the surgery. Renal water conservation-related mechanisms seem to contribute to the development of increased plasma creatinine after surgery., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hahn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Patients' perception of postoperative recovery is a key aspect of perioperative care. Self-reported quality of recovery (QoR) has evolved as a relevant endpoint in perioperative research. Several psychometric instruments have been introduced to assess self-reported recovery 24 hours after surgery. However, there is no questionnaire suitable for use in the postanesthesia care unit (PACU). We aimed to develop and psychometrically evaluate a QoR questionnaire for the PACU (QoR-PACU)., Methods: The QoR-PACU was developed in German language based on the 40-item QoR-40 questionnaire. Between March and November 2020, adult patients scheduled for elective urologic surgery completed the QoR-PACU preoperatively and during the PACU stay. We evaluated feasibility, validity, reliability, and responsiveness., Results: We included 375 patients. After two piloting phases including 72 and 48 patients, respectively, we administered the final version of the QoR-PACU to 255 patients, with a completion rate of 96.5%. Patients completed the QoR-PACU at a median of 125.0 (83.0; 156.8) min after arrival in the PACU. Construct validity was good with postoperative QoR-PACU sum scores correlating with age (r = 0.23, 95% CI: 0.11 to 0.35, p < 0.001), length of PACU stay (r = -0.15, 95%CI: -0.27 to -0.03, p = 0.02), pain in the PACU (r = -0.48, 95% CI: -0.57 to -0.37, p < 0.001) and piritramide dose administered (r = -0.29, 95% CI: -0.40 to -0.17, p < 0.001). Cronbach's alpha was 0.67 (95% CI: 0.61-0.73) with moderate test-retest reliability (ICC of 0.67, 95% CI: 0.38 to 0.83). Cohen's effect size was 3.08 and the standardized response mean was 1.65 indicating adequate responsiveness., Conclusion: The assessment of QoR in the early postoperative period is feasible. We found high acceptability, good validity, adequate responsiveness, and moderate reliability. Future studies should evaluate the psychometric properties of the QoR-PACU in more heterogeneous patient populations including female and gender-diverse patients with varying degress of perioperative risk., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kahl et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Non-beneficial stays in the intensive care unit (ICU) may have repercussions for patients and their families, but can also cause suffering among the nursing staff. We aimed explore the perceptions of nursing staff in the ICU about patient stays that are deemed to be "non-beneficial" for the patient, to identify areas amenable to intervention, with a view to improving how the nursing staff perceive the patient pathway before, during and after intensive care., Methods: Multicentre, qualitative study using individual, semi-structured interviews. All qualified nurses and nurses' aides who were full-time employees in the ICU of three participating centres were invited to participate. Interviews were recorded, transcribed and analyzed using textual content analysis., Results: A total of 21 interviews were performed from February 2020 to October 2021, at which point saturation was reached in the data. Average age of participants was 38.5±7.5 years, and they had an average of 10.7±7.4 years of experience working in the ICU. Four major themes emerged from the interviews, namely: (1) the work is oriented towards life-threatening emergencies, technical procedures and burdensome care; (2) a range of specific criteria and circumstances influence the decisions to admit patients to ICU; (3) there are significant organisational, physical and psychological repercussions associated with a non-beneficial stay in the ICU; (4) respondents made some proposals for improvements to the patient care pathway., Conclusion: Nursing staff have a similar perception to physicians regarding admission decisions and non-beneficial ICU stays. The possibility of future ICU admission needs to be anticipated, discussed systematically with patients and integrated into healthcare goals that are consistent with the patient's wishes and preferences, in multi-professional collaboration including nursing and medical staff., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mathey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Linezolid (LZD) is one of the antibiotics used to treat methicillin-resistant Staphylococcus aureus. In Japan, the dose of LZD is not generally adjusted by renal function or therapeutic drug monitoring and is readily available for critically ill patients. The adverse effects of LZD include pancytopenia, especially thrombocytopenia. We investigated the effect of LZD on platelet counts in critically ill patients with thrombocytopenia during admission to the intensive care unit (ICU)., Methods: Fifty-five critically ill patients with existing thrombocytopenia (platelet count < 100 ×103 /μL) who received LZD for five days or more during the period from January 2011 to October 2018 were included. Changes in platelet count and frequency of platelet concentrate (PC) transfusion were evaluated retrospectively., Results: Mean (± standard error) platelet count prior to initiation of LZD was 47 ± 4 ×103 /uL, which increased significantly to 86 ± 13 ×103 /uL on day 15 (p<0.01). Median [interquartile range] duration of LZD therapy was 9 [8-12] days. Thirty-two patients (58.2%) required PC transfusion in the 15-day study period. The daily rate of PC transfusion decreased from 30.2% on days 1-5 to 18.2% on days 11-15. Similar tendencies were observed in patients with non-hematological and hematological disease., Conclusion: Thrombocytopenia in critically ill patients in the ICU did not worsen after initiation of LZD therapy, and may be considered for the treatment of MRSA in this setting., Competing Interests: Tatsumi H received lecture fees from TSUMURA & CO and industry-academia collaborative research grant from Otsuka Pharmaceutical Factory, Inc. Masuda Y received lecture fees from MSD K.K., Asahi Kasei Pharma Corp. and Japan Blood Product and industry-academia collaborative research grant from JIMRO Co., Ltd. Other authors declare that they have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Tatsumi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Up to 80% of Intensive Care Unit patients experience physical, cognitive, and/or psychological complications post-discharge, known as 'Post Intensive Care Syndrome' (PICS). Early diagnosis and intervention are a priority, but while current post-intensive care follow-up processes endorse a multidisciplinary model, incorporating a psychiatric consultation has not been studied., Methods: A pilot, open-label randomised controlled trial was developed by a multidisciplinary team to evaluate the feasibility and acceptability of incorporating a psychiatric review into an existing post-ICU clinic. The study will run for 12 months and aim to recruit 30 participants. Inclusion criteria for participants: a) ICU admission greater than 48 hours, b) no cognitive impairment that prevents participation, c) ≥ 18 years old, d) residing in Australia, e) fluent in English, f) able to provide GP information, and g) likely to be contactable in 6 months. Patient recruitment will be at Redcliffe Hospital, Queensland, Australia, and will involve patients attending the Redcliffe post intensive care clinic. Participants will be allocated to intervention or control using block randomisation and allocation concealment. Participants allocated to the control arm will receive the standard cares provided by the clinic, which involves an unstructured interview about their ICU experience and a battery of surveys about their psychological, cognitive, and physical function. Those allocated to the intervention arm will receive these same cares as well as an appointment with a psychiatrist for a single session intervention. The psychiatric intervention will involve a comprehensive review, including comorbid disorders, substance use, suicidal ideation, psychosocial stressors, social/emotional supports. Psychoeducation and initial treatment will be provided as indicated and recommendations given to the patient and their GP about how to access ongoing care. In addition to surveys conducted as part of standard clinic cares, all participants will complete additional questionnaires about their history, hospital experience, mental and physical health as well as employment circumstances. All participants will be followed up 6 months after their appointment and will be invited to complete follow-up questionnaires about their mental and physical health, as well as health service use and employment circumstances. The trial has been registered with ANZCTR (ACTRN12622000894796)., Results: To evaluate the feasibility and acceptability of the intervention to the patient population. Differences between groups will be assessed using an independent samples t-test. Resource requirements to administer the intervention will be evaluated by reporting the mean duration of the EPARIS assessment and approximate cost per patient to provide this service. To estimate the effect size of any treatment effects, changes in secondary outcome measures between baseline and 6 months will be compared between intervention and control groups using Analysis of Covariance regression. As this is a pilot, we will not use p-values or test a null hypothesis, but will give confidence intervals., Conclusions: This protocol provides a pragmatic evaluation of the acceptability of introducing early psychiatric assessment into an existing post-ICU follow-up process, and if considered acceptable will inform future research into the efficacy and generalisability of the intervention. The strengths of EPARIS are the prospective, longitudinal design with a control population, and its use of validated post-ICU outcome measures., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Flaws et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The angiotensin receptor neprilysin inhibitor LCZ696 affords superior cardioprotection and renoprotection compared with renin-angiotensin blockade monotherapy, but the underlying mechanisms remain elusive. Herein, we evaluated whether LCZ696 attenuates renal fibrosis by inhibiting ASK1/JNK/p38 mitogen-activated protein kinase (MAPK)-mediated apoptosis in a rat model of unilateral ureteral obstruction (UUO) and in vitro. Rats with UUO were treated daily for 7 days with LCZ696, valsartan, or the selective ATP competitive inhibitor of apoptosis signal-regulating kinase 1 (ASK1), GS-444217. The effects of LCZ696 on renal injury were examined by assessing the histopathology, oxidative stress, intracellular organelles, apoptotic cell death, and MAPK pathways. H2O2-exposed human kidney 2 (HK-2) cells were also examined. LCZ696 and valsartan treatment significantly attenuated renal fibrosis caused by UUO, and this was paralleled by downregulation of proinflammatory cytokines and decreased inflammatory cell influx. Intriguingly, LCZ696 had stronger effects on renal fibrosis and inflammation than valsartan. UUO-induced oxidative stress triggered mitochondrial destruction and endoplasmic reticulum stress, which resulted in apoptotic cell death; these effects were reversed by LCZ696. Both GS-444217 and LCZ696 hampered the expression of death-associated ASK1/JNK/p38 MAPKs. In H2O2-treated HK-2 cells, LCZ696 and GS-444217 increased cell viability but decreased the production of intracellular reactive oxygen species and MitoSOX and apoptotic cell death. Both agents also deactivated H2O2-stimulated activation of ASK1/JNK/p38 MAPKs. These findings suggest that LCZ696 protects against UUO-induced renal fibrosis by inhibiting ASK1/JNK/p38 MAPK-mediated apoptosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ding et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: In critically ill patients, sleep and circadian rhythms are greatly altered. These disturbances have been associated with adverse consequences, including increased mortality. Factors associated with the ICU environment, such as exposure to inadequate light and noise levels during the day and night or inflexible schedules of daily care activities, have been described as playing an essential role in sleep disturbances. The main objective of this study is to evaluate the impact of the use of a multifaceted environmental control intervention in the ICU on the quantity and quality of sleep, delirium, and post-intensive care neuropsychological impairment in critically ill patients., Methods: This is a prospective, parallel-group, randomized trial in 56 critically ill patients once they are starting to recover from their acute illness. Patients will be randomized to receive a multifaceted intervention of environmental control in the ICU (dynamic light therapy, auditory masking, and rationalization of ICU nocturnal patient care activities) or standard care. The protocol will be applied from enrollment until ICU discharge. Baseline parameters, light and noise levels, polysomnography and actigraphy, daily oscillation of plasma concentrations of Melatonin and Cortisol, and questionnaires for the qualitative evaluation of sleep, will be assessed during the study. In addition, all patients will undergo standardized follow-up before hospital discharge and at 6 months to evaluate neuropsychological impairment., Discussion: This study is the first randomized clinical trial in critically ill patients to evaluate the effect of a multicomponent, non-pharmacological environmental control intervention on sleep improvement in ICU patients. The results will provide data about the potential synergistic effects of a combined multi-component environmental intervention in ICU on outcomes in the ICU and long term, and the mechanism of action., Trial Registration: ClinicalTrials.gov, NCT. Registered on January 10, 2023. Last updated on 24 Jan 2023., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Alegria et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The coagulation system is crucial in the pathogenesis of infective endocarditis and undergoes significant changes during course of the disease. However, little is known about the implications of those changes in the perioperative period. Aim of the present study was to delineate the specific coagulation patterns and their clinical consequence in patients undergoing cardiac surgery due to infective endocarditis., Methods: In this single-centre, exploratory, prospective observational study, we investigated the incidence and degree of coagulopathy in patients with (n = 31) and without infective endocarditis (n = 39) undergoing cardiac valve surgery. The primary outcome was the differences between these two groups in rotational thromboelastometry (ROTEM) results before, during and after surgery. The secondary outcomes were the differences between the groups in heparin sensitivity, bleeding complications, and transfusion requirements., Results: Most ROTEM parameters in EXTEM, INTEM and FIBTEM assays were significantly altered in patients with infective endocarditis. Clotting time in the EXTEM assay was significantly prolonged in the endocarditis group at all time-points, while all clot firmness parameters (A5, A10 and MCF) were significantly increased. The heparin sensitivity index was significantly lower in the endocarditis group (median index 0.99 vs 1.17s. IU-1.kg-1, p = .008), indicating increased heparin resistance. Patients with infective endocarditis had more bleeding complications as assessed by the universal definition of perioperative bleeding score (OR 3.0, p = .018), and more patients with endocarditis underwent early re-exploration (p = .018)., Conclusions: The findings of this exploratory investigation show significantly altered coagulation profiles in patients with infective endocarditis, with concomitant hyper- and hypocoagulability. Furthermore, the incidence of bleeding complications and transfusion requirements were increased in patients with endocarditis. These results show the potential of ROTEM to detect coagulation abnormalities in patients with infective endocarditis. Existing point-of-care coagulation testing guided algorithms for optimizing perioperative coagulation management possibly need to be adjusted for these high-risk patients undergoing cardiac surgery., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Breel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality after open abdominal surgery. Optimized perioperative lung expansion may minimize the synergistic factors responsible for the multiple-hit perioperative pulmonary dysfunction. This ongoing study will assess whether an anesthesia-centered bundle focused on perioperative lung expansion results in decreased incidence and severity of PPCs after open abdominal surgery., Methods: Prospective multicenter randomized controlled pragmatic trial in 750 adult patients with at least moderate risk for PPCs undergoing prolonged (≥2 hour) open abdominal surgery. Participants are randomized to receive either a bundle intervention focused on perioperative lung expansion or usual care. The bundle intervention includes preoperative patient education, intraoperative protective ventilation with individualized positive end-expiratory pressure to maximize respiratory system compliance, optimized neuromuscular blockade and reversal management, and postoperative incentive spirometry and early mobilization. Primary outcome is the distribution of the highest PPC severity by postoperative day 7. Secondary outcomes include the proportion of participants with: PPC grades 1-2 through POD 7; PPC grades 3-4 through POD 7, 30 and 90; intraoperative hypoxemia, rescue recruitment maneuvers, or cardiovascular events; and any major extrapulmonary postoperative complications. Additional secondary and exploratory outcomes include individual PPCs by POD 7, length of postoperative oxygen therapy or other respiratory support, hospital resource use parameters, Patient-Reported Outcomes Measurements (PROMIS®) questionnaires for dyspnea and fatigue collected before and at days 7, 30 and 90 after surgery, and plasma concentrations of lung injury biomarkers (IL6, IL-8, RAGE, CC16, Ang-2) analyzed from samples obtained before, end of, and 24 hours after surgery., Discussion: Participant recruitment for this study started January 2020; results are expected in 2024. At the conclusion of this trial, we will determine if this anesthesia-centered strategy focused on perioperative lung expansion reduces lung morbidity and healthcare utilization after open abdominal surgery., Trial Registration: ClinicalTrial.gov NCT04108130., Competing Interests: AFB reports additional research funding from the US Department of Defense, the Merck Investigator-initiated Studies Program and the Institute for Healthcare Quality, Safety and Efficiency for projects unrelated to the discussed work. The rest of authors report no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Fernandez-Bustamante et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)