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Objective: To investigate the effectiveness of oral antiviral agents - nirmatrelvir - ritonavir or molnupiravir in non-hospitalized COVID-19 patients aged <60 years., Methods: This retrospective cohort study analyzed data of patients aged 18-60 years diagnosed with COVID-19 between 1 January 2022, and 30 June 2023. Propensity score matching was used to balance the demographic and clinical characteristics of patients receiving oral antivirals (nirmatrelvir - ritonavir or molnupiravir) and untreated controls. The primary outcome was a composite of all-cause emergency department visits, hospitalizations, or mortality within 30 days. The secondary outcomes included each individual component of the primary composite outcome., Results: Two matched cohorts (antiviral group and control group) comprising 52,585 patients with balanced baseline characteristics were created using propensity score-matching. During follow-up period, the antiviral group demonstrated a lower risk of the primary outcome than the control group (hazard ratio [HR] 0.772, 95% confidence interval [CI] 0.736-0.808, p  < 0.001). The antiviral group also exhibited a reduced risk of individual secondary outcomes, including emergency department visits (HR 0.780, 95% CI, 0.738-0.825), hospitalization (HR 0.755, 95% CI, 0.715-0.840), and mortality (HR 0.297, 95% CI, 0.147-0.600)., Conclusion: Oral antiviral agents were associated with lower risks of all-cause emergency department visits, hospitalizations, and mortality in non-hospitalized COVID-19 patients aged <60 years.

Background: SM-like (LSM) genes a family of RNA-binding proteins, are involved in mRNA regulation and can function as oncogenes by altering mRNA stability. However, their roles in B-cell progression and tumorigenesis remain poorly understood., Methods: We analyzed gene expression profiles and overall survival data of 123 patients with mantle cell lymphoma (MCL). The LSM index was developed to assess its potential as a prognostic marker of MCL survival., Results: Five of the eight LSM genes were identified as potential prognostic markers for survival in MCL, with particular emphasis on the LSM.index. The expression levels of these LSM genes demonstrated their potential utility as classifiers of MCL. The LSM.index-high group exhibited both poorer survival rates and lower RNA levels than did the overall transcript profile. Notably, LSM1 and LSM8 were overexpressed in the LSM.index-high group, with LSM1 showing 2.5-fold increase (p < 0.001) and LSM8 depicting 1.8-fold increase (p < 0.01) than those in the LSM.index-low group. Furthermore, elevated LSM gene expression was associated with increased cell division and RNA splicing pathway activity., Conclusions: The LSM.index demonstrates potential as a prognostic marker for survival in patients with MCL. Elevated expression of LSM genes, particularly LSM1 and LSM8, may be linked to poor survival outcomes through their involvement in cell division and RNA splicing pathways. These findings suggest that LSM genes may contribute to the aggressive behavior of MCL and represent potential targets for therapeutic interventions., (© 2024. The Author(s).)

Purpose: Glycemic control poses a challenge in intensive care unit (ICU) patients and dysglycemia is associated with poor outcomes. Continuous glucose monitoring (CGM) has been successfully implemented in the type 1 diabetes out-patient setting and renewed interest has been directed into the transition of CGM into the ICU. This scoping review aimed to provide an overview of CGM accuracy in ICU patients to inform future research and CGM implementation., Methods: We systematically searched PubMed and EMBASE between 5th of December 2023 and 21st of May 2024 and reported findings in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline for scoping reviews (PRISMA-ScR). We assessed studies reporting the accuracy of CGM in the ICU and report study characteristics and accuracy outcomes., Results: We identified 2133 studies, of which 96 were included. Most studies were observational (91.7%), conducted in adult patients (74%), in mixed ICUs (47.9%), from 2014 and onward, and assessed subcutaneous CGM systems (80%) using arterial blood samples as reference test (40.6%). Half of the studies (56.3%) mention the use of a prespecified reference test protocol. The mean absolute relative difference (MARD) ranged from 6.6 to 30.5% for all subcutaneous CGM studies. For newer factory calibrated CGM, MARD ranged from 9.7 to 20.6%. MARD for intravenous CGM was 5-14.2% and 6.4-13% for intraarterial CGM., Conclusions: In this scoping review of CGM accuracy in the ICU, we found great diversity in accuracy reporting. Accuracy varied depending on CGM and comparator, and may be better for intravascular CGM and potentially lower during hypoglycemia., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: New-onset atrial fibrillation or flutter (NOAF) is a common arrhythmia in adult intensive care unit (ICU) patients. Intravenous amiodarone is one of the most used anti-arrhythmic drugs, despite its risk of inducing acute amiodarone-induced pulmonary toxicity (APT). We aimed to outline the body of evidence on acute APT in ICU patients with NOAF., Methods: We performed a systematic search using the population, intervention, comparison, and outcome (PICO) approach. We included studies of adults admitted to the ICU, who developed NOAF during their ICU stay, were treated with amiodarone, and reported on acute APT, irrespective of research design. The CASE guidelines were applied to evaluate the quality of the included studies, and study results are reported in accordance with the preferred reporting items for systematic reviews and meta-analyses., Results: No randomised controlled trials or observational studies were identified. Nine case reports and one retrospective case series of fatal outcomes in ICU patients treated with amiodarone for NOAF constituted the evidence base. The quality of the included studies was high with a mean of 10 (range 8-12) of the 13 CASE guideline criteria fulfilled. The studies included a total of 16 critically ill adults who was diagnosed with acute APT after a mean of 9 days (range 2-20 days) following initiation of amiodarone with a mean total dose of amiodarone of 4553 mg (range 1100-13,500 mg) predominantly administrated intravenously. Three out of nine patients in the case reports died in the ICU during the amiodarone treatment. No long-term follow-up was conducted for the survivors., Conclusion: Acute APT in adult ICU patients treated with amiodarone for NOAF is poorly described and is based on a total of 16 reported cases. Additional studies assessing the safety of amiodarone in critically ill adults with NOAF in the ICU is warranted., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Hepatocellular carcinoma (HCC), the most common primary liver cancer, typically arises from chronic liver conditions such as hepatitis, cirrhosis, or other chronic liver diseases, and is characterized by its aggressive nature and poor prognosis. The purpose of this research was to clarify the function of achaete-scute family bHLH transcription factor 1 (ASCL1) and solute carrier family 6 member 13 (SLC6A13) in influencing tumor cell behavior, inflammatory responses, and the regulation of inflammasomes. We analyzed the differentially expressed genes (DEGs) in the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database, as well as in the GSE14520 and GSE67764 datasets, to identify the expression changes of SLC6A13 in liver cancer. The prognostic significance of SLC6A13 in LIHC was assessed through Kaplan-Meier survival curve analysis. Transcriptional regulation of SLC6A13 by ASCL1 was explored using the Joint Annotation of the Human Genome and other species by the Systematic Pipeline for the Annotation of Regulatory Regions (JASPAR) database and dual-luciferase assays. In vitro experiments investigated the impact of ASCL1 and SLC6A13 overexpression on HCC cell growth. Additionally, the effects of ethanol treatment and glycine modulation on the inflammatory response in HCC cell lines were evaluated. HCC samples showed reduced levels of SLC6A13, which correlates with a better prognosis for liver metastases. Elevated SLC6A13 expression correlated with improved overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-specific survival (DSS). ASCL1 upregulated SLC6A13 and inhibited proliferation, migration, and invasion of HCC cells. Ethanol induced the production of inflammatory cytokines, which was enhanced by overexpression of SLC6A13 but counteracted by glycine. This study highlighted elevated expression of SLC6A13 in LIHC which has been correlated with improved OS, PFS, RFS, and DSS. Overexpression of SLC6A13 and ASCL1 in HCC cells enhanced inflammasome activation, which was exacerbated by ethanol and attenuated by glycine.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: The relationship between Triglyceride-glucose (TyG) index and clinical outcomes in patients with alcohol use disorder (AUD) is unclear. The aim of this study was to evaluate the association between TyG index and all-cause mortality in critically ill patients with AUD., Methods: We used data from the multi-parameter intelligent monitoring in intensive care IV (MIMIC-IV) database. The patients were equally divided into quartiles. Kaplan-Meier curves were used for survival analysis. The primary endpoint of the study was 28-day mortality, followed by 1-year mortality. We used Cox proportional hazard models to assess the relationship between TyG index and all-cause mortality at different endpoints., Results: A total of 537 AUD patients were included. Using TyG value as a continuous variable (HR 1.460, 95% CI 1.121-1.903, p = 0.005) and categorical variable (HR 1.447-3.477 from Q2 to Q4, with Q1 as reference), elevated TyG value was significantly associated with increased 28-day mortality. TyG was positively associated with 1-year mortality in AUD patients with an HR of 1.295 (95% CI 1.011-1.659, p = 0.041)., Conclusion: TyG index is positively associated with different clinical outcomes of critically ill AUD patients., (© 2024. The Author(s).)

Mesenchymal stem cells (MSC) have immune regulatory properties that may ameliorate pathophysiological processes in sepsis. We determined the effect of allogeneic adipose-derived MSCs (Cx611) on the host response during sepsis due to community-acquired bacterial pneumonia (CABP) by measuring 29 plasma biomarkers and blood transcriptomes at six time points in 82 patients randomised to two intravenous infusions of Cx611 or placebo. Cx611 treatment enhanced several endothelial cell and procoagulant response plasma biomarkers, and led to increased expression of pathways related to innate immunity, haemostasis and apoptosis. Cx611 infusion in sepsis due to CABP is associated with broad host response alterations., Competing Interests: Competing interests: DVO, KJG and EL are employed by Takeda Pharmaceuticals, which produces Cx611., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The aim of this study was to assess whether hypothermia increased survival and improved functional outcome when compared with normothermia in out-of-hospital cardiac arrest (OHCA) patients with similar characteristics than in previous randomized studies showing benefits for hypothermia., Methods: Post hoc analysis of a pragmatic, multicenter, randomized clinical trial (TTM-2, NCT02908308). In this analysis, the subset of patients included in the trial who had similar characteristics to patients included in one previous randomized trial and randomized to hypothermia at 33 °C or normothermia (i.e. target < 37.8 °C) were considered. The primary outcome was survival at 6 months; secondary outcomes included favorable functional outcome at 6 months, defined as a modified Rankin scale of 0-3. Time-to-death and the occurrence of adverse events were also reported., Results: From a total of 1891 included in the TTM-2 study, 600 (31.7%) were included in the analysis, 294 in the hypothermia and 306 in the normothermia group. At 6 months, 207 of the 294 patients (70.4%) in the hypothermia group and 220 of the 306 patients (71.8%) in the normothermia group had survived (relative risk with hypothermia, 0.96; 95% confidence interval [CI], 0.81 to 1.15; P = 0.71). Also, 198 of the 294 (67.3%) in the hypothermia group and 202 of the 306 (66.0%) in the normothermia group had a favorable functional outcome (relative risk with hypothermia, 1.03; 95% CI, 0.87 to 1.23; P = 0.79). There was a significant increase in the occurrence of arrythmias in the hypothermia group (62/294, 21.2%) when compared to the normothermia group (43/306, 14.1%-OR 1.49, 95% CI 1.05-2.14; p = 0.026)., Conclusions: In this study, hypothermia at 33˚C did not improve survival or functional outcome in a subset of patients with similar cardiac arrest characteristics to patients in whom benefit from hypothermia was shown in prior studies., (© 2024. The Author(s).)

Background: Clinical trials and validation studies demonstrate promising hypotension prediction capability by the Hypotension Prediction Index (HPI). Most studies that evaluate HPI derive it from invasive blood pressure readings, but a direct comparison with the noninvasive alternative remains undetermined. Such a comparison could provide valuable insights for clinicians in deciding between invasive and noninvasive monitoring strategies., Objectives: Evaluating predictive differences between HPI when obtained through noninvasive versus invasive blood pressure monitoring., Design: Post hoc analysis of a prospective observational study conducted between 2018 and 2020., Setting: Single-centre study conducted in an academic hospital in the Netherlands., Patients: Adult noncardiac surgery patients scheduled for over 2 h long elective procedures. After obtaining informed consent, 91 out of the 105 patients had sufficient data for analysis., Main Outcome Measures: The primary outcome was the difference in area under the receiver-operating characteristics (ROC) curve (AUC) obtained for HPI predictions between the two datasets. Additionally, difference in time-to-event estimations were calculated., Results: AUC (95% confidence interval (CI)) results revealed a nonsignificant difference between invasive and noninvasive HPI, with areas of 94.2% (90.5 to 96.8) and 95.3% (90.4 to 98.2), respectively with an estimated difference of 1.1 (-3.9 to 6.1)%; P = 0.673. However, noninvasive HPI demonstrated significantly longer time-to-event estimations for higher HPI values., Conclusion: Noninvasive HPI is reliably accessible to clinicians during noncardiac surgery, showing comparable accuracy in HPI probabilities and the potential for additional response time., Trial Registration: Clinicaltrials.gov (NCT03795831) on 10 January 2019. https://clinicaltrials.gov/study/NCT03795831., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society of Anaesthesiology.)

Aims: This study investigated the status and influencing factors of organizational silence among 624 nurses in general hospitals in eastern coastal cities of China., Methods: This study followed STROBE guidelines. During the period from January to April 2024, the researchers investigated 624 clinical in-service nurses in terms of general information, employee silence behavior, work engagement, and peer support, and analyzed the related factors affecting nurses' organizational silence., Results: The total average score of nurses' organizational silence was (33.88 ± 6.88), and the total score of work engagement was (69.23 ± 10.76); The total score of the colleague support scale was (90.02 ± 13.72), which was at the medium level. Univariate analysis showed that the scores of organizational silence of 610 nurses had statistical differences in departments, employment methods and professional titles (P < 0.05); Pearson correlation analysis showed that nurses' work engagement (r=-0.530, P < 0.05), perceived colleague support a scale (r=-0.530, P < 0.05), colleague support B scale (r=-0.363, P < 0.05) were negatively correlated with organizational silence; Multiple linear regression analysis showed that department (β'value = 0.256, P = 0.001), employment mode (β'value = 0.115, P = 0.001), professional title (β'value = 0.741, P = 0.023), working years (β'value = 1.1110, P = 0.000), work engagement (β'value6.182, P = 0.000), colleague support scale A (β'value = 0.198, P = 0.003), and scale B (β'value = 0.485, P = 0.001) were the main influencing factors of nurses' organizational silence behavior., Conclusions: In this study, nurses' organizational silence is at the medium level, and nursing workers with low outpatient service, contract system, professional title and working years, less work investment and poor support from colleagues are prone to silence behavior., (© 2024. The Author(s).)

Critically ill patients are at risk of presenting with gastrointestinal dysfunction at intensive care unit admission or during their stay. However, identifying gastrointestinal dysfunction is difficult because clinical evaluation is frequently nonspecific and validated biomarkers are lacking. In this context, ultrasound of the digestive tract may help to identify gastrointestinal dysfunction. In this narrative review, we summarize available evidence and propose a protocol for assessment of the gastrointestinal tract with ultrasound. First, we report available evidence from use of four available protocols: the gastrointestinal and urinary tract sonography protocol, the acute gastrointestinal injury ultrasound score, the transabdominal gastrointestinal ultrasound protocol, and the Lai protocol, each addressing somewhat different aspects. Outputs from these protocols have been associated with clinical scores of gastrointestinal failure, feeding intolerance, and 28-day mortality. Second, we describe the potential pitfalls of using ultrasound in the critically ill, such as obesity, abdominal dressings, or the presence of intraluminal gas. Third, we suggest perspectives of ultrasound in monitoring the response to enteral nutrition and for early identification of nonocclusive mesenteric ischemia. Fourth, we propose a structured protocol for gastrointestinal ultrasound describing all the different structures that should be evaluated and provide detailed guidance for a clockwise abdominal examination. In conclusion, the use of a specific and structured protocol might help to identify patients presenting with gastrointestinal dysfunction, guide nutrition, and allow the proposal of pathophysiological hypotheses (complications of enteral nutrition, intra-abdominal infection, bowel ischemia, etc.). The benefit of using a structured protocol requires further investigation., (© 2024 The Author(s). Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Background: The clinical characteristics and survival outcomes of patients who underwent concomitant coronary artery bypass grafting during septal myectomy have not been well studied., Methods and Results: We reviewed patients who underwent both septal myectomy and coronary artery bypass grafting from 2009 to 2020. Causes of concomitant grafting and their impact on survival were analyzed. The median follow-up period was 5.1 years. A total of 320 patients underwent both grafting and myectomy. Of these, 69.7% and 28.1% underwent grafting attributed to atherosclerotic coronary artery disease and myocardial bridging, respectively. Patients who underwent grafting for coronary artery disease tended to be older, had a longer bypass time, and required more grafts compared with patients undergoing procedures because of myocardial bridging (all P <0.05). Postoperatively, the left ventricular outflow gradient significantly decreased from 85.4 mm Hg to 12.8 mm Hg ( P <0.001) without perioperative death. The cumulative survival rates were 96.2% and 97.6% at 5 years in the coronary artery disease and myocardial bridging groups, respectively, and they were comparable to that of general myectomy cohort (hazard ratio [HR], 1.06 [95% CI, 0.47-2.36], P =0.895 and HR 0.75 [95% CI, 0.23-2.46], P =0.636, respectively). Sudden death accounted for 45.5% (5 of 11) of postoperative mortality. Analysis of composite end point events showed decreased morbidity with at least one arterial graft in the overall cohort (HR, 0.47 [95% CI, 0.23-0.94], P =0.034)., Conclusions: Concomitant grafting in septal myectomy was found to be a safe procedure. Patients who underwent such surgery experienced favorable postoperative outcomes comparable to those who underwent septal myectomy alone, with a 5-year survival rate of >95% and improved functional class of >90%.

Sepsis is a systemic inflammatory response syndrome in which the host response to infection is dysregulated, leading to circulatory dysfunction and multi-organ damage. It has a high mortality rate and its incidence is increasing year by year, posing a serious threat to human life and health. Mesenchymal stem cells (MSC) have the following properties: hematopoietic support, provision of nutrients, activation of endogenous stem/progenitor cells, repair of tissue damage, elimination of inflammation, immunomodulation, promotion of neovascularization, chemotaxis and migration, anti-apoptosis, anti-oxidation, anti-fibrosis, homing, and many other effects. A large number of studies have confirmed that MSC from different sources have their own characteristics. This article reviews the pathogenesis of sepsis, the biological properties of MSC, and the advantages and disadvantages of different sources of MSC for the treatment of sepsis and their characteristics.

Background: A phase II clinical trial of metformin (MET) for the treatment of doxorubicin (DOX)-induced cardiotoxicity (NCT02472353) failed., Objectives: The aims of this study were to confirm MET-mediated protection against DOX-induced cardiotoxicity and its mechanism using H9C2 cells, and to establish a Wistar rat model of DOX-induced cardiotoxicity. Subsequently, Wistar rats were utilized to identify clinically relevant indicators for evaluating MET-mediated protection against DOX-induced cardiotoxicity, thereby facilitating early transition towards successful clinical trials., Methods: MET-mediated protection was assessed using cell viability and cytotoxicity experiments. Additionally, intramitochondrial reactive oxygen species (ROS) levels were measured using an ROS fluorescent probe (dihydroethidium) to confirm the oxidative stress mechanism. Eighteen Wistar rats were randomly allocated to the control, DOX, and DOX+MET groups; and the body weight, adverse drug reactions (ADRs), myocardial injury, cardiac function, oxidative stress, and histopathology of heart tissues were compared between groups., Results: H9C2 cells treated with MET/Dexrazoxane demonstrated dose-dependent protection against DOX-induced cardiotoxicity. The fluorescence intensity of H9C2 cells suggested DOX-induced cardiomyocyte toxicity and MET-mediated protection against DOX-induced cardiotoxicity. In vivo experiments confirmed that a rat model of DOX-induced cardiotoxicity was successfully established, but MET-mediated protection against DOX-induced cardiotoxicity was not demonstrated. This was attributed to insufficient energy intake because of ADRs, such as vomiting., Conclusions: We confirmed the MET-mediated protection against DOX-induced cardiomyocyte toxicity and its mechanism involving the inhibition of oxidative stress in vitro experiments. It is imperative to investigate the optimal conditions for MET-mediated protection against DOX-induced cardiotoxicity in vivo or clinical trials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Cardiac lymphatic vessels are important channels for cardiac fluid circulation and immune regulation. In myocardial infarction and chronic heart failure, promoting cardiac lymphangiogenesis is beneficial in reducing cardiac edema and inflammation. However, the specific involvement of cardiac lymphangiogenesis in viral myocarditis (VMC) has not been studied. Despite the recognized participation of macrophages in lymphangiogenesis, the contribution of macrophages to cardiac lymphangiogenesis in VMC is still unclear., Methods: The male Balb/c mice with VMC were grouped according to the time to explore changes in inflammation, cardiac function and lymphangiogenesis. Adeno-associated virus (AAV) was used to determine the effect of cardiac lymphangiogenesis in VMC. Macrophage depletion and VEGF-C C156S treatment were used to investigate the connection between macrophages and cardiac lymphangiogenesis., Results: Cardiac inflammation and lymphatic vessel density were both upregulated, peaking on day 7 following CVB3 infection. After treatment with AAV-sVEGFR3, lymphangiogenesis was inhibited, leading to worsened cardiac dysfunction and aggravated inflammation. However, these effects were reversed by AAV-VEGF-C treatment. Furthermore, macrophages infiltrated the inflamed myocardium and secreted VEGF-C. In vitro, VEGF-C was upregulated when RAW264.7 cells were co-cultured with CVB3. Macrophage depletion in mice with VMC inhibited lymphangiogenesis, while supplementation with VEGF-C C156S depressed it., Conclusion: Collectively, these results indicate that activation of the VEGF-C/VEGFR3 axis exerts a protective effect in CVB3-induced VMC by resolving inflammation and alleviating cardiac dysfunction through increased lymphatic vasculature density, with macrophage-derived VEGF-C partially contributing to this effect., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Prone positioning is commonly applied to improve gas exchange in mechanically ventilated patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). Whilst prone positioning is effective, specific complications may arise. We aimed to assess the prevalence of specific complications related to prone positioning in patients mechanically ventilated for COVID-19-related ARDS., Design: Multicentre, retrospective observational study., Methods: Multi-centre observational study of mechanically ventilated patients with COVID-19-related ARDS admitted to intensive care units in Melbourne, Australia, from August to November 2021. Data on baseline characteristics, prone positioning, complications, and patient outcomes were collected., Results: We assessed 553 prone episodes in 220 patients across seven sites (mean ± standard deviation age: 54 ± 13 years, 61% male). Overall, 58% (127/220) of patients experienced at least one prone-positioning-related complication. Pressure injury was the most prevalent (n = 92/220, 42%) complication reported. Factors associated with increased risk of pressure injury were male sex (adjusted odds ratio = 1.15, 95% confidence interval: [1.02-1.31]) and the total number of prone episodes (adjusted odds ratio = 1.11, 95% confidence interval: [1.07-1.15]). Device dislodgement was the next most common complication, occurring in 28 of 220 (13%) patients. There were no nerve or retinal injuries reported., Conclusions: Pressure injuries and line dislodgement were the most prevalent complications associated with prone positioning of patients mechanically ventilated for COVID-19. The risk of pressure injuries was associated with male sex and the number of prone positioning episodes., Competing Interests: Conflict of interest The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

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.)

The study was to evaluate the clinical outcomes of azvudine versus nirmatrelvir-ritonavir against omicron strains of coronavirus disease 2019 infections and determine their comparative effectiveness. This retrospective study included 716 patients who received nirmatrelvir-ritonavir (NR group) or azvudine (FNC group) at Peking Union Medical College Hospital between 1 November 2022 and 27 February 2023. Patients in the FNC group (n = 304) were younger, exhibited less severe symptoms, started antiviral therapy later, received corticosteroids more frequently, and used tocilizumab less frequently than patients in the NR group (n = 412). Within 28 d of therapy, 40 (9.7%) and 20 (6.6%) deaths were in the NR and FNC groups, respectively. No differences were observed between drugs and mortality rates (odds ratio [OR] 0.78, 95% CI 0.40-1.5, P = 0.45), clinical improvement (OR 0.79, 95% CI 0.79-1.3, P = 0.38), and clinical progression (OR 1.0, 95% CI 0.58-1.8, P = 0.96). More patients in the NR group experienced platelet decline than those in the FNC group (17.6% vs. 8.9%, P = 0.034). This study indicated that the effectiveness and safety of azvudine were comparable to those of nirmatrelvir-ritonavir., (© 2024. The Author(s).)

The declining birth rate and aging population are becoming increasingly serious social issues in Japan. In this report, we summarize the current congenital heart surgery and pediatric perfusion practices in Japan and Vietnam. In addition we report the rapid growth and development of congenital heart surgery in Vietnam made possible by medical education support provided by Japan over the past decade., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The clinical relevance of cardiac troponin (cTn) elevation in takotsubo syndrome (TTS) remains uncertain. The present study sought to investigate the role of cardiac troponin (cTn) elevations in mortality prediction of patients with Takotsubo syndrome (TTS)., Methods: Patients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to February 2020 with available data on peak cTn levels were included in the analysis. Peak cTn levels during the index hospitalization were used to define clinically relevant myocardial injury. The threshold at which clinically relevant myocardial injury drives mortality at 1 year was identified using restricted cubic spline analysis., Results: Out of 2'938 patients, 222 (7.6%) patients died during 1-year follow-up. A more than 28.8-fold increase of cTn above the upper reference limit was identified as threshold for clinically relevant myocardial injury. The presence of clinically relevant myocardial injury was significantly associated with an increased risk of mortality at 5 years (adjusted HR 1.58, 95% CI 1.18-2.12, p =.002). Clinically relevant myocardial injury was related to an increased 5-year mortality risk in patients with apical TTS (adjusted HR 1.57, 95% CI 1.21-2.03, p =.001), in presence of physical stressors (adjusted HR 1.60, 95% CI 1.22-2.11, p =.001), and in absence of emotional stressors (adjusted HR 1.49, 95% CI, 1.17-1.89, p =.001)., Conclusion: This study for the first time determined a troponin threshold for the identification of TTS patients at excess risk of mortality. These findings advance risk stratification in TTS and assist in identifying patients in need for close monitoring and follow-up., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Objectives: To analyze dynamic changes in the renin-angiotensin system (RAS) during septic shock, focusing on angiotensin-converting enzyme (ACE) activity and the balance between angiotensin peptides, using a mass spectrometry method., Design: Experimental septic shock model induced by peritonitis in swine., Setting: Experimental Laboratory, Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles., Subjects: Forty time points from eight mechanically ventilated pigs., Interventions: Septic shock was induced using intraperitoneal instillation of autologous feces, followed by standardized fluid resuscitation, norepinephrine infusion, antibiotic administration, and peritoneal lavage., Measurements and Main Results: The induction of sepsis resulted in a significant increase in plasma renin activity and levels of angiotensin I and II, with a significant decrease in ACE activity observed from 4 hours post-resuscitation and a notable rise in the angiotensin I/angiotensin II ratio at 12 hours. Additionally, a shift toward the angiotensin-(1-7) axis was observed, evidenced by an increased angiotensin-(1-7)/angiotensin II ratio., Conclusions: The study highlighted dynamic shifts in the RAS during septic shock, characterized by reduced circulating ACE activity, elevated angiotensin I/II ratio, and a shift toward the angiotensin-(1-7) axis. These findings suggest an adaptive response within the RAS, potentially offering new insights into sepsis management and therapeutic targets., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: The clinical characteristics and management of late-onset chylothorax after lung cancer surgery remained unknown. Here we aimed to provide evidence on the management of late-onset chylothorax by analysis of several cases with the largest sample size., Methods: We retrospectively collected clinical data of patients who developed late-onset chylothorax after lung cancer surgery and were re-admitted by a single surgeon in our center from 2016 to 2022. The clinical characteristics and management for these patients were analysed. The role of Hem-o-lok clipping after lymphadenectomy in preventing late-onset chylothorax was further explored by comparing the surgical outcomes between treated group and control group., Result: A total of six patients who were re-admitted for late-onset chylothorax after lung cancer surgery were included for analysis. The mean age of them was 60.7 years old. The symptom of late-onset chylothorax was mainly dyspnea and cough and the diagnosis was all made by Sudan III staining between postoperative day 17 to 42. All patients were firstly treated with thoracocentesis and low-fat diet with intravenous nutrition. Four patients were successfully managed with low-fat diet and thoracocentesis, while the other two patients were further managed with pleurodesis with 50% glucose fluid solution. We found a significantly decreased risk of late-onset chylothorax in the treated group with improved procedure of applying Hem-o-lok clipping after lymphadenectomy than in the control group (0% versus 2.6%, P < 0.01)., Conclusion: Late-onset chylothorax after lung cancer surgery was a rare and negligible complication, which may usually be managed by non-surgical methods. Hem-o-lok clipping during lymphadenectomy seemed to be an effective method to prevent late-onset chylothorax after lung cancer surgery., (© 2024 Royal Australasian College of Surgeons.)

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used in case of potentially reversible cardiac failure and restores systemic hemodynamics. However, whether this is followed by improvement of microcirculatory perfusion is unknown. Moreover, critically ill patients have possible pre-existing microcirculatory perfusion disturbances. Therefore, this review provides an overview of alterations in sublingual microcirculatory perfusion in critically ill adult patients receiving VA-ECMO support. Pubmed, Embase (Ovid), Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched according to PRISMA guidelines. Studies reporting sublingual microcirculatory perfusion measurements in adult patients supported by VA-ECMO were included. Outcome parameters included small vessel density (SVD), perfused vessel density (PVD), perfused small vessel density (PSVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) and the heterogeneity index (HI). The protocol was registered at PROSPERO (CRD42021243930). The search identified 1215 studies of which 11 were included. Cardiogenic shock was the most common indication for VA-ECMO (n=8). Three studies report increased PSVD, PPV, and MFI 24 hours after initiation of ECMO compared to pre-ECMO. Nonetheless, microcirculatory perfusion stabilized thereafter. Four out of four studies showed higher PSVD and PPV in survivors compared to non-survivors. Over time, survivors showed recovery of microcirculatory perfusion within hours of initiation of ECMO, whereas this was absent in non-survivors. Notwithstanding the limited sample, VA-ECMO seems to improve microcirculatory perfusion shortly after initiation of ECMO, especially in survivors. Further research in larger cohorts is needed to clarify the longitudinal effects of ECMO on microcirculatory perfusion., (© 2024 The Author(s). Microcirculation published by John Wiley & Sons Ltd.)

In Lausanne, Switzerland, Interprofessional Education (IPE) is embedded in the curriculum of every undergraduate healthcare student. Since 2011, five educational and healthcare institutions have implemented a short interprofessional education course to bring together 2307 undergraduates from six different disciplines (medicine, midwifery, nursing, occupational therapy, physiotherapy, medical radiology technician) between 2017 and 2020. This pre-post study aimed to explore how this course influenced students' attitudes toward IPE using a French translation of the validated questionnaire called the "University West of England Interprofessional Questionnaire." Students were asked to complete an online survey prior to and at the end of the IPE course to measure students' attitudes toward interprofessional (IP) relationships and collaborative learning. A total of 942 students answered the survey between 2017 and 2020, before and after the course. Each year, students' attitudes toward IP relationships improved after the course whereas a positive change in students' attitudes toward IP learning was observed only in 2020. A short exposure to an IPE course could improve students' attitudes toward IPE and, more specifically, toward IP relationships. Our findings could inform IP leaders to design repetitive, various, and longitudinal IPE experiences to balance the development of uniprofessional and interprofessional identity.

Background: Health systems are striving to improve delivery of mechanical thrombectomy (MT) for ischaemic stroke. With the move to 24/7 provision, we aimed to assess (1) the change in referral and procedural frequency and timing, (2) reasons referrals did not proceed to MT, and (3) nocturnal procedural efficacy and safety., Methods: This was an observational study comparing 12-month data for an extended daytime service (2021/2022, hours, 0800-2000) to that for a 12-month period delivering 24/7 cover (2023-2024). Nocturnal and daytime outcomes (rate of recanalisation using modified TICI scoring), extent of postprocedural infarction (using ASPECTS grading), rate of early neurological improvement (using 24-h NIHSS change), 90-day mortality, and complicating symptomatic intracranial haemorrhage (SICH) in the latter period were compared., Results: Both referrals (432 to 851) and procedural caseload (191 to 403) approximately doubled with the move to 24/7 cover; 36% of procedures occurred overnight (n = 145). The dominant reasons for referrals not proceeding to MT were a large core infarct (n = 144) or absence of a large vessel occlusion on baseline imaging (n = 140). There were no significant differences in successful recanalisation (TICI 2B/3: 85.5% vs 87.1%, P = .233), rates of postprocedural ASPECTS≥7 (74.9% vs 75.8%, P = .987), early neurological improvement (NIHSS reduction ≥30%: 43.4% vs 42.4%, P = .917), 90-day mortality (19.6% vs 18.6%, P = .896), or SICH (1.9% vs 4.1%, P = .214) obtained for daytime vs nighttime hours., Conclusion: 24/7 MT provision has resulted in a rapid rise in the number of patients who may benefit from MT. This service can be provided with an acceptable safety profile during nighttime hours in a high-volume comprehensive UK centre., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cardiogenic shock (CS) is a highly complex clinical condition that requires a management strategy focused on early resolution of the underlying cause and the provision of circulatory support. In cases of refractory CS, mechanical circulatory support (MCS) is employed to replace the failed cardiocirculatory system, thereby preventing the development of multiorgan failure. There are various types of MCS, and patients with CS typically require devices that are either short-term (< 15 days) or intermediate-term (15-30 days). When choosing the device the underlying cause of CS, as well as the presence or absence of concomitant conditions such as failed ventricle, respiratory failure, and the intended purpose of the support should be taken into consideration. Patients with MCS require the comprehensive care indicated in complex critically ill patients with multiorgan dysfunction, with an emphasis on device monitoring and control. Different complications may arise during support management, and its withdrawal must be protocolized., (Copyright © 2024 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Background: Extracorporeal membrane oxygenation (ECMO) is increasingly employed to support lung function in patients with acute respiratory failure (ARF). However, the long-term outcomes of the approach have not been encouraging when compared to those of conventional mechanical ventilation. Further, the long-term effects of ECMO on lung function and recovery are unclear. For this review, we examined the long-term lung function outcomes of patients with ARF treated with and without ECMO., Methods: We searched the Embase, CENTRAL, Web of Science, and PubMed sites for studies comparing long-term (≥ 6 months) pulmonary function test results in patients with ARF treated with and without ECMO published until January 2024. We conducted a meta-analysis for percentage predicted values., Results: We included five studies. Our meta-analysis showed similar values of forced vital capacity (FVC%) (MD, 0.47; 95% CI, -3.56-4.50) and forced expiratory flow in the first second % (MD, 1.79; 95% CI, -2.17-5.75) in patients with ARF treated with or without ECMO. The FEV1/FVC % values were slightly higher in patients treated with ECMO than in those without ECMO (MD, 2.03; 95% CI, 0.01-4.04; p-value = 0.05). According to the meta-analysis, the values for total lung capacity % (MD, -3.20; 95% CI, -8.83-2.44) and carbon monoxide diffusion capacity % (MD, -0.72; 95% CI, -3.83-2.39) were also similar between patients undergoing ECMO and those without it., Conclusion: The meta-analysis of a small number of studies with significant selection bias indicates that patients with ARF treated with ECMO may have comparable long-term pulmonary function recovery to those treated with conventional strategies. Further investigations including a larger number of patients and focusing on the long-term impact of ECMO are needed to supplement the current evidence., (© 2024. The Author(s).)

Background: The impact of liver fibrosis on the clinical outcomes of patients with sepsis-induced coagulopathy (SIC) is not well understood. This study aimed to evaluate the association between liver fibrosis scores and in-hospital mortality in SIC patients., Methods: In this retrospective observational cohort study, data were collected from patients diagnosed with sepsis and admitted to the ICU at the First Affiliated Hospital of Wenzhou Medical University between January 2017 and December 2023. Liver fibrosis was evaluated using three scores: Fibrosis-4 (Fib-4), Aspartate Aminotransferase-to-Platelet Ratio Index (APRI), and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS). Patients were divided into tertiles according to their liver fibrosis scores, and the primary outcome was in-hospital mortality. Multivariable logistic regression and restricted cubic spline regression analyses were used to assess associations, complemented by sensitivity analyses through subgroup evaluations., Results: The cohort included 948 patients diagnosed with SIC with an in-hospital mortality of 26.16%. Multivariate logistic regression analysis revealed a significant association between higher liver fibrosis scores and increased in-hospital mortality. Specifically, patients in the highest tertile of Fib-4, APRI, and NFS scores had significantly higher odds of mortality (FIB-4: OR 3.62, 95% CI 1.03-12.69; APRI: OR 2.16, 95% CI 0.88-5.30; NFS: OR 6.80, 95% CI 2.11-21.93) compared to those in the lowest tertile. The restricted cubic spline regression model showed a linear increase in the risk of in-hospital mortality with increasing liver fibrosis score. Sensitivity analysis confirmed the consistency and stability of the results across the different subgroups., Conclusion: Our study suggests that elevated liver fibrosis scores, particularly Fib-4 and NFS, are associated with higher in-hospital mortality in SIC patients. Further research, especially larger prospective studies, are needed to validate these findings., (© 2024. The Author(s).)

Background: Critically ill patients with a traumatic brain injury (TBI) may require prolonged intensive care unit (ICU) admission and hence receive greater exposure to hospital enteral nutrition. It is unknown if augmented energy delivery with enteral nutrition during ICU admission impacts quality of life in survivors or gastrointestinal tolerance during nutrition delivery in the ICU., Objectives: The objective of this study was to compare health-related quality of life, using the EuroQol five-dimensions five-level visual analogue scale at 6 months, in survivors who presented with a TBI and received augmented energy (1.5 kcal/ml) to those who received routine energy (1.0 kcal/ml). Secondary objectives were to explore differences in total energy and protein delivery, gastrointestinal tolerance, and mortality between groups., Methods: Secondary analysis of participants admitted with a TBI in the Augmented versus Routine Approach to Giving Energy Trial (TARGET) randomised controlled trial. Data are represented as n (%) or median (interquartile range)., Results: Of the 3957 patients in TARGET, 231 (5.8%) were admitted after a TBI (augmented = 124; routine = 107). Patients within TARGET who were admitted with a TBI were relatively young (42 [27, 61] years) and received TARGET enteral nutrition for an extended period (9 [5, 15] days). At 6 months, EuroQol five-dimensions five-level quality-of-life scores were available for 166 TBI survivors (72% of TBI cohort randomised, augmented = 97, routine = 69). There was no evidence of a difference in quality of life (augmented = 70 [52, 90]; routine = 70 [55, 85]; median difference augmented vs routine = 0 [95% confidence interval: -5, 10]). TBI participants assigned to augmented energy received more energy with a similar protein than the routine group. Gastrointestinal tolerance was similar between groups., Conclusion: While patients admitted after a TBI received enteral nutrition for an extended period, an increased exposure to augmented energy did not affect survivors' quality-of-life scores., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Patients with chronic kidney disease (CKD) often have impaired immune function, making them more prone to infections that can lead to sepsis. The coexistence of these conditions can result in decreased hemoglobin levels and is associated with a higher mortality rate. To investigate whether the transfusion of red blood cells (RBCs) improves the prognosis of septic patients with concomitant CKD and to explore the indications for red blood cell transfusion. This retrospective cohort study utilizes data from the MIMIC-IV (v2.0) database. The study enrolled 6,604 patients with sepsis and concomitant CKD admitted to the Intensive Care Unit (ICU). Propensity score matching (PSM) was applied to adjust for confounding factors. Multivariate Cox regression analysis revealed an association between RBC transfusion and a decreased risk of 28-day mortality (HR: 0.61, 95% CI: 0.54-0.70, P < 0.001). Following a meticulous 1:1 propensity score matching analysis between the two cohorts, the matched population revealed a notable decrease in 28-day mortality within the RBC transfusion group (HR: 0.60, 95% CI: 0.51-0.71; P < 0.001). Additionally, we observed that a SOFA score ≥ 5, a Base Excess (BE) value < 3, and an estimated Glomerular Filtration Rate (eGFR) < 30 may be considered when evaluating the potential need for RBC transfusion. This study demonstrated an association between RBC transfusion and decreased 28-day mortality in patients with sepsis accompanied by CKD. The patient's BE value, SOFA score, and eGFR are crucial factors influencing the treatment outcome and should be considered when deciding on RBC transfusion., (© 2024. The Author(s).)

Rationale: Due to effects of aging on the respiratory system, it is conceivable that the association between driving pressure and mortality depends on age., Objective: We endeavored to evaluate whether the association between driving pressure and mortality of patients with acute respiratory distress syndrome (ARDS) varies across the adult lifespan, hypothesizing that it is stronger in older, including very old (≥80 years), patients., Methods: We performed a secondary analysis of individual patient-level data from seven ARDS Network and PETAL Network randomized controlled trials ("ARDSNet cohort"). We tested our hypothesis in a second, independent, national cohort ("Hellenic cohort"). We performed both binary logistic and Cox regression analyses including the interaction term between age (as a continuous variable) and driving pressure at baseline (i.e., the day of trial enrollment) as the predictor, and 90-day mortality as the dependent variable., Findings: Based on data from 4567 patients with ARDS included in the ARDSNet cohort, we found that the effect of driving pressure on mortality depended on age (p=0.01 for the interaction between age as a continuous variable and driving pressure). The difference in driving pressure between survivors and non-survivors significantly changed across the adult lifespan (p<0.01). In both cohorts, a driving pressure threshold of 11 cmH 2 O was associated with mortality in very old patients., Interpretation: Data from randomized controlled trials with strict inclusion criteria suggest that the effect of driving pressure on mortality of patients with ARDS may depend on age. These results may advocate for a personalized age-dependent mechanical ventilation approach.

We describe here the first case of cerebral air embolism (CAE) due to a dysfunctional long-term central venous catheter for hemodialysis in a 39-year-old woman with a history of lung transplantation. Air emboli are rare but potentially fatal complications of hemodialysis, in particular, when they involve the brain. Early management with hyperbaric oxygen therapy (HBOT) is critical to prevent deterioration of the patient's condition. In this case, our patient presented her first symptoms, likely a seizure due to multiple cerebral air emboli, during her hemodialysis session. She was then monitored in the Nephrology Intensive Care Unit in accordance to the medical reference center (with HBOT). Twelve hours later, she experienced secondary deterioration, presenting with acute aphasia, left hemineglect syndrome, and hemiplegia. She was rapidly transferred to the medical reference center for HBOT. The patient fully recovered after receiving three sessions of HBOT. She also presented a seizure during each HBOT session, attributed to hyperoxia. She never experienced another seizure after the episode of CAE. This case highlights the importance of considering patients who have a lung transplant to be at increased risk for air emboli during hemodialysis and the need to rapidly recognize symptoms and start treatment, including HBOT, to optimize recovery., (© The Author(s), 2024.)

Objective: The objective of this research was to evaluate the extent of harm for critically ill patients, family members, and healthcare professionals associated with writing and reading intensive care unit (ICU) diaries., Review Method Used: A systematic literature review and a synthesis of qualitative data were performed. The protocol of this study has been registered in the International prospective register of systematic reviews (CRD42022376393)., Data Sources: Databases were PubMed, Cochrane Library, CINAHL, PsychNet, and Livivo., Review Methods: The search included qualitative and mixed-methods studies related to harm with an ICU diary. Deductive content analysis was used to create abstractions of quotations. Study quality was assessed with the Critical Appraisal Skills Programme., Results: Of 12 827 titles, 27 studies with 476 participants were included. Events involving the patients, family members, and healthcare professionals occurred but did not result in harm. A total of 68 quotations from patients, family members, and healthcare professionals were extracted. Those patients, their families, and healthcare professionals who mentioned intense emotions regarding diaries experienced writing and reading diaries as an emotional journey (patients), a help with tears (families), or a question of emotional distance (healthcare professionals)., Conclusions: Writing and reading ICU diaries can be associated with intense emotions, which are natural reactions when coping with a stressful situation. No study reported harm. Based on uncertain qualitative evidence, the benefits of writing and reading ICU diaries as coping strategies outweigh the potential harm. More research is needed., Registration of Review: The International prospective register of systematic reviews CRD42022376393., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To report the outcomes of patients with severe tuberculosis (TB)-related acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO), including predictors of 90-day mortality and associated complications., Methods: An international multicenter retrospective study was conducted in 20 ECMO centers across 13 countries between 2002 and 2022., Results: We collected demographic data, clinical details, ECMO-related complications, and 90-day survival status for 79 patients (median APACHE II score of 20 [25th to 75th percentile, 16 to 28], median age 39 [28 to 48] years, PaO 2 /FiO 2 ratio of 69 [55 to 82] mmHg before ECMO) who met the inclusion criteria. Thoracic computed tomography showed that 61 patients (77%) had cavitary TB, while 18 patients (23%) had miliary TB. ECMO-related complications included major bleeding (23%), ventilator-associated pneumonia (41%), and bloodstream infections (32%). The overall 90-day survival rate was 51%, with a median ECMO duration of 20 days [10 to 34] and a median ICU stay of 42 days [24 to 65]. Among patients on VV ECMO, those with miliary TB had a higher 90-day survival rate than those with cavitary TB (90-day survival rates of 81% vs. 46%, respectively; log-rank P = 0.02). Multivariable analyses identified older age, drug-resistant TB, and pre-ECMO SOFA scores as independent predictors of 90-day mortality., Conclusion: The use of ECMO for TB-related ARDS appears to be justifiable. Patients with miliary TB have a much better prognosis compared to those with cavitary TB on VV ECMO., (© 2024. The Author(s).)

Background: Severe adenovirus pneumonia in children has a high mortality rate, but research on risk prediction models is lacking. Such models are essential as they allow individualized predictions and assess whether children will likely progress to severe disease., Methods: A retrospective analysis was performed on children with adenovirus pneumonia who were hospitalized at the Children's Hospital of Nanjing Medical University from January 2017 to March 2024. The patients were grouped according to clinical factors, and the groups were compared using Ridge regression and multiple logistic regression to identify risk factors associated with severe adenovirus pneumonia. A prediction model was constructed, and its value in clinical application was evaluated., Results: 699 patients were included in the study, with 284 in the severe group and 415 in the general group. Through the screening of 44 variables, the final risk factors for severe adenovirus pneumonia in children as the levels of neutrophils (OR = 1.086, 95% CI: 1.054‒1.119, P < 0.001), D-dimer (OR = 1.005, 95% CI: 1.003‒1.007, P < 0.001), fibrinogen degradation products (OR = 1.341, 95% CI: 1.034‒1.738, P = 0.027), B cells (OR = 1.076, 95%CI: 1.046‒1.107, P < 0.001), and lactate dehydrogenase (OR = 1.008, 95% CI: 1.005‒1.011, P < 0.001). The value of the area under the receiver operating characteristic curve was 0.974, the 95% CI was 0.963-0.985, and the P-value of the Hosmer-Lemeshow test was 0.547 (P > 0.05), indicating that the model had strong predictive power., Conclusion: In this study, the clinical variables of children with adenovirus pneumonia were retrospectively analyzed to identify risk factors for severe disease. A prediction model for severe disease was constructed and evaluated, showing good application value., (© 2024. The Author(s).)

Sports doping remains a significant challenge in competitive sports. Given that urine analysis is the standard for detecting doping, developing rapid, sensitive, accurate, and high-throughput methods for stimulant detection in urine is crucial. Surface-enhanced Raman scattering (SERS) tag-based immunoassays have emerged as powerful analytical tools known for their high sensitivity and specificity, holding particular promise for stimulant detection in urine samples. However, both the Raman signals of typical SERS tags and sample matrices are within the Raman fingerprint region (<1800 cm -1 ), which could lead to spectrum overlap, potentially reducing detection accuracy and sensitivity. By recognizing this, we designed a competitive immunoassay that integrates two types of zero-background SERS tags and magnetic separation. These innovative SERS tags exhibit distinctive Raman peaks within the Raman-silent region (1800-2800 cm -1 ), effectively mitigating potential spectrum overlap with background sample signals. Moreover, magnetic separation not only enhances operational simplicity but also improves the system's anti-interference capability. Using clenbuterol (CL) and higenamine (HM) as model targets, the SERS-based competitive immunoassay demonstrated sensitive detection of individual CL or HM standards, with limits of detection (LODs) of 0.87 and 0.71 pg/mL, respectively. In multiplex mode, CL and HM can be simultaneously detected with LODs of 1.0 and 0.81 pg/mL, respectively. Furthermore, the recovery rates in urine samples ranged from 83 to 116% (relative standard deviation, RSD ≤ 6.4%) for CL and from 82 to 103% (RSD ≤ 5.1%) for HM, further confirming the reliability of the SERS-based immunoassay for practical applications.

Background: The development of controlled donation after circulatory death (cDCD) is both important and challenging. The tension between end-of-life care and organ donation raises significant ethical issues for healthcare professionals in the intensive care unit (ICU). The aim of this prospective, multicenter, observational study is to better understand ICU physicians' and nurses' experiences with cDCD., Methods: In 32 ICUs in France, ICU physicians and nurses were invited to complete a questionnaire after the death of end-of-life ICU patients identified as potential cDCD donors who had either experienced the withdrawal of life-sustaining therapies alone or with planned organ donation (OD(-) and OD( +) groups). The primary objective was to assess their anxiety (State Anxiety Inventory STAI Y-A) following the death of a potential cDCD donor. Secondary objectives were to explore potential tensions experienced between end-of-life care and organ donation., Results: Two hundred six ICU healthcare professionals (79 physicians and 127 nurses) were included in the course of 79 potential cDCD donor situations. STAI Y-A did not differ between the OD(-) and OD( +) groups for either physicians or nurses (STAI Y-A were 34 (27-38) in OD(-) vs. 32 (27-40) in OD( +), p = 0.911, for physicians and 32 (25-37) in OD(-) vs. 39 (26-37) in OD( +), p = 0.875, for nurses). The possibility of organ donation was a factor influencing the WLST decision for nurses only, and a factor influencing the WLST implementation for both nurses and physicians. cDCD experience is perceived positively by ICU healthcare professionals overall., Conclusions: cDCD does not increase anxiety in ICU healthcare professionals compared to other situations of WLST. WLST and cDCD procedures could further be improved by supporting professionals in making their intentions clear between end-of-life support and the success of organ donation, and when needed, by enhancing communication between ICU physician and nurses., Trial Registration: This research was registered in ClinicalTrials.gov (Identifier: NCT05041023, September 10, 2021)., (© 2024. The Author(s).)

Objectives: The aim of this study is to examine the potential correlation between periodontitis and the risk of cardiovascular mortality and all-cause mortality in individuals diagnosed with hypertension, despite the established association between periodontitis and hypertension., Methods: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted in 1999-2014 involving hypertensive individuals. Following the criteria proposed by Eke et al., periodontitis was classified. Survival estimates were calculated using Kaplan Meier analyses and a Kaplan Meier curve was generated. Weighted multivariate cox regression were employed to assess the association between periodontitis and all-cause mortality, as well as cardiovascular mortality., Results: Of the 21,645 individuals, 6,904 individuals were diagnosed with periodontitis. The Kaplan-Meier survival analysis revealed significantly higher rates of all-cause mortality (34.766% vs. 14.739%) and cardiovascular mortality (12.469% vs. 3.736%) in the periodontitis group compared to the non-periodontitis group. Hazard ratios (HRs) for all-cause mortality were 3.19 (95% CI 2.88-3.53) and for cardiovascular mortality were 3.80 (95% CI 3.13-4.61) in individuals with periodontitis compared to those without periodontitis., Conclusion: Periodontitis is a risk factor for mortality in patient with hypertension, especially if it is moderate to severe. Improving periodontal health could lead to better outcomes for these patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Blood transfusions are commonly administered to patients with acute brain injury. The optimal hemoglobin transfusion threshold is uncertain in this patient population., Objective: To assess the impact on neurological outcome of 2 different hemoglobin thresholds to guide red blood cell transfusions in patients with acute brain injury., Design, Setting, and Participants: Multicenter, phase 3, parallel-group, investigator-initiated, pragmatic, open-label randomized clinical trial conducted in 72 intensive care units across 22 countries. Eligible patients had traumatic brain injury, aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage; hemoglobin values below 9 g/dL within the first 10 days after injury; and an expected intensive care unit stay of at least 72 hours. Enrollment occurred between September 1, 2017, and December 31, 2022. The last day of follow-up was June 30, 2023., Interventions: Eight hundred fifty patients were randomly assigned to undergo a liberal (transfusion triggered by hemoglobin <9 g/dL; n = 408) or a restrictive (transfusion triggered by hemoglobin <7 g/dL; n = 442) transfusion strategy over a 28-day period., Main Outcomes and Measures: The primary outcome was occurrence of an unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score between 1 and 5, at 180 days following randomization. There were 14 prespecified serious adverse events, including occurrence of cerebral ischemia after randomization., Results: Among 820 patients who completed the trial (mean age, 51 years; 376 [45.9%] women), 806 had available data on the primary outcome, 393 in the liberal strategy group and 413 in the restrictive strategy group. The liberal strategy group received a median of 2 (IQR, 1-3) units of blood, and the restrictive strategy group received a median of 0 (IQR, 0-1) units of blood, with an absolute mean difference of 1.0 unit (95% CI, 0.87-1.12 units). At 180 days after randomization, 246 patients (62.6%) in the liberal strategy group had an unfavorable neurological outcome compared with 300 patients (72.6%) in the restrictive strategy group (absolute difference, -10.0% [95% CI, -16.5% to -3.6%]; adjusted relative risk, 0.86 [95% CI, 0.79-0.94]; P = .002). The effect of the transfusion thresholds on neurological outcome at 180 days was consistent across prespecified subgroups. In the liberal strategy group, 35 (8.8%) of 397 patients had at least 1 cerebral ischemic event compared with 57 (13.5%) of 423 in the restrictive strategy group (relative risk, 0.65 [95% CI, 0.44-0.97])., Conclusions and Relevance: Patients with acute brain injury and anemia randomized to a liberal transfusion strategy were less likely to have an unfavorable neurological outcome than those randomized to a restrictive strategy., Trial Registration: ClinicalTrials.gov Identifier: NCT02968654.

Smoking is a risk factor for multiple diseases. We performed mendelian randomization (MR) analyses to investigate the causal association of smoking initiation on pain conditions and the potential mediating pathways. Genetic associated with smoking initiation at the genome-wide significance level were selected as instrumental variables. Genetic associations with 10 pain conditions were derived from the FinnGen and UK Biobank study. Multivariable MR analysis was conducted to explore the mediation effects of depression, insomnia and sedentary behavior. A series of sensitivity analyses were conducted to assess the stability of our research findings. Genetic liability to smoking initiation was associated with an increased risk of angina pectoris, dorsalgia, low back pain, pain in limb, pain in joint, pain in thoracic spine and sciatica in both FinnGen and UK Biobank study. These causal associations were largely mediated by major depression (2.9- 39.5%), sedentary behavior (13.0- 31.2%), insomnia (10.3- 33.1%) and combination of all three mediators (30.2- 65.3%). The effects of smoking on outcomes were partly attenuated after adjusting for depression, sedentary behavior and insomnia respectively, and the direct effect of smoking initiation on pain was diminished toward null after adjusting for combined three mediators. These results were robust to sensitivity analyses. Our findings illustrated the causal effect of smoking and a broad range of pain conditions, and major depression, sedentary behavior and insomnia mediate many of these associations., (© 2024. The Author(s).)

Exploration of the incidence and outcomes of Acute Kidney Injury (AKI) broadly, and sepsis associated AKI specifically, in Aboriginal and Torres Strait Islander (First Nations) people has been limited. We compared a nested cohort of First Nations people drawn from a multinational randomised controlled trial of hydrocortisone in septic shock, to a cohort matched for age, sex and severity of illness. Acute Kidney Injury was defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, as well as incident use of kidney replacement therapy (KRT). Major Adverse Kidney Events (MAKE) were described as the composite of death, new dialysis requirement or persisting kidney dysfunction at hospital discharge. A cohort of 57 Aboriginal and/or Torres Strait Islander patients with septic shock was identified. 91.2% (52) of the First Nations cohort met KDIGO criteria for Stage 1 AKI or greater and 63% (36) met Stage 3 criteria. 59.6% (34) of the First Nations required dialysis as compared to 45.6% (26) in the matched cohort. 60.7% (34) of First Nations participants met criteria for MAKE at hospital discharge. The proportions requiring dialysis at 6, 12 and 24 months were 8.3%, 9.1% and 6.9% respectively. The incidences of AKI and MAKE reported in this First Nations cohort are substantially higher than in previously published cohorts of patients with sepsis, even those that use sensitive definitions of AKI. Measures to promote better management of infectious diseases in First Nations communities are required., (© 2024 Asian Pacific Society of Nephrology.)