Ventilation In Intensive Care Unit Research Articles

The efficacy of P0.1-guided sedation protocol in critically ill patients receiving invasive mechanical ventilation: A randomized controlled trial

Background: Mechanical ventilation is a lifesaving treatment in patients with acute respiratory failure. Despite optimal support, some patients still exhibit excessive respiratory drive, leading to patient self-inflicted lung injury (P-SILI) and diaphragmatic dysfunction. Sedation and muscle relaxants are commonly used to reduce respiratory efforts and manage patient-ventilator asynchrony (PVA). Conventionally, sedative drugs are adjusted based on the sedation level assessed by the Richmond Agitation-Sedation Scale (RASS), which may not correlate with the patient’s respiratory drive. Drop in airway pressure at the first 100 milliseconds of the beginning of the inspiration after the end-expiratory occlusion (P0.1) is a simple and reliable method of respiratory drive monitoring by mechanical ventilation at the bedside and may be the more suitable sedation target. Objectives: To assess the efficacy of a sedation protocol targeting optimal P0.1 and RASS score compared to conventional sedation strategy in patients requiring invasive mechanical ventilation in the medical intensive care units in terms of successful extubation. Methods: This is an open-labeled, single-center, randomized controlled trial conducted in medical intensive care units at a tertiary care hospital in Bangkok, Thailand. We randomly allocated mechanically ventilated patients in a 1:1 ratio to receive a sedation protocol targeting both optimal respiratory drive measured by P0.1 (intervention group) and light sedation (RASS 0 to -2) or standard of care (control group targeting RASS alone). The primary outcome is the rate of successful extubation within 14 days after randomization. Hypothesis: We hypothesize that sedation protocol targeting optimal P0.1 and light sedation will increase the rate of successful extubation at 14 days in mechanically ventilated patients compared to conventional sedation strategy. Conclusions: This study aims to evaluate the efficacy of a sedation protocol using P0.1 measurement to monitor and target optimal respiratory drive, in conjunction with sedation scores, in critically ill patients receiving invasive mechanical ventilation. Ethics and dissemination: This study protocol was approved by the Human Research Protection Unit of the Faculty of Medicine, Siriraj Hospital, Mahidol University (Certificate of Approval no. Si 915/2023). Trial registration: NCT06203405

Incidence and factors associated with prolonged use of mechanical ventilation in pediatric intensive care unit in a single tertiary care hospital

Introduction Invasive mechanical ventilation (IMV) is frequently used as a life-supporting device in Pediatric Intensive Care Units (PICU). To date, there are few studies evaluating the impact of prolonged mechanical ventilation (PMV) in children which is associated with high morbidity and mortality. We aimed to determine the incidence and factors associated with PMV in PICU at our institution. Methods A retrospective review was performed of children aged 1 month to 18 years who were admitted to the PICU at Chiang Mai University Hospital, Thailand between January and December 2020. PMV was defined if the duration of IMV was ≥ 96 hours. Baseline characteristics and factors associated with PMV were analyzed by descriptive statistics, and univariable and multivariable logistic regression analysis, respectively. A p-value of < 0.05 was considered significant. Results Ninety-two episodes of IMV were performed in 90 children. The median (IQR) age of the children was 22.8 (7.2–111.9) months (male 64.1%). Forty-six of 92 (50%) children received PMV and 32.6% of children with PMV required a tracheostomy. Following multivariable analysis, factors associated with PMV were age <2 years old (OR 2.86, 95% CI 1.04–7.84, p = 0.041), male gender (OR 3.21, 95% CI 1.15–8.94, p = 0.026), and multiple antibiotics administration during PICU admission (OR 7.83, 95% CI 1.87–32.78, p = 0.005), respectively. Conclusions Pediatric PMV was notably common, with younger age, male gender, and multiple antibiotic use contributing to higher risk. Developing weaning protocols and strategies to reduce PMV duration is crucial.

Evaluation of nursing workload and predictive factors of mortality in patients admitted to mechanical ventilation in an adult Intensive Care Unit

Evaluation of nursing workload and predictive factors of mortality in patients admitted to mechanical ventilation in an adult Intensive Care Unit

Hospital costs of COVID-19, post-COVID-19 condition and other viral pneumonias: a cost comparison analysis.

To compare hospital admission costs for coronavirus disease 2019 (COVID-19) cases to hospital admission costs for other viral pneumonia cases in Australia, and to describe hospital admission costs for post-COVID-19 condition. A cost comparison analysis of hospital admissions due to COVID-19 or other viral pneumonias between 1 January 2020 and 30 June 2021 at Victorian public health acute and subacute services. Demographic characteristics, clinical outcomes (including diagnoses, impairment, subacute admission, intensive care unit admissions, ventilation, and length of stay) and cost data (including diagnostic-related groups, and total, direct and indirect costs). During the study period, 3197 patients were admitted to hospital due to COVID-19 and 15 761 were admitted for other viral pneumonias. Admissions for COVID-19 cost 29% more than admissions for other viral pneumonias. Admissions for COVID-19 requiring intensive care unit admission incurred significantly higher mean costs (A$120 504 or US$90 595) compared with those not requiring intensive care unit admission (A$19 634 or US$14 761). The adjusted cost of admissions related to post-COVID-19 condition was A$11 090 or US$8 337, and these admissions were significantly more likely to be elective. Direct costs accounted for most of the costs for all groups, and admissions for post-COVID-19 condition used less allied health services than other groups. Given its recent emergence, cases of acute COVID-19 and post-COVID-19 condition have had a significant additional financial impact on Australian hospitals. Further studies are required to understand long term costs and identify trends over time in the context of increased vaccination rates and subsequent variants of severe acute respiratory syndrome coronavirus 2.

Molecular displacement approach for the electrochemical detection of protein-bound propofol

Propofol is one of the principal drugs used for the sedation of patients undergoing mechanical ventilation in intensive care units. The correct dosage of such sedative drugs is highly important, but current methods of determining infusion rates are limited and there is a lack of suitable methods for directly determining patient blood propofol concentrations. A significant challenge for the development of propofol sensors is that propofol demonstrates very high protein binding, leading to a low free fraction in blood. Here we present a method for improving the efficacy of an electrochemical propofol sensor by increasing the free fraction via a molecular displacement approach. When used in conjunction with a carbon nanotube/graphene oxide/iron oxide nanoparticle functionalised screen-printed electrode, it was found that this approach dramatically improved the sensor's sensitivity towards propofol. Ibuprofen was found to be the most effective displacement agent, with an optimal concentration of 30 mM. The resultant sensitivity was 2.82 nA/μg/ml/mm2 with a coefficient of variation of 0.07, and the limit of detection was 0.2 μg/ml. This approach demonstrates high specificity towards drugs commonly administered to intensive care patients.

Development of a core predictor set of weaning in critically ill patients: a Delphi-based study protocol

IntroductionProlonged mechanical ventilation in intensive care units (ICUs) leads to increased morbidity, higher mortality rates, and elevated healthcare costs. Predicting successful weaning from mechanical ventilation with accuracy is essential for optimizing resource use and improving patient outcomes. The International Classification of Functioning, Disability and Health (ICF) framework offers a holistic perspective on health conditions and can be adapted to identify key predictors of weaning readiness. This study aims to develop a Delphi-based core predictor set for weaning in critically ill patients, utilizing the ICF model.Methods and analysisThe core predictor set development comprises three steps: (1) Literature review and expert consultation to gather weaning predictors, (2) Predictor alignment with ICF categories per established rules, and (3) Three-round Delphi survey with a multidisciplinary team. A systematic review across major databases will be conducted to identify predictors related to weaning predictors in critically ill adults from cohort studies, trials, and reviews. Predictors will then be categorized within ICF domains. A multidisciplinary expert panel will evaluate the relevance of each predictor using a 9-point Likert scale to achieve consensus.DiscussionThis study will contribute to the development of a standardized, evidence-based predictor set for weaning readiness in critically ill patients. Using the ICF framework, this study aims to encompass the complex factors that influence weaning, thereby enabling personalized care plans and improving weaning outcomes. The Delphi methodology guarantees a thorough, iterative process for building consensus by integrating diverse clinical perspectives.ConclusionThe proposed Delphi-based study protocol aims to establish a core set of predictors for weaning in the ICU setting, guided by the ICF model. Successful implementation of this predictor set could enhance decision-making around weaning trials, reduce unnecessary ventilation days, and ultimately improve patient outcomes and healthcare efficiency. Future validation and implementation studies will be essential to confirm the utility and generalizability of this predictor set in clinical practice.

Sociodemographic Disparities in 1-Year Outcomes of Children With Community-Acquired Acute Kidney Injury

Racial disparities have been identified in pediatric community-acquired acute kidney injury (CA-AKI), and they are associated with increased risk of child mortality, morbidity, and progression of kidney disease. To assess clinical outcomes at 1 year among children with CA-AKI, stratified by age, race, and ethnicity. This retrospective cohort study is a population-based analysis of deidentified, aggregated electronic health record data collected by 61 large health care organizations from 2003 to 2023 and accessed through the TriNetX platform. Outcomes were assessed at 1 year after a CA-AKI episode. Participants included pediatric patients (aged <18 years) with AKI. Data were accessed in January 2024. A diagnosis of CA-AKI and sociodemographic factors such as race, ethnicity, and age, as reported in electronic health records. The primary end point of this study was to assess differences in clinical outcomes within 1 year of an episode of CA-AKI, including all-cause emergency department (ED) visits, intensive care unit (ICU) admissions, mechanical intubation and ventilation, and mortality. Risk was compared between White children and Asian (including Asian, Native Hawaiian, and Other Pacific Islander), Black, and Hispanic children, stratified by age group. Measures of association, Cox proportional hazard analyses, and Kaplan-Meier survival curves were performed within the TriNetX Advanced Analytics Platform between racial and ethnic groups for each analysis. From the total sample of 18 152 children, those with hospital-acquired AKI, chronic kidney disease, end-stage kidney failure, or dialysis dependence were excluded, leaving a final cohort of 17 125 children (mean [SD] age, 11.2 [5.2] years; 9424 male [55.3%]). Eligible patients were divided into racial and ethnic groups as follows: non-Hispanic Asian, 1169 children (6.5%); non-Hispanic Black, 4636 children (27.3%); Hispanic, 1786 children (10.2%); and non-Hispanic White, 9534 children (55.9%). Patients were further subdivided into groups aged 0 to 9 years (546 Asian children, 1675 Black children, 689 Hispanic children, and 3340 White children) and 10 to 18 years (623 Asian children, 2961 Black children, 1091 Hispanic children, and 6104 White children). Within 1 year of CA-AKI diagnosis, compared with White children, Black children experienced greater rates of ED visits (hazard ratio [HR], 1.53; 95% CI, 1.40-1.67), ICU admissions (HR, 1.31; 95% CI, 1.16-1.47), mechanical ventilation (HR, 1.33; 95% CI, 1.13-1.56), and all-cause mortality (HR, 1.27; 95% CI, 1.09-1.48), as well as the greatest risk for composite outcomes (HR, 1.43; 95% CI, 1.33-1.53). Hispanic children experienced greater rates of ED visits (HR, 1.40; 95% CI, 1.21-1.62) and the greatest risk of all-cause mortality (HR, 1.66; 95% CI, 1.31-2.09), whereas Asian children experienced greater rates of mechanical ventilation (HR, 1.69; 95% CI, 1.26-2.27), compared with White children. Black and Hispanic children aged 0 to 9 years were at greatest risk of experiencing poor clinical outcomes. Black children had a 11.41% lower survival probability and Hispanic children had a 7.14% lower survival probability compared with White children after an initial ED encounter. Among children with an identified episode of CA-AKI diagnosed in an ED, within 1 year, Black and Hispanic children had a poorer survival probability compared with White children. Future studies are needed to understand these disparities and improve awareness and follow-up after emergency care.

Gastric ultrasound for the monitoring of enteral nutrition in ventilated intensive care unit patients

Gastric ultrasound for the monitoring of enteral nutrition in ventilated intensive care unit patients

Healthcare resource utilisation and costs in infants with confirmed respiratory syncytial virus infections: a national population cohort study

BackgroundRespiratory syncytial virus (RSV) is the leading cause of severe respiratory infections in infants worldwide, significantly affecting their health and contributing to the global healthcare burden. We aimed to examine healthcare resource utilisation patterns and costs for infants under one year old with confirmed RSV infection across subgroups of different gestational ages and health conditions and the cost implications of RSV infections over time, thereby demonstrating the economic burden of the disease.MethodsThis retrospective cohort study utilised nationwide claims data from the Korea Health Insurance Review and Assessment Service for infants under one year of age with confirmed RSV infection in the first year of life from January 2017 to April 2022. The infants were stratified into three subgroups based on their gestational age and health status: unhealthy preterm, healthy preterm, and full-term infants. A descriptive analysis was conducted to estimate healthcare utilization by type of resource and costs related to the treatment of RSV.ResultsOut of 93,585 RSV infections identified, 31,206 patients met the inclusion criteria; these included 963 unhealthy preterm, 1,768 healthy preterm and 28,475 full-term infants. In our study, 76.3% of the infants with confirmed RSV infection required intensive care, including hospitalisation and more critical interventions such as intensive care unit (ICU) or mechanical ventilation (MV). The total average cost of RSV management was notably higher for unhealthy preterm infants ($ 6,325; 95% confidence interval (CI): $ 5,484-7,165) than for healthy preterm ($ 1,134; 95% CI: $ 1,006 − 1,261) and full-term infants ($ 606; 95% CI: 583–630). Our findings confirmed a significant epidemiological and economic burden, with infants at greater risk–shorter gestational age and poorer health conditions. Furthermore, we observed a marked increase in the total average cost of RSV management during COVID-19, reflecting the complex interplay between RSV and pandemic-related healthcare dynamics.ConclusionOur findings provide evidence for the significant economic burden of RSV infection among infants, with considerable disparities based on gestational age and health status subgroups. However, RSV prevention policies should also recognise that healthy preterm or full-term infants who receive intensive care face a significant disease burden.

Ventilator performances for non-invasive ventilation: a bench study

IntroductionA wide range of recent ventilators, dedicated or not, is available for non-invasive ventilation (NIV) in respiratory or intensive care units (ICU). We conducted a bench study to compare their...

Validity of a new weaning index of discontinuation from mechanical ventilation in intensive care unit

Background Failure to wean from mechanical ventilation (MV) is a frequent problem in the intensive care unit (ICU) setting. Herein, we investigate a new WI measured at the initial spontaneous breathing trial (SBT) in order to predict successful liberation from MV in mechanically ventilated ICU cases. Patients and methods This prospective cross-sectional study consisted of two phases; Phase I was designed to create a new WI from the criteria of 60 mechanically ventilated patients, while Phase II aimed to assess the accuracy of that index in another 40 patients. Results The incidence of failed weaning was 33.3% in phase I, and 35% in phase II. Multivariate regression analysis was done for phase I variables, and the following equation was created; (((Cough strength×0.743)–1.927)×0.05+((PaCO2 (mmHg)×-0.126)+6.786)×0.08+((mean airway pressure (CmH2O)×-1.304)+14.119)×0.193+((PaO2/FIO2 × 0.268)-58.555)×0.328+((rapid shallow breathing index×-0.485)+24.406)×0.353). Using a cut-off value of &gt;0.69 and Applying this index in phase II, it showed a mean value of -1.43 and 4.67 in the failure and success groups, respectively (P&lt;0.001). This new WI with cut-off value (&gt;0.69) had 88.5% sensitivity, 57.1% specificity, and a 77.5% accuracy to predict the success of weaning from MV. Conclusion We developed a new WI using formula including (semiquantitative Cough strength, PCO2 gradient mean airway pressure, PO2/FIO2 ratio, Rapid shallow breathing index) with accepted sensitivity and moderate specificity for predicting successful weaning from MV in ICU patients. Its use should be encouraged in the ICU setting, especially by less experienced ICU physicians.

Combination of the chemokine receptor type 2 (CCR2) antagonist DMX-200 and candesartan for COVID-19: a randomised controlled trial

ObjectiveTo determine whether a chemokine receptor type 2 antagonist, DMX-200 (repagermanium), in combination with an angiotensin receptor blocker, candesartan, improves clinical outcomes in people with COVID-19.DesignProspective, multicentre, double-blind, placebo-controlled trial.SettingTen...

INhaled Sedation versus Propofol in REspiratory failure in the Intensive Care Unit (INSPiRE-ICU1): protocol for a randomised, controlled trial

IntroductionSedation in mechanically ventilated adults in the intensive care unit (ICU) is commonly achieved with intravenous infusions of propofol, dexmedetomidine or benzodiazepines. Significant limitations associated with each can impact their...

Validation of necrotising infection clinical composite endpoint in a retrospective cohort of patients with necrotising soft tissue infections.

Rapidly progressive necrotising soft tissue infections (NSTIs) are associated with high mortality and morbidity. Low incidence and disease heterogeneity contribute to low event rates and inadequately powered studies. The Necrotising Infections Clinical Composite Endpoint (NICCE) provides a binary outcome with which to assess interventions for NSTIs. Partly with a view towards studies of hyperbaric oxygen treatment in NSTIs we aimed to validate NICCE in a retrospective cohort of NSTI patients. Eligible patients were admitted between 2012 and 2021 to an adult major referral hospital in Victoria, Australia with surgically confirmed NSTI. The NICCE and its constituents were assessed in the whole cohort (n = 235). The cohort was divided into two groups using the modified sequential organ failure assessment (mSOFA) score, with an admission mSOFA score ≥ 3 defined as high acuity. Baseline characteristics of the whole (n = 235), the high (n = 188) and the low acuity cohorts (n = 47) were similar. Survival rates were high (91.1%). Patients with an admission mSOFA ≥ 3 were less likely to meet NICCE criteria for 'success' compared to the lower acuity cohort (34.1% and 64.7% respectively). Meeting NICCE criteria was significantly associated with lower resource utilisation, measured by intensive care unit days, ventilator days, and hospital length of stay for all patients and for those with high acuity on presentation. The NICCE provides greater discriminative ability than mortality alone. It accurately selects patients at high risk of adverse outcomes, thereby enhancing feasibility of trials. Adaptation of NICCE to include patient-centred outcomes could strengthen its clinical relevance.

Effectiveness of ulinastatin in critical care patients in real world: a retrospective multi-center study

ABSTRACT Objectives Ulinastatin has been applied in various diseases associated with inflammation, but its effectiveness lacks real-world evidence. We aimed to evaluate the effectiveness of ulinastatin based on a real-world database in the intensive care unit (ICU) patients. Methods This was a retrospective cohort study. ICU patient data from multi-centers in China were collected. Propensity score matching (PSM) was applied. The effectiveness of ulinastatin was evaluated by mortality, length of stay in the ICU and mechanical ventilation duration. Kaplan-Meier method was used to estimate the hazard ratio and plot the survival curve. Results A total of 2036 patients were analyzed after PSM. Mortality was significantly lower in the ulinastatin group than in the non-ulinastatin group (hazard ratio for death: 0.77; 95% confidence interval: 0.62–0.96; p = 0.018). Ulinastatin significantly reduced mortality at 28 days (10.0% vs. 13.6%), 60 days (13.9% vs. 18.2%) and 90 days (14.7% vs. 18.5%), length of stay in the ICU (median 8.0 d vs. 13.0 d), and mechanical ventilation duration (median 24.0 h vs. 25.0 h; p < 0.05). Conclusions Ulinastatin was beneficial for patients in the ICU, mainly by reducing mortality, length of ICU stay, and mechanical ventilation duration. This study provides evidence of the clinical effectiveness of ulinastatin.

Derivation and external validation of predictive models for invasive mechanical ventilation in intensive care unit patients with COVID-19

BackgroundThis study aimed to develop prognostic models for predicting the need for invasive mechanical ventilation (IMV) in intensive care unit (ICU) patients with COVID-19 and compare their performance with the Respiratory rate-OXygenation (ROX) index.MethodsA retrospective cohort study was conducted using data collected between March 2020 and August 2021 at three hospitals in Rio de Janeiro, Brazil. ICU patients aged 18 years and older with a diagnosis of COVID-19 were screened. The exclusion criteria were patients who received IMV within the first 24 h of ICU admission, pregnancy, clinical decision for minimal end-of-life care and missing primary outcome data. Clinical and laboratory variables were collected. Multiple logistic regression analysis was performed to select predictor variables. Models were based on the lowest Akaike Information Criteria (AIC) and lowest AIC with significant p values. Assessment of predictive performance was done for discrimination and calibration. Areas under the curves (AUC)s were compared using DeLong’s algorithm. Models were validated externally using an international database.ResultsOf 656 patients screened, 346 patients were included; 155 required IMV (44.8%), 191 did not (55.2%), and 207 patients were male (59.8%). According to the lowest AIC, arterial hypertension, diabetes mellitus, obesity, Sequential Organ Failure Assessment (SOFA) score, heart rate, respiratory rate, peripheral oxygen saturation (SpO2), temperature, respiratory effort signals, and leukocytes were identified as predictors of IMV at hospital admission. According to AIC with significant p values, SOFA score, SpO2, and respiratory effort signals were the best predictors of IMV; odds ratios (95% confidence interval): 1.46 (1.07–2.05), 0.81 (0.72–0.90), 9.13 (3.29–28.67), respectively. The ROX index at admission was lower in the IMV group than in the non-IMV group (7.3 [5.2–9.8] versus 9.6 [6.8–12.9], p < 0.001, respectively). In the external validation population, the area under the curve (AUC) of the ROX index was 0.683 (accuracy 63%), the AIC model showed an AUC of 0.703 (accuracy 69%), and the lowest AIC model with significant p values had an AUC of 0.725 (accuracy 79%).ConclusionsIn the development population of ICU patients with COVID-19, SOFA score, SpO2, and respiratory effort signals predicted the need for IMV better than the ROX index. In the external validation population, although the AUCs did not differ significantly, the accuracy was higher when using SOFA score, SpO2, and respiratory effort signals compared to the ROX index. This suggests that these variables may be more useful in predicting the need for IMV in ICU patients with COVID-19.ClinicalTrials.gov identifier:NCT05663528.

Modes of administration of nitric oxide devices and ventilators flow-by impact the delivery of pre-determined concentrations

BackgroundNitric oxide (NO) is a strong vasodilator, selectively directed on pulmonary circulation through inhaled administration. In adult intensive care units (ICU), it is mainly used for refractory hypoxemia in mechanically ventilated patients. Several medical delivery devices have been developed to deliver inhaled nitric oxide (iNO). The main purpose of those devices is to guarantee an accurate inspiratory NO concentration, whatever the ventilator used, with NO2 concentrations lower than 0.3 ppm. We hypothesized that the performances of the different available iNO delivery systems could depend on their working principle and could be influenced by the ventilator settings. The objective of this study was to assess the accuracy of seven different iNO-devices combined with different ICU ventilators’ flow-by to reach inspiratory NO concentration targets and to evaluate their potential risk of toxicity.MethodsWe tested seven iNO-devices on a test-lung connected to distinct ICU ventilators offering four different levels of flow-by. We measured the flow in the inspiratory limb of the patient circuit and the airway pressure. The nitric oxide/nitrogen (NO/N2) flow was measured on the administration line of the iNO-devices. NO and NO2 concentrations were measured in the test-lung using an electrochemical analyzer.ResultsWe identified three iNO-device generations based on the way they deliver NO flow: “Continuous”, “Sequential to inspiratory phase” (I-Sequential) and “Proportional to inspiratory and expiratory ventilator flow” (Proportional). Median accuracy of iNO concentration measured in the test lung was 2% (interquartile range, IQR -19; 36), -23% (IQR -29; -17) and 0% (IQR -2; 0) with Continuous, I-Sequential and Proportional devices, respectively. Increased ventilator flow-by resulted in decreased iNO concentration in the test-lung with Continuous and I-Sequential devices, but not with Proportional ones. NO2 formation measured to assess potential risks of toxicity never exceeded the predefined safety target of 0.5 ppm. However, NO2 concentrations higher than or equal to 0.3 ppm, a concentration that can cause bronchoconstriction, were observed in 19% of the different configurations.ConclusionWe identified three different generations of iNO-devices, based on their gas administration modalities, that were associated with highly variable iNO concentrations’ accuracy. Ventilator’s flow by significantly impacted iNO concentration. Only the Proportional devices permitted to accurately deliver iNO whatever the conditions and the ventilators tested.

COVID-19-Related Cholangiopathy: Histological Findings.

We subjected post-COVID-19 cholestasis liver samples to routine staining techniques and cytokeratin 7 immunostaining and semi-quantitatively analyzed the portal and parenchymal changes. All ten patients, five men, had a median age of 56, an interquartile range (IQR) of 51-60, and required intensive care unit and mechanical ventilation. The median and IQR liver enzyme concentrations proximal to biopsy were in IU/L: ALP 645 (390-1256); GGT 925 (664-2169); ALT 100 (86-113); AST 87 (68-106); and bilirubin 4 (1-9) mg/dL. Imaging revealed intrahepatic bile duct anomalies and biliary casts. We performed biopsies at a median of 203 (150-249) days after molecular confirmation of infection. We found portal and periportal fibrosis, moderate-to-severe ductular proliferation, and bile duct dystrophy in all patients, while we observed hepatocyte biliary metaplasia in all tested cases. We observed mild-to-severe parenchymal cholestasis and bile plugs in nine and six cases. We also observed mild swelling of the arteriolar endothelial cells in five patients. We observed a thrombus in a small portal vein branch and mild periductal fibrosis in one case each. One patient developed multiple small biliary infarctions. We did not observe ductopenia in any patient. The alterations were like those observed in SSC-CIP; however, pronounced swelling of endothelial cells, necrosis of the vessel walls, and thrombosis in small vessels were notable.

Novel High-tech, Low-cost Ventilation for Military Use, Mass Casualty Incidents, Stockpiling, and Underserved Communities.

Despite the significant need for mechanical ventilation in- and out-of-hospital, mechanical ventilators remain inaccessible in many instances because of cost or size constraints. Mechanical ventilation is especially critical in trauma scenarios, but the impractical size and weight of standard mechanical ventilators restrict first responders from carrying them in medical aid bags, leading to reliance on imprecise manual bag-mask ventilation. This is particularly important in combat-related injury, where airway compromise and respiratory failure are leading causes of preventable death, but medics are left without necessary mechanical ventilation. To address the serious gaps in mechanical ventilation accessibility, we are developing an Autonomous, Modular, and Portable Ventilation platform (AMP-Vent) suitable for austere environments, prolonged critical care, surgical applications, mass casualty incidents, and stockpiling. The core system is remarkably compact, weighing <2.3 kg, and can fit inside a shoebox (23.4 cm × 17.8 cm × 10.7 cm). Notably, this device is 65% lighter than standard transport ventilators and astoundingly 96% lighter than typical intensive care unit ventilators. Beyond its exceptional portability, AMP-Vent can be manufactured at less than one-tenth the cost of conventional ventilators. Despite its reduced size and cost, the system's functionality is uncompromised. The core system is equipped with closed-loop sensors and advanced modes of ventilation (pressure-control, volume-control, and synchronized intermittent mandatory ventilation), enabling quality care in a portable form factor. The current prototype has undergone preliminary preclinical testing and optimization through trials using a breathing simulator (ASL 5000) and in a large animal model (swine). This report aims to introduce a novel ventilation system and substantiate its promising performance through evidence gathered from preclinical studies. Lung simulator testing was performed using the ASL 5000, in accordance with table201.105 "pressure-control inflation-type testing" from ISO 80601-2-12:2020. Following simulations, AMP-Vent was tested in healthy 10-kg female domestic piglets. The Children's Hospital of Philadelphia Institutional Animal Care and Use Committee approved all animal procedures. Swine received 4-min blocks of alternating ventilation, where AMP-Vent and a conventional anesthesia ventilator (GE AISYS CS2) were used to titrate to varied end-tidal carbon dioxide (EtCO2) goals with the initial ventilator switching for each ascending target (35, 40, 45, 50, 55 mmHg). During ASL 5000 simulations, AMP-Vent exhibited consistent performance under varied conditions, maintaining a coefficient of variation of 2% or less within each test. In a large animal study, AMP-Vent maintained EtCO2 and SpO2 targets with comparable performance to a conventional anesthesia ventilator (GE AISYS CS2). Furthermore, the comparison of minute ventilation (Ve) distributions between the conventional anesthesia ventilator and AMP-Vent at several EtCO2 goals (35, 40, 45, 50, and 55 mmHg) revealed no statistically significant differences (p = 0.46 using the Kruskal-Wallis rank sum test). Preclinical results from this study highlight AMP-Vent's core functionality and consistent performance across varied scenarios. AMP-Vent sets a benchmark for portability with its remarkably compact design, positioning it to revolutionize trauma care in previously inaccessible medical scenarios.

Predicting the Risk of In-Hospital Mortality in Traumatic Brain Injury Patients on Invasive Mechanical Ventilation in the Intensive Care Unit: Construction and Validation of an Online Nomogram

To explore mortality risk factors and to construct an online nomogram for predicting in-hospital mortality in traumatic brain injury (TBI) patients receiving invasive mechanical ventilation (IMV) in intensive care unit (ICU). We retrospectively analyzed TBI patients on IMV in ICU from Medical Information Mart for Intensive Care IV database and 2 hospitals. Least absolute shrinkage and selection operation regression and multiple logistic regression were used to detect predictors of in-hospital mortality and to construct an online nomogram. The predictive performance of nomogram was evaluated using area under the receiver operating characteristic curves (AUC), calibration curves, decision curve analysis, and clinical impact curves. Five hundred ten from Medical Information Mart for Intensive Care IV database were enrolled for nomogram construction (80%, n= 408) and internal validation (20%, n= 102). One hundred eighty-five from 2 hospitals were enrolled for external validation. Least absolute shrinkage and selection operation-logistic regression revealed predictors of in-hospital mortality among TBI patients on IMV in ICU included Glasgow Coma Scale (GCS) after ICU admission, Acute Physiology Score III (APS III) after ICU admission, neutrophil and lymphocyte ratio after IMV, blood urea nitrogen after IMV, arterial serum lactate after IMV, and in-hospital tracheotomy. The AUC, calibration curves, decision curve analysis, and clinical impact curves indicated the nomogram had good discrimination, calibration, clinical benefit, and applicability. The multimodel comparisons revealed the nomogram had higher AUC than GCS, APS III, and Simplified Acute Physiology Score II. We constructed and validated an online nomogram based on routinely recorded factors at admission to ICU and at the beginning of IMV to target prediction of in-hospital mortality among TBI patients on IMV in ICU.