方山 真朱

OBJECTIVES: To operationalize and temporally validate an electronic medical record (EMR)-integrated machine learning system (Big data-driven Evaluation of Survival and Treatment in Acute Illness [BEST-AI]) that generates hourly predictions for multiple ICU outcomes, with emphasis on discrimination, calibration, and workflow integration. DESIGN: Single-center hybrid study with stepwise clinical deployment and forward-in-time temporal validation. SETTING: Thirty-bed tertiary mixed medical-surgical ICU in Japan. PATIENTS: All ICU admissions from August 2017 to March 2025. Exclusions: age younger than 16 years or ICU stay less than 4 hours. Development cohort (n = 11,176; from August 2017 to July 2024) and temporal validation cohort (n = 1,127; from August 2024 to March 2025). INTERVENTIONS: EMR-integrated deployment of BEST-AI providing hourly probabilistic predictions to clinicians within the EMR; no protocolized clinical interventions were mandated. MEASUREMENTS AND MAIN RESULTS: Six prediction tasks (in-hospital mortality, ICU mortality, ICU discharge ≤ 72 hr, intubation ≤ 72 hr, extubation ≤ 72 hr, tracheostomy at ICU discharge) were evaluated. In temporal validation, the area under the receiver operating characteristic curves ranged from 0.856 to 0.960, and the area under the precision-recall curves from 0.302 to 0.786. Decile-based calibration showed overall good agreement; hospital mortality was slightly overestimated at higher predicted probabilities, whereas ICU mortality remained well aligned. The intubation task had comparatively lower discrimination and greater deviation from perfect calibration, consistent with low event counts and heterogeneous timing. A 24-hour landmark sensitivity analysis (one prediction per patient at 24 hr after ICU admission) preserved discrimination and calibration relative to the main analysis, supporting robustness beyond repeated-measures evaluation. The system was successfully maintained with automated hourly updates and EMR-embedded patient- and unit-level visualizations, without prescriptive alerts. CONCLUSIONS: A continuously deployed, EMR-integrated ICU prediction system achieved strong temporal discrimination and generally good calibration. Embedding real-time predictions into routine workflow was feasible, and the system was maintained with automated hourly updates. Prospective multicenter studies are warranted to assess transportability and clinical impact.

IMPORTANCE: The optimal intensity of care for older patients (age ≥80 years) in intensive care units (ICUs) remains uncertain. Although institutional variation in critical care practice has been described, less is known about case-mix-adjusted variation in life-sustaining treatment use among older patients admitted to ICUs and whether greater institutional treatment intensity is associated with improved survival. OBJECTIVE: To quantify institutional variation in the use of life-sustaining treatments for older patients among ICUs and examine the association of treatment intensity with in-hospital mortality. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used nationwide data from the Japanese Intensive Care Patient Database (JIPAD) for patients aged 80 years or older admitted to 127 ICUs at JIPAD-participating institutions in Japan between April 1, 2015, and March 31, 2023. EXPOSURES: Intensive care unit admission and age 80 years or older. MAIN OUTCOMES AND MEASURES: Institutional treatment intensity was quantified using standardized treatment ratio (STR), defined as the ratio of observed-to-expected life-sustaining treatment use after adjustment for patient-level characteristics. The association between STR category and in-hospital mortality was evaluated using both logistic regression and hierarchical bayesian multilevel logistic regression models. RESULTS: Among 60 713 patients (median age, 84 years [IQR, 82-87 years]; 32 302 male [53.2%]), the crude institutional rate of life-sustaining treatment use ranged from 4.8% (8 of 167 patients) to 38.0% (322 of 847 patients). After adjustment for patient case mix, the STR ranged from 0.24 (95% CI, 0.11-0.48) to 2.34 (95% CI, 1.91-2.85) across participating ICUs. In multilevel analyses adjusted for patient- and institution-level factors, higher institutional treatment intensity was not associated with in-hospital survival compared with intermediate treatment intensity (high STR category: odds ratio, 1.17; 95% credible interval, 0.91-1.39). CONCLUSIONS AND RELEVANCE: In this cohort study of older patients admitted to ICUs, institutional use of life-sustaining treatments varied substantially even after case-mix adjustment and higher institutional treatment intensity was not associated with better in-hospital survival. These findings suggest that increasing treatment intensity alone may not be associated with improved outcomes in this population and support the need for better approaches to identify patients most likely to benefit from intensive treatment.

OBJECTIVE: The aim of this study was to identify factors that predict admission to the intensive care unit (ICU) after activation of a rapid response system (RRS). METHODS: We conducted a retrospective observational study using data from 12,306 RRS activations recorded in the In-Hospital Emergency Registry in Japan database between November 2017 and September 2023. Patients aged under 18 years, noninpatients, and those who died or were transferred immediately after RRS activation were excluded. The primary outcome was ICU admission after RRS activation. Predictive factors were identified using multivariable logistic regression models: Model 1 included all available data, while model 2 was restricted to data available at the time of RRS activation. RESULTS: We analysed data from 8532 patients; 2298 (26.9%) were admitted to the ICU following RRS activation. Significant factors of ICU admission in model 1 included weekend activation (odds ratio [OR] = 1.17; 95% confidence interval [CI] = 1.02, 1.34), oxygen administration prior to activation (OR = 1.23; 95% CI = 1.08, 1.4), ICU discharge within 72 h before the index event (OR = 1.65; 95% CI = 1.28, 2.11), physician-initiated activation (OR = 2.16; 95% CI = 1.87, 2.50), and multiple abnormal vital signs. Model 2, which was limited to information available at the time of RRS activation, identified a similar pattern of associations. CONCLUSION: This study identified several important factors associated with ICU admission following RRS activation. These findings may support improved clinical decision-making regarding ICU transfers and provide a foundation for future work to develop and validate prediction models tailored to this setting.

BACKGROUND: The Sequential Organ Failure Assessment (SOFA)-2 score was developed to better reflect contemporary critical care practice by incorporating modern organ support modalities and updated thresholds based on recent data. However, the generalizability of this framework to intensive care unit (ICU) populations beyond the development cohort, particularly across organ support subgroups and major disease categories, remains uncertain. We aimed to evaluate the external validity of SOFA-2 using the OneICU database, a large Japanese critical care database with comprehensive domain-level data. METHODS: Adult ICU stays between February 2013 and August 2025 were included and classified into two cohorts: those with complete SOFA-1 and SOFA-2 component data on the day of ICU admission, and those with complete SOFA-2 data on that day. Discriminatory performance for ICU mortality was evaluated using the area under the receiver operating characteristic curve (AUROC) and compared between SOFA-1 and SOFA-2 using the DeLong test. Subgroup analyses were performed by major organ support device use and across disease categories. RESULTS: Among 152,883 eligible ICU stays, 67,116 had complete SOFA-1 and SOFA-2 data, and 121,443 had complete SOFA-2 data. SOFA-2 showed a slightly higher AUROC for ICU mortality than SOFA-1 (0.859 vs. 0.853; p < 0.001), although the absolute difference was small. Across subgroups defined by mechanical circulatory support use, SOFA-2 showed higher discrimination than SOFA-1. Discrimination was similar in other device-defined subgroups and in patients readmitted to the ICU. SOFA-2 also demonstrated good discrimination across major diagnostic groups. CONCLUSIONS: SOFA-2 showed similar discrimination for ICU mortality compared with SOFA-1 and maintained broadly comparable performance across clinically relevant subgroups, supporting its applicability for early severity assessment in heterogeneous ICU populations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-026-06020-x.

RATIONALE: Positive end-expiratory pressure (PEEP) balances recruitment against over-inflation in ARDS. The early response to a PEEP step-down remains under-characterized. Four-dimensional computed tomography (4D-CT) can quantify within-breath mechanics with anatomy-specific resolution. OBJECTIVES: Using 4D-CT to characterize the early (3-5 min) effects of PEEP step-down (15 to 5 cmH2O) on tidal recruitment and over-inflation in ARDS patients. METHODS: In a prospective, single-center, physiological study, 40 patients with stabilized ARDS (77.5% with PaO2/FIO2 ≥ 150, median normalized respiratory system compliance 0.78 mL/cmH2O/kg) received lung-protective volume-controlled ventilation with median PEEP of 8 cmH2O. 4D-CT was obtained at PEEP 15 cmH2O and 3-5 min after a PEEP step-down to 5 cmH2O. We quantified tidal recruitment (-200 to + 100 HU) and over-inflation (-1000 to - 901 HU). MEASUREMENTS AND MAIN RESULTS: Tidal recruitment was low at high PEEP and minimally increased at low PEEP, from 1.15% to 1.84% of expiratory tissue weight (P < .001). End-inspiratory over-inflation decreased from 11.9% to 5.2% of end-inspiratory lung volume (P < .001), and tidal over-inflation decreased from 42.5% to 18.3% of tidal volume (P < .001). End-expiratory lung volume (EELV) substantially decreased (median -787 mL, 95% CI -952 mL to - 743 mL, P < .001) and the volume loss exceeded the passive elastic prediction, indicating substantial alveolar derecruitment. In exploratory analyses, the recruitment-to-inflation ratio did not modify the tidal recruitment response. CONCLUSIONS: At 3-5 minutes after a PEEP step-down from 15 to 5 cmH2O, 4D-CT showed large EELV loss, substantial alveolar derecruitment and reduced over-inflation, while tidal recruitment slightly increased and remained low. These results are compatible with a condition in which alveolar units prone to closure respond by closing and remaining closed.

BACKGROUND: The role of arterial blood gas (ABG) testing in the intensive care unit (ICU) remains debated within the "less is more" paradigm. While unnecessary testing may pose risks without benefit, timely ABGs provide critical information in unstable patients. Institutional variation in early ABG utilization and its association with outcomes remains unclear. METHODS: We conducted a multicenter retrospective cohort study using the Japanese Intensive Care PAtient Database (JIPAD) between April 2015 and March 2023. Adult ICU patients with a stay ≥24 h and arterial line placement were included. The standardized number of ABGs (SNABGs) within the first 24 h was calculated as the ratio of observed to expected values, where expectations were derived from a multivariable model adjusting for patient covariates. ICUs were categorized into tertiles according to SNABG utilization. The primary outcome was in-hospital mortality, analyzed using multilevel logistic regression with ICU-level random intercepts. Restricted cubic splines were used to explore non-linear associations. RESULTS: Among 117,546 patients from 87 ICUs, the mean number of ABGs varied widely. After standardization, SNABGs ranged from 0.73-0.90 in the low tertile to 1.09-1.15 in the high tertile. In the multilevel model, SNABG was not significantly associated with in-hospital mortality (adjusted OR 0.942 [95% CI 0.807-1.100] for tertile 2; 0.874 [95% CI 0.751-1.017] for tertile 3). Flexible modeling suggested a non-linear trend toward better outcomes with higher utilization, but confidence intervals included unity. CONCLUSION: Early ABG utilization varied across ICUs, yet was not significantly associated with mortality. Sensitivity analysis suggested a non-linear relationship, with a tendency toward better outcomes at higher utilization. These findings warrant further investigation to clarify the role of early ABG utilization in critical care.

BACKGROUND: The airway closure phenomenon occurs when the airway collapses, isolating the proximal airway from the distal alveoli. Airway opening pressure (AOP) is required to reopen closed airways. Two methods are available to measure AOP: the low-constant flow (AOPflow) and constant low-slope pressure ramp methods (AOPpres). The discrepancies between these two methods remain unclear. We investigated whether there is a difference between AOPflow and AOPpres when used for mechanically ventilated patients. METHODS: In this single-center retrospective observational study, we included 42 patients who were mechanically ventilated owing to respiratory failure in the intensive care unit of a university hospital between January 2023 and October 2024. AOP was measured using two methods: AOPflow (5 L/min) and AOPpres (2 cmH2O/s). Agreement and correlation between the two methods were evaluated using Bland-Altman plots, Passing-Bablok regression, and Spearman's rank correlation. RESULTS: AOP measured using AOPflow (median: 4.7 cmH2O) was higher than that measured using AOPpres (median: 1.9 cmH2O, P < 0.001). Nevertheless, the two were strongly correlated (ρ = 0.86, P < 0.001) in all patients. The regression equation was y = 1.39x + 0.90 (95% confidence interval [CI] for slope b: 1.20-1.65, 95% CI for intercept a: 0.48-1.64). In patients with AOPflow ≥5cmH2O, AOPflow was moderately correlated with AOPpres (ρ = 0.77, P < 0.001). The regression equation was y = 0.82x + 4.51 (95% CI for slope b: 0.50-1.17, 95% CI for intercept a: 2.57-6.72). The rate of pressure increase from the pressure at the beginning (0 cmH2O) of inflation up to AOPflow was 26.4 cmH2O/s (10.5-30.0) in all patients and was moderately correlated with the difference between AOPflow and AOPpres (ρ = 0.61, P < 0.001). CONCLUSIONS: Systematic biases were observed between AOPflow and AOPpres, with AOPflow tending to yield higher values. However, the physiological significance of the AOP values obtained from each method remains unclear, and caution is needed for clinical application.

BACKGROUND: Postoperative delirium is a common complication associated with prolonged hospitalization, cognitive decline, and increased mortality. Intraoperative hypotension (IOH) is a potential modifiable risk factor for postoperative delirium, but previous studies have shown inconsistent results due to methodological limitations. High-risk surgical patients, particularly those with comorbidities or advanced age, may be especially vulnerable. We evaluated the association between IOH and postoperative ICU delirium within 48 h. METHODS: We conducted a single-center retrospective study of high-risk adult patients who underwent surgery under general anesthesia without cardiopulmonary bypass and were admitted to the ICU between 2017 and 2024. IOH exposure was quantified using the cumulative area where mean arterial pressure (MAP) was below 65 mmHg (hypotension area) and total time under this threshold (hypotension time). Multivariable logistic regression was used to assess the association between IOH and postoperative ICU delirium, adjusting for preoperative comorbidities, intraoperative medications, and anesthetic depth. Subgroup and interaction analyses explored effect modifiers. RESULTS: Among 4798 patients, both hypotension area (OR 1.16, 95% CI 1.05-1.29, P = 0.003) and hypotension time (OR 3.42, 95% CI 1.21-9.65, P = 0.02) were significantly associated with postoperative ICU delirium within 48 h. Subgroup analyses suggested stronger associations in patients with advanced age, higher ASA-PS, inhalational anesthesia, neurosurgery, and intubation at ICU admission. CONCLUSIONS: IOH was significantly associated with postoperative ICU delirium. These findings underscore the importance of vigilant blood pressure management during surgery, particularly in high-risk patients. Interventional studies are needed to confirm these results and guide preventive strategies.

BACKGROUND: The optimal strategy for discontinuing arginine vasopressin and norepinephrine in patients recovering from shock remains uncertain. Although prior studies have suggested a higher risk of hypotension when arginine vasopressin is discontinued first, these findings may have been influenced by baseline imbalances and tapering practices. We conducted a retrospective study to evaluate whether the order of discontinuation between arginine vasopressin and norepinephrine was associated with the incidence of hypotension during the recovery phase of shock, with vasopressor end doses converted to norepinephrine equivalents for analysis. METHODS: This was a single-center retrospective cohort study of intensive care unit patients with shock who received both arginine vasopressin and norepinephrine from August 2017 to March 2024. Patients were categorized based on whether arginine vasopressin or norepinephrine was discontinued first. The primary outcome was the incidence of hypotension within 24 h of vasopressor cessation, defined as mean arterial pressure < 60 mmHg requiring a ≥ 25% increase in the remaining vasopressor, reinstitution of the stopped agent, or a bolus of ≥ 500 mL crystalloid or 25 g albumin. Overlap weighting using propensity scores was applied to adjust for baseline imbalances both in the overall cohort and in the septic shock subgroup. Propensity scores were estimated using logistic model, including baseline characteristics, hemodynamic parameters, and vasopressor end doses in norepinephrine equivalents. RESULTS: A total of 524 patients were analyzed, with 293 discontinuing AVP first and 231 discontinuing NE first. In the unadjusted cohorts, hypotension occurred in 19% of the AVP-first group and 26% of the NE-first group. After overlap weighting, all baseline covariates were balanced between the groups, and the incidence of hypotension was not significantly different (19% vs 21%, P = 0.59). In the septic shock subgroup (n = 267), the weighted analysis showed no significant difference in the incidence of hypotension between groups. CONCLUSIONS: In patients recovering from shock who received both arginine vasopressin and norepinephrine, discontinuing arginine vasopressin first was not associated with a higher risk of hypotension.

BACKGROUND: Polypharmacy, defined as the concurrent use of multiple medications, poses significant health risks, particularly among aging populations. While polypharmacy is a recognized concern, limited research has examined its spatial distribution or its association with demographic and socioeconomic factors. This study aimed to examine the spatial patterns of polypharmacy across Japan and identify regional characteristics associated with higher polypharmacy rates. This study could contribute to evaluating the effectiveness of current local and national policies and may also inform future policy initiatives. METHODS: An ecological study was conducted across 335 local health units in Japan using data from national health, demographic, and geographic databases. Polypharmacy was defined as prescriptions containing seven or more drugs, and the standardized polypharmacy ratio (SPR) was calculated by age-group population. Spatial autocorrelation of SPR was assessed using Moran's I statistic. Clustering analysis incorporating SPR and regional variables identified distinct high-risk areas. RESULTS: The prediction model for polypharmacy prescriptions achieved an R² of 0.98, indicating high accuracy, though SPR remained heterogeneous. Significant spatial autocorrelation was observed for both polypharmacy prescriptions (Moran's I = 0.4; P < 0.001) and SPR (Moran's I = 0.24; P < 0.001), highlighting regional clustering. Clustering analysis identified four groups by polypharmacy risk (critical, high, moderate, and low). High-SPR areas were associated with higher population density, a greater proportion of younger adults (ages 20 to 60), and increased levels of education, income, and tertiary industry workers. CONCLUSION: Polypharmacy in Japan exhibits significant spatial clustering, with higher rates in urbanized regions driven by demographic and socioeconomic factors. Region-specific interventions addressing these unique characteristics are essential for improving polypharmacy management.

BACKGROUND: Clinically important gastrointestinal bleeding (CIGIB) is a serious complication in critically ill patients, contributing to prolonged ICU stays and increased mortality. Despite efforts to identify high-risk patients, no previous studies have employed machine learning models to predict CIGIB during ICU stay or identify key predictors in this context. METHODS: This single-center retrospective study included ICU patients aged 18 years or older admitted between 2017 and 2024. Patients with ICU stays of less than 24 hours or GIB within 24 hours of admission were excluded. Machine learning models, including XGBoost, Random Forest, and L1-regularized logistic regression, were trained using patient data from the first 24 hours of ICU admission. Model performance was assessed using AUROC, precision, recall, and F1 scores. Shapley Additive Explanations (SHAP) were employed to evaluate key predictors. RESULTS: A total of 7,357 ICU patients were included, of whom 171 (2.3%) experienced CIGIB. The XGBoost model demonstrated the highest predictive performance with an AUROC of 0.84. Key predictors included APACHE III scores, hematocrit levels, APTT, creatinine and respiratory rate, while invasive mechanical ventilation and stress ulcer prophylaxis within the first 24 hours of ICU admission did not rank among the top 20 predictors based on SHAP values. CONCLUSIONS: This study represents the first application of machine learning for predicting CIGIB in ICU patients, providing valuable insights into risk stratification. The model demonstrated high predictive accuracy and interpretability, highlighting its potential to guide early intervention and prophylaxis. Further multi-center studies and interventional trials are needed to validate these findings and refine clinical risk prediction strategies.

Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), is used in combination with chemotherapy for various malignancies, including metastatic colorectal cancer. While effective, bevacizumab can inhibit normal blood vessel growth, leading to cardiovascular side effects not typically associated with conventional chemotherapy. We report a rare case, from an international perspective, of a 73-year-old man with a history of gastric cancer and newly diagnosed metastatic colorectal cancer complicated by a pre-existing abdominal aortic aneurysm (AAA) measuring 52 mm. The aneurysm was initially managed conservatively, as the multidisciplinary team (MDT) and the patient agreed to prioritize chemotherapy despite the known rupture risk, given his wish to avoid delaying treatment for his cancer. After the diagnosis of colorectal cancer during chemotherapy, bevacizumab was added to his regimen. He developed a rupture of the AAA two days after the fourth dose. Emergent open surgical repair was successfully performed without wound healing complications. This case highlights the potential risk of large-vessel complications associated with bevacizumab, especially in patients with known vascular anomalies. Careful imaging assessment and monitoring are imperative when considering bevacizumab for patients at risk of aortic rupture. In selected cases, prophylactic measures such as preemptive aneurysm repair should be contemplated to optimize safety.

BACKGROUND: Reduced or delayed access to medical resources on weekends could lead to worsening outcomes, in critically ill infected patients requiring intensive care unit (ICU) admission. OBJECTIVE: To investigate the "weekend effect," on critically ill infected patients in Japanese ICUs for the first time. DESIGN: Multicenter retrospective cohort study. METHODS: We examined data from Japanese ICU patients participating in the DIANA study, a multicenter international observational cohort study. This prospective investigation enrolled critically ill patients with infections admitted to the ICU. The primary endpoint was successful discharge from the ICU within 28 days of admission. Outcome measures were evaluated through both univariate and covariate Cox regression analyses, providing hazard ratios (HRs) along with estimated 95% confidence intervals (CIs). RESULTS: Out of the 276 patients enrolled in the DIANA study across 31 facilities, 208 patients (75.4%) meeting the inclusion criteria were included in the analysis. The weekday ICU admission group comprised 156 patients (75.0%), while the weekend ICU admission group comprised 52 patients (25.0%). In the multivariate Cox regression analysis, there were no statistically significant differences observed in the rates of ICU discharge alive within 28 days and 14 days (28 days, HR: 0.94, 95% CI: 0.63-1.40; 14 days, HR: 0.97, 95% CI: 0.64-1.48). Furthermore, the overall ICU mortality rates at 28 days and 14 days after ICU admission did not show statistical significance between patients admitted on weekends and those admitted on weekdays (ICU mortality, 28 days: 13.5% vs 11.5%, p = 0.806; 14 days: 7.7% vs 10.9%, p = 0.604). CONCLUSION: The rates of ICU discharge alive within 28 days after ICU admission did not differ significantly between weekday and weekend admissions, both in the unadjusted and adjusted analyses. Moreover, further well-designed studies are warranted to thoroughly assess this effect.

BACKGROUND: The dynamic regional accuracy of electrical impedance tomography has not yet been validated. We aimed to compare the regional accuracy of electrical impedance tomography with that of four-dimensional computed tomography during dynamic ventilation. METHODS: This single-center, prospective, observational study conducted in a general intensive care unit included adult patients receiving mechanical ventilation from July 2021 to February 2024. The patients were mechanically ventilated passively and underwent electrical impedance tomography and four-dimensional computed tomography on the same day. RESULTS: Overall, 45 patients were analyzed. The correlation coefficients in regional dynamic ventilation between four-dimensional computed tomography and electrical impedance tomography in each region were 0.963, 0.963, 0.835 (ventral, central, and dorsal, respectively) in the right lung and 0.947, 0.927, 0.823 (ventral, central, and dorsal, respectively) in the left lung. The correlation coefficient was low when the regional ventilation distribution detected by the electrical impedance tomography was < 2%. After excluding nine patients with a regional ventilation distribution of < 2%, the ventral, central, and dorsal correlation coefficients were 0.963, 0.963, and 0.946 in the right lung and 0.942, 0.924, and 0.951, respectively, in the left lung. CONCLUSIONS: Regional ventilation using electrical impedance tomography during dynamic ventilation was highly accurate and consistent with the time phase compared to four-dimensional computed tomography. Given the high correlation between these modalities, they can contribute significantly to further studies on regional ventilation dynamics. Trial registration number ClinicalTrials.gov (No. UMIN00044386).

Normally aerated lung tissue on computed tomography (CT) is correlated with static respiratory system compliance (Crs) at zero end-expiratory pressure. In clinical practice, however, patients with acute respiratory failure are often managed using elevated PEEP levels. No study has validated the relationship between lung volume and tissue and Crs at the applied positive end-expiratory pressure (PEEP). Therefore, this study aimed to demonstrate the relationship between lung volume and tissue on CT and Crs during the application of PEEP for the clinical management of patients with acute respiratory distress syndrome due to COVID-19. Additionally, as a secondary outcome, the study aimed to evaluate the relationship between CT characteristics and Crs, considering recruitability using the recruitment-to-inflation ratio (R/I ratio). We analyzed the CT and respiratory mechanics data of 30 patients with COVID-19 who were mechanically ventilated. The CT images were acquired during mechanical ventilation at PEEP level of 15 cmH2O and were quantitatively analyzed using Synapse Vincent system version 6.4 (Fujifilm Corporation, Tokyo, Japan). Recruitability was stratified into two groups, high and low recruitability, based on the median R/I ratio of our study population. Thirty patients were included in the analysis with the median R/I ratio of 0.71. A significant correlation was observed between Crs at the applied PEEP (median 15 [interquartile range (IQR) 12.2, 15.8]) and the normally aerated lung volume (r = 0.70 [95% CI 0.46-0.85], P < 0.001) and tissue (r = 0.70 [95% CI 0.46-0.85], P < 0.001). Multivariable linear regression revealed that recruitability (Coefficient = - 390.9 [95% CI - 725.0 to - 56.8], P = 0.024) and Crs (Coefficient = 48.9 [95% CI 32.6-65.2], P < 0.001) were significantly associated with normally aerated lung volume (R-squared: 0.58). In this study, Crs at the applied PEEP was significantly correlated with normally aerated lung volume and tissue on CT. Moreover, recruitability indicated by the R/I ratio and Crs were significantly associated with the normally aerated lung volume. This research underscores the significance of Crs at the applied PEEP as a bedside-measurable parameter and sheds new light on the link between recruitability and normally aerated lung.

Whether empirical therapy with carbapenems positively affects the outcomes of critically ill patients with bacterial infections remains unclear. This study aimed to investigate whether the use of carbapenems as the initial antimicrobial administration reduces mortality and whether the duration of carbapenem use affects the detection of multidrug-resistant (MDR) pathogens. This was a post hoc analysis of data acquired from Japanese participating sites from a multicenter, prospective observational study [Determinants of Antimicrobial Use and De-escalation in Critical Care (DIANA study)]. A total of 268 adult patients with clinically suspected or confirmed bacterial infections from 31 Japanese intensive care units (ICUs) were analyzed. The patients were divided into two groups: patients who were administered carbapenems as initial antimicrobials (initial carbapenem group, n = 99) and those who were not administered carbapenems (initial non-carbapenem group, n = 169). The primary outcomes were mortality at day 28 and detection of MDR pathogens. Multivariate logistic regression analysis revealed that mortality at day 28 did not differ between the two groups [18 (18%) vs 27 (16%), respectively; odds ratio: 1.25 (95% confidence interval (CI): 0.59-2.65), P = 0.564]. The subdistribution hazard ratio for detecting MDR pathogens on day 28 per additional day of carbapenem use is 1.08 (95% CI: 1.05-1.13, P < 0.001 using the Fine-Gray model with death regarded as a competing event). In conclusion, in-hospital mortality was similar between the groups, and a longer duration of carbapenem use as the initial antimicrobial therapy resulted in a higher risk of detection of new MDR pathogens.IMPORTANCEWe found no statistical difference in mortality with the empirical use of carbapenems as initial antimicrobial therapy among critically ill patients with bacterial infections. Our study revealed a lower proportion of inappropriate initial antimicrobial administrations than those reported in previous studies. This result suggests the importance of appropriate risk assessment for the involvement of multidrug-resistant (MDR) pathogens and the selection of suitable antibiotics based on risk. To the best of our knowledge, this study is the first to demonstrate that a longer duration of carbapenem use as initial therapy is associated with a higher risk of subsequent detection of MDR pathogens. This finding underscores the importance of efforts to minimize the duration of carbapenem use as initial antimicrobial therapy when it is necessary.

BACKGROUND: Sepsis-3 emphasizes the recognition of sepsis-induced cellular metabolic abnormalities, and utilizes serum lactate level as a biomarker of cellular metabolic abnormalities. Magnesium plays an important role as a cofactor in glucose metabolism, although it is not well known that magnesium deficiency causes elevated serum lactate levels. Additionally, it remains unclear how magnesium status affects the role of serum lactate levels as a marker of metabolic abnormalities in sepsis. Thus, this study aimed to investigate the association between serum magnesium and lactate levels in patients with sepsis and explore this relationship from the perspectives of time course and circulatory abnormalities. METHODS: This retrospective observational study of adult patients with sepsis was performed at the 16-bed intensive care unit of Jichi Medical University Hospital between June 2011 and December 2017. The relationship between serum magnesium and lactate levels for 5 days from intensive care unit admission was investigated along the time course. Multivariate logistic regression analysis was performed to evaluate the association between serum magnesium and lactate levels during intensive care unit admission. RESULTS: Among 759 patients included, 105 had hypomagnesemia (magnesium level < 1.6 mg/dL), 558 had normal serum magnesium levels (1.6-2.4 mg/dL), and 96 had hypermagnesemia (magnesium level > 2.4 mg/dL) at intensive care unit admission. From intensive care unit admission to day 5, the hypomagnesemia group had higher serum lactate levels and a higher frequency of lactic acidosis than the normal magnesium level and hypermagnesemia groups (70% vs. 51.6% vs. 50%; P < 0.001). Hypomagnesemia at intensive care unit admission was independently associated with lactic acidosis, i.e., lactic acid level > 2 mmol/L (odds ratio, 2.76; 95% confidence interval, 1.60-4.76; P < 0.001). CONCLUSIONS: Hypomagnesemia was associated with serum lactate levels in the early and post-resuscitation phases of sepsis. Further studies are needed to elucidate whether the magnesium status is associated with sepsis-induced cellular and metabolic abnormalities.

A 45-year-old woman was hospitalized with severe coronavirus disease 2019 pneumonia. Following cytokine storm-induced multiorgan failure and lethal arrhythmia, the patient developed a sustained coma with flaccid quadriplegia. A cerebrospinal fluid examination excluded infectious and immunogenic encephalopathies, and diffusion-weighted magnetic resonance imaging demonstrated high-intensity areas in the white matter with a cortex-sparing distribution, suggesting delayed post-hypoxic leukoencephalopathy. As a result of intensive cardiopulmonary support for a month, the neurological function gradually recovered. Based on the reversible clinical course noted in this patient, accurate diagnosis and persistent medical approaches are important for the management of coronavirus disease 2019-related delayed post-hypoxic leukoencephalopathy.

BACKGROUND: Most ventilators measure airway occlusion pressure (occlusion P0.1) by occluding the breathing circuit; however, some ventilators can predict P0.1 for each breath without occlusion. Nevertheless, few studies have verified the accuracy of continuous P0.1 measurement. The aim of this study was to evaluate the accuracy of continuous P0.1 measurement compared with that of occlusion methods for various ventilators using a lung simulator. METHODS: A total of 42 breathing patterns were validated using a lung simulator in combination with 7 different inspiratory muscular pressures and 3 different rise rates to simulate normal and obstructed lungs. PB980 and Dräger V500 ventilators were used to obtain occlusion P0.1 measurements. The occlusion maneuver was performed on the ventilator, and a corresponding reference P0.1 was recorded from the ASL5000 breathing simulator simultaneously. Hamilton-C6, Hamilton-G5, and Servo-U ventilators were used to obtain sustained P0.1 measurements (continuous P0.1). The reference P0.1 measured with the simulator was analyzed by using a Bland-Altman plot. RESULTS: The 2 lung mechanical models capable of measuring occlusion P0.1 yielded values equivalent to reference P0.1 (bias and precision values were 0.51 and 1.06, respectively, for the Dräger V500, and were 0.54 and 0.91, respectively, for the PB980). Continuous P0.1 for the Hamilton-C6 was underestimated in both the normal and obstructive models (bias and precision values were -2.13 and 1.91, respectively), whereas continuous P0.1 for the Servo-U was underestimated only in the obstructive model (bias and precision values were -0.86 and 1.76, respectively). Continuous P0.1 for the Hamilton-G5 was mostly similar to but less accurate than occlusion P0.1 (bias and precision values were 1.62 and 2.06, respectively). CONCLUSIONS: The accuracy of continuous P0.1 measurements varies based on the characteristics of the ventilator and should be interpreted by considering the characteristics of each system. Moreover, measurements obtained with an occluded circuit could be desirable for determining the true P0.1.

PURPOSE OF REVIEW: The last 25 years have seen considerable development in modes of closed-loop ventilation and there are now several of them commercially available. They not only offer potential benefits for the individual patient, but may also improve the organization within the intensive care unit (ICU). Clinicians are showing both greater interest and willingness to address the issues of a caregiver shortage and overload of bedside work in the ICU. This article reviews the clinical benefits of using closed-loop ventilation modes, with a focus on control of oxygenation, lung protection, and weaning. RECENT FINDINGS: Closed-loop ventilation modes are able to maintain important physiological variables, such as oxygen saturation measured by pulse oximetry, tidal volume (VT), driving pressure (ΔP), and mechanical power (MP), within target ranges aimed at ensuring continuous lung protection. In addition, these modes adapt the ventilator support to the patient's needs, promoting diaphragm activity and preventing over-assistance. Some studies have shown the potential of these modes to reduce the duration of both weaning and mechanical ventilation. SUMMARY: Recent studies have primarily demonstrated the safety, efficacy, and feasibility of using closed-loop ventilation modes in the ICU and postsurgery patients. Large, multicenter randomized controlled trials are needed to assess their impact on important short- and long-term clinical outcomes, the organization of the ICU, and cost-effectiveness.