Sepsis is a critical illness characterized by pronounced temporal dynamics and marked heterogeneity of organ perfusion. Current hemodynamic management relies largely on global macro-circulatory variables such as MAP and CO, but these measures provide limited insight into inter-organ blood-flow redistribution and often fail to detect occult hypoperfusion in vulnerable tissues. Consequently, organ dysfunction may continue to progress even when systemic targets appear to be achieved. The arterial resistance index (RI) can be repeatedly assessed in specific organs with relatively high temporal resolution, it provides a practical signal for tracking perfusion heterogeneity in sepsis. On this basis, this review reframes sepsis as a process dominated by dynamic blood-flow redistribution rather than a single, homogeneous state of circulatory failure and proposes the Arterial Resistance Index Series in Echography (ARISE) framework. ARISE focuses on four representative vascular beds that capture key dimensions of circulatory regulation-including central control, vulnerable organs, and peripheral perfusion: the cerebral, renal, and superior mesenteric arteries, as well as the anatomical snuffbox artery. The framework emphasizes RI trajectories over time, inter-organ flow distribution, and the structured integration of these patterns. Available evidence indicates that arterial RI in different organs exhibits pronounced temporal variation and inter-organ heterogeneity during sepsis. Distinct trajectories are observed across central, vulnerable, and peripheral vascular beds, reflecting ongoing redistribution of blood flow as the disease evolves. Multi-organ RI assessment can reveal pathophysiological phenomena not captured by conventional macro-circulatory indices, including occult hypoperfusion, macro-microcirculatory uncoupling, and "sacrificial" redistribution. Advances in critical care ultrasonography now enable bedside, real-time, quantitative monitoring of multi-organ RI, providing the technical foundation for dynamic perfusion assessment. Overall, ARISE shifts sepsis assessment from a static pressure-flow paradigm to a dynamic framework centered on organ blood-flow distribution and evolving perfusion patterns.

With advances in the understanding of shock pathophysiology and the development of hemodynamic theory and monitoring technologies, clinical strategies for shock assessment and treatment are undergoing substantial changes. First, finer delineation of the pathophysiological stages of shock enables multidimensional evaluation of circulatory status and thereby improves therapeutic precision. Second, individualized interpretation of monitoring variables within evidence-based and physiological frameworks provides a feasible approach to personalized hemodynamic interventions in critically ill patients. Third, because shock evolves in distinct temporal phases, hemodynamic phenotypes and treatment responsiveness change over the disease course, necessitating concomitant dynamic adjustment of therapeutic targets. Accordingly, defining an overall therapeutic goal, decomposing it into operational, tiered sub-targets, and continuously recalibrating these targets throughout the clinical course have become key requirements of contemporary critical care hemodynamic management. This review organizes hemodynamic management around clinically verifiable endpoints. The overarching goal of hemodynamic management is to maintain adequate tissue perfusion and oxygenation while minimizing treatment-related iatrogenic injury, thereby reducing the risk of cellular hypoxic damage and multiple organ dysfunction. Guided by this goal, clinical decision-making can be structured as a continuous loop of “identifying hypoperfusion—qualitative mechanistic phenotyping (allowing mixed shock)—tiered quantitative monitoring—goal decomposition (perfusion pressure, flow, oxygen metabolism)—intervention with metric binding—reassessment and dynamic recalibration,” consistent with the time-varying nature of shock pathophysiology.

Acute respiratory distress syndrome (ARDS) is a highly heterogeneous syndrome with substantial mortality, for which existing subphenotyping strategies based on single-modal data have limited ability to guide targeted therapies. A comprehensive, multimodal framework is urgently needed to decipher its complexity and advance precision care. The BIOWARE study is a prospective, multicenter cohort aiming to enroll 2,000 ARDS patients across nine Chinese centers. The protocol integrates longitudinal data from clinical assessments, ventilator waveforms, advanced imaging (CT, EIT, lung ultrasound), and biospecimen analyses. As of August 2025, 169 patients have been enrolled (median age 62 years, 74

BACKGROUND:Reverse triggering is a complex form of asynchrony with different phenotypes. The exposure burden and clinical outcomes of reverse triggering during pressure-controlled ventilation (PCV) are underexplored. We aimed at determining the incidence of reverse triggering and characterizing the impact of breath-stacking. METHODS:This was a prospective, observational analysis. Adult subjects with PCV under long-term monitoring were included. The primary outcome was duration of invasive mechanical ventilation. Secondary outcomes included changes in mechanics and tidal volumes associated with breath-stacking, factors correlated with increased frequency of reverse triggering, and testing for thresholds of volume, which could be associated with harm. RESULTS:Among 429 subjects with PCV and >24 h of usable waveform recording, 174 subjects (40.6%) were found to have reverse triggering, and 80 subjects had reverse triggering with breath-stacking. Reverse triggering with breath-stacking was associated with higher peak inspiratory pressure (PIP) (15.4 [14.3-17.0] versus 13.7 [11.4, 15.0] cm H2O, P < .001), driving pressure (ΔP) [8.5(7.5,10.0) versus 7.0(5.8,9.0) cm H2O, P < .001] and longer duration of invasive mechanical ventilation [7(3,15) versus 4(2,7) days, P = .015]. Higher level of ΔP (odds ratio [OR] = 1.49, 95% CI: 1.06-2.11, P = .02) and tidal volume (OR = 1.02, 95% CI: 1.01-1.03, P < .001), more fentanyl infusion (OR,1.19, 95% CI: 1.17-1.20, P = .033) and lower value of PaO2/FIO2 (OR = 0.99, 95% CI: 0.98-1.00, P = .02) were risk factors possibly related to reverse triggering with breath-stacking. Receiver operating characteristic analysis suggests that a breath-stacked volume threshold of 141 mL might be associated with prolonged invasive mechanical ventilation. CONCLUSIONS:Reverse triggering with breath-stacking during PCV was characterized by higher PIP, ΔP, and longer duration of invasive mechanical ventilation. Larger volumes with breath-stacking may be associated with prolonged mechanical ventilation. Fentanyl usage and worse PaO2/FIO2 were risk factors related to reverse triggering with breath-stacking.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

Critical care medicine is at a pivotal stage of transformation from symptom-based approaches toward systems science. Building on a first-principles understanding of the mechanisms underlying critical illness, we propose the entropic critical illness theory (ECIT). Grounded in the second law of thermodynamics, ECIT posits that critical illness arises when the body’s capacity to regulate entropy production is impaired, leading to systemic disorder. This process is manifested by the concurrent escalation of host response entropy and hemodynamic entropy, resulting in disruptions in blood flow and oxygen delivery, ischemia, and hypoxia at the level of the critical unit, which is defined as the terminal microcirculatory–mitochondrial functional unit, ultimately culminating in multi-organ dysfunction. This study delineates the theoretical foundations of ECIT and outlines an entropy-based critical care framework that may inform future multimodal entropy-informed monitoring, risk stratification, and AI-assisted precision intervention in critical care medicine.

OBJECTIVE:This study aimed to investigate the association of abdominal obesity indicators (Waist circumference (WC), lipid accumulation product (LAP), a body shape index (ABSI), body roundness index (BRI), weight-adjusted waist index (WWI), and visceral adiposity index (VAI)) with the risk of all-cause mortality in familial hypercholesterolemia (FH) and to compare their prognostic performance. METHODS:A cohort of 1,188 FH patients from the National Health and Nutrition Examination Survey (1999-2018) was analyzed. Mortality outcomes through 2019 were identified via linkage to the National Death Index. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality. The incremental predictive value of each indicator beyond a base model was assessed using the C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). RESULTS:During a median follow-up of 8.4 years, 215 patients (18.1 %) died. After full multivariable adjustment, individuals in the highest tertile of ABSI exhibited a significantly elevated mortality risk compared to the lowest tertile (HR = 1.97, 95 % CI: 1.31-2.95). Similarly, the highest WWI tertile was associated with increased mortality (HR = 1.49, 95 % CI: 1.01-2.22). No significant associations were observed for WC, LAP, BRI, or VAI. Among all evaluated indicators, ABSI conferred the most substantial incremental predictive value when added to the base model, significantly improving discrimination (C-statistic: 0.809, 95 % CI: 0.781-0.838), integrated discrimination (IDI: 0.033, 95 % CI: 0.011-0.063), and risk reclassification (NRI: 0.256, 95 % CI: 0.138-0.347). CONCLUSIONS:Elevated ABSI and WWI independently predicted increased all-cause mortality in familial hypercholesterolemia patients. Crucially, ABSI demonstrated superior prognostic performance, significantly enhancing mortality risk stratification beyond established factors, and its incorporation into clinical models may improve prognostication and guide tailored management.

Patients taking oral EGFR inhibitors should be alert to the risk of TEN if they suddenly develop widespread rash.

Objectives Acute type A aortic dissection is a life-threatening cardiovascular disease commonly seen in emergency department, resulting in substantial mortality and morbidity. We aimed to investigate the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) among this critically ill population.Design The design of this study was a retrospective cohort study.Setting The study population was recruited in the Emergency Department of Fuwai hospital in China from 2018 to 2020.Participants We consecutively enrolled 829 patients with acute type A aortic dissection and measurable baseline NT-proBNP.Primary outcome The primary endpoint was 1-year all-cause death.Results Based on tertiles of NT-proBNP (pg/mL), patients were stratified into low (≤150.3, n=276), intermediate (150.3–667.6, n=277) and high (>667.6, n=276) NT-proBNP groups. Compared with patients with low NT-proBNP, the Kaplan-Meier estimates for primary 1-year mortality were higher in intermediate (32.5% vs 18.1%; HR 1.91, 95% CI 1.35 to 2.69) and high (42.0% vs 18.1%; HR 2.56, 95% CI 1.84 to 3.57) NT-proBNP groups, respectively. After multivariable regression adjusted for confounders, NT-proBNP tertiles were independent predictors for 1-year mortality (adjusted HR for intermediate group 1.52, 95% CI 1.02 to 2.27; adjusted HR for high group 2.17, 95% CI 1.41 to 3.32). Notably, the predictive performance of NT-proBNP for 1-year mortality was greater in patients receiving surgery than conservative treatment (between-cohorts difference in area under the curve 0.13, Delong’s test p=0.04).Conclusion NT-proBNP provides incremental prognostic information for mortality in patients with acute type A aortic dissection who underwent surgical repairment, which could aid in risk stratification as a pragmatic and versatile biomarker in this critically ill population while having limited prognostic value for those receiving conservative treatment.

Organophosphorus flame retardants (OPFRs) are recognized as potential endocrine disruptors. Several studies have demonstrated that contamination with OPFRs increases the risk of infertility. Our prior research showed that inhibition of the nuclear factor erythroid-derived 2-related factor (Nrf2)/p53 signaling pathway is an essential regulator of DPhP-induced reproductive injury. In this study, we aimed to uncover potential epigenetic mechanisms involved in DPhP-induced GC-2 cell dysfunction. Our results established that DPhP promoted miR-128-3p expression in GC-2 cells, targeted the Nrf2 signaling pathway, thereby suppressing its activity, and thus inhibited autophagy to promote apoptosis. These findings indicate that DPhP causes reproductive damage and potentially modulates autophagy and apoptosis in GC-2 cells through the miR-128-3p/Nrf2 regulatory axis. Our results further elucidated the possible mechanism of DPhP-induced reproductive damage and provided new clues to study the potential reproductive toxicity of OPFRs.

Lung ultrasound has been extensively used to assess the etiology of respiratory failure. Additionally, lung ultrasound-based scoring systems have been proposed to semi-quantify the loss of lung aeration in the ICU. The one most frequently used distinguishes four steps of progressive loss of aeration (scores from 0 to 3) and 3 scores mean tissue-like pattern. However, the burden of consolidation is not considered as tissue-like pattern is defined as 3 scores independently of its dimension. In this study, we present an ultrasound method for quantitative measurement of consolidation size and investigate the relationship between consolidation size and outcome in ICU patients with respiratory failure. A total of 124 patients in ICU were prospectively enrolled and 13 patients were excluded due to failure to obtain LUS measurements. Among the remaining 111 patients, 17 patients were non-intubated, and 94 patients under sedation and analgesia were intubated. All patients underwent lung ultrasound examination for the measurement of lung consolidation size between 24 and 48 h after ICU admission. Lung consolidation size was assessed by consolidation area index (CA), which was determined by tracing the maximum cross-sectional area of the region of consolidation. The Cox-regression model was constructed for 28- and 90-day mortality. Consolidation size was successfully evaluated in all patients. The CA was 24.2cm2[15.9–36.6] (median [25th -75th percentiles]). CA was negatively correlated with PaO2/FiO2 ratio (r=-0.26, P < 0.0001). Upon univariate and multivariate analysis, only CA [Odds ratio (OR) 1.04, 95

Over millions of years, the circulatory system evolved from primitive forms into a highly specialized network capable of overcoming time-distance constraints and enhancing diffusion efficiency. This structural advancement laid the physiological foundation for the regulation of hemodynamics and systemic homeostasis. Hemodynamic homeostasis is a fundamental biological process that ensures the continuous delivery of oxygen and substrates while facilitating the removal of carbon dioxide and metabolic waste. Such balance is essential for sustaining cellular metabolism and maintaining the function of vital organs throughout embryonic development and the human lifespan. Disruption of this equilibrium, primarily driven by the Host/Organ Unregulated Response (HOUR), compromises the cardiovascular-respiratory system, resulting in hemodynamic homeostasis disequilibrium. HOUR specifically targets the critical unit—a constellation of elements essential for oxygenation and cell energetics, including the microcirculation, endothelial glycocalyx, and mitochondria, impairing the oxygenation process, ultimately triggering critical illness. Although intervention targeting systemic hemodynamic variables (e.g., pressure, flow) may temporarily improve regional perfusion, restoring full homeostasis remains challenging. This is largely due to the activation of multiple positive feedback loops (e.g., coagulation cascades) and impairment of key negative feedback mechanisms (e.g., blood pressure regulation). In the presence of ongoing HOUR, inappropriate or delayed interventions may exacerbate injury and accelerate irreversible organ damage or death. Therefore, it is both essential and urgent to elucidate the initiation, recognition, progression, and modulation of hemodynamic homeostasis disequilibrium.

Background::Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China.Methods::Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran’s I analysis. Results::The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603) of total cases and cirrhosis cases accounted for 11.23% (180/1603). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (Moran’s I <0) and percentage of urban population (Moran’s I <0), and positively correlated with the number of pediatric beds per million population (Moran’s I >0). Conclusion::The number of severe hepatitis B cases is low in areas with high gross domestic product levels and high urban population ratios, and health care costs have been declining over the years.

Clonal hematopoiesis of indeterminate potential (CHIP) is a prominent risk factor for atherosclerosis, but effective medications for CHIP-associated risk are still lacking. This study aimed to assess prognostic impacts of P2Y12 inhibitors in the context of CHIP with a prospective cohort of 1332 patients of ST-segment elevation myocardial infarction (STEMI). Using targeted deep sequencing, CHIP was defined by any CHIP-gene mutations with variant allele frequency (VAF) > 2 %. Patients were stratified into four groups according to CHIP status and the prescribed types of P2Y12 inhibitors (ticagrelor and clopidogrel). The primary outcome was major adverse cardiovascular events (MACE), a composite of death, recurrent MI, re-hospitalization due to heart failure and ischemic stroke. During a median follow-up of 1458 days, CHIP patients receiving ticagrelor exhibited lower risk of MACE (hazard ratio [HR]: 0.42, 95 % confidence interval [CI]: 0.20-0.88, P = 0.022), followed by non-CHIP patients on clopidogrel (HR: 0.60, 95 % CI: 0.41-0.88, P = 0.010) and ticagrelor (HR: 0.66, 95 % CI: 0.44-0.99, P = 0.044), as compared to CHIP patients on clopidogrel, with significant interactions detected between ticagrelor and CHIP (P interaction = 0.015, relative excess risk due to interaction: -1.53, 95 % CI: -4.91- -0.66). In sum, CHIP and P2Y12 inhibitors jointly affected outcomes of STEMI patients, and ticagrelor was associated to greater risk reduction in the presence of CHIP. These findings would promote more personalized antiplatelet medications for patients with STEMI.

Functional complete revascularization (CR) after percutaneous coronary intervention (PCI) as determined by classic residual functional SYNTAX score (c-rFSS) has been associated with improved prognosis. In this study, the c-rFSS algorithm is optimized for a novel modified rFSS (m-rFSS) and prognostic implications of this novel scoring is determined. The m-rFSS algorithm is updated for 2 clinical scenarios, i.e., 1) lesions with suboptimal functional results, and 2) angiographic diameter stenosis <50% but functionally significant stenoses, which are not scored by c-rFSS. The major outcome is a 2-year major adverse cardiac event (MACE). A total of 1,555 patients analyzable for both c-rFSS and m-rFSS are included. After calculating m-rFSS, 12.0% (187/1,555) of patients with c-rFSS-based functional CR (c-rFSS = 0) are reclassified as having m-rFSS-based incomplete revascularization (IR, m-rFSS>0); thus, 377 (21.7%) patients have c-rFSS-based functional IR whereas 524 (33.7%) has m-rFSS-based IR. Patients with m-rFSS-based functional IR (m-rFSS>0) show a significantly higher risk for major MACE outcome (20.8% vs 5.9%; adjusted hazard ratio 3.32, 95% confidence interval: 2.34-4.71) than patients with functional CR (m-rFSS = 0). The m-rFSS is more predictive of 2-year MACE than c-rFSS (difference in C-index 0.07, p < 0.001). In this study, we optimized the classic scoring algorithm to develop a novel scoring system (m-rFSS), and revascularization completeness determined by m-rFSS is markedly associated with a 2-year prognosis.