Bao Fu

Objective: To examine whether sublingual high-velocity blood flow (HVBF), assessed within 6 hours of hospital admission, is associated with incident sepsis (study-defined) within 48 hours in patients with suspected infection but without sepsis at admission. Methods: In this prospective single-center observational study, hospitalized adults with suspected infection underwent sublingual sidestream dark field imaging within 6 hours of admission. HVBF positivity was predefined as a mean field-specific maximal red blood cell velocity ≥ 1000 μm/s. The primary cohort comprised 109 patients without sepsis at admission, of whom 59 developed incident sepsis within 48 hours. Associations were examined using multivariable logistic regression adjusted for the National Early Warning Score (NEWS) and lactate. Results: HVBF positivity was present in 78.0% of patients who developed incident sepsis versus 26.0% of those who did not (crude odds ratio [OR] 10.07, 95% confidence interval [CI] 4.17– 24.33, P < 0.001) and persisted after adjustment (adjusted OR 4.32, 95% CI 1.32– 14.22, P = 0.016). HVBF showed lower discrimination than NEWS (area under the curve [AUC] 0.760 vs 0.887, P = 0.007), and adding HVBF to NEWS plus lactate did not improve discrimination (AUC 0.920 vs 0.917, P = 0.833). After additional adjustment for the admission Sequential Organ Failure Assessment (SOFA) score, the HVBF association became non-significant (OR 1.21, P = 0.813). Conclusion: Sublingual HVBF positivity was associated with incident sepsis within 48 hours but was not independent of minor baseline organ dysfunction and added no incremental discrimination beyond NEWS and lactate. HVBF may represent a bedside-visible microcirculatory phenotype of the pre-criteria phase of the infection-to-sepsis trajectory.

Sepsis-induced cardiomyopathy (SICM) is a common and severe complication of sepsis that contributes substantially to circulatory instability, organ dysfunction, and adverse clinical outcomes. Mitochondrial dysfunction and metabolic reprogramming have emerged as central mechanisms underlying its pathogenesis. Because the adult myocardium depends heavily on mitochondrial lipid metabolism for continuous energy production, disruption of lipid metabolic homeostasis may critically impair myocardial bioenergetics and stress adaptation during sepsis. Current evidence indicates that SICM is accompanied by extensive abnormalities in mitochondrial lipid metabolism, including impaired fatty acid uptake and oxidation, pathological cardiolipin remodeling, excessive lipid peroxidation, ferroptosis, disrupted lipid droplet–mitochondria interactions, and defective mitochondrial dynamics and quality control. These alterations interact with inflammatory signaling, redox imbalance, and metabolism-associated post-translational modifications, collectively promoting adenosine triphosphate (ATP) depletion, lipotoxicity, oxidative injury, and cardiac dysfunction. This review summarizes the physiological organization of mitochondrial lipid metabolism in the healthy myocardium and systematically examines the mechanisms responsible for its dysregulation in SICM. Particular emphasis is placed on cardiolipin remodeling and mitochondrial membrane lipid homeostasis as potential links among impaired substrate oxidation, respiratory chain instability, oxidative stress amplification, and myocardial injury. Emerging therapeutic strategies aimed at restoring metabolic flexibility, preserving mitochondrial membrane integrity, limiting lipid peroxidation, and improving mitochondrial quality control are also evaluated. A better understanding of these mechanisms may support earlier recognition of metabolically distinct SICM phenotypes, improve the timing and selection of targeted interventions, and facilitate the development of more precise approaches to reducing sepsis-related cardiac injury and improving patient outcomes.

Chronic obstructive pulmonary disease (COPD) is a common reason for admission to the intensive care unit (ICU), where accurate risk stratification is cruci

The precise mechanisms underlying the modulation and transformation of consciousness during propofol anesthesia remain inadequately understood. Both the paraventricular thalamus (PVT)-medial prefrontal cortex (mPFC) pathway and the parabrachial nucleus (PB) are implicated in the regulation of sleep-wake cycles. Consequently, this study aimed to explore whether projections from the PB to the PVT-mPFC pathway are involved in the effects of propofol anesthesia. Anterograde and retrograde viral tracing techniques were employed to map the projections from the PB to the PVT and from the PVT to the mPFC. The activity within this pathway was monitored using fiber photometry during propofol anesthesia. The study further examined the role of this pathway during the induction and emergence phases of propofol anesthesia through optogenetic modulation in conjunction with cortical electroencephalography (EEG) recordings. Glutamatergic neurons in the PB exhibit dense projections to the PVT, and in turn, PVT glutamatergic neurons project densely to the mPFC. Administration of propofol resulted in a reduction of calcium signals in the parabrachial glutamatergic nucleus to paraventricular thalamus (PB_Glu-PVT) pathway. Moreover, it has been observed that optogenetic activation of the PB_Glu-PVT pathway significantly enhances cortical activation during propofol anesthesia, whereas optogenetic inhibition of this pathway yields the opposite effect. Additionally, optogenetic stimulation of the PVT_Glu-mPFC pathway accelerates the induction of propofol anesthesia but prolongs the emergence time. Conversely, inhibition of the PVT_Glu-mPFC pathway facilitates cortical activation under propofol anesthesia. Collectively, this study provides supportive evidence for the involvement of a brainstem-thalamic-cortical glutamatergic circuit in propofol anesthesia. The findings offer a preliminary perspective on how propofol may modulate consciousness and highlight potential pathways worthy of further investigation.

Background: Patients resuscitated from cardiac arrest (CA) commonly have poor outcomes with a high mortality rate. We aimed to determine the predictive values of serum soluble triggering receptor expressed on myeloid cells 1 and 2 (sTREM-1 and sTREM-2) in patients after return of spontaneous circulation (ROSC) and to develop machine learning (ML) prediction models. Methods: We prospectively enrolled adult CA patients successfully resuscitated after cardiopulmonary resuscitation between November, 2021 to December, 2023. Serum sTREM-1, sTREM-2 and other biomarkers were measured on days 1, 3 and 5 after ROSC. The primary outcome was 28-day all-cause mortality. The secondary outcome was 3-month neurological prognosis. The performance of serum sTREM-1, sTREM-2, as well as the developed ML prediction models, to predict 28-day all-cause mortality and 3-month neurological prognosis were studied. Results: The study enrolled 120 patients, including 32 survivors and 88 non-survivors, with 30 healthy volunteers. Both sTREM-1 and sTREM-2 levels increased in patients after ROSC, with a larger increase in the non-survivors than survivors. Moreover, eleven features, including sTREM-1 and sTREM-2, were ultimately identified to build ML models. Among other ML models, the eXtreme Gradient Boosting (XGBoost) and Random Forest (RF) models showed strong performances for predicting 28-day all-cause mortality and 3-month neurological prognosis, respectively. Conclusion: Serum sTREM-1 performed better than sTREM-2 to predict mortality and neurological outcome after ROSC. Furthermore, the newly developed XGBoost and RF models incorporating sTREM-1 and/or sTREM-2 demonstrated superior predictive accuracy compared to conventional clinical scoring systems.

The mammalian colon lumen exists in a highly anaerobic environment (oxygen partial pressure (PO ₂ ) < 1 mmHg), which promotes the growth of beneficial obligate anaerobes (OA) while limiting the expansion of pathogenic facultative anaerobes (FA). Gut dysbiosis is associated with a wide range of human diseases, and is often characterized by an overgrowth of FA, particularly those in the Enterobacteriaceae family. Oxygen (O ₂ ) plays a crucial role in bacterial physiology and ecology, and increased O ₂ availability is a key driver of gut dysbiosis. O ₂ therapy is commonly used for hypoxic patients, either through inhalation or extracorporeal membrane oxygenation (ECMO), both of which can expose the gut to excess O ₂ , known as hyperoxia. Hyperoxia leads to the overproduction of reactive O ₂ species, resulting in organ injury and worsening clinical outcomes. Viewing gut dysbiosis from an ecological perspective highlights the disruption of host mechanisms that regulate the gut microbiota, particularly in the context of antibiotic use and a western (low fiber) diet, where physiological hypoxia in the colonic epithelium is compromised. This review extends that perspective to O ₂ therapy in acute care, discussing the rationale and experimental evidence linking hyperoxia to gut dysbiosis, with a focus on venoarterial (VA)-ECMO support as a potential contributor. Understanding these mechanisms could help clinicians optimize O ₂ management during therapy.