Characteristics and Clinical Prognosis of Septic Patients With Persistent Lymphopenia.

Background: Septic patients with persistent lymphopenia may be in an immunosuppressed state. Therefore, we evaluated and compared the clinical characteristics and outcomes of septic patients with persistent lymphopenia (≥2d) and those with nonpersistent lymphopenia. Methods: A retrospective cohort study was designed. A total of 1306 patients with sepsis who were attended to the First Affiliated Hospital of Dalian Medical University from March 2016 to August 2022 were included. The primary clinical outcome was 90d mortality. The secondary clinical outcomes were the length of stay, hospital mortality, 28d mortality, the incidence of secondary infection, and differences in clinical characteristics. Results: Among 1306 patients with sepsis, 913 (69.9%) patients developed persistent lymphopenia. Compared with patients with nonpersistent lymphopenia, patients with persistent lymphocytopenia were admitted to intensive care unit (75.7% vs 52.7%, P < .05), treated with mechanical ventilation (67.6% vs 39.2%, P < .05), positive rate of microbial culture pathogens (86.7% vs 71.2%, P < .05), SOFA [8.0 (6.0-10.0) vs 6.0 (4.0-8.0), P < .05], length of stay [17.0d (12.0-27.0) vs 13.0d (10.0-21.0), P < .05], hospital mortality (37.7% vs 24.2%, P < .05), 28d mortality (38.0% vs 22.9%, P < .05), and 90d mortality (51.2% vs 31.3%, P < .05) were higher. As the duration of lymphocytopenia increased, so did the mortality rate in hospital. In addition, the onset time of persistent lymphopenia was not associated with SOFA. But we found that the frequency of persistent lymphopenia during hospitalization was positively associated with SOFA. Conclusion: Septic patients with persistent lymphopenia have higher mortality, worse conditions, increased risk of secondary infection, and poor prognosis regardless of shock.

Protective Effects of Sesamol on Renal Ischemia-Reperfusion Injury Via Regulation of Nuclear Factor Erythroid 2-Related Factor 2 Pathway.

BACKGROUND: Sesamol is a natural antioxidant known for its potent antioxidant and free radical scavenging properties. This study aimed to explore the therapeutic effects and underlying mechanisms of sesamol in the development of renal ischemia-reperfusion injury (IRI) in mice. METHODS: C57BL/6J wild-type mice were divided into 3 groups: IR group, treated with normal saline after undergoing the IRI procedure; Sesamol + IR group, treated with 30 mg/kg/d of sesamol after the IRI procedure; and Sham group, treated with normal saline but not subjected to the IRI process. Renal IRI was induced by performing a right kidney nephrectomy and subjecting the left kidney to 30-minute ischemia, followed by 24-hour reperfusion. Kidney tissues and serum were collected 24 hours post-IRI to assess the impact of sesamol on renal function after IRI. Serum creatinine and blood urea nitrogen levels were assessed, and renal cell apoptosis was detected through terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. The levels of interleukin 1ß and interleukin 18 in kidney tissues, as well as indicators of oxidative stress, were also measured. Furthermore, Nrf2-deficient mice were used to examine the protective function of the nuclear factor erythroid 2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1) signaling pathways induced by sesamol, as determined by western blot assay. RESULTS: Sesamol demonstrated significant improvement in renal function, along with reductions in renal tubular injury, cell necrosis, and apoptosis in mice. It also effectively lowered key inflammatory mediator levels. Sesamol exhibited antioxidant properties by reducing malondialdehyde levels and enhancing superoxide dismutase activities 24 hours after IRI. Western blot assay revealed increased Nrf2, HO-1, and NQO-1 protein levels with sesamol treatment. Notably, Nrf2-deficient mice did not exhibit the beneficial effects of sesamol. CONCLUSIONS: This study demonstrates that sesamol effectively alleviates renal IRI by enhancing antioxidant defenses and reducing inflammation potentially through the Nrf2/HO-1 and NQO1 signaling pathways.

High-dose vitamin C improves norepinephrine level in patients with septic shock: A single-center, prospective, randomized controlled trial.

BACKGROUND: The effects of vitamin C supplementation on patients with septic shock remain controversial. We aimed to evaluate the effects of different vitamin C dosages on norepinephrine (NE) synthesis in adult patients with septic shock. METHODS: A total of 58 patients with septic shock admitted to our intensive care unit (ICU) between July 2021 and December 2022 were included. Patients were randomly divided into 3 groups: high-dose vitamin C (150 mg/kg/d, group A), low-dose vitamin C (50 mg/kg/d, group B), and placebo (group C). NE synthesis-related indicators (dopamine-ß-hydroxylase [DßH], tyrosine hydroxylase [TH], tetrahydrobiopterin [BH4], and dopamine [DA]), plasma NE, and vitamin C levels were measured every 24 hours and analyzed. All-cause mortality within 28 days and other clinical outcomes (including Acute Physiology and Chronic Health Evaluation [APACHE], Sequential Organ Failure Assessment [SOFA], and Multiple-Organ Dysfunction Syndrome [MODS] scores) were compared. RESULTS: Changes in TH, BH4, and DßH levels at 96 hours in groups A and B were greater than those in group C. These differences became more pronounced over the course of the intravenous vitamin C administration. Significant differences between groups A and C were detected at 96-hours TH, 72-hours BH4, 96-hours BH4, 96-hours DA, and DßH levels every 24 hours. The 96-hours TH, 96-hours BH4, and 48-hours DßH in group B were significantly higher than those in group C. The NE levels every 24 hours in groups A and B were higher than those in group C, group A and group C had a statistically significant difference. The 96-hours exogenous NE dosage in groups A and B was significantly lower than that in group C. No significant reductions in APACHE, SOFA, or MODS scores were observed in the vitamin C group, including the duration of ICU stay and mechanical ventilation. The 28-days mortality was lower in groups A and B than in group C (0%, 10%, and 16.67%, P = .187), but the difference was not significant. CONCLUSION: For patients with septic shock, treatment with vitamin C significantly increased TH, BH4, and DßH levels and reduced the exogenous NE dosage, but did not significantly improve clinical outcomes.

Experimental study of a novel mouse model of tibial shaft fracture combined with blunt chest trauma.

BACKGROUD: Thoracic Trauma and Limb Fractures Are the Two most Common Injuries in Multiple Trauma. However, there Is Still a Lack of Mouse Models of Trauma Combining Tibial Shaft Fracture (TSF) and Thoracic Trauma. In this Study, we Attempted to Develop a Novel Mouse Model of TSF Combined with Blunt Chest Trauma (BCT). METHODS: A total of 84 C57BL/6J male mice were used as the multiple trauma model. BCT was induced by hitting the chests of mice with heavy objects, and TSF was induced by hitting the tibia of mice with heavy objects after intramedullary fixation. Serum specimens of mice were received by cardiac puncture at defined time points of 0, 6, 12, 24, 48, and 72 h. RESULTS: Body weight and body temperature tended to decrease within 24 h after multiple trauma. Hemoglobin analyses revealed a decrease during the first 24 h after multiple trauma. Some animals died by cardiac puncture immediately after chest trauma. These animals exhibited the most severe pulmonary contusion and hemorrhage. The level of lung damage varied in diverse mice but was apparent in all animals. Classic hematoxylin and eosin (H&E)-stained paraffin pulmonary sections of mice with multiple trauma displayed hemorrhage and an immunoinflammatory reaction. Bronchoalveolar lavage fluid (BALF) and serum samples of mice with multiple trauma showed an upregulation of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-1α (TNF-1α) compared with the control group. Microimaging confirmed the presence of a tibia fracture and pulmonary contusion. CONCLUSIONS: The novel mouse multiple trauma model established in this study is a common trauma model that shows similar pathological mechanisms and imaging characteristics in patients with multiple injuries. This study is useful for determining whether blockade or intervention of the cytokine response is beneficial for the treatment of patients with multiple trauma. Further research is needed in the future.

A novel clinical prediction model for in-hospital mortality in sepsis patients complicated by ARDS: A MIMIC IV database and external validation study.

Background: Sepsis complicated by ARDS significantly increases morbidity and mortality, underscoring the need for robust predictive models to enhance patient management. Methods: We collected data on 6390 patients with ARDS-complicated sepsis from the MIMIC IV database. Following rigorous data cleaning, including outlier management, handling missing values, and transforming variables, we conducted univariate analysis and logistic multivariate regression. We employed the LASSO machine learning algorithm to identify risk factors closely associated with patient outcomes. These factors were then used to develop a new clinical prediction model. The model underwent preliminary assessment and internal validation, and its performance was further tested through external validation using data from 225 patients at a major tertiary hospital in China. This validation assessed the model's discrimination, calibration, and net clinical benefits. Results: The model, illustrated by a concise nomogram, demonstrated significant discrimination with an area under the curve (AUC) of 0.711 in the internal validation set and 0.771 in the external validation set, outperforming conventional severity scores such as the SOFA and SAPS II. It also showed good calibration and net clinical benefits. Conclusions: Our model serves as a valuable tool for identifying sepsis patients with ARDS at high risk of in-hospital mortality. This could enable the implementation of personalized treatment strategies, potentially improving patient outcomes.