BACKGROUND Sepsis-associated encephalopathy(SAE)is a common complication of sepsis,characterized by cognitive impairment,altered consciousness,and psychiatric symptoms,including anxiety and depression.These psychiatri...BACKGROUND Sepsis-associated encephalopathy(SAE)is a common complication of sepsis,characterized by cognitive impairment,altered consciousness,and psychiatric symptoms,including anxiety and depression.These psychiatric symptoms often exacerbate the overall prognosis and quality of life of affected patients.However,the underlying metabolic and proteomic features associated with SAE-induced psychiatric symptoms remain poorly understood.AIM To investigate the clinical manifestations of anxiety and depression in patients with sepsis and SAE and to explore their associated metabolic and proteomic characteristics.METHODS A total of 88 patients were enrolled,comprising 30 healthy controls,29 patients with sepsis,and 29 with SAE.Anxiety and depression symptoms were evaluated using the Hamilton anxiety rating scale(HAM-A)and Hamilton depression rating scale(HAM-D)in sepsis and SAE.Cognitive function was assessed using the Montreal Cognitive Assessment(MoCA),and quality of life was measured using the 36-Item Short Form Health Survey.Plasma samples were analyzed for metabolomic and proteomic profiling.Metabolic alterations were identified through liquid chromatography-mass spectrometry,while protein expression was assessed using Olink targeted proteomics.RESULTS Compared to the sepsis group,patients with SAE exhibited significantly higher levels of anxiety(HAM-A:15.2±4.0 vs 10.4±3.0,P=0.012)and depression(HAM-D:16.0±3.5 vs 9.1±2.3,P=0.003).Cognitive function,as measured by MoCA,was notably impaired in the SAE group(MoCA:18.5±4.0 vs 24.5±3.2,P=0.007).Quality of life scores,particularly in physical functioning,emotional well-being,and mental health,were significantly lower in patients with SAE.Metabolomic and proteomic analyses revealed substantial alterations in oxidative stress and nicotinamide adenine dinucleotide(NAD+)metabolism pathways,with cluster of differentiation(CD)38 emerging as a potential biomarker associated with psychiatric symptoms in SAE.Further validation in an independent cohort confirmed the diagnostic relevance of CD38.CONCLUSION This study highlights the significant psychological burden of SAE,manifested as anxiety and depression.Multiomics analysis identified distinct metabolic alterations,particularly in NAD+metabolism,that may contribute to psychiatric symptom development and progression.Furthermore,CD38 was identified as a promising biomarker for the early detection of SAE,providing potential avenues for early intervention and therapeutic targeting.展开更多
Background： Antimicrobial de-escalation refers to starting the antimicrobial treatment with broad-spectrum antibiotics, followed by narrowing the drug spectrum according to culture results. The present study evaluate...Background： Antimicrobial de-escalation refers to starting the antimicrobial treatment with broad-spectrum antibiotics, followed by narrowing the drug spectrum according to culture results. The present study evaluated the effect of de-escalation on ventilator-associated pneumonia （VAP） in trauma patients. Methods： This retrospective study was conducted on trauma patients with VAP, who received de-escalation therapy （de-escalation group） or non-de-escalation therapy （non-de-escalation group）. Propensity score matching method was used to balance the baseline characteristics between both groups. The 28-day mortality, length of hospitalization and Intensive Care Unit stay, and expense of antibiotics and hospitalization between both groups were compared. Multivariable analysis explored the factors that influenced the 28-day mortality and implementation of de-escalation. Results： Among the 156 patients, 62 patients received de-escalation therapy and 94 patients received non-de-escalation therapy. No significant difference was observed in 28-day mortality between both groups （28.6% vs. 23.8%, P = 0.620）. The duration of antibiotics treatment in the de-escalation group was shorter than that in the non-de-escalation group （11 [8-13] vs. 14 [8-19] days, P = 0.045）. The expenses of antibiotics and hospitalization in de-escalation group were significantly lower than that in the non-de-escalation group （6430 ± 2730 vs. 7618 ± 2568 RMB Yuan, P = 0.043 and 19,173 ± 16,861 vs. 24,184 ± 12,039 RMB Yuan, P = 0.024, respectively）. Multivariate analysis showed that high Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE Ⅱ） score, high injury severity score, multi-drug resistant （MDR） infection, and inappropriate initial antibiotics were associated with patients＇ 28-day mortality, while high APACHEⅡ score, MDR infection and inappropriate initial antibiotics were independent factors that prevented the implementation of de-escalation. Conclusions： De-escalation strategy in the treatment of trauma patients with VAP could reduce the duration of antibiotics treatments and expense of hospitalization, without increasing the 28-day mortality and MDR infection.展开更多
Background： Inflammation is supposed to play a key role in the pathophysiological processes of intestinal ischemia-reperlhsion injury （IIRI）, and Candida albicans in human gut commonly elevates inflammatory cytokin...Background： Inflammation is supposed to play a key role in the pathophysiological processes of intestinal ischemia-reperlhsion injury （IIRI）, and Candida albicans in human gut commonly elevates inflammatory cytokines in intestinal mucosa. This study aimed to explore the effect of C. albicans on IIRI. Methods： Fifty female Wistar rats were divided into five groups according to the status of C. a/bicans infection and IIRI operation： group blank and sham; group blank and IIRI; group cetbperazone plus IIR1; group C. albicans plus cetbperazone and IIRI （CCI）; and group C. albicans plus cefbperazone and sham. The levels of inflammatory factors tumor necrosis factor （TNF）-a, interleukin （IL）-6, IL- 1 β, and diamine oxidase （DAO） measured by enzyme-linked immunosorbent assay were used to evaluate the inflammation reactivity as well as the integrity of small intestine. Histological scores were used to assess the mucosal damage, and the C. albicans blood translocation was detected to judge the permeability of intestinal mucosal barrier. Results： The levels of inflammatory factors TNF-a, IL-6, and IL-1β in serum and intestine were higher in rats undergone both C. albicans infection and IIRI operation compared with rats in other groups. The levels of DAO （serum： 44.13 ± 4.30 pg/ml, intestine： 346.21 ± 37.03 pg/g） and Chiu scores （3.41 ± 1.09） which reflected intestinal mucosal disruption were highest in group CCI after the operation. The number ofC. albicans translocated into blood was most in group CCI （[33.80 ± 6.60] x 10-2 colony forming unit （CFU）/ml）. Conclusion： Intestinal C. albicans infection worsened the llRl-induced disruption of intestinal mucosal barrier and facilitated the subsequent C. alhicans translocation and dissemination.展开更多
基金the Shanghai Municipal Health Commission Medical New Technology Research and Translation Seed Program,No.2024ZZ2052Scientific Research Project funded by Shanghai Fifth People’s Hospital,Fudan University,No.2023WYRH03 and No.2025GZRFY05+2 种基金Shanghai Putuo District Health System Clinical Medicine Discipline Construction Project,No.2024tszk01Shanghai Health System Key Discipline,No.2024ZDXK0005Shanghai Minhang District Health and Family Planning Commission,No.2024MWDXK01.
文摘BACKGROUND Sepsis-associated encephalopathy(SAE)is a common complication of sepsis,characterized by cognitive impairment,altered consciousness,and psychiatric symptoms,including anxiety and depression.These psychiatric symptoms often exacerbate the overall prognosis and quality of life of affected patients.However,the underlying metabolic and proteomic features associated with SAE-induced psychiatric symptoms remain poorly understood.AIM To investigate the clinical manifestations of anxiety and depression in patients with sepsis and SAE and to explore their associated metabolic and proteomic characteristics.METHODS A total of 88 patients were enrolled,comprising 30 healthy controls,29 patients with sepsis,and 29 with SAE.Anxiety and depression symptoms were evaluated using the Hamilton anxiety rating scale(HAM-A)and Hamilton depression rating scale(HAM-D)in sepsis and SAE.Cognitive function was assessed using the Montreal Cognitive Assessment(MoCA),and quality of life was measured using the 36-Item Short Form Health Survey.Plasma samples were analyzed for metabolomic and proteomic profiling.Metabolic alterations were identified through liquid chromatography-mass spectrometry,while protein expression was assessed using Olink targeted proteomics.RESULTS Compared to the sepsis group,patients with SAE exhibited significantly higher levels of anxiety(HAM-A:15.2±4.0 vs 10.4±3.0,P=0.012)and depression(HAM-D:16.0±3.5 vs 9.1±2.3,P=0.003).Cognitive function,as measured by MoCA,was notably impaired in the SAE group(MoCA:18.5±4.0 vs 24.5±3.2,P=0.007).Quality of life scores,particularly in physical functioning,emotional well-being,and mental health,were significantly lower in patients with SAE.Metabolomic and proteomic analyses revealed substantial alterations in oxidative stress and nicotinamide adenine dinucleotide(NAD+)metabolism pathways,with cluster of differentiation(CD)38 emerging as a potential biomarker associated with psychiatric symptoms in SAE.Further validation in an independent cohort confirmed the diagnostic relevance of CD38.CONCLUSION This study highlights the significant psychological burden of SAE,manifested as anxiety and depression.Multiomics analysis identified distinct metabolic alterations,particularly in NAD+metabolism,that may contribute to psychiatric symptom development and progression.Furthermore,CD38 was identified as a promising biomarker for the early detection of SAE,providing potential avenues for early intervention and therapeutic targeting.
文摘Background： Antimicrobial de-escalation refers to starting the antimicrobial treatment with broad-spectrum antibiotics, followed by narrowing the drug spectrum according to culture results. The present study evaluated the effect of de-escalation on ventilator-associated pneumonia （VAP） in trauma patients. Methods： This retrospective study was conducted on trauma patients with VAP, who received de-escalation therapy （de-escalation group） or non-de-escalation therapy （non-de-escalation group）. Propensity score matching method was used to balance the baseline characteristics between both groups. The 28-day mortality, length of hospitalization and Intensive Care Unit stay, and expense of antibiotics and hospitalization between both groups were compared. Multivariable analysis explored the factors that influenced the 28-day mortality and implementation of de-escalation. Results： Among the 156 patients, 62 patients received de-escalation therapy and 94 patients received non-de-escalation therapy. No significant difference was observed in 28-day mortality between both groups （28.6% vs. 23.8%, P = 0.620）. The duration of antibiotics treatment in the de-escalation group was shorter than that in the non-de-escalation group （11 [8-13] vs. 14 [8-19] days, P = 0.045）. The expenses of antibiotics and hospitalization in de-escalation group were significantly lower than that in the non-de-escalation group （6430 ± 2730 vs. 7618 ± 2568 RMB Yuan, P = 0.043 and 19,173 ± 16,861 vs. 24,184 ± 12,039 RMB Yuan, P = 0.024, respectively）. Multivariate analysis showed that high Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE Ⅱ） score, high injury severity score, multi-drug resistant （MDR） infection, and inappropriate initial antibiotics were associated with patients＇ 28-day mortality, while high APACHEⅡ score, MDR infection and inappropriate initial antibiotics were independent factors that prevented the implementation of de-escalation. Conclusions： De-escalation strategy in the treatment of trauma patients with VAP could reduce the duration of antibiotics treatments and expense of hospitalization, without increasing the 28-day mortality and MDR infection.
文摘Background： Inflammation is supposed to play a key role in the pathophysiological processes of intestinal ischemia-reperlhsion injury （IIRI）, and Candida albicans in human gut commonly elevates inflammatory cytokines in intestinal mucosa. This study aimed to explore the effect of C. albicans on IIRI. Methods： Fifty female Wistar rats were divided into five groups according to the status of C. a/bicans infection and IIRI operation： group blank and sham; group blank and IIRI; group cetbperazone plus IIR1; group C. albicans plus cetbperazone and IIRI （CCI）; and group C. albicans plus cefbperazone and sham. The levels of inflammatory factors tumor necrosis factor （TNF）-a, interleukin （IL）-6, IL- 1 β, and diamine oxidase （DAO） measured by enzyme-linked immunosorbent assay were used to evaluate the inflammation reactivity as well as the integrity of small intestine. Histological scores were used to assess the mucosal damage, and the C. albicans blood translocation was detected to judge the permeability of intestinal mucosal barrier. Results： The levels of inflammatory factors TNF-a, IL-6, and IL-1β in serum and intestine were higher in rats undergone both C. albicans infection and IIRI operation compared with rats in other groups. The levels of DAO （serum： 44.13 ± 4.30 pg/ml, intestine： 346.21 ± 37.03 pg/g） and Chiu scores （3.41 ± 1.09） which reflected intestinal mucosal disruption were highest in group CCI after the operation. The number ofC. albicans translocated into blood was most in group CCI （[33.80 ± 6.60] x 10-2 colony forming unit （CFU）/ml）. Conclusion： Intestinal C. albicans infection worsened the llRl-induced disruption of intestinal mucosal barrier and facilitated the subsequent C. alhicans translocation and dissemination.
