New-onset psychiatric disorders are frequent after COVID-19. We aim to determine whether acute COVID-19 severity markers can predict post-COVID new-onset psychiatric disorders. We conducted an electronic health records (EHR) cohort study of patients hospitalized for COVID-19 and without any known history of psychiatric disorders. Patients were included between January 2020 and September 2022 in one of the 36 university hospitals of the Assistance Publique - Hôpitaux de Paris. Acute COVID-19 clinical and biological severity markers were recorded during hospitalization for COVID-19. Psychiatric ICD-10 diagnoses were recorded up to 2 years and 9 months after hospitalization for COVID-19. Predictors of post-COVID new-onset psychiatric disorders were identified based on Cox regression models and sensitivity analyses. Predictive scores were built and tested in age- and sex-stratified populations. A total 34,489 patients hospitalized for COVID-19 were included; 3717 patients (10.8%) had at least one post-COVID new-onset psychiatric disorder. Hospital stay >7 days (HR = 1.72, 95%CI [1.59-1.86], p < 0.001), acute delirium (HR = 1.49, 95%CI [1.28-1.74], p < 0.001), elevated monocyte count (HR = 1.14, 95%CI [1.06-1.23], p < 0.001) and elevated plasma CRP (HR = 0.92, 95%CI [0.86-0.99], p = 0.04) independently predicted post-COVID new-onset psychiatric disorders. Sensitivity analyses confirmed hospital stay >7 days, acute delirium, and elevated monocyte count as predictors. Predictive scores based on these variables had good 12-month positive predictive values, up to 7.5 times more accurate than random in women < 65 years. In conclusion, hospital stay >7 days, acute delirium, and elevated monocyte count during acute COVID-19 predict post-COVID new-onset psychiatric disorders.

Neuronal ferroptosis is a characteristic pathological change of sepsis-associated encephalopathy (SAE), which can be induced by activated microglia. CXCL2 is mainly secreted by inflammatory cells (neutrophil and microglia) and involved in neuronal damage. However, the specific mechanism behind microglia-neuron crosstalk in SAE remains unclear.

This study is to explore in which way microglia-secreted CXCL2 induced neuronal ferroptosis. For this purpose, the present study used CXCL2 knockdown (KD) mice to generate SAE model and determined effects of CXCL2 on neuronal ferroptosis. Afterward, BV2 and HT22 were used to instead of microglia and neuron respectively and the co-cultured system was used to simulate their interaction in vivo environment. RNA-sequencing technology was applied to investigate the key mechanism and targets of CXCL2-induced neuronal ferroptosis. siRNA was used to evaluate the function of key molecules.

Cecum ligation perforation (CLP) induced an obvious cognitive dysfunction, shorten the survival time and promoted the activation of microglia and neuronal loss. The level of inflammatory cytokines, ferroptosis-related markers and malonaldehyde was obviously lower and the level of glutathione was significantly higher in CXCL2 KD mice when compared with wide-type SAE mice. RNA-seq revealed that Jun is a potential target of CXCL2. The following experiments further demonstrated that microglia-secreted CXCL2 induced the neuronal ferroptosis, but siRNA-Jun in neuron can abolish this effect. In addition, siRNA-CXCL2 of microglia mitigated the neuronal ferroptosis induced by sepsis, while Jun agonist reversed this protective effect.

In conclusion, microglia-derived CXCL2 could induce the occurrence of neuronal ferroptosis by targeting Jun. Thus, regulating the expression and secretion of CXCL2 will probably be a crucially novel strategy for the treatment of SAE.

Sepsis-associated encephalopathy (SAE) is a complication of impaired neurologic function during the development of sepsis. Its occurrence is closely related to severe systemic infection. The increase of serum Interleukin 6 kit and other inflammatory cytokines has certain clinical significance in the diagnosis of sepsis, However, there is no research at home or abroad indicating whether the high expression of related inflammatory cytokines (inflammatory cytokine storm, ICS) is valuable for the diagnosis and prognosis of SAE patients.

The aim of this study was to analyze serum inflammatory cytokines 6 kit [IL-2/4/6/10, TNF-α, and gamma interferon (IFN-γ)], heparin-binding protein (HBP), and serum cholinesterase levels and their clinical significance in septic patients. In this study, we defined the values of inflammatory storm (IL-6 > 5000 pg/ml, IL-10 > 1000 pg/ml, and HBP > 300 ng/ml) to analyze the diagnostic value and 28-day prognostic predictive ability of inflammatory cytokine storm and the severity score in SAE patients.

A total of 140 patients with sepsis in the ICU and EICU of the Lianyungang First People's Hospital were included in the present study from October 2021 to March 2023. Based on the Diagnostic criteria for SAE, the 140 cases were divided into 62 cases in the SAE group and 78 cases in the non-SAE group. On admission to the ICU/EICU, the patients gender, age, vital signs, and serum levels of various cytokines were recorded. The Glasgow Coma Scale (GCS), Sequential Organ Failure Scale (SOFA), and Acute Physiological and Chronic Health Score II (APACHE-II) scores were also assessed to analyze the risk cytokines for the occurrence of SAE.

The age, Sofa score, APACHE-II score, 28-day mortality rate, serological cellular inflammatory cytokines (IL-2/6/10, INF-α, and interferon-gamma), HBP were significantly higher in the SAE group than in the non-SAE group (P < 0.05). In addition, the GCS score and serum cholinesterase levels in the SAE group were lower than in the non-SAE group (P < 0.05). Subsequently, Multi-factor logistic regression analysis revealed that ultra-high IL-6 (> 5000 pg/ml), IL-10 (> 1000 pg/ml), and HBP (> 300 ng/ml) levels and elevated SOFA and APACHE-II scores were risk cytokines for the development of SAE (P < 0.05). 28-day mortality was significantly higher in patients in the SAE group and in the IL-6 > 5000 pg/ml group compared to patients in the USAE and IL-6 < 5000 pg/ml groups(P < 0.001).The four screened predictors of HBP > 300 ng/ml, IL-6 > 5000 pg/ml, decreased GCS score, and decreased APACHEII score were combined into a new predictive data model (risk score).In the SAE group, patients with high risk scores had a higher 28-day mortality rate compared with the low risk score group (P < 0.001).

The occurrence of SAE is closely correlated with age, concomitant diabetes, SOFA score, APACHE II score, serum cytosolic inflammatory cytokine levels (IL-2/6/10, TNF-α, and IFN-γ), HBP, and serum cholinesterase levels. In addition, inflammatory storms are associated with the mechanism of SAE, and high expression levels of the inflammatory cytokines IL-6 > 5000 pg/ml, IL-10 > 1000 pg/ml, and HBP > 300 ng/ml in patients with sepsis contribute to the early diagnosis of SAE. In addition, IL-6 > 5000 pg/ml was also associated with an increase in 28-day mortality (P < 0.05), suggesting that the level of inflammatory storms may be related to the mechanism of sepsis-related SAE and 28-day mortality. According to the LASSO results, when SAE patients admitted to the intensive care unit satisfy HBP > 300 ng/ml, IL6 > 5000 pg/ml, decreased GCS score, and increased APACHEII score, it suggests that the patient's 28-day mortality rate is higher, and it also validates that inflammatory storm can be used as a predictor of prognosis for SAE patients.

Delirium is not a harmless transient event during ICU hospitalization; rather, it is a severe complication of critical illness associated with increased mortality, morbidity, and persistent disability. Despite being recognized for decades, it remains underdiagnosed. Employing validated tools for detection helps reduce missed cases. Early detection facilitates prompt management. Sedatives, opioids, and antipsychotics should be avoided whenever possible. Optimizing environmental triggers, minimizing iatrogenicity, and treating underlying critical illness constitute the basis of the currently recommended approach to diminish the burden of delirium in ICU patients.

Sepsis-associated encephalopathy (SAE) is a serious condition in which the immune system uncontrollably responds to infection, causing organ dysfunction. Neuroinflammation is one of the primary mechanisms underlying SAE. N6-methyladenosine (m6A) methylation is a common and reversible chemical modification of RNA molecules. Increasing evidence suggests that this modification plays a vital role in the inflammatory immune response. AlkB homolog 5 (ALKBH5) is an enzyme responsible for removing m6A modifications from RNA molecules and is known as a demethylase. However, the specific role of ALKBH5 in neuroinflammation remains unclear. To explore the role of ALKBH5 in neuroinflammation, researchers have used lipopolysaccharide (LPS) to induce inflammation in BV2 cells and mice. This study found that treatment of BV2 cells with LPS (1 μg/mL) significantly increased the total RNA m6A level and the ALKBH5 protein decreased significantly. Meanwhile, the NF-κB inflammatory signaling pathway was activated, leading to an obvious increase in IL-1β, IL-6, and TNF-α mRNA. The LPS-induced inflammatory response was alleviated when ALKBH5 was overexpressed in BV2 cells. This is due to a slower degradation rate of NFKBIA mRNA, an increase in NFKBIA protein levels, and inhibition of the NF-κB inflammatory signal pathway. When ALKBH5 was overexpressed in mice, as expected, there was an improvement in behavioral abnormalities induced by LPS. Compared to healthy volunteers, ALKBH5 mRNA levels were significantly decreased in peripheral blood mononuclear cells (PBMCs) from patients with sepsis and correlated with GCS and IL-6 levels. In summary, this study suggested that ALKBH5 is a potential therapeutic target for enhancing NFKBIA mRNA stability and alleviating neuroinflammation. Thus, ALKBH5 may provide new insights into the diagnosis and treatment of SAE.

Cognitive impairment affects nearly half of vascular surgery patients, but its association with postoperative outcomes remains poorly understood. This study explores the link between preoperative cognitive performance and postoperative complications, including postoperative delirium, in vascular surgery patients.

A prospective cohort study was conducted on vascular surgery patients aged ≥65. Preoperative cognitive performance was assessed using the Montreal Cognitive Assessment, and postoperative complications were evaluated using the Comprehensive Complication Index. The association was analyzed through multivariable logistic regression.

Among 110 patients (18.2 ​% female, mean age 73.8 ​± ​5.7 years), cognitive impairment was evident in 48.2 ​%. Of the participants, 29 (26.3 ​%) experienced postoperative complications, among which 11 (10 ​%) experienced postoperative delirium. The adjusted odds ratio for the association between cognitive performance and postoperative complications was 1.19 (95 ​% CI 1.02-1.38; p ​= ​0.02).

Worse preoperative cognitive performance correlated with increased odds of postoperative complications and postoperative delirium in vascular surgery patients.

Neuroinflammation is one of the essential pathogeneses of cognitive damage suffering from sepsis-associated encephalopathy (SAE). Lots of evidences showed the microglia presented mitochondrial fragmentation during SAE. This study investigated the protective effects and novel mechanisms of inhibiting microglia mitochondrial fragmentation via mitochondrial division inhibitor 1 (Mdivi-1) on cognitive damage in SAE.

The SAE model was performed by cecal ligation and puncture (CLP), and Mdivi-1 was administrated via intraperitoneal injection. Morris water maze was performed to assess cognitive function. Mitochondrial morphology was observed by electron microscope or MitoTracker staining. The qRT-PCR, immunofluorescence staining, and western blots were used to detect the inflammatory factors and protein content, respectively. Flow cytometry was used to detect the polarization of hippocampal microglia. Bioinformatics analysis was used to verify hypotheses.

Mdivi-1 administration alleviated sepsis-induced mitochondrial fragmentation, microglia activation, polarization, and cognitive damage. The mechanisms study showed neuroinflammation and oxidative stress were suppressed via NF-κB and Keap1/Nrf2/HO-1 pathways following Mdivi-1 administration; meanwhile, pyroptosis in microglia was reduced, which was associated with enhanced autophagosome formation via p62 elevation following Mdivi-1 administration.

Inhibition of microglia mitochondrial fragmentation is beneficial to SAE cognitive disturbance, the mechanisms are related to alleviating neuroinflammation, oxidative stress, and pyroptosis.

Deficits in cholinergic function are assumed to cause cognitive decline. Studies have demonstrated that changes in serum cholinesterase activities are associated with a higher incidence of delirium in critically ill patients. Additionally, basic research indicates that the cholinergic and circadian systems are interconnected, with each system influencing the functionality of the other. This data analysis of a proof-of-concept pilot study investigates whether modification in ICU design, including dynamic light therapy, may influence the circadian oscillation of serum cholinesterase activities.

We enrolled adult critically ill patients who were on mechanical ventilation and had an anticipated ICU stay of at least 48 h. The patients were treated in either modified or standard ICU rooms. The modified rooms received extensive architectural modifications, including a new dynamic lighting system. Serum acetylcholinesterase and butyrylcholinesterase activities were measured every four hours for up to three 24-h assessment periods.

We included 64 patients in the data analysis (n = 34 patients in modified rooms, n = 30 in standard rooms). The median values of serum acetylcholinesterase and butyrylcholinesterase activities showed different patterns. Acetylcholinesterase activities differed significantly between the groups during the first assessment period (p = 0.04) and the second assessment period (p = 0.045). The intensity of light, as quantified by the effective circadian irradiance, significantly influenced the activities of acetylcholinesterase and butyrylcholinesterase throughout all assessment periods for patients in both groups (p < 0.001). The analysis showed significant interaction (p < 0.001), indicating that the differences in acetylcholinesterase and butyrylcholinesterase activities between the groups were inconsistent over time but apparent during specific periods of the day.

Implementing a comprehensive set of changes to the design of ICU rooms, including a dynamic lighting system, may influence the course of the activity patterns of acetylcholinesterase and butyrylcholinesterase in critically ill patients. Modifications to environmental factors could potentially offer neuroprotective benefits and facilitate the realignment of circadian rhythms within the cholinergic system. Clinical trial registration ClinicalTrials.gov: NCT02143661. Registered May 21, 2014.

The negative effects of delirium in intensive care unit (ICU) patients necessitate the identification and management of risk factors. This study aimed to determine the incidence of delirium and its associated modifiable and non-modifiable factors in the ICU setting to provide valuable insights for better patient care and outcomes.

Patients admitted to the ICU underwent delirium screening twice daily. Comprehensive records of modifiable and non-modifiable risk factors were maintained throughout the ICU stay.

The incidence of delirium was 32.5%. Age [odds ratio (OR) 1.04, confidence interval (CI) 1.02-1.06, P < 0.001)]. Illiteracy (OR 4, CI 1.19-13.35, P=0.02), hearing impairment (OR 3.37, CI 1.71-7.01, P=0.001), visual impairment (OR 3.90, CI 2.13-7.15, P < 0.001), hypertension (OR 2.56, CI 1.42-4.62, P=0.002), Sequential Organ Failure Assessment score (OR 1.21, CI 1.08-1.36, P=0.001), Acute Physiology and Chronic Health Evaluation II score (OR 1.20, CI 1.12-1.28, P < 0.001), presence of a nasogastric catheter/drain (OR 2.15, CI 1.18-3. 90, P=0.01), tracheal aspiration (OR 3.63, CI 1.91-6.90, P < 0.001), enteral nutrition (OR 2.54, CI 1.12-5.76, P=0.02), constipation (OR 1.65, Cl 1.11-2.45, P=0.02), oliguria (OR 1.56, Cl 1.06-2.28, P=0.02), midazolam infusion (OR 3. 4, Cl 1.16-10.05, P=0.02), propofol infusion (OR 2.91 Cl 1.03-8.19, P=0.04), albumin use (OR 2.39, Cl 1.11-5.14 P=0.02) and steroid use (OR 2.17, Cl 1.06-4.40, P=0.03) were found to be independent risk factors for delirium.

This study highlights several risk factors contributing to delirium, such as age, sensory impairment, educational level, procedural interventions, and medications. Oral nutrition and mobilization are effective strategies for reducing delirium incidence in the ICU.

Postoperative delirium (POD) is a common complication in older adult patients after surgery. A patient's preoperative anticholinergic (AC) burden is a potentially modifiable risk factor for POD. As the influence of the drug dose remains unknown, we aimed to compare three AC burden scores in relation to POD, two of which were dose-related.

This retrospective cohort study (03/22-10/22) included orthopaedic and trauma surgery patients > 65 years. POD was assessed using the four A's test (4AT), delirium diagnosis, and chart review. The AC burden was determined using the non-dose-related German Anticholinergic Burden score (GerACB), an extension of the dose-related Muscarinic Acetylcholinergic Receptor ANTagonist Exposure scale (extMARANTE), and the dose-related German Drug Burden Index (GerDBI). Multivariable logistic regression analysis determined the association between the preoperative AC burden and POD. Scores were compared using kappa statistics, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

POD was observed in 71 of 385 patients (18.4%). For all three scores, a high AC burden was significantly associated with POD after adjusting for age, sex, dementia, preoperative physical status, and number of prescribed drugs (p < 0.001). The overall agreement among the burden classifications was substantial (no POD: κ = 0.645, POD: κ = 0.632). The GerACB had the lowest sensitivity with 23.9% (extMARANTE: 42.3%, GerDBI: 40.8%), but the highest PPV with 48.6% (extMARANTE: 38.5%, GerDBI: 43.3%).

Both dose-related and non-dose-related AC burden scores have limited sensitivity and modest PPV for screening a patient's medication for POD. However, given the additional effort required for dose consideration, the non-dose-related GerACB remains sufficient in clinical practice, with the lowest sensitivity but highest PPV.

Scopolamine is a widely used antiemetic in anesthetic practice, particularly for postoperative and post-discharge nausea and vomiting. Despite its frequent usage and recognized efficacy, concerns have emerged regarding the potential for increased side effects, particularly in elderly patients. Further research is needed to assess safety and determine age thresholds for adverse events. This study hypothesizes associations between perioperative scopolamine use, worse clinical outcomes, increased pneumonia, delirium, urinary retention, and readmissions.

A large, retrospective cohort study was performed using the TriNetX Analytics Network database on patients undergoing major surgical procedures between Jan 1, 2009, and March 21, 2018, to examine the impact of perioperative scopolamine use on in-hospital adverse events. Patients were divided into age groups and compared to a control group. The primary outcomes assessed were delirium, pneumonia, in-hospital death, new antipsychotic use, readmission, and new onset urinary retention within 7 days post-surgery. 1:1 propensity score matching was performed to reduce bias. Relative risk and risk differences with 95% confidence intervals were estimated.

After 1:1 propensity score matching, we identified a total of 403,816 (201,908 pairs) perioperative scopolamine users and nonusers. The cohorts of 20-29, 30-39, 40-49, 50-59, 60-69, and 70 + contained 22,910 (11,455 pairs), 44,170 (22,085 pairs), 58,590 (29,295 pairs), 71,660 (35,830 pairs), 88,386 (44,193 pairs), and 118,100 (59,050 pairs) patients respectively. Across older age cohorts, after propensity score matching, perioperative scopolamine recipients had significantly increased relative risk and risk difference of delirium, pneumonia, in-hospital mortality, new antipsychotic use, readmission, and new-onset urinary retention.

In this cohort study, perioperative scopolamine usage was associated with a significantly increased risk of in-hospital adverse events, both within the 70 + age cohort and among the 20-29, 30-39, 40-49, 50-59, and 60-69 age cohorts after major surgery. These findings highlight the need for careful assessment of scopolamine's risks and benefits, especially for patients aged 40 and older. Scopolamine may be most suited for post-discharge nausea and vomiting in ambulatory patients and clinicians should reassess its standard use for postoperative nausea and vomiting, favoring shorter-acting agents with fewer side effects.

Cognitive impairments are common in patients with AUD and worsen the prognosis of addiction management. There are no clear guidelines for screening cognitive impairments in hospitalized patients with AUD.

Fifty-seven patients with an AUD history who were admitted to an acute hospital and assessed by the addiction care team were included. Those patients were screened for cognitive impairments using the Montreal Cognitive Assessment (MoCA) test. We collected clinical information regarding addiction history, comorbidities, and current treatments. Chi-square tests, t-tests, and Mann-Whitney tests were performed to determine factors associated with a pathological MoCA score (<26).

A pathological MoCA score was positively associated with spatial-temporal disorientation, difficulty in recalling addiction history, patient underreporting of AUD and a date of last alcohol consumption lower than 11 days ago, and negatively associated with a reason for hospitalization due to alcohol-related health issues. No medication was associated with cognitive impairments.

Clinical elements from assessment by the addiction care team allow for relevant indication for screening cognitive impairments.

Delirium is an acute, global cognitive disorder syndrome, also known as acute brain syndrome, characterized by disturbance of attention and awareness and fluctuation of symptoms. Its incidence is high among critically ill patients. Once patients develop delirium, it increases the risk of unplanned extubation, prolongs hospital stay, increases the risk of nosocomial infection, post-intensive care syndrome-cognitive impairment, and even death. Therefore, it is of great importance to understand how delirium occurs and to reduce the incidence of delirium in critically ill patients. This paper reviews the potential pathophysiological mechanisms of delirium in critically ill patients, with the aim of better understanding its pathophysiological processes, guiding the formulation of effective prevention and treatment strategies, providing a basis for clinical medication.

Delirium in patients with sepsis can be life-threatening. This study aims to investigate the impact of the use of beta-blockers on the occurrence of delirium in patients with sepsis in the ICU by utilizing a comprehensive dataset.

This is a cross-sectional study conducted using the data obtained from a single ICU in the USA. Patients diagnosed with sepsis and receiving beta-blockers were compared with those not receiving beta-blockers. Propensity score matching (PSM) and multiple regression analysis were employed to adjust for potential confounders.

Among the 19,660 patients hospitalized for sepsis, the beta-blocker and non-user groups comprised 13,119 (66.73%) and 6,541 (33.27%) patients, respectively. Multivariable logistic regression models revealed a significant reduction of 60% in 7-day delirium for beta-blocker users (OR = 0.40, 95% CI: 0.37-0.43, p < 0.001), for 30-day delirium (OR = 0.32, 95% CI: 0.29-0.35, p < 0.001), and for 90-day delirium (OR = 0.33, 95% CI: 0.30-0.35, p < 0.001). The PSM results further strengthen the validity of these findings. An analysis of safety issues demonstrated that beta-blockers may have an impact on the risk of acute kidney injury. However, following PSM, the results are not considered robust. Furthermore, there was no discernible change in the odds of renal replacement therapy and the length of ICU stays.

Our findings suggest a potential protective effect of beta-blockers against delirium in patients with sepsis. Nevertheless, the observational design limits causal inference, necessitating future randomized controlled trials to validate these findings.

Sepsis-associated encephalopathy (SAE) is a critical neurological complication of sepsis and represents a crucial factor contributing to high mortality and adverse prognosis in septic patients. This study explored the contribution of NAT10-mediated messenger RNA (mRNA) acetylation in cognitive dysfunction associated with SAE, utilizing a cecal ligation and puncture (CLP)-induced SAE mouse model. Our findings demonstrate that CLP significantly upregulates NAT10 expression and mRNA acetylation in the excitatory neurons of the hippocampal dentate gyrus (DG). Notably, neuronal-specific Nat10 knockdown improved cognitive function in septic mice, highlighting its critical role in SAE. Proteomic analysis, RNA immunoprecipitation, and real-time qPCR identified GABABR1 as a key downstream target of NAT10. Nat10 deletion reduced GABABR1 expression, and subsequently weakened inhibitory postsynaptic currents in hippocampal DG neurons. Further analysis revealed that microglia activation and the release of inflammatory mediators lead to the increased NAT10 expression in neurons. Microglia depletion with PLX3397 effectively reduced NAT10 and GABABR1 expression in neurons, and ameliorated cognitive dysfunction induced by SAE. In summary, our findings revealed that after CLP, NAT10 in hippocampal DG neurons promotes GABABR1 expression through mRNA acetylation, leading to cognitive dysfunction.

Postoperative delirium is a severe complication of flap transplantation surgery, adversely affecting surgical prognoses. The intricate pathophysiology of postoperative delirium renders the elucidation of its risk factors challenging. This research aims to delineate the prevalence and the specific risk factors of postoperative delirium in patients with cancer undergoing free flap reconstruction through a systematic review and meta-analysis to enlighten proactive prevention measures.

The researchers systematically queried both the international and Chinese databases. Searches were performed for publications from inception until September 14, 2023, using the terms "free tissue flaps," "delirium," "neoplasms," and "risk factors." Data synthesis and statistical analysis were conducted using Stata SE (version 15.0) to calculate the combined effect size for identified risk factors. Reported outcomes included weighted mean differences or odds ratios with their respective 95% confidence intervals.

Twelve case-control studies were included (ntotal = 3,256). Among them, 515 patients developed postoperative delirium after free flap surgery, compared with 2,741 patients who did not. The outcomes suggest that the risk factors include but are not limited to age, male, late neoplasm staging, use of hypnotic or antipsychotic, history of background diseases, psychiatric review, tracheotomy, and impaired wound healing. In contrast, early neoplasm staging and others are the protective factors with statistical significance. Multivariate analysis further identified significant correlations between preoperative albumin, perioperative blood transfusion, sleep disturbance, postoperative visual analog scale, postoperative albumin, smoking, and the appearance of postoperative delirium.

The determined risk factors were grouped into preoperative, intraoperative, and postoperative categories substantiated by current data to present instructions for postoperative delirium prevention.

Sevoflurane (Sev) is a commonly used inhalation anaesthetic that has been shown to cause hippocampus dysfunction through multiple underlying molecular processes, including mitochondrial malfunction, oxidative stress and inflammation. Dihydromyricetin (DHM) is a 2,3-dihydroflavonoid with various biological properties, such as anti-inflammation and anti-oxidative stress. The purpose of this study was to investigate the effect of DHM on Sev-induced neuronal dysfunction. HT22 cells were incubated with 10, 20 and 30 μM of DHM for 24 h, and then stimulated with 4% Sev for 6 h. The effects and mechanism of DHM on inflammation, oxidative stress and mitochondrial dysfunction were explored in Sev-induced HT22 cells by Cell Counting Kit-8, flow cytometry, enzyme-linked immunosorbent assay, reverse transcription-quantitative polymerase chain reaction, colorimetric detections, detection of the level of reactive oxygen species (ROS), mitochondrial ROS and mitochondrial membrane potential (MMP), immunofluorescence and western blotting. Our results showed that DHM increased Sev-induced cell viability of HT22 cells. Pretreatment with DHM attenuated apoptosis, inflammation, oxidative stress and mitochondrial dysfunction in Sev-elicited HT22 cells by remedying the abnormality of the indicators involved in these progresses, including apoptosis rate, the cleaved-caspase 3 expression, as well as the level of tumour necrosis factor α, interleukin (IL)-1β, IL-6, malondialdehyde, superoxide dismutase, catalase, ROS, mitochondrial ROS and MMP. Mechanically, pretreatment with DHM restored the Sev-induced the expression of SIRT1/FOXO3a pathway in HT22 cells. Blocking of SIRT1 counteracted the mitigatory effect of DHM on apoptosis, inflammation, oxidative stress and mitochondrial dysfunction in Sev-elicited HT22 cells. Collectively, pretreatment with DHM improved inflammation, oxidative stress and mitochondrial dysfunction via SIRT1/FOXO3a pathway in Sev-induced HT22 cells.

Sepsis-associated encephalopathy (SAE) is a collection of clinical syndromes resulting from sepsis and characterized by widespread brain dysfunction. The high prevalence of SAE has adverse outcomes on the clinical management and prognosis of sepsis patients. However, currently, there are no effective treatments to ameliorate SAE. The pathogenesis of SAE is complex, including neuroinflammation and microglia activation, destruction of the blood-brain barrier (BBB), neurotransmitter dysfunction, cerebral metabolism and mitochondrial impairment, accumulation of amyloid beta and tauopathy, complement activation, among others. Furthermore, these mechanisms intertwine with each other, further complicating the comprehension of SAE. Among them, neuroinflammation mediated by hyperactivated microglia is considered the primary etiology of SAE. This instigates a detrimental cycle wherein BBB permeability escalates, facilitating direct damage to the central nervous system (CNS) by various neurotoxic substances. Activation of the NLRP3 inflammasome, situated within microglia, can be triggered by diverse danger signals, leading to cell pyroptosis, apoptosis, and tauopathy. These complex processes intricately regulate the onset and progression of neuroinflammation. In this review, we focus on elucidating the inhibitory regulatory mechanism of the NLRP3 inflammasome in microglia, which ultimately manifests as suppression of the inflammatory response. Our ultimate objective is to augment comprehension regarding the role of microglial NLRP3 inflammasome as we explore potential targets for therapeutic interventions against SAE.

It is well known that glucose and lipid metabolism disorders and insulin resistance are common in sepsis, which affect the occurrence and prognosis of multiple organ dysfunction in septic patients. Previous study reported the predictive value of triglyceride-glucose index (TyG), a clinical indicator for insulin resistance, in postoperative delirium patients. However, it remains unclear whether the TyG index is a novel predictive biomarker for sepsis-associated delirium. The aim of this study is to explore the relationship between TyG index and the risk of delirium in patients with sepsis.

Adult septic patients were identified from the MIMIC-IV database and divided into four groups based on the mean value of TyG. The primary outcome was the incidence of delirium. The association between TyG and the risk of developing delirium was evaluated by restricted cubic spline (RCS), multivariate logistic regression and subgroup analysis. Propensity Score Matching (PSM) method was used to balance the baseline data.

A total of 3,331 septic patients were included in the analysis, and further divided into four groups: Q1 (TyG ≤ 8.67), Q2 (8.67 < TyG ≤ 9.08), Q3 (9.08 < TyG ≤ 9.61), and Q4 (TyG > 9.61). The RCS curves demonstrated a non-linear positive relationship between TyG index and the risk of developing delirium, and an optimal cut-of value 9.09 was recommended. After balancing the baseline information by PSM, patients in the TyG > 9.09 group had a significant higher incidence of delirium compared with those in the TyG ≤ 9.09 group. In logistic regression analysis, TyG > 9.09 was significantly associated with lower risk of developing delirium in both original cohort (OR 1.54-1.78, all P < 0.001) and the PSM cohort (OR 1.41-1.48, all P < 0.001). No association was found between the TyG index and mortality (all P > 0.05). In subgroup analysis, our findings were consistent (all OR > 1 in all subgroups).

Our study demonstrated an independent association between TyG index and increased risk of delirium in septic patients, indicating that TyG index can serve as a biomarker for delirium in sepsis.

Delirium is common among elderly patients in the intensive care unit (ICU) and is associated with prolonged hospitalization, increased healthcare costs, and increased risk of death. Understanding the potential risk factors and early prevention of delirium is critical to facilitate timely intervention that may reverse or mitigate the harmful consequences of delirium.

To clarify the effects of pre-admission falls on ICU outcomes, primarily delirium, and secondarily pressure injuries and urinary tract infections.

The study relied on data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Statistical tests (Wilcoxon rank-sum or chi-squared) compared cohort characteristics. Logistic regression was employed to investigate the association between a history of falls and delirium, as well as secondary outcomes, while Kaplan-Meier survival curves were used to assess short-term survival in delirium and non-delirium patients.

Study encompassed 22,547 participants. Delirium incidence was 40%, significantly higher in patients with a history of falls (54.4% vs. 34.5%, p < 0.001). Logistic regression, controlling for confounders, not only confirmed that a history of falls elevates the odds of delirium (OR: 2.11; 95% CI: 1.97-2.26; p < 0.001) but also showed it increases the incidence of urinary tract infections (OR:1.50; 95% CI:1.40-1.62; p < 0.001) and pressure injuries (OR:1.36; 95% CI:1.26-1.47; p < 0.001). Elderly delirium patients exhibited lower 30-, 180-, and 360-day survival rates than non-delirium counterparts (all p < 0.001).

The study reveals that history of falls significantly heighten the risk of delirium and other adverse outcomes in elderly ICU patients, leading to decreased short-term survival rates. This emphasizes the critical need for early interventions and could inform future strategies to manage and prevent these conditions in ICU settings.

The purpose of this study was to determine associations between markers of inflammation and endogenous anticoagulant activity with delirium and coma during critical illness.

In this prospective cohort study, we enrolled adults with respiratory failure and/or shock treated in medical or surgical intensive care units (ICUs) at 5 centers. Twice per day in the ICU, and daily thereafter, we assessed mental status using the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method-Intensive Care Unit (CAM-ICU). We collected blood samples on study days 1, 3, and 5, measuring levels of C-reactive protein (CRP), interferon gamma (IFN-γ), interleukin (IL)-1 beta (IL-1β), IL-6, IL-8, IL-10, IL-12, matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor receptor 1 (TNFR1), and protein C using validated protocols. We used multinomial logistic regression to analyze associations between biomarkers and the odds of delirium or coma versus normal mental status the following day, adjusting for age, sepsis, Sequential Organ Failure Assessment (SOFA), study day, corticosteroids, and sedatives.

Among 991 participants with a median age (interquartile range, IQR) of 62 [53-72] years and enrollment SOFA of 9 [7-11], higher concentrations of IL-6 (odds ratio [OR] [95% CI]: 1.8 [1.4-2.3]), IL-8 (1.3 [1.1-1.5]), IL-10 (1.5 [1.2-1.8]), TNF-α (1.2 [1.0-1.4]), and TNFR1 (1.3 [1.1-1.6]) and lower concentrations of protein C (0.7 [0.6-0.8])) were associated with delirium the following day. Higher concentrations of CRP (1.4 [1.1-1.7]), IFN-γ (1.3 [1.1-1.5]), IL-6 (2.3 [1.8-3.0]), IL-8 (1.8 [1.4-2.3]), and IL-10 (1.5 [1.2-2.0]) and lower concentrations of protein C (0.6 [0.5-0.8]) were associated with coma the following day. IL-1β, IL-12, and MMP-9 were not associated with mental status.

Markers of inflammation and possibly endogenous anticoagulant activity are associated with delirium and coma during critical illness.

Vascular dementia (VaD) is the second most common type of dementia and is characterized by memory impairment, blood-brain barrier disruption, neuronal cell loss, glia activation, impaired synaptic plasticity, and cholinergic system abnormalities. To effectively prevent and treat VaD a good understanding of the mechanisms underlying its neuropathology is needed. Brain-derived neurotrophic factor (BDNF) is an important neurotrophic factor with multiple functions in the systemic circulation and the central nervous system and is known to regulate neuronal cell survival, synaptic formation, glia activation, and cognitive decline. Recent studies indicate that when compared with normal subjects, patients with VaD have low serum BDNF levels and that BDNF deficiency in the serum and cerebrospinal fluid is an important indicator of VaD. Here, we review current knowledge on the role of BDNF signaling in the pathology of VaD, such as cerebrovascular dysfunction, synaptic dysfunction, and cholinergic system impairment.

We monitored CSF (cerebrospinal fluid) for Th1/Th2 inflammatory cytokines in a patient with unexplained postoperative disturbance of consciousness after craniotomy and found that the level of IL-6 (interleukin-6) concentrations was extremely high, meeting the traditional criteria for an inflammatory cytokine storm. Subsequently, the cerebrospinal fluid specimens of several patients were tested, and it was found that IL-6 levels were increased in different degrees after craniotomy. Previous studies have focused more on mild and long-term IL-6 elevation, but less on the effects of this short-term IL-6 inflammatory cytokine storm. Cerebrospinal fluid rich in IL-6 may play a significant role in patients after craniotomy. The objective is to explore the degree of IL-6 elevation and the incidence of IL-6 inflammatory cytokine storm in patients after craniotomy, as well as the effect of IL-6 elevation on the brain. In this study, the levels and clinical manifestations of inflammatory factors in cerebrospinal fluid after craniotomy were statistically classified, and the underlying mechanisms were discussed preliminarily. CSF specimens of patients after craniotomy were collected, IL-6 level was measured at 1, 5, and 10 days after operation, and cognitive function was analyzed at 1, 10, and 180 days after surgery. Craniotomy mouse model, cerebrospinal fluid of patients with the appearance of IL-6 storm after craniotomy, and IL-6 at the same concentration stimulation model were established. Behavioral tests, fluorescence in situ hybridization (FISH), pathological means, western blot, and ELISA (enzyme-linked immune-sorbent assay) were performed for verification. CSF from patients after craniotomy caused disturbance of consciousness in mice, affected neuronal damage in the hypothalamus, activation of microglia in the hypothalamus, and decreased expression of barrier proteins in the hypothalamus and brain. The large amount of interleukin-6 in CSF after craniotomy was found to be mainly derived from astrocytes. The IL-6 level in CSF after craniotomy correlated inversely with patients' performance in MoCA test. High levels of IL-6 in the cerebrospinal fluid derived from astrocytes after craniotomy may lead to disruption of the brain-cerebrospinal fluid barrier, most notably around the hypothalamus, which might result in inflammatory activation of microglia to damage the hypothalamic neurons and impaired cognitive function/more gradual cognitive repairment in patients after craniotomy with the appearance of IL-6 storm.

Sepsis is a leading cause of death resulting from an uncontrolled inflammatory response to an infectious agent. Multiple organ injuries, including brain injuries, are common in sepsis. The underlying mechanism of sepsis-associated encephalopathy (SAE), which is associated with neuroinflammation, is not yet fully understood. Recent studies suggest that the release of interleukin-1β (IL-1β) following activation of microglial cells plays a crucial role in the development of long-lasting neuroinflammation after the initial sepsis episode. This review provides a comprehensive analysis of the recent literature on the molecular signaling pathways involved in microglial cell activation and interleukin-1β release. It also explores the physiological and pathophysiological role of IL-1β in cognitive function, with a particular focus on its contribution to long-lasting neuroinflammation after sepsis. The findings from this review may assist healthcare providers in developing novel interventions against SAE.

Traumatic brain injury (TBI) is a leading cause of death and morbidity in the trauma population. Microglia drive the secondary neuroinflammatory response after TBI. We sought to determine if the microglial response to neurologic injury was exacerbated by a second stimulus after exposure to neurologic injury.

Sprague-Dawley rats (age 2-3 wk) were divided into injured and noninjured groups. Injured rats underwent a controlled cortical impact injury; noninjured rats remained naïve to any injury and served as the control group. Primary rat microglia were isolated and applied to in vitro cultures. After incubation for 24 h, the microglia were stimulated with lipopolysaccharide (LPS) or norepinephrine. Twenty-four hours after stimulation, cell culture supernatant was collected. Tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) production were measured by standard enzyme-linked immunosorbent assays. GraphPad Prism was used for statistical analysis.

When compared to noninjured microglia, LPS induced a significantly greater production of TNF-α in microglia isolated from the injured ipsilateral (versus noninjured = 938.8 ± 155.1, P < 0.0001) and injured contralateral hemispheres (versus noninjured = 426.6 ± 155.1, P < 0.0001). When compared to microglia from noninjured cerebral tissue, IL-6 production was significantly greater after LPS stimulation in the injured ipsilateral hemisphere (mean difference versus noninjured = 9540 ± 3016, P = 0.0101) and the contralateral hemisphere (16,700 ± 3016, P < 0.0001). Norepinephrine did not have a significant effect on IL-6 or TNF-α production.

LPS stimulation may amplify the release of proinflammatory cytokines from postinjury microglia. These data suggest that post-TBI complications, like sepsis, may propagate neuroinflammation by augmenting the proinflammatory response of microglia.

Community-acquired pneumonia (CAP) is globally one of the major causes of hospitalization and mortality. Severe CAP (sCAP) presents great challenges and need a comprehensive understanding of its long-term outcomes. Cardiovascular events and neurological impairment, due to persistent inflammation and hypoxemia, contribute to long-term outcomes in CAP, including mortality. Very few data are available in the specific population of sCAP. Multiple studies have reported variable 1-year mortality rates for patients with CAP up to 40.7%, with a clear influence by age, comorbidities, and disease severity. In terms of treatment, the potential protective role of macrolides in reducing mortality emphasizes the importance of appropriate empiric antibiotic therapy. This narrative review explores the growing interest in the literature focusing on the long-term implications of sCAP. Improved understanding of long-term outcomes in sCAP can facilitate targeted interventions and enhance posthospitalization care protocols.

Frailty is a multidimensional clinical syndrome characterized by low physical activity, reduced strength, accumulation of multiorgan deficits, decreased physiological reserve, and vulnerability to stressors. Frailty has key social, psychological, and cognitive implications. Frailty is accelerated by uremia, leading to a high prevalence of frailty in patients with advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD) as well as contributing to adverse outcomes in this patient population. Frailty assessment is not routine in patients with CKD; however, a number of validated clinical assessment tools can assist in prognostication. Frailty assessment in nephrology populations supports shared decision-making and advanced communication and should inform key medical transitions. Frailty screening and interventions in CKD or ESKD are a developing research priority with a rapidly expanding literature base.

The rising prevalence of neurodegenerative and mental disorders, combined with the challenges posed by their frailty, has presented intensivists with complex issues in the intensive care unit (ICU). This review article explores specific aspects of care for patients with catatonia, Parkinson's disease (PD), and dementia within the context of the ICU, shedding light on recent developments in these fields.

Catatonia, a neuropsychiatric syndrome with potentially life-threatening forms, remains underdiagnosed, and its etiologies are diverse. PD patients in the ICU present unique challenges related to admission criteria, dopaminergic treatment, and respiratory care. Dementia increases the risk of delirium. Delirium is associated with long-term cognitive impairment and dementia.

While evidence is lacking, further research is needed to guide treatment for ICU patients with these comorbidities.

Delirium is a form of brain dysfunction with high incidence and is associated with many negative outcomes in the intensive care unit. However, few studies have been large enough to reliably examine the associations between body mass index (BMI) and delirium, especially in critically ill patients. The objective of this study was to investigate the association between BMI and delirium incidence in critically ill patients.

A retrospective cohort study.

Data were collected from the Medical Information Mart for Intensive Care-IV V2.0 Database consisting of critically ill participants between 2008 and 2019 at the Beth Israel Deaconess Medical Center in Boston.

A total of 20 193 patients with BMI and delirium records were enrolled in this study and were divided into six groups.

Delirium incidence.

Generalised linear models and restricted cubic spline analysis were used to estimate the associations between BMI and delirium incidence. A total of 30.81% of the patients (6222 of 20 193) developed delirium in the total cohort. Compared with those in the healthy weight group, the patients in the different groups (underweight, overweight, obesity grade 1, obesity grade 2, obesity grade 3) had different relative risks (RRs): RR=1.10, 95% CI=1.02 to 1.19, p=0.011; RR=0.93, 95% CI=0.88 to 0.97, p=0.003; RR=0.88, 95% CI=0.83 to 0.94, p<0.001; RR=0.94, 95% CI=0.86 to 1.03, p=0.193; RR=1.14, 95% CI=1.03 to 1.25, p=0.010, respectively. For patients with or without adjustment variables, there was an obvious U-shaped relationship between BMI as a continuous variable and delirium incidence.

BMI was associated with the incidence of delirium. Our results suggested that a BMI higher or lower than obesity grade 1 rather than the healthy weight in critically ill patients increases the risk of delirium incidence.

The association between prolonged delirium during hospitalization and long-term prognosis in patients with acute heart failure (AHF) admitted to the cardiac intensive care unit (CICU) has not been fully elucidated.

We conducted a prospective registry study of patients with AHF admitted to the CICU at 2 hospitals from 2013 to 2021. We divided study patients into 3 groups according to the presence or absence of delirium and prolonged delirium as follows: no delirium, resolved delirium, or prolonged delirium. Main outcomes were in-hospital mortality and 3-year mortality after discharge.

A total of 1555 patients with AHF (median age, 80 years) were included in the analysis. Of these, 406 patients (26.1%) developed delirium. We divided patients with delirium into 2 groups: the resolved delirium group (n = 201) or the prolonged delirium group (n = 205). Multivariate Cox proportional hazards models for long-term prognosis demonstrated that the prolonged delirium group had a higher incidence of all-cause death (hazard ratio [HR], 1.52; 95% CI, 1.08 to 2.14) and non-cardiovascular death (HR, 1.84; 95% CI, 1.21 to 2.78) than the resolved delirium group. Regarding in-hospital outcomes, multivariate logistic regression modeling showed that prolonged delirium is associated with all-cause death (odds ratio [OR], 9.55; 95% confidential interval [CI], 2.99 to 30.53) and cardiovascular death (OR, 13.02; 95% CI, 2.86 to 59.27) compared with resolved delirium.

Prolonged delirium is associated with worse long-term and short-term outcomes than resolved delirium in patients with AHF.

Postoperative delirium is a frequent and severe complication after cardiac surgery. Activity of butyrylcholinesterase (BChE) has been discussed controversially regarding a possible role in its development. This study aimed to investigate the relevance of BChE activity as a biomarker for postoperative delirium after cardiac surgery or percutaneous valve replacement.

A total of 237 patients who received elective cardiothoracic surgery or percutaneous valve replacement at a tertiary care centre were admitted preoperatively. These patients were tested with the Montreal Cognitive Assessment investigating cognitive deficits, and assessed for postoperative delirium twice daily for three days via the 3D-CAM or the CAM-ICU, depending on their level of consciousness. BChE activity was measured at three defined time points before and after surgery.

Postoperative delirium occurred in 39.7% of patients (n = 94). Univariate analysis showed an association of pre- and postoperative BChE activity with its occurrence (p = 0.037, p = 0.001). There was no association of postoperative delirium and the decline in BChE activity (pre- to postoperative, p = 0.327). Multivariable analysis including either preoperative or postoperative BChE activity as well as age, MoCA, type 2 diabetes mellitus, coronary heart disease, type of surgery and intraoperative administration of red-cell concentrates was performed. Neither preoperative nor postoperative BChE activity was independently associated with the occurrence of postoperative delirium (p = 0.086, p = 0.484). Preoperative BChE activity was lower in older patients (B = -12.38 (95% CI: -21.94 to -2.83), p = 0.011), and in those with a history of stroke (B = -516.173 (95% CI: -893.927 to -138.420), p = 0.008) or alcohol abuse (B = -451.47 (95% CI: -868.38 to -34.55), p = 0.034). Lower postoperative BChE activity was independently associated with longer procedures (B = -461.90 (95% CI: -166.34 to -757.46), p = 0.002), use of cardiopulmonary bypass (B = -262.04 (95% CI: -485.68 to -38.39), p = 0.022), the number of administered red cell-concentrates (B = -40.99 (95% CI: -67.86 to -14.12), p = 0.003) and older age (B = -9.35 (95% CI: -16.04 to -2.66), p = 0.006).

BChE activity is not independently associated with the occurrence of postoperative delirium. Preoperative BChE values are related to patients' morbidity and vulnerability, while postoperative activities reflect the severity, length and complications of surgery.

To investigate whether central sensitization (CS) in elderly patients was a predictive risk factor for postoperative neurocognitive dysfunction (PNCD).

One hundred and thirty-three aged patients undergoing total knee arthroplasty (TKA) who received femoral nerve block and general anesthesia were recruited in this research and prospectively assigned into two groups according to the Central Sensitization Inventory (CSI) score: group C (n = 106, CSI score less than 40) and group CS (n = 27, CSI score higher than 40). Scores of Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Confusion Assessment Method (CAM), Numerical Rating Scale (NRS) and Quality of recovery-40 (QoR-40) questionnaires were assessed. Basic information and clinical records of all participants were also collected.

PNCD occurred in 24 (22.6%) of patients in group C and 16 (59.3%) in group CS (p < .05). Multivariate logistic regression analysis revealed that patients with CSI score ≥40 before surgery exhibited higher risk of PNCD after adjustment for other risk factors (p < .05). Compared to group C, the pre- and post-operative NRS scores, pain duration, the WOMAC score, and propofol consumptions for anesthesia induction were significantly increased in group CS (p < .05).

Hospitalized elderly patients with clinical symptoms of CS scores may have increased risk of PNCD following TKA.

To identify the incidence and outcomes of postoperative delirium after cardiopulmonary bypass machine in adult cardiac surgery patients.

A prospective observational study was conducted in a single-center institution in the Republic of China. This study included 273 patients who underwent cardiac surgical procedures requiring cardiopulmonary bypass machine utilization.

This study used the Confusion Assessment Method to screen for delirium. Univariate analysis identified advanced age, emergency surgery and prolonged aortic cross-clamping time as significant predisposing factors for delirium, which occurred in 19.8% (n = 54) of cases and typically developed in average of 4.8 ± 3.28 days after the surgery. The analysis also identified that delirium was associated with increased complications and external referrals. A total of 142 patients (52.1%) were discharged to their homes, wherein the discharge rate in the delirium group was notably lower, with only 35.2% (n = 19) of patients, than in the delirium-free group with 56.2% (n = 123) of patients.

Considering the increased probability of delirium-related complications following cardiac surgery, it is important to develop effective preventive strategies for patients with perioperative risk factors, such as advanced age, emergency surgery and prolonged cross-clamp time, by implementing practical measures to minimize the risk of delirium.

Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide and has a high incidence in the elderly. Unfortunately, there is no effective therapy for AD owing to its complicated pathogenesis. However, the development of lipid-lowering anti-inflammatory drugs has heralded a new era in the treatment of Alzheimer's disease. Several studies in recent years have shown that lipid metabolic dysregulation and neuroinflammation are associated with the pathogenesis of AD. 3-Hydroxyl 3-methylglutaryl CoA reductase (HMGCR) is a rate-limiting enzyme in cholesterol synthesis that plays a key role in cholesterol metabolism. HMGCR inhibitors, known as statins, have changed from being solely lipid-lowering agents to neuroprotective compounds because of their effects on lipid levels and inflammation. In this review, we first summarize the main regulatory mechanism of HMGCR affecting cholesterol biosynthesis. We also discuss the pathogenesis of AD induced by HMGCR, including disordered lipid metabolism, oxidative stress, inflammation, microglial proliferation, and amyloid-β (Aβ) deposition. Subsequently, we explain the possibility of HMGCR as a potential target for AD treatment. Statins-based AD treatment is an ascent field and currently quite controversial; therefore, we also elaborate on the current application prospects and limitations of statins in AD treatment.

Sepsis-associated encephalopathy (SAE) is frequently present at the acute and chronic phase of sepsis, which is characterized by delirium, coma, and cognitive dysfunction. Despite the increased morbidity and mortality of SAE, the pathogenesis of SAE remains unclear. This study aims to discover the potential biomarkers, so as to clear the pathogenesis potentially contributing to the development of SAE and provide new therapeutic strategies for the treatment of SAE.

The GSE135838 dataset was obtained from the Gene Expression Omnibus (GEO) database and utilized for analysis the differentially expressed genes (DEGs). The DEGs were analyzed by limma package of R language and the extracellular protein-differentially expressed genes (EP-DEGs) were screened by the Human Protein Atlas (HPA) and UniProt database. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out to analyze the function and pathway of EP-DEGs. STRING, Cytoscape, MCODE and Cytohubba were used to construct a protein-protein interaction (PPI) network and screen key EP-DEGs. Key EP-DEGs levels were detected in the cerebrospinal fluid (CSF) of SAE patients and non-sepsis patients with critical illness. ROC curve was used to evaluate the diagnostic of SAE.

We screened 82 EP-DEGs from DEGs. EP-DEGs were enriched in cytokine-cytokine receptor interaction, IL-17 signaling pathway and NOD-like receptor signaling pathway. We identified 2 key extracellular proteins IL-1B and IL-8. We clinically verified that IL-6 and IL-8 levels were increased in CSF of SAE patients and CSF IL-8 (AUC = 0.882, 95 % CI = 0.775-0.988) had a higher accuracy in the diagnosis of SAE than CSF IL-6 (AUC = 0.824, 95 % CI = 0.686-0.961). Furthermore, we found that the IL-8 levels in CSF might not associated with Glasgow Coma Scale (GCS) scores of SAE patients.

IL-8 may be the key extracellular cytokine in the pathogenesis of SAE. Bioinformatics methods were used to explore the biomarkers of SAE and validated the results in clinical samples. Our findings indicate that the IL-8 in CSF might be the potential diagnostic biomarker and therapeutic target in SAE.

Delirium is an acute brain disorder associated with disorganized thinking, difficulty focusing, and confusion that commonly follows major surgery, severe infection, and illness. Older patients are at high risk for developing delirium during hospitalization, which may contribute to increased morbidity, longer hospitalization, and increased risk of institutionalization following discharge. The pathophysiology underlying delirium remains poorly studied. This review delves into the findings from biomarker studies and animal models, and highlights the potential for tissue-engineered models of the brain in studying this condition. The aim is to bring together the existing knowledge in the field and provide insight into the future direction of delirium research.

In this study, the relationship between preoperative neutrophil-to-lymphocyte ratio (NLR) and Alzheimer-related biomarkers in cerebrospinal fluid (CSF) was investigated to determine whether high NLR is a potential risk factor for postoperative delirium (POD) and to evaluate its predictive efficacy.

We selected 1000 patients from the perioperative neurocognitive disorder risk factor and prognosis (PNDRFAP) database and 999 patients from the perioperative neurocognitive disorder and biomarker lifestyle (PNDABLE) database. Patients in the PNDABLE database have been measured for Alzheimer-related biomarkers in CSF (Aβ40 , Aβ42 , P-tau, and tau protein). Mini-mental state examination was used to assess the preoperative mental status of patients. POD was diagnosed using the confusion assessment method and assessed for severity using the memorial delirium assessment scale. Logistic regression analysis was utilized to explore the association of preoperative NLR with POD. What's more, we also performed sensitivity analysis by adding corrected confounders, and the results were almost unchanged. Spearman's rank correlation was used to determine the associations between NLR and Alzheimer-related biomarkers. Mediation analyses with 10,000 bootstrapped iterations were used to explore the mediation effects. Finally, we use decision curves and the nomogram model to evaluate the efficacy of preoperative NLR in predicting POD; we also performed external validation using data from Qilu Hospital.

Logistic regression results showed that an elevated preoperative NLR was a risk factor for the development of POD in patients (PNDRFAP: OR = 1.067, 95% CI 1.020-1.116; PNDABLE: OR = 1.182, 95% CI 1.048-1.335, p < .05). Spearman's rank correlation analysis showed a positive but weak correlation between NLR and P-tau/T-tau (R = .065). The mediating effect results indicate that NLR likely mediates the occurrence of POD through elevated tau protein levels (proportion: 47.47%). The results of the box plots showed statistically significant NLR and CSF biomarkers between the POD and non-POD (NPOD) groups (p < .05), with higher NLR, P-tau, and T-tau in the POD group than in the NPOD group. In contrast, the NPOD group had higher Aβ42 levels compared to the POD group. In addition, we used R package to plot the decision curve and nomogram both suggesting a good predictive effect of preoperative NLR on the occurrence of POD.

Elevated preoperative NLR levels may be a risk factor for POD and likely mediate the development of POD through elevated P-tau/T-tau levels.

Delirium is a complex and heterogeneous condition that significantly affects patient outcome. This study aimed to conduct a systematic review and meta-analysis to investigate the effects of melatonin and melatonin receptor agonists (MRAs) on delirium prevention and treatment.

Randomized controlled studies, using MRAs as an intervention and placebo as a control were included. We conducted meta-analyses with random-effects model and trial sequential analysis.

A total of 33 studies involving 4850 participants were included. The meta-analysis revealed a significant preventive effect of MRAs on delirium (risk ratio = 0.65, p < 0.01), while no significant therapeutic effect was observed. Additionally, MRAs were associated with a significant reduction in mortality rate (risk ratio = 0.90, p = 0.02) in delirium prevention studies. Furthermore, subgroup analyses revealed that assessment scales and the frequency of delirium detection may be significant moderators of the delirium-preventive efficacy of MRAs.

This study provides evidence of the potential effects of MRAs in preventing delirium and reducing mortality. Further research is required to elucidate the therapeutic potential of MRAs for delirium and identify specific patient populations that may benefit from this agent.

To analyze the incidence, timing, risk factors and prognosis of delirium after liver transplantation (LT).

The clinical data of 321 patients undergoing LT in the Third Xiangya Hospital of Central South University from January 2018 to December 2022 were collected to investigate the incidence, onset, and risk factors for post-LT delirium and the impact of delirium on LT recipients' prognosis by statistical analysis.

The incidence of post-LT delirium was 19.3% (62/321), and the median interval between LT and onset of delirium was 20.1 h. Univariate analysis showed that pre-LT variables (Model for End Stage Liver Disease (MELD) score, hospital stay, hepatic encephalopathy, infection, white blood cell (WBC) count, lymphocyte count, abnormal potassium, lactulose use), intraoperative variables (red blood cell transfusion, remimazolam use, dexmedetomidine use) and post-LT variables (hypernatraemia, acute rejection, reoperation, basiliximab use, tacrolimus concentration) were associated with post-LT delirium. Multivariate logistic regression analysis revealed that MELD score at LT ≥22 [OR = 3.400, 95% CI:1.468-7.876, p = 0.004], pre-LT hepatic encephalopathy [OR = 3.224, 95% CI:1.664-6.244, p = 0.001], infection within 2 months prior to LT [OR = 2.238, 95% CI:1.151-4.351, p = 0.018], acute rejection [OR = 2.974, 95% CI:1.322-6.690, p = 0.008], and reoperation [OR = 11.919, 95% CI:2.938-48.350, p = 0.001] were independent risk factors for post-LT delirium. Post-LT delirium was reduced in LT recipients exposing to intraoperative remimazolam [OR = 0.287, 95% CI: 0.113-0.733, p = 0.009] or ≥ 25 μg of intraoperative dexmedetomidine [OR = 0.441, 95% CI 0.225-0.867, p = 0.018]. As for clinical outcomes, patients with delirium had a higher percentage of staying at the (ICU) ≥7 d after LT than those without delirium [OR = 2.559, 95% CI 1.418-4.617, p = 0.002].

The incidence of delirium was high and the onset of delirium was early after LT. Risk factors for post-LT delirium included high MELD score at LT, pre-LT hepatic encephalopathy and infections, acute rejection and reoperation. Intraoperative use of remimazolam or dexmedetomidine reduced post-LT delirium. Delirium had a negative impact on the length of ICU stay.