High on-treatment platelet reactivity is associated with poor outcomes after ischemic stroke: A meta-analysis.

OBJECTIVES: High on-treatment platelet reactivity (HTPR) determined by platelet function assays is present in certain patients with ischemic stroke or transient ischemic attack (TIA). However, it is unclear whether HTPR is associated with poor clinical outcomes. Our study aimed to investigate the relationship of HTPR with recurrent vascular events in ischemic stroke or TIA. METHODS: Pubmed (MEDLINE), EMBASE, and Cochrane Library were searched for eligible studies from inception to January 1, 2022. Stata 17.0 software was used to calculate the risk ratio (RR). Subgroup and sensitivity analyses were conducted to assess the source of heterogeneity. A random-effects model was used when heterogeneity was present. Primary endpoint of the meta-analysis was the risk ratio of recurrent vascular events in HTPR Patients. While stroke and TIA, all-cause death, early neurological deterioration, early new ischemic lesions, and stroke severity measured by National Institute of Health Stroke Scale (NIHSS) scores at admission were also pooled. RESULTS: Thirty articles (7995 patients) were eligible including 28 cohort studies and 2 prospective case-control studies. The prevalence of HTPR varied from 5.9% to 60%. HTPR was associated with an increased risk of recurrent vascular events (RR = 2.94, 95% CI 2.04-4.23), stroke recurrence (RR = 2.05; 95% CI 1.43-2.95), and all-cause mortality (RR = 2.43; 95% CI 1.83-3.22). Subgroup analysis showed that HTPR determined by optical aggregometry, Verify-Now system and 11dh TXB2 is related to a higher risk of recurrent vascular events (RR = 3.53, 95% CI 1.51-9.40; RR = 2.16, 95% CI 1.02-4.56; RR = 3.76, 95% CI 1.51-9.40, respectively). Moreover, patients with HTPR had an increased incidence of early neurological deterioration (RR = 2.75; 95% CI 1.76-4.30) and higher NIHSS scores at admission (Mean difference 0.19, 95% CI 0.01-0.36). CONCLUSIONS: This meta-analysis demonstrates HTPR is associated with higher risk of recurrent vascular events, early neurological deterioration and increased severity in patients with ischemic stroke and TIA. HTPR measured by platelet function assays may guide the use of antiplatelet agents in ischemic stroke and TIA.

Role of anti-allergic agents on attenuating transfusion reactions in adults: A systematic review and meta-analysis.

BACKGROUND: Anti-allergic agents (e.g. dexamethasone, chlorpheniramine or promethazine) are commonly administered to patients prior to blood product transfusions. However, the use of these agents is largely experience-based instead of evidence-based. This meta-analysis aimed to explore the evidence behind using anti-allergic agents to attenuate transfusion reactions. MATERIALS AND METHODS: The Pubmed, EMBASE, Cochrane Library, Wanfang, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical literature (CMB) databases were all queried for related articles. Data from groups treated with and without anti-allergic agents were collected for meta-analysis using RevMan 5.3. Baseline characteristics and univariate statistics between groups were compared using SPSS 19.0. RESULTS: Eight eligible articles (six case control studies and two randomized controlled trials, all with high risks of bias) were identified (22060 total cases). Administered anti-allergic agents in these studies only included dexamethasone, chlorpheniramine or promethazine. Baseline characteristics showed no significant age or gender differences between treatment or control groups. There were no significant differences between the pooled experimental or control groups (for each of the three medications) in terms of fever, pruritis, rash, airway spasm or overall transfusion reaction rates. CONCLUSION: There is no evidence that dexamethasone, chlorpheniramine or promethazine can prevent transfusion reactions. Avoiding the arbitrary use of such anti-allergic agents before blood transfusions may potentially avoid needless adverse drug reactions.

Efficacy and safety of corticosteroids for septic shock in immunocompromised patients: A cohort study from MIMIC.

BACKGROUND: Corticosteroids have been widely used as adjunct therapy for septic shock for many decades, but both the efficacy and safety remain unclear. The study was designed to investigate overall benefits and potential risks of corticosteroids in immunocompromised patients with septic shock. METHODS: The Medical Information Mart for Intensive Care III (MIMIC-III) database was employed to conduct a cohort study. Immunocompromised patients with septic shock were enrolled and categorized by whether exposure to intravenous corticosteroids. Cox Proportional-Hazards models were used to control for confounders and assess the relationship between corticosteroids use and mortality. RESULTS: A total of 866 patients were enrolled in this study, including 395 in the corticosteroids group and 471 in the non-corticosteroids group. Corticosteroids infusion was not associated with improved 30-day mortality in overall immunocompromised population [34.7% vs 32.1%; adjusted hazard ratio (HR) 1.11, 95% confidence interval (CI) 0.87-1.43, p = 0.37]. The mortality effects were similar in 90-day, 180-day, 1-year and hospital mortality. For the subgroup of patients with metastatic cancer, corticosteroids infusion was associated with a statistically significant increase in the 30-day mortality risk (HR 1.58, 95% CI 1.06-2.37; p = 0.02). Corticosteroids had adverse effects on hemodynamic stability, prolonged ICU and hospital duration, and increased risk of hyperglycemia. CONCLUSIONS: Corticosteroids therapy for the maintenance of blood pressure was not associated with improved mortality or hemodynamic stability in overall immunocompromised population with septic shock. Future randomized clinical trials are required to validate the effects of corticosteroids for septic shock in the special immunocompromised population.

Prognosis of Patients with Sepsis and Non-Hepatic Hyperammonemia: A Cohort Study.

BACKGROUND Hyperammonemia has been reported in some critically ill patients with sepsis who do not have hepatic failure. A significant proportion of patients with non-hepatic hyperammonemia have underlying sepsis, but the association between non-hepatic hyperammonemia and prognosis is unclear. MATERIAL AND METHODS Information about patients with sepsis and non-hepatic hyperammonemia was retrieved from the Medical Information Mart for Intensive Care-III database. Survival rates were analyzed using the Kaplan-Meier method. Multivariate logistic regression models were employed to identify prognostic factors. Receiver operating characteristic (ROC) curve analysis was used to measure the predictive ability of ammonia in terms of patient mortality. RESULTS A total of 265 patients with sepsis were enrolled in this study. Compared with the non-hyperammonemia group, the patients with hyperammonemia had significantly higher rates of hospital (59.8% vs. 43.0%, P=0.007), 30-day (47.7% vs. 34.8%, P=0.036), 90-day (61.7% vs. 43.7%, P=0.004), and 1-year mortality (67.3% vs. 49.4%, P=0.004). In the survival analysis, hyperammonemia was associated with these outcomes. Serum ammonia level was an independent predictor of hospital mortality. The area under the ROC curve for the ammonia levels had poor discriminative capacity. The hyperammonemia group also had significantly lower Glasgow Coma Scale scores (P=0.020) and higher incidences of delirium (15.9% vs. 8.2%, P=0.034) and encephalopathy (37.4% vs. 19.6%, P=0.001). Intestinal infection and urinary tract infection with organisms such as Escherichia coli may be risk factors for hyperammonemia in patients who have sepsis. CONCLUSIONS Higher ammonia levels are associated with poorer prognosis in patients with sepsis. Ammonia also may be associated with sepsis-associated encephalopathy. Therefore, we recommend that serum ammonia levels be measured in patients who are suspected of having sepsis.

Transcriptome and metabolome analysis of Pichia stipitis to three representative lignocellulosic inhibitors.

During the bioconversion of xylose to ethanol, Pichia stipitis cells are often inhibited by substances generated in the lignocellulosic hydrolysate. However, the response mechanism of P. stipitis to inhibitors has not been completely understood till date. With this aim, integrated transcriptomic and metabolomic analyses were performed on P. stipitis to investigate the interactive effects of three representative inhibitors [vanillin, 5-hydroxymethylfurfural (5-HMF), and acetic acid] present in lignocellulosic hydrolysates. The genes involved in carbohydrate metabolism were observed to significantly down-regulated in the presence of the three combined inhibitors in both lag and middle exponential phases. In addition, inhibitor addition induced amino acid metabolism (e.g., glutamine and asparagine syntheses), since the yeast cells required more amino acids in stressful conditions. The metabolomic analysis yielded similar results, particularly those related with the analysis of metabolic biomarkers including fatty acids, amino acids, and sugars. 70 intracellular metabolites were detected by gas chromatography coupled with mass spectrometry (GC-MS), and samples from different phases were clearly separated by principal component analysis (PCA). The large amount of specific responsive genes and metabolites highlighted the complex regulatory mechanisms involved in the fermentation process in the presence of the three combined inhibitors.

Efficacy and outcomes of lipid resuscitation on organophosphate poisoning patients: A systematic review and meta-analysis.

OBJECTIVE: Organophosphate (OP) pesticides are still widely available in developing countries, leading to numerous accidental or suicidal poisonings every year. Lipid emulsion treatments are commonly used in resuscitating OP poisoning patients but few studies regarding their use have been reported. Our meta-analysis aimed to analyze the efficacy and outcomes of lipid resuscitation on OP poisoning patients. METHODS: A systematic search for associated studies was conducted in Pubmed, EMBASE, MEDLINE, the Cochrane Library and the Chinese National Knowledge Infrastructure. Collected data was pooled using Revman v5.3. Outcomes included prognosis (cured vs. mortality rates), hepatic function (serum ALT, AST, Total Bilirubin (TBIL) level), serum acetylcholinesterase (AchE) level and respiratory function (rate of respiratory muscular paralysis). RESULTS: Seven randomized controlled studies consisting of 630 patients meeting inclusion criteria were identified. Lipid emulsion helped to improve the cure rate [OR = 2.54, 95% CI (1.33, 4.86), p = 0.005] and lower the mortality rate [OR = 0.31, 95% CI (0.13, 0.74), p = 0.009]. Serum ALT, AST and TBIL in patients undergoing lipid resuscitation were lower than those in the control groups [ALT, SMD = -1.52, 95% CI (-2.64, 0.40), p = 0.008; AST, SMD = -1.66, 95% CI (-3.15, 0.16), p = 0.03; TBIL, SMD = -1.26, 95% CI (-2.32, 0.20), p = 0.02]. Serum AchE level were increased in patients treated with lipid emulsion [SMD = 2.15, 95% CI (1.60, 2.71), p < 0.00001]. Rate of respiratory muscular paralysis was lower in patients undergoing lipid resuscitation than those in the control groups [OR = 0.19, 95% CI (0.05, 0.71), p = 0.01]. CONCLUSION: Based on our meta-analysis of included RCT reports, lipid resuscitation seems likely to help improve prognosis and liver function of OP poisoning patients. However, larger multi-center RCTs are still recommended.

Outcomes of endoscopic and microscopic transsphenoidal surgery on non-functioning pituitary adenomas: a systematic review and meta-analysis.

Both microscopic and endoscopic transsphenoidal surgery are effective approaches for nonfunctioning pituitary adenomas. The issue on the comparison of their efficacy and safety remains inconsistent. A thorough search of the literatures (PubMed, EMBASE, MEDLINE) were performed up to March 2017. Studies reporting outcomes of microscopic or endoscopic transsphenoidal surgery on nonfunctioning pituitary adenomas were included. A meta-analysis was performed focusing on the early stage and long term outcomes. The final search yielded 19 eligible studies enrolling 3847 patients, 389 of them underwent microscopic approach and 3458 of them with endoscopic approach. As to the early stage outcomes, the rate of gross tumor resection was significantly higher in the endoscopic group than that in microscopic group (73% versus 60%, P < 0.001). Meanwhile, endoscopic approach showed priority over microscopy on postoperative hypopituitarism (63% versus 65%, P < 0.001) and CSF leakage (3% versus 7%, P < 0.001). For the long term outcomes, the rate of visual improvement was significant higher in the endoscopic group than that in microscopic group (77% versus 50%, P < 0.001). However, there was no significant difference between the groups regarding the rate of permanent diabetic insipidus and meningitis. The endoscopic approach may be associated with higher rate of gross tumor movement and lower risk of postoperatively complications for treating nonfunctioning pituitary adenoma, when compared with microscopic approach. However, the confidence was shorted due to limited high quality evidence (largely randomized and controlled studies).

Quantitative lipidomic insights in the inhibitory response of Pichia stipitis to vanillin, 5-hydroxymethylfurfural, and acetic acid.

To obtain a global view of the dynamic phospholipids in Pichia stipitis during the ethanol fermentation in the presence of three representative inhibitors (vanillin, 5-hydroxymethylfurfural, and acetic acid). Considerable efforts have been expended to elucidate the biochemical mechanisms of inhibitors interaction with phospholipids. In this study, a comparative lipidomic analysis was performed using liquid chromatography-mass/mass spectrometry (LC-MS/MS) on P. stipitis. Partial least squares-discriminate analysis (PLS-DA) was used to deal with the large quantity of data generated using the systematic methods. PLS-DA revealed that phosphatidylinositol (PI) (PI34:1, PI34:2 and PI34:6), phosphatidylserine (PS) (PS34:1 and PS34:2), phosphatidylethanolamine (PE) (PE34:1 and PE34:2), and phosphatidylcholine (PC) (PC34:1, PC34:2, and PC34:3) were the predominant biomarkers. Further analysis of different classes of phospholipids indicated that: (a) the samples from three combined inhibitors condition during the lag phase possessed the lowest PI/PS value 1.4%, (b) alterations in PC/PE ratios with changes in inhibitors were coincident with the changes in xylose utilization rates, and (c) the levels of unsaturated and the relatively long chain phospholipids increased in the inhibitor-plus condition. These findings suggest that regulation of membrane properties with inhibitors might offer a way of self-protection of yeast to inhibitors stress.

Efficient bioconversion of oleuropein from olive leaf extract to antioxidant hydroxytyrosol by enzymatic hydrolysis and high-temperature degradation.

Hydroxytyrosol (HT), a powerful antioxidant, clears free radicals and exhibits many biological activities. Because contents of HT are low in natural sources, bioconversion of oleuropein (OLE) to HT is of increasing interest. A biotechnological process was investigated to produce HT from OLE presented in olive leaf extract. Enzymatic hydrolysis using two cellulases with high ß-glucosidase activity, Novozymes CTec2 and commercial cellulase KDN (Qingdao, People's Republic of China) was carried out at 50 °C for 12 H followed by raising the temperature to 90 °C for chemical hydrolysis. After 48 H of hydrolysis, an OLE degradation rate of 100% and a HT yield of 86-88% were achieved. These cellulases degrade OLE and release a glucose molecule. Chemical hydrolysis at a high temperature promotes the cleavage of ester bond and the formation of HT. This process has a promising alternative for production of HT comparing with acid hydrolysis which not only causes significant pollution to the environment but also makes difficult to the subsequent separation.

Regular enzyme recovery enhances cellulase production by Trichoderma reesei in fed-batch culture.

OBJECTIVE: To protect the enzymes during fed-batch cellulase production by means of partial enzyme recovery at regular intervals. RESULTS: Extracellular enzymes were partially recovered at the intervals of 1, 2, or 3 days. Mycelia were also removed to avoid contamination. Increases in the total harvested cellulase (24-62%) and ß-glucosidase (22-76%) were achieved. In fermentor cultivation when the enzymes were recovered every day with 15% culture broth. The total harvested cellulase and ß-glucosidase activity increased by 43 and 58%, respectively, with fungal cell concentration maintained at 3.5-4.5 g l-1. CONCLUSION: Enzyme recovery at regular intervals during fed-batch cellulase cultivation could protect the enzyme in the culture broth and enhance the enzyme production when the fungal cell concentration is maintained in a reasonable range.

A two-step bioprocessing strategy in pentonic acids production from lignocellulosic pre-hydrolysate.

Efficient utilization (over needless disposal) of biorefinery pre-hydrolysate is an economically relevant practice for improving biorefinery financial prospects. The liquid fraction obtained after acid hydrolysis pretreatment of lignocellulosic biomass, called pre-hydrolysate, are predominantly comprised of hemicellulosic carbohydrates. Using a two-step bioprocess, the hexoses were selectively fermented to ethanol by S. cerevisiae to clear the path for Gluconobacter oxydans transformation of pentoses to a high purity pentonic acids solution. Finally, approximately 180 g pentonic acids and 19 g ethanol could be produced starting from pre-hydrolysate produced from 1 kg corn stover. The results demonstrate execution of our objective to prove this bioconversion method for producing high purity pentonic acids starting from crude lignocellulosic pre-hydrolysate, a wastefully disregarded biorefinery process stream.

Improving the production yield and productivity of 1,3-dihydroxyacetone from glycerol fermentation using Gluconobacter oxydans NL71 in a compressed oxygen supply-sealed and stirred tank reactor (COS-SSTR).

In this study, a compressed oxygen gas supply was connected to a sealed aerated stirred tank reactor (COS-SSTR) bio-system, leading to a high-oxygen pressure bioreactor used to improve the bio-transformative performance in the production of 1,3-dihydroxyacetone (DHA) from glycerol using Gluconobacter oxydans NL71. A concentration of 301.2 ± 8.2 g L(-1) DHA was obtained from glycerol after 32 h of fed-batch fermentation in the COS-SSTR system. The volumetric productivity for this process was 9.41 ± 0.23 g L(-1) h(-1), which is presently the highest obtained level of glycerol bioconversion into DHA. These results show that the application of this bioreactor would enable microbial production of DHA from glycerol at the industrial scale.

Difference analysis of the enzymatic hydrolysis performance of acid-catalyzed steam-exploded corn stover before and after washing with water.

The difference in the enzymatic hydrolysis yield of acid-catalyzed steam-exploded corn stover (ASC) before and after washing with water reached approximately 15 % under the same conditions. The reasons for the difference in the yield between ASC and washed ASC (wASC) were determined through the analysis of the composition of ASC prehydrolyzate and sugar concentration of enzymatic hydrolyzate. Salts produced by neutralization (CaSO4, Na2SO4, K2SO4, and (NH4)2SO4), sugars (polysaccharides, oligosaccharides, and monosaccharides), sugar-degradation products (weak acids and furans), and lignin-degradation products (ethyl acetate extracts and nine main lignin-degradation products) were back-added to wASC. Results showed that these products, except furans, exerted negative effect on enzymatic hydrolysis. According to the characteristics of acid-catalyzed steam explosion pretreatment, the five sugar-degradation products' mixture and salts [Na2SO4, (NH4)2SO4] showed minimal negative inhibition effect on enzymatic hydrolysis. By contrast, furans demonstrated a promotion effect. Moreover, soluble sugars, such as 13 g/L xylose (decreased by 6.38 %), 5 g/L cellobiose (5.36 %), 10 g/L glucose (3.67 %), as well as lignin-degradation products, and ethyl acetate extracts (4.87 %), exhibited evident inhibition effect on enzymatic hydrolysis. Therefore, removal of soluble sugars and lignin-degradation products could effectively promote the enzymatic hydrolysis performance.

Cause analysis of the effects of acid-catalyzed steam-exploded corn stover prehydrolyzate on ethanol fermentation by Pichia stipitis CBS 5776.

The prehydrolyzate obtained from acid-catalyzed steam-exploded corn stover (ASC) mainly contains xylose and a number of inhibitory compounds that inhibit ethanol fermentation by Pichia stipitis. In this study, the effects of the ASC prehydrolyzate, specifically those of the carbohydrate-degradation products, lignin-degradation products (which were extracted from ASC prehydrolyzate using ethyl acetate), and six major phenolic compounds (added to pure-sugar media individually or in combination), on ethanol fermentation were investigated. Results indicate that the effects of the carbohydrate-degradation products were negligible (10 h delayed) compared with those of pure-sugar fermentation, whereas the effects of the lignin-degradation products were significant (52 h delayed). Meanwhile, the inhibitory effects of the major phenolic compounds were not caused by certain types of inhibitors, but were due to the synergistic effects of various inhibitors.

The association between levosimendan and mortality in patients with sepsis or septic shock: a systematic review and meta-analysis.

BACKGROUND: Levosimendan is increasingly being used in patients with sepsis or septic shock because of its potential to improve organ function and reduce mortality. We aimed to determine if levosimendan can reduce mortality in patients with sepsis or septic shock via meta-analysis. EVIDENCE SOURCES AND STUDY SELECTION: We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane Library databases from inception through 1 October 2022. Literature evaluating the efficacy of levosimendan in patients with sepsis or septic shock was included. DATA EXTRACTION AND OUTCOME MEASUREMENTS: Two reviewers extracted data and assessed study quality. A meta-analysis was performed to calculate an odds ratio (OR), 95% confidence intervals (CI), and P -values for 28-day mortality (primary outcome). Secondary outcomes included changes in indexes reflecting cardiac function before and after treatment, changes in serum lactate levels in the first 24 h of treatment, and the mean SOFA score during the study period. Safety outcomes included rates of tachyarrhythmias and total adverse reactions encountered with levosimendan. RESULTS: Eleven randomized controlled trials were identified, encompassing a total of 1044 patients. After using levosimendan, there was no statistical difference between groups for 28-day mortality (34.9% and 36.2%; OR: 0.93; 95% CI [0.72-1.2]; P  = 0.57; I 2  = 0%; trial sequential analysis-adjusted CI [0.6-1.42]) and sequential organ failure assessment (SOFA) score, and more adverse reactions seemed to occur in the levosimendan group, although the septic shock patient's heart function and serum lactate level improved. CONCLUSION: There was no association between the use of levosimendan and 28-day mortality and SOFA scores in patients with septic shock, though there was statistically significant improvement in cardiac function and serum lactate.

[Transcript profile of converting xylose and glucose to ethanol by Candida shehatae].

OBJECTIVE: We detected and analyzed transcript profile differences between hexose and pentose fermentation by Candida shehatae, a typical xylose fermenting yeast strain. On this basis, the encoding genes of key enzymes and functional protein were screened for discovering candidates of metabolism and regulation. METHODS: To discover the key genes of xylose metabolism and ethanol fermentation in Candida shehatae, we performed a new high throughout de novo transcriptome sequencing technology on Roche 454 GS FLX Titanium platform. Two cDNA libraries were constructed and sequenced for xylose and glucose fermentation for comparison of its expressed sequence tags differences. RESULTS: Second sequencing run resulted in 600000 reads with the average length of 400bp for each cDNA library. We got 7250 and 7168 contigs by assembly, and annotated 2412 and 2456 unique genes by BLAST and Gene Ontology analysis for xylose and glucose respectively. By comparison, we identified 158 genes as different expression genes candidates at p < 0.05 for xylose metabolism and ethanol fermentation in Candida shehatae. CONCLUSIONS: The group genes for xylose metabolism and ethanol fermentation in Candida shehatae was discovered by using transcript profile sequencing and comparison. It will provide fundamental data for the relative research on molecular biology and metabolic regulation.

The Impact of Wearable Devices on Physical Activity for Chronic Disease Patients: Findings from the 2019 Health Information National Trends Survey.

BACKGROUND: Wearable devices are shown to be an advanced tool for chronic disease management, but their impacts on physical activity remain uninvestigated. This study aims to examine the effect of wearable devices on physical activity in general people and chronic patients. METHODS: Our sample was from the third cycle of the fifth iteration of the Health Information National Trends Survey (HINTS), which includes a total of 5438 residents. Genetic matching was used to evaluate the effect of wearable devices on physical activity in different populations. RESULTS: (1) Both using wearable devices and using them with high frequency will improve physical activity for the whole population. (2) Wearable devices may have greater positive effects on physical activity for chronic patients. (3) Especially in patients with hypertension, high-frequency use of wearable devices can significantly improve the duration and frequency of physical activity. CONCLUSIONS: Wearable devices lead to more physical activity, and the benefit is more noticeable for chronic patients, particularly those with hypertension.

Dexmedetomidine use for patients in palliative care with intractable pain and delirium: A retrospective study.

Patients seen by the palliative care team often have difficult and intractable symptoms. The current standard of practice to manage these symptoms is the deeply sedating midazolam continuous subcutaneous infusion for patients who are expected to expire within hours to days. Dexmedetomidine provides sedation but lacks evidence in palliative care use. This study describes continuous subcutaneous infusion of dexmedetomidine's effect on refractory pain and delirium. Retrospective, observational chart review and conducted in accordance with SQUIRE (quality improvement study). Twenty adult patients (18 years of age or older) with metastatic cancer disease admitted to three palliative complex care units of Fraser Health who received continuous subcutaneous infusion of dexmedetomidine between January 2017 to August 31, 2019. Average length of dexmedetomidine use was 9 days (1/3 length of stay). Eight of the 13 patients with pain symptoms exhibited an overall decline in pain. Four of the 6 patients with delirium had an initial decrease in delirium, but it did not last beyond the first day. Despite progressive clinical deterioration, adjunctive medications decreased or remained the same for 53% of as needed medications and 65% for regularly scheduled medications. Forty-five percent of patients had ≥50% days of rousable sedation. Hypotension occurred in 85% of patients. Dexmedetomidine provided benefit in managing intractable pain while allowing patients to remain rousable, but only had a short effect on delirium symptoms.

CLINICAL PHENOTYPES OF SEPSIS-ASSOCIATED ENCEPHALOPATHY: A RETROSPECTIVE COHORT STUDY.

ABSTRACT: Background: Sepsis-associated encephalopathy (SAE) is a dysfunction of the central nervous system experienced during sepsis with variable clinical and pathophysiologic features. We sought to identify distinct SAE phenotypes in relation to clinical outcomes. Methods: The Medical Information Mart for Intensive Care IV (MIMIC-IV) database and the eICU database were used to conduct a retrospective cohort study. Adult sepsis patients were included and SAE was defined as having a Glasgow Coma Scale (GCS) score ˂15 or delirium. The following our clinical phenotypes were defined as: ischemic-hypoxic, metabolic, mixed (ischemic-hypoxic and metabolic), and unclassified. The primary outcome was in-hospital mortality. Results: The study enrolled 4,120 sepsis patients, 2,239 from MIMIC-IV (including 1,489 patients with SAE, 67%), and 1,881 from eICU (1,291, 69%). For the SAE cohort, 2,780 patients in total were enrolled (median age, 67 years; interquartile range, 56-76.8; 1,589 (57%) were male; median GCS score was 12 [8-14]; median Sequential Organ Failure Assessment score was 6 [4-9]). The SAE phenotype distributions between the MIMIC-IV and eICU cohorts were as follows (39% vs. 35% ischemic-hypoxic, P = 0.043; 38% vs. 40% metabolic, P = 0.239; 15% vs. 15% mixed, P = 0.972; 38% vs. 40% unclassified, P = 0.471). For the overall cohort, the in-hospital mortality for patients with ischemic-hypoxic, metabolic, mixed, or unclassified phenotypes was 33.9% (95% confidence interval, 0.3-0.37), 28.4% (0.26-0.31), 41.5% (0.37-0.46), and 14.2% (0.12-0.16), respectively. In the multivariable logistic analysis, the mixed phenotype was associated with the highest risk of in-hospital mortality after adjusting for age, sex, GCS, and modified Sequential Organ Failure Assessment score (adjusted odds ratio, 2.11; 95% confidence interval, 1.67-2.67; P < 0.001). Conclusions: Four SAE phenotypes had different clinical outcomes. The mixed phenotype had the worst outcomes. Further understanding of these phenotypes in sepsis may improve trial design and targeted SAE management.

Norepinephrine use in cardiogenic shock patients is associated with increased 30 day mortality.

AIMS: Norepinephrine is recommended as a first-line vasopressor agent in the haemodynamic stabilization of cardiogenic shock. The survival benefit of norepinephrine therapy has not been demonstrated in clinical practice, however. This study aimed to explore the relationship between norepinephrine use and outcomes in cardiogenic shock patients in real-world conditions. METHODS AND RESULTS: We conducted a retrospective cohort study based on the Medical Information Mart for Intensive Care III (MIMIC-III) database. Cardiogenic shock patients were enrolled and categorized into a norepinephrine group or a non-norepinephrine group. Propensity score matching (PSM) was used to control for confounders. Cox proportional-hazards models and multivariable logistic regression were used to investigate the relationship between norepinephrine treatment and mortality. A total of 927 eligible patients were included: 552 patients in the norepinephrine group and 375 patients in the non-norepinephrine group. After PSM, 222 cases from each group were matched using a 1:1 matching algorithm. Thirty day mortality for patients treated with norepinephrine was significantly higher than for those in the non-norepinephrine group (41% vs. 30%, OR 1.61, 95% CI 1.09-2.39, P = 0.017; HR 1.50, 95% CI 1.09-2.06, P = 0.013). In the multivariable analysis, there was no significant difference between norepinephrine therapy and long-term (90 day, 180 day, or 1 year) mortality (90 day (OR 1.19, 95% CI 0.82-1.74, P = 0.363), 180 day (OR 1.17, 95% CI 0.80-1.70, P = 0.418), 1 year (OR 1.14, 95% CI 0.79-1.66, P = 0.477). Patients in the norepinephrine group required more mechanical ventilation (84% vs. 67%, OR 2.67, 95% CI 1.70-4.25, P < 0.001) and experienced longer ICU stays (median 7 vs. 4 days, OR 7.92, 95% CI 1.40-44.83, P = 0.020) than non-norepinephrine group. CONCLUSIONS: Cardiogenic shock patients treated with norepinephrine were associated with significantly increased short-term mortality, while no significant difference was found on long-term survival rates. Future trials are needed to validate and explore this association.