Nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis.

Transcriptional coactivators regulate the rate of gene expression in the nucleus. Nuclear receptor coactivator 6 (NCOA6), a coactivator, has been implicated in embryonic development, metabolism, and cancer pathogenesis, but its role in innate immunity and inflammatory diseases remains unclear. Here, we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory conditions. Unexpectedly, nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC, forming cytoplasmic specks. Mechanistically, NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3, promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1ß and active caspase-1. Of note, Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3R258W gain-of-function mutation in macrophages. Genetic ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases, folic-induced acute tubular necrosis and crystal-induced arthritis, in mice. Consistent with these findings, NCOA6 was highly expressed in macrophages derived from gout patients, and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling results. Conclusively, NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases, including gout.

Regulation of Dihydropyrimidinase-like 3 Gene Expression by MicroRNAs in PC12 Cells with Induced Ischaemia and Hypothermia.

Although hypothermic treatment has been reported to have some beneficial effects on ischaemia at the clinical level, the mechanism of ischaemia suppression by hypothermia remains unclear due to a lack of mechanism understanding and insufficient data. The aim of this study was to isolate and characterize microRNAs specifically expressed in ischaemia-hypothermia for the dihydropyrimidinase-like 3 (Dpysl3) gene. PC12 cells were induced with CoCl2 for chemical ischaemia and incubated at 32 ℃ for hypothermia. In ischaemia-hypothermia, four types of microRNAs (miR-106b-5p, miR-194-5p, miR-326-5p, and miR-497-5p) were highly related to the Dpysl3 gene based on exosomal microRNA analysis. Dpysl3 gene expression was up-regulated by miR-497-5p but down-regulated by miR-106b-5p, miR-194-5p and miR-326-5p. Our results suggest that these four microRNAs are involved in the regulation of Dpysl3 gene expression. These findings provide valuable clues that exosomal microRNAs could be used as therapeutic targets for effective treatment of ischaemia.

Peripheral Microneedle Patch for First-Aid Hemostasis.

Despite the minimized puncture sizes and high efficiency, microneedle (MN) patches have not been used to inject hemostatic drugs into bleeding wounds because they easily destroy capillaries when a tissue is pierced. In this study, a shelf-stable dissolving MN patch is developed to prevent rebleeding during an emergency treatment. A minimally and site-selectively invasive hemostatic drug delivery system is established by using a peripheral MN (p-MN) patch that does not directly intrude the wound site but enables topical drug absorption in the damaged capillaries. The invasiveness of MNs is histologically examined by using a bleeding liver of a Sprague-Dawley (SD) rat as an extreme wound model in vivo. The skin penetration force is quantified to demonstrate that the administration of the p-MN patch is milder than that of the conventional MN patch. Hemostatic performance is systematically studied by analyzing bleeding weight and time and comparing them with that of conventional hemostasis methods. The superior performance of a p-MN for the heparin-pretreated SD rat model is demonstrated by intravenous injection in vivo.

Development of a strategy for assessing blood-brain barrier disruption using serum S100 calcium-binding protein B and neuron-specific enolase in early stage of neuroemergencies: A preliminary study.

BACKGROUND: Rapid disease progression in neuroemergencies is associated with blood-brain barrier (BBB) disruption. We investigated a less invasive strategy for assessing BBB status by evaluating S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) at early stages of the hypoxic-ischemic brain injury (HIBI) cascade. METHODS: This retrospective study used prospectively collected data from patients with out-of-hospital cardiac arrest (August 2019-July 2021). Albumin specimens obtained from serum and cerebrospinal fluid via arterial catheter and lumbar puncture were used to measure the albumin quotient (Qa), which is widely accepted as the gold standard method for detecting BBB disruption. Serum S100B and NSE levels were measured simultaneously following the return of spontaneous circulation. We conducted linear regression to evaluate the relationship between S100B and Qa and the predictive performance of S100B for abnormal Qa. The primary study outcome was abnormal Qa (>0.007). RESULTS: Forty-one patients were enrolled; 30 showed an abnormal Qa suggestive of BBB disruption. S100B levels were significantly higher than in those with a normal Qa (0.244 µg/L [interquartile range [IQR], 0.146-0.823 vs 0.754 µg/L [IQR, 0.317-2.228], P = .03). We report a positive correlation between serum S100B and Qa (R2 = 0.110; P = .04). The area under the receiver operating characteristics curve (AUROC) evaluating the predictive performance of S100B with respect to abnormal Qa was 0.718 (95% confidence interval, 0.556-0.847). The cutoff value for S100B (with respect to BBB disruption) in the total cohort was 0.283 µg/L (sensitivity, 80.0%; specificity, 72.7%). Subgroup analyses in patients with serum neuron-specific enolase (NSE) levels of <40.8 ng/mL (excluding those with established neuronal cell injury) showed an improved correlation coefficient (R2 = 0.382; P < .01) and predictive performance (AUROC, 0.836 [95% confidence interval, 0.629-0.954]) compared with the total cohort. CONCLUSIONS: Serum S100B obtained at an early stage of the HIBI cascade is associated with abnormal Qa, suggesting BBB disruption. The predictive performance of S100B and the correlation between serum S100B and Qa can be improved using a complementary strategy (i.e., evaluations of S100B and NSE levels) that combines considerations of cell damage in astrocytes and neurons.

Regulation of Hepatic Gluconeogenesis by Nuclear Receptor Coactivator 6.

Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator of nuclear receptors and other transcription factors. A general Ncoa6 knockout mouse was previously shown to be embryonic lethal, but we here generated liver-specific Ncoa6 knockout (Ncoa6 LKO) mice to investigate the metabolic function of NCOA6 in the liver. These Ncoa6 LKO mice exhibited similar blood glucose and insulin levels to wild type but showed improvements in glucose tolerance, insulin sensitivity, and pyruvate tolerance. The decrease in glucose production from pyruvate in these LKO mice was consistent with the abrogation of the fasting-stimulated induction of gluconeogenic genes, phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose-6-phosphatase (G6pc). The forskolin-stimulated inductions of Pck1 and G6pc were also dramatically reduced in primary hepatocytes isolated from Ncoa6 LKO mice, whereas the expression levels of other gluconeogenic gene regulators, including cAMP response element binding protein (Creb), forkhead box protein O1 and peroxisome proliferator-activated receptor γ coactivator 1α, were unaltered in the LKO mouse livers. CREB phosphorylation via fasting or forskolin stimulation was normal in the livers and primary hepatocytes of the LKO mice. Notably, it was observed that CREB interacts with NCOA6. The transcriptional activity of CREB was found to be enhanced by NCOA6 in the context of Pck1 and G6pc promoters. NCOA6-dependent augmentation was abolished in cAMP response element (CRE) mutant promoters of the Pck1 and G6pc genes. Our present results suggest that NCOA6 regulates hepatic gluconeogenesis by modulating glucagon/cAMP-dependent gluconeogenic gene transcription through an interaction with CREB.

Blood-brain barrier disruption as a cause of various serum neuron-specific enolase cut-off values for neurological prognosis in cardiac arrest patients.

We compared the cut-off and prognostic value of serum neuron-specific enolase (NSE) between groups with and without severe blood-brain barrier (BBB) disruption to reveal that a cause of various serum NSE cut-off value for neurological prognosis is severe BBB disruption in out-of-hospital cardiac arrest (OHCA) patients underwent target temperature management (TTM). This was a prospective, single-centre study conducted from January 2019 to June 2021. Severe BBB disruption was indicated using cerebrospinal fluid-serum albumin quotient values > 0.02. The area under the receiver operating characteristic curve of serum NSE obtained on day 3 of hospitalisation to predict poor outcomes was used. In patients with poor neurologic outcomes, serum NSE in those with severe BBB disruption was higher than in those without (P = 0.006). A serum NSE cut-off value of 40.4 µg/L for poor outcomes in patients without severe BBB disruption had a sensitivity of 41.7% and a specificity of 96.0%, whereas a cut-off value of 34.6 µg/L in those with severe BBB disruption had a sensitivity of 86.4% and a specificity of 100.0%. We demonstrated that the cut-off and prognostic value of serum NSE were heterogeneous, depending on severe BBB disruption in OHCA patients treated with TTM.

Detection of Testicular Torsion With Preserved Intratesticular Flow By Point of Care Ultrasound in the Emergency Department: A Case Report.

BACKGROUND: Ultrasonography is an effective diagnostic tool for testicular torsion (TT), which is typically characterized by the absence of blood flow in the affected testicle on color Doppler mode. However, there are a few reported cases of TT with symmetrical preserved flow. We report a case of TT with the preserved intratesticular flow on color Doppler ultrasound. CASE REPORT: A 14-year-old boy was admitted due to sudden-onset right scrotal pain. Point-of-care ultrasound (POCUS) revealed that the right testicle was larger than the left. The intratesticular flow in both testicles was preserved. Radiology-performed ultrasound confirmed the preserved intratesticular flow observed on POCUS, but also demonstrated a whirlpool sign of the right spermatic cord. TT was confirmed surgically. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should investigate the presence of intratesticular blood flow and the whirlpool sign of the spermatic cord or other ultrasound features suggestive of TT, even if testicular blood flow is preserved. Suspicion of TT from POCUS findings warrants further evaluation to preserve the patient's fertility.

Efficacy of cardiopulmonary resuscitation performance while wearing a powered air-purifying respirator.

BACKGROUND: The use of personal protective equipment for respiratory infection control during cardiopulmonary resuscitation (CPR) is a physical burden to healthcare providers. The duration for which CPR quality according to recommended guidelines can be maintained under these circumstances is important. We investigated whether a 2-min shift was appropriate for chest compression and determined the duration for which chest compression was maintained in accordance with the recommended guidelines while wearing personal protective equipment. METHODS: This prospective crossover simulation study was performed at a single center from September 2020 to October 2020. Five indicators of CPR quality were measured during the first and second sessions of the study period. All participants wore a Level D powered air-purifying respirator (PAPR), and the experiment was conducted using a Resusci Anne manikin, which can measure the quality of chest compressions. Each participant conducted two sessions. In Session 1, the sequence of 2 min of chest compressions, followed by a 2-min rest, was repeated twice; in Session 2, the sequence of 1-min chest compressions followed by a 1-min rest was repeated four times. RESULTS: All 34 participants completed the study. The sufficiently deep compression rate was 65.9 ± 31.1% in the 1-min shift group and 61.5 ± 30.5% in the 2-min shift group. The mean compression depth was 52.8 ± 4.3 mm in the 1-min shift group and 51.0 ± 6.1 mm in the 2-min shift group. These two parameters were significantly different between the two groups. There was no significant difference in the other values related to CPR quality. CONCLUSIONS: Our findings indicated that 1 min of chest compressions with a 1-min rest maintained a better quality of CPR while wearing a PAPR.

Induction of apoptosis through the up-regulation of endoplasmic reticulum stress sensors by 5-hydroxy-7- (4"-hydroxy-3"-methoxyphenyl)-1-phenyl-3-heptanone.

The diarylheptanoid, 5-hydroxy-7-(4"-hydroxy-3"-metho-xyphenyl)-1-phenyl-3-heptanone (HPH), is isolated from rhizomes of Alpinia officinarum. There is no reported biological function for this compound other than the inhibition of pancreatic lipase. Cell viability, the expression of endoplasmic reticulum (ER) stress genes, the activation of ER stress sensors, and the induction of apoptosis and autophagy were confirmed following HPH treatment of PC12 cells. No cytotoxicity was observed when the cells were treated with 50 µg/ml HPH, but 40% cell death was observed using MTT assays with 100 µg/ml HPH. Although HPH did not change the expression of the ER chaperones PDI, binding BiP, and calnexin, it upregulated the expression of genes for the ER stress sensors ATF6, eIF2α, and PERK. HPH also induced apoptosis via the activation of ATF6 fragmentation, the phosphorylation of eIF2α, and XBP1 mRNA splicing. Eventually, the results of this study demonstrated that HPH induces apoptosis through upregulation of gene expression of ER stress sensors, which may provide a basis for the development of new drugs using HPH.

Relationships between serum levels of lactate dehydrogenase and neurological outcomes of patients who underwent targeted temperature management after out-of-hospital cardiac arrest.

ABSTRACT: This study aimed to evaluate times for measuring serum lactate dehydrogenase levels (SLLs) to predict neurological prognosis among out-of-hospital cardiac arrest (OHCA) survivors.This retrospective study examined patients who experienced OHCA treated with targeted temperature management (TTM). The SLLs were evaluated at the return of spontaneous circulation (ROSC) and at 24, 48, and 72 hours later. Neurological outcomes after 3 months were evaluated for relationships with the SLL measurement times.A total of 95 comatose patients with OHCA were treated using TTM. Seventy three patients were considered eligible, including 31 patients (42%) who experienced good neurological outcomes. There were significant differences between the good and poor outcome groups at most time points (P < .001), except for ROSC (P = .06). The ROSC measurement had a lower area under the receiver operating characteristic curve (AUC: 0.631, 95% confidence interval [CI]: 0.502-0.761) than at 48 hours (AUC: 0.830, 95% CI: 0.736-0.924), at 24 hours (AUC: 0.786, 95% CI: 0.681-0.892), and at 72 hours (AUC: 0.821, 95% CI: 0.724-0.919).A higher SLL seemingly predicted poor neurological outcomes, with good prognostic values at 48 hours and 72 hours. Prospective studies should be conducted to confirm these results.

Using Out-of-Hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP) Scores with Modified Objective Data to Improve Neurological Prognostic Performance for Out-of-Hospital Cardiac Arrest Survivors.

This study aimed to determine whether accuracy and sensitivity concerning neurological prognostic performance increased for survivors of out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM), using OHCA and cardiac arrest hospital prognosis (CAHP) scores and modified objective variables. We retrospectively analyzed non-traumatic OHCA survivors treated with TTM. The primary outcome was poor neurological outcome at 3 months after return of spontaneous circulation (cerebral performance category, 3-5). We compared neurological prognostic performance using existing models after adding objective data obtained before TTM from computed tomography (CT), magnetic resonance imaging (MRI), and biomarkers to replace the no-flow time component of the OHCA and CAHP models. Among 106 patients, 61 (57.5%) had poor neurologic outcomes. The area under the receiver operating characteristic (AUROC) curve for the OHCA and CAHP models was 0.89 (95% confidence interval (CI) 0.81-0.94) and 0.90 (95% CI 0.82-0.95), respectively. The prediction of poor neurological outcome improved after replacing no-flow time with a grey/white matter ratio measured using CT, high-signal intensity (HSI) on diffusion-weighted MRI (DWI), percentage of voxel using apparent diffusion coefficient value, and serum neuron-specific enolase levels. When replaced with HSI on DWI, the AUROC and sensitivity of the OHCA and CAHP models were 0.96 and 74.5% and 0.97 and 83.8%, respectively (100% specificity). Prognoses concerning neurologic outcomes improved compared with existing OHCA and CAHP models by adding new objective variables to replace no-flow time. External validation is required to generalize these results in various contexts.

Negative pressure wound therapy for skin necrosis prevention after snakebite in the emergency department: A retrospective cohort study.

ABSTRACT: This retrospective cohort study aimed to compare the effectiveness of conventional treatment and ultra-early application of negative pressure wound therapy (NPWT) in patients with snakebites.Patients who visited the emergency department within 24 hours after a snakebite were assigned to the non- NPWT or NPWT group. Swelling resolution time and rates of necrosis, infection, and operations were compared between the 2 groups. The Stony Brook Scar Evaluation Scale was used to measure short- and long-term wound healing results.Among the included 61 patients, the swelling resolution time was significantly shorter in the NPWT group than in non- NPWT group (P = .010). The NPWT group showed lower necrosis (4.3% versus 36.8%; P = .003) and infection (13.2% and 4.3%; P = .258) rates than the non- NPWT group. The median Stony Brook Scar Evaluation Scale scores were higher in the NPWT group than in the non- NPWT group (P< .001).These findings suggest that ultra-early application of NPWT reduces edema, promotes wound healing, and prevents necrosis in patients with snakebites.

Clinical relationship between blood concentration and clinical symptoms in aconitine intoxication.

BACKGROUND: Aconitine is well-known for its potential analgesic, anti-inflammatory, and circulation promoting effects and has been widely used as a folk medicine in South Korea. Owing to its extremely toxic nature and relatively low safety margin, intoxication is sometimes fatal. The toxic compound mainly affects the central nervous system, heart, and muscle, resulting in cardiovascular complications. PURPOSE: To determine the exact relationship between blood concentration of aconitine and clinical manifestation. BASIC PROCEDURES: The National Forensic Service (NFS) was commissioned to assist in a quantitative analysis of highly toxic aconitine and corresponding blood concentrations by analyzing the body fluids of three patients who were suspected of aconitine poisoning. MAIN FINDINGS: Aconitine blood values tested by the NFS showed that patients with a blood concentration below a certain level developed symptoms slowly and showed a high severity of clinical manifestation. There was no correlation between blood concentration and symptoms or ECG results. CONCLUSIONS: In case of suspected aconitine poisoning, an emergency care department should be visited, even with symptomatic improvement, and the patient should be monitored for at least 24 h, depending on the level of recovery and changes in ECG results.

Impact of Endoplasmic Reticulum Stress Sensors on Pectolinarin Induced Apoptosis.

Pectolinarin, [5,7-Dihydroxy 4',6-dimethoxyflavone 7-rutinoside, 7-[[6-O-(6-Deoxy-α-L-mannopyranosyl)-ß-D-glucopyranosyl] oxy]-5-hydroxy-6-methoxy-2-(4-ethoxyphenyl)-4H-1-benzopyran-4-one], has been stated one of the major compounds in Cirsium nipponicum (Maxim.) Makino. It is characterized by biological functions of hepatoprotective, anti-inflammatory and antiobesity activities. In this research, it was explained that pectolinarin causes apoptosis in PC12 cells conducted by DNA fragmentation and formation on apoptotic bodies through the activation of ER stress sensors (ATF6 fragmentation and eIF2α phosphorylation). The result of treating the PC12 cells with 50 µM pectolinarin for 24 h has come to increase ATF6 mRNA expression up to 1.6 times, PERK expression up to 1.7 times and IRE1 expression up to 1.4 times, respectively, compared to those of the control. ATF6 fragmentation by pectolinarin treatment was increased about 2 times compared with its control, and phosphorylation of eIF2α was increased 2.5 times. The results proposed that the perception of the molecular mechanisms underlying pectolinarin-caused apoptosis may be useful in new natural medicinal products and health supplements for the apoptosis-related diseases.

Regulation of adipocyte differentiation by clusterin-mediated Krüppel-like factor 5 stabilization.

Clusterin (CLU) is a heterodimeric glycoprotein involved in a range of biological processes. We investigated the function of CLU as a novel regulator of adipogenesis. CLU expression increased during 3T3-L1 preadipocyte differentiation. CLU overexpression promoted adipogenic differentiation of preadipocytes and increased the mRNA levels of adipogenic markers including peroxisome proliferator-activated receptor γ (Pparg) and CCAAT enhancer-binding protein α (Cebpa). Conversely, knockdown of CLU attenuated adipogenesis and reduced transcript levels of Pparg and Cebpa. However, the promoter activities of both the Pparg and the Cebpa gene were not affected by alteration of CLU expression on its own. Additionally, the protein level of Krüppel-like factor 5 (KLF5), an upstream transcription factor of Pparg and Cebpa involved in adipogenic differentiation, was upregulated by CLU overexpression, although the mRNA level of Klf5 was not altered by changes in the expression level of CLU. Cycloheximide chase assay showed that the increased level of KLF5 by CLU overexpression was due to decreased degradation of KLF5 protein. Interestingly, CLU increased the stability of KLF5 by decreasing KLF5 ubiquitination. CLU inhibited the interaction between KLF5 and F-box/WD repeat-containing protein 7, which is an E3 ubiquitin ligase that targets KLF5. The adipogenic role of CLU was also addressed in mesenchymal stem cells (MSCs) and Clu-/- mouse embryonic fibroblasts (MEFs). Furthermore, CLU enhanced KLF5-mediated transcriptional activation of both the Cebpa and the Pparg promoter. Taken together, these results suggest that CLU is a novel regulator of adipocyte differentiation by modulating the protein stability of the adipogenic transcription factor KLF5.

The cut-off value of a qualitative brain diffusion-weighted image (DWI) scoring system to predict poor neurologic outcome in out-of-hospital cardiac arrest (OHCA) patients after target temperature management.

AIM: We presented the cut-off value of a diffusion-weighted image (DWI) scoring system to predict poor neurologic outcome using DWI taken 72-96 h after out-of-hospital cardiac arrest (OHCA) patients underwent target temperature management (TTM). METHODS: This was a prospective single-centre observational study, conducted from March 2018 to April 2020 in OHCA patients after TTM. Neurological status was assessed 6 months after return of spontaneous circulation (ROSC) using the Glasgow-Pittsburgh cerebral performance categories (CPC) scale. CPC of 1-2 demonstrated good neurologic outcomes whilst a CPC of 3-5 was related to poor neurologic outcomes. The receiver operating characteristic curves and DeLong method were used to evaluate the cut-off value of the DWI scoring system to predict poor neurologic outcome. RESULTS: The good and poor neurologic outcome groups consisted of 38 (54.3%) and 32 (45.7%) patients, respectively. The area under the receiver operating characteristic curve (AUROC) of the overall, cortex, deep grey nuclei, and cortex plus deep grey nuclei scores, white matter, brainstem, and cerebellum measured 72-96 h after ROSC were 0.96, 0.96, 0.97, 0.96, 0.95, 0.95, and 0.93 respectively. For 100.0% specificity to predict poor neurologic outcome, the overall scores of the DWI scoring system measured 72-96 h after ROSC with a cut-off value of 52 had a sensitivity of 81.3% (95% CI: 63.6-92.8). CONCLUSION: This study demonstrated that the DWI scoring systems measured between 72 and 96 h after ROSC were valuable tools to predict poor neurologic outcome in post-OHCA patients treated with TTM.

Impact of low and high partial pressure of carbon dioxide on neuron-specific enolase derived from serum and cerebrospinal fluid in patients who underwent targeted temperature management after out-of-hospital cardiac arrest: A retrospective study.

AIM: In a previous study, low and high-normal arterial carbon dioxide tension (PaCO2) were not associated with serum neuron-specific enolase (NSE) in cardiac arrest survivors. We assessed the effect of PaCO2 on NSE in cerebrospinal fluid (CSF) and serum. METHODS: This was a retrospective study. PaCO2 for the first 24 h was analysed in four means, qualitative exposure state (qES), time-weighted average (TWA), median, and minimum-maximum (Min-Max). These subgroups were divided into low (LCO2) and high PaCO2 (HCO2) groups defined as PaCO2 ≤ 35.3 and PaCO2 > 43.5 mmHg, respectively. NSE was measured at 24, 48, and 72 h (sNSE24,48,72 and cNSE24,48,72) from return of spontaneous circulation (ROSC). The primary outcome was the association between PaCO2 and the NSE measured at 24 h after ROSC. RESULTS: Forty-two subjects (male, 33; 78.6%) were included in total cohort. PaCO2 in TWA subgroup was associated with cNSE24,48,72, while PaCO2 in the other subgroup were only associated with cNSE24. PaCO2 and cNSE in qES subgroup showed good correlation (r = -0.61; p < 0.01), and in TWA, median, and Min-Max subgroup showed moderate correlations (r = -0.57, r = -0.48, and r = -0.60; p < 0.01). Contrastively, sNSE was not associated and correlated with PaCO2 in all analysis. Poor neurological outcome in LCO2 was significantly higher than HCO2 in qES, TWA, and median subgroups (p < 0.01, p < 0.01, and p = 0.02). CONCLUSION: Association was found between NSE and PaCO2 using CSF, despite including normocapnic ranges; TWA of PaCO2 may be most strongly associated with CSF NSE levels. A prospective, multi-centre study is required to confirm our results.

The value of cerebrospinal fluid ubiquitin C-terminal hydrolase-L1 protein as a prognostic predictor of neurologic outcome in post-cardiac arrest patients treated with targeted temperature management.

AIM: We evaluated the prognostic value of serum- and cerebrospinal fluid (CSF)-ubiquitin carboxyl-terminal esterase L1 protein (UCHL1) measurements in post- post-out of hospital cardiac arrest (OHCA) patients treated with target temperature management (TTM), to predict neurologic outcome. METHODS: This was a prospective single-centre observational cohort study, conducted from April 2018 to September 2019. Serum- and CSF-UCHL1 were obtained immediately (UCHL1initial), 24 h (UCHL124), 48 h (UCHL148), and 72 h (UCHL172) after return of spontaneous circulation (ROSC). The area under the receiver operating characteristic curves (AUROC) and Delong method were used to identify cut-off values of serum- and CSF-UCHL1initial, UCHL124, UCHL148, UCHL172 for predicting neurologic outcomes. RESULTS: Of 38 patients enrolled, 16 comprised the poor outcome group. The AUROCs for serum- and CSF-UCHL1initial were 0.71 and 0.93 in predicting poor neurological outcomes, respectively (p = 0.01). The AUROCs for serum- and CSF-UCHL124 were 0.85 and 0.91 (p = 0.24). The AUROCs for serum- and CSF-UCHL148 were 0.90 and 0.97 (p = 0.07). The AUROCs for serum- and CSF-UCHL172 were 0.94 and 0.98 (p = 0.25). CONCLUSION: Findings of this study demonstrate that CSF-UCHL1 measured immediately, 24, 48, and 72 h after ROSC is a valuable predictor for evaluating neurologic outcomes, whereas serum-UCHL1 measured at 24, 48, and 72 h after ROSC showed a significant performance in the prognostication of poor outcomes in post-OHCA patients treated with TTM.

Does Combining Biomarkers and Brain Images Provide Improved Prognostic Predictive Performance for Out-Of-Hospital Cardiac Arrest Survivors before Target Temperature Management?

We examined whether combining biomarkers measurements and brain images early after the return of spontaneous circulation improves prognostic performance compared with the use of either biomarkers or brain images for patients with cardiac arrest following target temperature management (TTM). This retrospective observational study involved comatose out-of-hospital cardiac arrest survivors. We analyzed neuron-specific enolase levels in serum (NSE) or cerebrospinal fluid (CSF), grey-to-white matter ratio by brain computed tomography, presence of high signal intensity (HSI) in diffusion-weighted imaging (DWI), and voxel-based apparent diffusion coefficient (ADC). Of the 58 patients, 33 (56.9%) had poor neurologic outcomes. CSF NSE levels showed better prognostic performance (area under the curve (AUC) 0.873, 95% confidence interval (CI) 0.749-0.950) than serum NSE levels (AUC 0.792, 95% CI 0.644-0.888). HSI in DWI showed the best prognostic performance (AUC 0.833, 95% CI 0.711-0.919). Combining CSF NSE levels and HSI in DWI had better prognostic performance (AUC 0.925, 95% CI 0.813-0.981) than each individual method, followed by the combination of serum NSE levels and HSI on DWI and that of CSF NSE levels and the percentage of voxels of ADC (AUC 0.901, 95% CI 0.792-0.965; AUC 0.849, 95% CI 0.717-0.935, respectively). Combining CSF/serum NSE levels and HSI in DWI before TTM improved the prognostic performance compared to either each individual method or other combinations.