Advanced age and neurological recovery in elderly patients with out-of-hospital cardiac arrest treated with targeted temperature management: a nationwide population­based registry study 2016-2020.

The likelihood of neurological recovery after out-of-hospital cardiac arrest (OHCA) may be influenced by advanced age. This study aims to evaluate the impact of advanced age on neurological recovery in elderly OHCA survivors treated with targeted temperature management (TTM). This retrospective observational study, using a nationwide population-based OHCA registry, was conducted from January 2016 to December 2020. Non-traumatic elderly (≥ 65 years) comatose OHCA survivors treated with TTM were categorized according to age (65-69, 70-74, 75-79, and ≥ 80 years). Among 23,336 admitted OHCA patients, 3,398 were treated with TTM. Excluding 2,033 non-elderly patients, 1,365 were analyzed. Among the four groups, the rate of good neurological outcomes decreased by advanced age (24.2%, 16.1%, 11.4%, and 5.9%, respectively), which was also observed after subgroup analysis based on the initial shockable (40.6%, 31.5%, 28.6%, and 14.9%, respectively) and non-shockable rhythm (10.6%, 7.2%, 4.1%, and 3.4%, respectively). Multivariate analysis showed the adjusted odds ratio (aOR) for good neurological outcome decreased as age increased (65-69: reference, 70-74: aOR 0.70, 75-79: aOR 0.49, and ≥ 80 years: aOR 0.25). The optimal age cutoffs for good outcomes in elderly OHCA survivors with shockable and non-shockable rhythm were 77 and 72 years, respectively. The neurologic recovery rate in OHCA survivors treated with TTM gradually decreased with increasing age. However, even patients aged ≥ 80 years with shockable rhythm had a good neurologic outcome of 14.9% compared with patients aged 65-69 years with non-shockable rhythm (10.6%).

Comparison of Modified Shock Index and Shock Index for Predicting Massive Transfusion in Women with Primary Postpartum Hemorrhage: A Retrospective Study.

BACKGROUND The modified shock index (MSI) is calculated as the ratio of heart rate (HR) to mean arterial pressure (MAP) and has been used to predict the need for massive transfusion (MT) in trauma patients. This retrospective study from a single center aimed to compare the MSI with the traditional shock index (SI) to predict the need for MT in 612 women diagnosed with primary postpartum hemorrhage (PPH) at the Emergency Department (ED) between January 2004 and August 2023. MATERIAL AND METHODS The patients were divided into the MT group and the non-MT group. The predictive power of MSI and SI was compared using the areas under the receiver operating characteristic curve (AUC). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated. RESULTS Out of 612 patients, 105 (17.2%) required MT. The MT group had higher median values than the non-MT group for MSI (1.58 vs 1.07, P<0.001) and SI (1.22 vs 0.80, P<0.001). The AUC for MSI, with a value of 0.811 (95% confidence interval [CI], 0.778-0.841), did not demonstrate a significant difference compared to the AUC for SI, which was 0.829 (95% CI, 0.797-0.858) (P=0.066). The optimal cutoff values for MSI and SI were 1.34 and 1.07, respectively. The specificity and PPV for MT were 77.1% and 40.2% for MSI, and 83.2% and 45.9% for SI. CONCLUSIONS Both MSI and SI were effective in predicting MT in patients with primary PPH. However, MSI did not demonstrate superior performance to SI.

Novel PAX9 Mutations Causing Isolated Oligodontia.

Hypodontia, i.e., missing one or more teeth, is a relatively common human disease; however, oligodontia, i.e., missing six or more teeth, excluding the third molars, is a rare congenital disorder. Many genes have been shown to cause oligodontia in non-syndromic or syndromic conditions. In this study, we identified two novel PAX9 mutations in two non-syndromic oligodontia families. A mutational analysis identified a silent mutation (NM_006194.4: c.771G>A, p.(Gln257=)) in family 1 and a frameshift mutation caused by a single nucleotide duplication (c.637dup, p.(Asp213Glyfs*104)) in family 2. A minigene splicing assay revealed that the silent mutation resulted in aberrant pre-mRNA splicing instead of normal splicing. The altered splicing products are ones with an exon 4 deletion or using a cryptic 5' splicing site in exon 4. Mutational effects were further investigated using protein expression, luciferase activity assay and immunolocalization. We believe this study will not only expand the mutational spectrum of PAX9 mutations in oligodontia but also strengthen the diagnostic power related to the identified silent mutation.

Respiratory rate­oxygenation (ROX) index for predicting high-flow nasal cannula failure in patients with and without COVID-19.

BACKGROUND: The predictive value of the respiratory rate­oxygenation (ROX) index for a high-flow nasal cannula (HFNC) in patients with COVID-19 with acute hypoxemic respiratory failure (AHRF) may differ from patients without COVID-19 with AHRF, but these patients have not yet been compared. We compared the diagnostic accuracy of the ROX index for HFNC failure in patients with AHRF with and without COVID-19 during acute emergency department (ED) visits. METHODS: We performed a retrospective analysis of patients with AHRF treated with an HFNC in an ED between October 2020 and April 2022. The ROX index was calculated at 1, 2, 4, 6, 12, and 24 h after HFNC placement. The primary outcome was the failure of the HFNC, which was defined as the need for subsequent intubation or death within 72 h. A receiver operating characteristic (ROC) curve was used to evaluate discriminative power of the ROX index for HFNC failure. RESULTS: Among 448 patients with AHRF treated with an HFNC in an ED, 78 (17.4%) patients were confirmed to have COVID-19. There was no significant difference in the HFNC failure rates between the non-COVID-19 and COVID-19 groups (29.5% vs. 33.3%, p = 0.498). The median ROX index was higher in the non-COVID-19 group than in the COVID-19 group at all time points. The prognostic power of the ROX index for HFNC failure as evaluated by the area under the ROC curve was generally higher in the COVID-19 group (0.73-0.83) than the non-COVID-19 group (0.62-0.75). The timing of the highest prognostic value of the ROX index for HFNC failure was at 4 h for the non-COVID-19 group, whereas in the COVID-19 group, its performance remained consistent from 1 h to 6 h. The optimal cutoff values were 6.48 and 5.79 for the non-COVID-19 and COVID-19 groups, respectively. CONCLUSIONS: The ROX index had an acceptable discriminative power for predicting HFNC failure in patients with AHRF with and without COVID-19 in the ED. However, the higher ROX index thresholds than those in previous publications involving intensive care unit (ICU) patients suggest the need for careful monitoring and establishment of a new threshold for patients admitted outside the ICU.

Association Between Body Weight Changes and Subsequent Development of Out-of-Hospital Cardiac Arrest: A Population-Based Nested Case-Control Study.

BACKGROUND: Body weight is a modifiable demographic factor. Although the association of body mass index (BMI) categories with sudden cardiac death was reported, dynamic changes of BMI and the risk of cardiac arrest remain unknown. This study aimed to evaluate the association between the out-of-hospital cardiac arrest (OHCA) occurrence within a year and the percent changes of BMI preceding the OHCA. METHODS: This population-based nested case-control study used the National Health Insurance Service Data of Korea. In all, 24,465 patients with non-traumatic OHCA between 2010 and 2018, who underwent national health check-up twice (one within a year and the other within 2-4 years before OHCA) and 32,434 controls without OHCA, were matched for age and sex. The association between the risk of OHCA and BMI percent change stratified by sex was investigated. RESULTS: All the BMI percent changes of ≥ 5% significantly increased the OHCA occurrence with a reverse J-shaped association. Compared to individuals with a stable weight, those with severe (> 15%) BMI decrease had the highest odds ratio (OR) of 4.29 (95% confidence intervals [CIs], 3.72-4.95) for OHCA occurrence followed by those with moderate (10-15%) weight loss (OR, 2.80; 95% CI, 2.55-3.08) and those with severe (> 15%) weigh gain (OR, 2.24; 95% CI, 1.96-2.57), respectively. The impact of weight loss on the cardiac arrest occurrence was more prominent in men, while the impact of weight gain was more prominent in women. CONCLUSION: Significant weight changes increase the risk of OHCA within a year with a reverse J-shaped association. Significant weight loss might be a warning sign for OHCA especially for men.

Recessive COL17A1 Mutations and a Dominant LAMB3 Mutation Cause Hypoplastic Amelogenesis Imperfecta.

Hereditary conditions that affect tooth enamel in quantity and/or quality are called amelogenesis imperfecta (AI). AI can occur as an isolated condition or as a symptom of a syndrome. An OMIM search with the term "AI" yielded 79 result entries. Mutations in the same gene cause syndromic or non-syndromic AI, depending on the nature of the mutations. In this study, we recruited two AI families and performed mutational analysis using whole-exome sequencing. The proband of family 1, with hypoplastic pitted AI and mild localized atopic dermatitis, had compound heterozygous COL17A1 mutations (paternal NM_000494.4: c.3598G>T, p.Asp1200Tyr and maternal c.1700G>A, p.Gly567Glu). The proband of family 2, with hypoplastic pitted AI and Jervell and Lange-Nielsen syndrome, had a recurrent LAMB3 mutation (NM_000228.3: c.3463_3475del, p.(Glu1155Thrfs*51)) in addition to compound heterozygous mutations in the KCNQ1 gene.

Oxidative Stress and DNA Damage in Pagrus major by the Dinoflagellate Karenia mikimotoi.

Karenia mikimotoi is a common species of red tide dinoflagellate that causes the mass mortality of marine fauna in coastal waters of Republic of Korea. Despite continuous studies on the ecophysiology and toxicity of K. mikimotoi, the underlying molecular mechanisms remain poorly understood. Red sea bream, Pagrus major, is a high-value aquaculture fish species, and the coastal aquaculture industry of red sea bream has been increasingly affected by red tides. To investigate the potential oxidative effects of K. mikimotoi on P. major and the molecular mechanisms involved, we exposed the fish to varying concentrations of K. mikimotoi and evaluated its toxicity. Our results showed that exposure to K. mikimotoi led to an accumulation of reactive oxygen species (ROS) and oxidative DNA damage in the gill tissue of P. major. Furthermore, we found that K. mikimotoi induced the activation of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, in the gill tissue of P. major, with a significant increase in activity at concentrations above 5000 cells/mL. However, the activity of glutathione S-transferase did not significantly increase at the equivalent concentration. Our study confirms that oxidative stress and DNA damage is induced by acute exposure to K. mikimotoi, as it produces ROS and hypoxic conditions in P. major. In addition, it was confirmed that gill and blood samples can be used as biomarkers to detect the degree of oxidative stress in fish. These findings have important implications for the aquaculture of red sea bream, particularly in the face of red tide disasters.

Effect of adjuvant thiamine and ascorbic acid administration on the neurologic outcomes of out-of-hospital cardiac arrest patients: A before-and-after study.

AIM: This study aimed to evaluate the impact of early thiamine and ascorbic acid administration on the neurologic outcome in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). METHODS: This before-and-after cohort study used data extracted from two hospitals of the Korean Hypothermia Network prospective registry. The treatment group incorporated patients enrolled from December 2019 to May 2021, that received intravenous thiamine (200 mg) and ascorbic acid (3 g) at 12-hour intervals for a total of six doses. The control group incorporated those enrolled from May 2018 to November 2019. The one-month good neurologic outcome, defined as a Cerebral Performance Category score ≤ 2, between the groups was evaluated using inverse probability of treatment weighting (IPTW). RESULTS: Among the 234 OHCA survivors with TTM, 102 were included in the treatment group and 132 were included in the control group. The one-month (31.4 % vs. 29.5 %, respectively; P = 0.76) good neurologic outcome rates did not differ between the treatment and control groups. After adjusting using the IPTW, vitamin supplementation was not associated with good neurologic outcome (odds ratio [OR], 1.134; 95 % confidence interval [CI], 0.644-1.999; P = 0.66). In subgroup analysis, vitamin administration was significantly associated with a good neurologic outcome in older (≥65 years) patients (adjusted OR, 5.53; 95 % CI, 1.21-25.23; P = 0.03). CONCLUSION: Adjuvant thiamine and ascorbic acid administration in OHCA survivors with TTM did not improve their neurologic outcome after one month. Further clinical trials are warranted.

Telephone-based evaluation of cognitive impairment and mood disorders in cardiac arrest survivors with good neurologic outcomes: a retrospective cohort study.

This study determined the occurrence of cognitive impairment and mood disorders in out-of-hospital cardiac arrest (OHCA) survivors with good neurologic outcomes. We performed a retrospective, cross-sectional, single-center study with a total of 97 patients. We evaluated cognitive dysfunction via the Montreal Cognitive Assessment and Alzheimer's disease-8 mood disorders via the Patient Health Questionnaire-9 and the Hospital Anxiety and Depression Scale. We measured quality of life with the European Quality of Life 5-Dimension 5-Levels questionnaire. Cognitive impairment and mood disorders were common among patients with good neurologic recovery. There were 23 patients who experienced cognitive impairments (23.7%) and 28 who suffered from mood disorders (28.9%). Age (adjusted OR 1.07, 95% CI 1.02-1.12), mood disorders (adjusted OR 22.80, 95% CI 4.84-107.49) and hospital length of stay (adjusted OR 1.05, 95% CI 1.02-1.09) were independent risk factors for cognitive impairment. The occurrence of cognitive impairments (adjusted OR 9.94, 95% CI 2.83-35.97) and non-cardiac causes of cardiac arrest (adjusted OR 11.51, 95% CI 3.15-42.15) were risk factors for mood disorders. Quality of life was significantly lower in the OHCA survivors with each disorder than the healthy individuals. Routine screening and intervention are needed for OHCA survivors.

Modification of HEART Pathway for Patients With Chest Pain: A Korean Perspective.

BACKGROUND AND OBJECTIVES: The History, Electrocardiography, Age, Risk factors, and Troponin (HEART) pathway was developed to identify patients at low risk of a major adverse cardiac event (MACE) among patients presenting with chest pain to the emergency department. METHODS: We modified the HEART pathway by replacing the Korean cut-off of 25 kg/m² with the conventional threshold of 30 kg/m² in the definition of obesity among risk factors. The primary outcome was a MACE within 30 days, which included acute myocardial infarction, primary coronary intervention, coronary artery bypass grafting, and all-cause death. RESULTS: Of the 1,304 patients prospectively enrolled, MACE occurred in 320 (24.5%). The modified HEART pathway identified 37.3% of patients as low-risk compared with 38.3% using the HEART pathway. Of the 500 patients classified as low-risk with HEART pathway, 8 (1.6%) experienced MACE, and of the 486 low-risk patients with modified HEART pathway, 4 (0.8%) experienced MACE. The modified HEART pathway had a sensitivity of 98.8%, a negative predictive value (NPV) of 99.2%, a specificity of 49.0%, and a positive predictive value (PPV) of 38.6%, compared with the original HEART pathway, with a sensitivity of 97.5%, a NPV of 98.4%, a specificity of 50.0%, and a PPV of 38.8%. CONCLUSIONS: When applied to Korean population, modified HEART pathway could identify patients safe for early discharge more accurately by using body mass index cut-off levels suggested for Koreans.

Different neuroprognostication thresholds of neuron-specific enolase in shockable and non-shockable out-of-hospital cardiac arrest: a prospective multicenter observational study in Korea (the KORHN-PRO registry).

BACKGROUND: Serum neuron-specific enolase (NSE) is the only recommended biomarker for multimodal prognostication in postcardiac arrest patients, but low sensitivity of absolute NSE threshold limits its utility. This study aimed to evaluate the prognostic performance of serum NSE for poor neurologic outcome in out-of-hospital cardiac arrest (OHCA) survivors based on their initial rhythm and to determine the NSE cutoff values with false positive rate (FPR) < 1% for each group. METHODS: This study included OHCA survivors who received targeted temperature management (TTM) and had serum NSE levels measured at 48 h after return of spontaneous circulation in the Korean Hypothermia Network, a prospective multicenter registry from 22 university-affiliated teaching hospitals in South Korea between October 2015 and December 2018. The primary outcome was poor outcome at 6 month, defined as a cerebral performance category of 3-5. RESULTS: Of 623 patients who underwent TTM with NSE measured 48 h after the return of spontaneous circulation, 245 had an initial shockable rhythm. Median NSE level was significantly higher in the non-shockable group than in the shockable group (104.6 [40.6-228.4] vs. 25.9 [16.7-53.4] ng/mL, P < 0.001). Prognostic performance of NSE assessed by area under the receiver operating characteristic curve to predict poor outcome was significantly higher in the non-shockable group than in the shockable group (0.92 vs 0.86). NSE cutoff values with an FPR < 1% in the non-shockable and shockable groups were 69.3 (sensitivity of 42.1%) and 102.7 ng/mL (sensitivity of 76%), respectively. CONCLUSION: NSE prognostic performance and its cutoff values with FPR < 1% for predicting poor outcome in OHCA survivors who underwent TTM differed between shockable and non-shockable rhythms, suggesting postcardiac arrest survivor heterogeneity. Trial registration KORHN-PRO, NCT02827422. Registered 11 September 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02827422.

Impact of Developing Dialysis-Requiring Acute Kidney Injury on Long-Term Mortality in Cancer Patients with Septic Shock.

(1) Background: Considering recent advances in both cancer and sepsis management, we chose to evaluate the associated factors for occurrence of septic acute kidney injury in cancer patients using a nationwide population-based cohort data. (2) Methods: Using data from the National Health Insurance Service of Korea, adult cancer patients who presented to emergency departments with septic shock from 2009 to 2017 were analyzed. A Cox-proportional hazard model was conducted to evaluate the clinical effect of sepsis-related acute kidney injury requiring dialysis. (3) Results: Among 42,477 adult cancer patients with septic shock, dialysis-requiring acute kidney injury occurred in 5449 (12.8%). Recovery from dialysis within 30 days was 77.9% and, overall, 30-day and 2-year mortality rates were 52.1% and 85.1%, respectively. Oncologic patients with dialysis-requiring acute kidney injury frequently occurred in males and patients with hematologic cancer. A multivariate Cox-proportional hazard model showed that dialysis-requiring acute kidney injury had the highest adjusted hazard ratio of 1.353 (95% confidence interval 1.313-1.395) for 2-year mortality. (4) Conclusions: Dialysis-requiring septic acute kidney injury did not occur commonly. However, it had a significant association with increased long-term mortality, which suggests emphasis should be placed on the prevention of acute kidney injury, particularly in male hematologic cancer patients.

Enhancing the interferon-γ release assay through omission of nil and mitogen values.

PURPOSE: To address the limited utility of the interferon (IFN)-γ release assay (IGRA) caused by its variability and inconsistency. METHODS: This retrospective cohort study was based on data obtained between 2011 and 2019. QuantiFERON-TB Gold-In-Tube was used to measure IFN-γ levels in nil, tuberculosis (TB) antigen, and mitogen tubes. RESULTS: Of 9,378 cases, 431 had active TB. The non-TB group comprised 1,513 IGRA-positive, 7,202 IGRA-negative, and 232 IGRA-indeterminate cases. Nil-tube IFN-γ levels were significantly higher in the active TB group (median = 0.18 IU/mL; interquartile range: 0.09-0.45 IU/mL) than in the IGRA-positive non-TB (0.11 IU/mL; 0.06-0.23 IU/mL) and IGRA-negative non-TB (0.09 IU/mL; 0.05-0.15 IU/mL) groups (P < 0.0001). From receiver operating characteristic analysis, TB antigen tube IFN-γ levels had higher diagnostic utility for active TB than TB antigen minus nil values. In a logistic regression analysis, active TB was the main driver of higher nil values. In the active TB group, after reclassifying the results based on a TB antigen tube IFN-γ level of 0.48 IU/mL, 14/36 cases with negative results and 15/19 cases with indeterminate results became positive, while 1/376 cases with positive results became negative. Overall, the sensitivity for detecting active TB improved from 87.2 to 93.7%. CONCLUSION: The results of our comprehensive assessment can aid in IGRA interpretation. Since nil values are governed by TB infection rather than reflecting background noise, TB antigen tube IFN-γ levels should be used without subtracting nil values. Despite indeterminate results, TB antigen tube IFN-γ levels can be informative.

Transcriptomic Changes Induced by Low and High Concentrations of Heavy Metal Exposure in Ulva pertusa.

The impact of sewage and wastewater pollution on marine ecosystems is of increasing concern due to the rapid accumulation of heavy metals in seaweeds inhabiting near-shore environments. Seaweeds can be severely damaged by heavy metals throughout their life cycles. Although the physiological and ecological effects of heavy metal exposure have been studied, there is limited research on their molecular responses. Ulva pertusa is a prevalent seaweed species in South Korea and is ecologically significant in coastal ecosystems. We utilized high-throughput RNA sequencing to analyze changes in the transcriptome profiles of U. pertusa under low concentrations of heavy metals (MPS) and high concentrations of copper (MPS-Cu) and cadmium (MPS-Cd). Differential gene expression analysis revealed that 53 (control vs. MPS), 27 (MPS vs. MPS-Cd), and 725 (MPS vs. MPS-Cu) genes were expressed differentially. Differentially expressed genes identified in our study included those with protective roles against oxidative stress and those involved in metal transport to the vacuole. Furthermore, exposure to heavy metal stress had a negative impact on the photosynthetic apparatus structural proteins of U. pertusa, resulting in photosynthetic inhibition. Moreover, exposure to high concentrations of copper resulted in the activation of carbon-related metabolism. These findings contribute to our understanding of the molecular mechanisms underlying heavy metal toxicity in U. pertusa.

Physiological effects of micro-plastics on the red algae, Grateloupia turuturu and Chondrus sp.

Plastics are the most abundant marine litter in the world's oceans and can be degraded into micro-plastics. These emerging pollutants negatively affect marine organisms, but little is known on the effects on macroalgae. In this study, we investigated the effects of micro-plastics on two species of red algae: Grateloupia turuturu and Chondrus sp. Grateloupia turuturu has a slippery surface while Chondrus sp. has a rough surface. Different surface characteristics of these macroalgae may affect adherence of micro-plastics. Both species were exposed to 5 different concentrations (0, 20, 200, 2000 and 20,000 ng/L) of polystyrene microspheres. Adherence capacity, accumulating micro-plastics on the surface was higher for Chondrus sp. than G. turuturu. Chondrus sp. at 20,000 ng/L only showed a decrease in growth rate and photosynthesis activity, and an increase of reactive oxygen species (ROS). However, G. turuturu was not significantly affected by micro-plastics at all tested concentrations. Shaded light and inhibition of gas flow by adhered micro-plastics may be a reason for the reduction of growth and photosynthesis and production of ROS. Based on this result, the toxic effects of micro-plastics appear to be species specific, dependent on the adherence capacity of macroalgae.

NXP032 ameliorates cognitive impairment by alleviating the neurovascular aging process in aged mouse brain.

Vascular aging is well known to be associated with the breakdown of the neurovascular unit (NVU), which is essential for maintaining brain homeostasis and linked to higher cognitive dysfunction. Oxidative stress is believed to be a significant cause of the vascular aging process. Vitamin C is easily oxidized under physiological conditions, so it loses its potent antioxidant activity. We developed a DNA aptamer that enhances the function of vitamin C. NXP032 is the binding form of the aptamer and vitamin C. In this study, we investigated the effect of NXP032 on neurovascular stabilization through the changes of PECAM-1, PDGFR-ß, ZO-1, laminin, and glial cells involved in maintaining the integrity of the blood-brain barrier (BBB) in aged mice. NXP032 was orally administered daily for 8 weeks. Compared to young mice and NXP032-treated mice, 20-month-old mice displayed cognitive impairments in Y-maze and passive avoidance tests. NXP032 treatment contributed to reducing the BBB damage by attenuating the fragmentation of microvessels and reducing PDGFR-ß, ZO-1, and laminin expression, thereby mitigating astrocytes and microglia activation during normal aging. Based on the results, we suggest that NXP032 reduces vascular aging and may be a novel intervention for aging-induced cognitive impairment.

Association between the number of prehospital defibrillation attempts and a sustained return of spontaneous circulation: a retrospective, multicentre, registry-based study.

BACKGROUND: Currently, there is no consensus on the number of defibrillation attempts that should be made before transfer to a hospital in patients with out-of-hospital cardiac arrest (OHCA). This study aimed to evaluate the association between the number of defibrillations and a sustained prehospital return of spontaneous circulation (ROSC). METHODS: A retrospective analysis of a multicentre, prospectively collected, registry-based study in Republic of Korea was conducted for OHCA patients with prehospital defibrillation. The primary outcome was sustained prehospital ROSC, and the secondary outcome was a good neurological outcome at hospital discharge, defined as Cerebral Performance Category score 1 or 2. Cumulative incidence of sustained prehospital ROSC and good neurological outcome according to number of defibrillations were examined. Multivariable logistic regression analysis was used to examine whether the number of defibrillations was independently associated with the outcomes. RESULTS: Excluding 172 patients with missing data, a total of 1983 OHCA patients who received prehospital defibrillation were included. The median time from arrest to first defibrillation was 10 (IQR 7-15) min. The numbers of patients with sustained prehospital ROSC and good neurological outcome were 738 (37%) and 549 (28%), respectively. Sustained ROSC rates decreased as the number of defibrillation attempts increased from the first to the sixth (16%, 9%, 5%, 3%, 2% and 1%, respectively). The cumulative sustained ROSC rate, and good neurological outcome rate from initial defibrillation to sixth defibrillation were 16%, 25%, 30%, 34%, 36%, 36% and 11%, 18%, 22%, 25%, 26%, 27%, respectively. With adjustment for clinical characteristics and time to defibrillation, a higher number of defibrillations was independently associated with a lower chance of a sustained ROSC (OR 0.81, 95% CI 0.76 to 0.86) and a lower chance of good neurological outcome (OR 0.86, 95% CI 0.80 to 0.92). CONCLUSIONS: We observed no significant increase in ROSC after five defibrillations, and no absolute increase in ROSC after seven defibrillations. These data provide a starting point for determination of the optimal defibrillation strategy prior to consideration for prehospital extracorporeal cardiopulmonary resuscitation (ECPR) or conveyance to a hospital with an ECPR capability. TRIAL REGISTRATION NUMBER: NCT03222999.

Predicting the probability of good neurological outcome after in-hospital cardiac arrest based on prearrest factors: validation of the good outcome following attempted resuscitation 2 (GO-FAR 2) score.

The Good Outcome Following Attempted Resuscitation (GO-FAR) 2 score is a prognostic tool developed to support decision-making for do-not-attempt-resuscitation (DNAR) orders by predicting neurological outcomes after in-hospital cardiac arrest (IHCA) based on prearrest variables. However, this scoring system requires further validation. We aimed to validate the GO-FAR 2 score for predicting good neurological outcome in Korean patients with IHCA. A single-centre registry of adult patients with IHCA from 2013 to 2017 was analysed. The primary outcome was discharge with good neurological outcome (Cerebral Performance Category score of 1 or 2). The patients were divided into four categories according to the GO-FAR 2 score: very poor (≥ 5), poor (2-4), average (- 3 to 1), and above-average (< - 3) likelihood of good neurological outcome. Of 1,011 patients (median age, 65 years), 63.1% were men. The rate of good neurological outcome was 16.0%. The proportions of patients categorised as having very poor, poor, average, and above-average probability of good neurological outcome were 3.9%, 18.3%, 70.2%, and 7.6%, respectively. In each category, good neurological outcome was observed in 0%, 1.1%, 16.8%, and 53.2%, respectively. Among patients in below-average categories (very poor + poor, GO-FAR 2 score ≥ 2), only 0.9% had good outcome. GO-FAR 2 score ≥ 2 showed a sensitivity of 98.8% and a negative predictive value of 99.1% in predicting good neurological outcome. The GO-FAR 2 score can predict neurological outcome after IHCA. In particular, GO-FAR 2 score ≥ 2 may support decision-making for DNAR orders.

Efficacy of Artemisia annua Linné in improving cognitive impairment in a chronic cerebral hypoperfusion-induced vascular dementia animal model.

BACKGROUND: Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. Currently, no FDA-approved drugs are available for the treatment of VaD. Artemisia annua Linné (AA) is known to have antioxidant properties, but its effects and mechanisms of action on cognitive impairment are still unknown. PURPOSE: In this study, the improvement in cognitive impairment by AA in terms of protection against oxidative stress, neuroinflammation, and preservation of the integrity of the neurovascular unit (NVU) was assessed in an animal model of VaD with bilateral common carotid artery occlusion (BCCAO). METHODS: Eight-week-old male Wistar rats were allowed to adapt for four weeks, and BCCAO was induced at 12 weeks of age. The rats were randomly assigned into four groups, with seven rats in each group: sham group without BCCAO, VaD group that received oral administration of distilled water after BCCAO surgery, and two AA groups that received oral administration of 150 mg/kg or 750 mg/kg AA after BCCAO surgery for 8 weeks. Nine weeks after BCCAO surgery, the cognitive function of the rats was evaluated and accumulated oxidative stress was assessed by immunohistochemistry, immunofluorescence, and western blotting. Damage to the components of the NVU was evaluated, and sirtuin (Sirt) 1 and 2 expression and nuclear factor-erythrocyte 2-associated factor 2 (Nrf2)/Kelch-like ECH-associated protein1 (Keap1) activation were investigated to assess the reduction in cell signaling and antioxidant pathways. RESULTS: BCCAO-induced cerebral perfusion decreased memory function and induced neuroinflammation and oxidative stress. But AA treatment mitigated cognitive impairment and reduced neuroinflammation and oxidative stress caused by chronic cerebral hypoperfusion. AA extracts activated the Nrf2/Keap1/activating antioxidant response elements pathway and maintained Sirt 1 and 2, subsequently leading to the maintenance of neurons, improved construct of microvessels, increased platelet-derived growth factor receptor beta, and platelet-endothelial cell adhesion molecule-1 associated with the blood-brain barrier integrity. CONCLUSION: AA is effective in alleviating BCCAO-induced cognitive decline and its administration may be a useful therapeutic approach for VaD.