Prognostic Value of Mitral Annular Calcification in Liver Transplant Patients: Implication in Posttransplant Outcomes.

BACKGROUND: With the rise of metabolic diseases and aging in liver transplant (LT) candidates, mitral annular calcification (MAC) is more recognizable. Despite cardiovascular risk becoming a leading cause of mortality in LT recipients, the influence of MAC remains unexamined. This study investigates the prevalence, related factors, and impact of MAC on LT outcomes. METHODS: We explored 4148 consecutive LT patients who underwent routine pretransplant echocardiography from 2008 to 2019. Multivariate logistic analysis and the tree-based Shapley additive explanation scores in machine learning were used to evaluate the significant and important related factors. The primary outcome was 30-d major adverse cardiac events (MACE), and the secondary outcome was a median of 5-y cumulative all-cause mortality. RESULTS: MAC was found in 123 (3.0%) patients. Significant and important related factors included age, alcoholic liver disease, chronic kidney disease, hyperuricemia, hypertension, and coronary artery disease. The MACE rate was higher in patients with MAC compared with those without MAC at 30 d (P < 0.001, adjusted hazard ratio 1.67; 95% confidence interval, 1.08-2.57). Patients with MAC had poorer cumulative overall survival probability compared with those without MAC (P = 0.0016; adjusted hazard ratio 1.47; 95% confidence interval, 1.01-2.15). Specifically, women with MAC had a poorer survival probability compared with men without MAC (65.0% versus 80.7%, P < 0.001) >10 y post-LT. CONCLUSIONS: The presence of MAC before LT was linked to increased 30-d MACE and lower long-term survival rates, especially in women. Identification and management of MAC and potential risk factors are crucial for improving post-LT survival.

Effect of dexmedetomidine on the incidence of postoperative acute kidney injury in living donor liver transplantation recipients: A randomized controlled trial.

BACKGROUND: Acute kidney injury (AKI) is one of the most common complications after living-donor liver transplantation (LDLT) that has great impact on recipient and graft outcomes. Dexmedetomidine is reported to decrease the incidence of AKI. In the current study, we investigated whether intraoperative dexmedetomidine infusion would reduce the AKI following LDLT. MATERIAL AND METHODS: In total, 205 adult patients undergoing elective LDLT were randomly assigned to the dexmedetomidine group (n=103) or the control group (n=102). Dexmedetomidine group received continuous dexmedetomidine infusion at a rate of 0.4 mcgÖ¼/kg/hr after the anesthesia induction until 2 hours after graft reperfusion. The primary outcome was to compare the incidence of AKI. Secondary outcomes included serial lactate levels during surgery, chronic kidney disease, major adverse cardiovascular events, early allograft dysfunction, graft failure, overall mortality, duration of mechanical ventilation, ICU and hospital length of stay. Intraoperative hemodynamic parameters were also collected. RESULTS: Of 205 recipients, 42.4% (n=87) developed AKI. The incidence of AKI was lower in the dexmedetomidine group (35.0%, n=36/103) compared with the control (50.0%, n=51/102) ( P =0.042). There were significantly lower lactate levels in the dexmedetomidine group after reperfusion (4.39 [3.99-4.8] vs 5.02 [4.62-5.42], P =0.031) until the end of surgery (4.23 [3.73-4.73] vs 5.35 [4.84-5.85], P =0.002). There were no significant differences in the other secondary outcomes besides lactate. Also, intraoperative mean blood pressure, cardiac output, and systemic vascular resistance did not show any difference. CONCLUSION: Our study suggests that intraoperative dexmedetomidine administration was associated with significantly decreased AKI incidence and lower intraoperative serum lactate levels in LDLT recipients, without untoward hemodynamic effects.

CD81 and CD82 expressing tumor-infiltrating lymphocytes in the NSCLC tumor microenvironment play a crucial role in T-cell activation and cytokine production.

Introduction: To understand the immune system within the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC), it is crucial to elucidate the characteristics of molecules associated with T cell activation. Methods: We conducted an in-depth analysis using single-cell RNA sequencing data obtained from tissue samples of 19 NSCLC patients. T cells were classified based on the Tumor Proportion Score (TPS) within the tumor region, and molecular markers associated with activation and exhaustion were analyzed in T cells from high TPS areas. Results: Notably, tetraspanins CD81 and CD82, belonging to the tetraspanin protein family, were found to be expressed in activated T cells, particularly in cytotoxic T cells. These tetraspanins showed strong correlations with activation and exhaustion markers. In vitro experiments confirmed increased expression of CD81 and CD82 in IL-2-stimulated T cells. T cells were categorized into CD81highCD82high and CD81lowCD82low groups based on their expression levels, with CD81highCD82high T cells exhibiting elevated activation markers such as CD25 and CD69 compared to CD81lowCD82low T cells. This trend was consistent across CD3+, CD8+, and CD4+ T cell subsets. Moreover, CD81highCD82high T cells, when stimulated with anti-CD3, demonstrated enhanced secretion of cytokines such as IFN-γ, TNF-α, and IL-2, along with an increase in the proportion of memory T cells. Bulk RNA sequencing results after sorting CD81highCD82high and CD81lowCD82low T cells consistently supported the roles of CD81 and CD82. Experiments with overexpressed CD81 and CD82 showed increased cytotoxicity against target cells. Discussion: These findings highlight the multifaceted roles of CD81 and CD82 in T cell activation, cytokine production, memory subset accumulation, and target cell cytolysis. Therefore, these findings suggest the potential of CD81 and CD82 as promising candidates for co-stimulatory molecules in immune therapeutic strategies for cancer treatment within the intricate TME.

Ginsenoside Rb1 alleviates lipopolysaccharide-induced inflammation in human dental pulp cells via the PI3K/Akt, NF-κB, and MAPK signalling pathways.

AIM: Among numerous constituents of Panax ginseng, a constituent named Ginsenoside Rb1 (G-Rb1) has been studied to diminish inflammation associated with diseases. This study investigated the anti-inflammatory properties of G-Rb1 on human dental pulp cells (hDPCs) exposed to lipopolysaccharide (LPS) and aimed to determine the underlying molecular mechanisms. METHODOLOGY: The KEGG pathway analysis was performed after RNA sequencing in G-Rb1- and LPS-treated hDPCs. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis were used for the assessment of cell adhesion molecules and inflammatory cytokines. Statistical analysis was performed with one-way ANOVA and the Student-Newman-Keuls test. RESULTS: G-Rb1 did not exhibit any cytotoxicity within the range of concentrations tested. However, it affected the levels of TNF-α, IL-6 and IL-8, as these showed reduced levels with exposure to LPS. Additionally, less mRNA and protein expressions of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were shown. With the presence of G-Rb1, decreased levels of PI3K/Akt, phosphorylated IκBα and p65 were also observed. Furthermore, phosphorylated ERK and JNK by LPS were diminished within 15, 30 and 60 min of G-Rb1 exposure; however, the expression of non-phosphorylated ERK and JNK remained unchanged. CONCLUSIONS: G-Rb1 suppressed the LPS-induced increase of cell adhesion molecules and inflammatory cytokines, while also inhibiting PI3K/Akt, phosphorylation of NF-κB transcription factors, ERK and JNK of MAPK signalling in hDPCs.

Analysis of tumor mutational burden and mutational landscape comparing whole-exome sequencing and comprehensive genomic profiling in patients with resectable early-stage non-small-cell lung cancer.

Background: Identifying actionable driver mutations via tissue-based comprehensive genomic profiling (CGP) is paramount in treatment decisions for metastatic non-squamous, non-small-cell lung cancer (NSCLC). However, the role of CGP remains elusive in resectable NSCLC. Here, we elucidate the feasibility of CGP in early-stage NSCLC Korean patients and compare the tumor mutational burden (TMB) and mutation landscape using three different platforms. Methods: All surgically resected NSCLC samples (N = 96) were analyzed to assess the concordance in TMB calculation and targetable mutations using whole-exome sequencing (WES) and TruSight Oncology 500 (TSO500). In all, 26 samples were analyzed with Foundation One CDx Assay (F1CDx). Programmed death-ligand 1 (PD-L1) expression was evaluated using Vectra Polaris. Results: Stage distribution post-surgery was 80% I (N = 77) and 20% II (N = 19). Ninety-nine percent (N = 95) were adenocarcinoma. The median TMB with WES and TSO500 was 1.6 and 4.7 mut/Mb, respectively (p < 0.05). Using all three platforms, the median TMB was 1.9, 5.5, and 4 mut/Mb for WES, TSO500, and F1CDx, respectively (p = 0.0048). Linear regression analysis of TMB values calculated between WES and TSO500 resulted in a concordance correlation coefficient of 0.83. For the PD-L1 tumor proportion score of <1% (negative, N = 18), 1-49% (low, N = 68), and ⩾50% (high, N = 10), the R2 values were 0.075, 0.79, and 0.95, respectively. The R2 values for TMB concordance were variable between the three platforms. Mutation landscape revealed EGFR mutation (51%, N = 49) as the most common actionable driver mutation, comprising L858R (N = 22), E19del (N = 20), and other non-common EGFR mutations (N = 7). Conclusion: TSO500 and F1CDx showed robust analytical performance for TMB assessment with TSO500 showing stronger concordance of TMB with high PD-L1 expression. As the paradigm for the management of early-resected NSCLC continues to evolve, understanding TMB and the mutation landscape may help advance clinical outcomes for this subset of patients.

Successful expansion and cryopreservation of human natural killer cell line NK-92 for clinical manufacturing.

Natural killer (NK) cells have recently shown renewed promise as therapeutic cells for use in treating hematologic cancer indications. Despite this promise, NK cell manufacturing workflows remain largely manual, open, and disconnected, and depend on feeders, as well as outdated unit operations or processes, often utilizing research-grade reagents. Successful scale-up of NK cells critically depends on the availability and performance of nutrient-rich expansion media and cryopreservation conditions that are conducive to high cell viability and recovery post-thaw. In this paper we used Cytiva hardware and media to expand the NK92 cell line in a model process that is suitable for GMP and clinical manufacturing of NK cells. We tested a range of cryopreservation factors including cooling rate, a range of DMSO-containing and DMSO-free cryoprotectants, ice nucleation, and cell density. Higher post-thaw recovery was seen in cryobags over cryovials cooled in identical conditions, and cooling rates of 1°C/min or 2°C/min optimal for cryopreservation in DMSO-containing and DMSO-free cryoprotectants respectively. Higher cell densities of 5x107 cells/ml gave higher post-thaw viability than those cryopreserved at either 1x106 or 5x106 cells/ml. This enabled us to automate, close and connect unit operations within the workflow while demonstrating superior expansion and cryopreservation of NK92 cells. Cellular outputs and performance were conducive to clinical dosing regimens, serving as a proof-of-concept for future clinical and commercial manufacturing.

Impact of preoperative nonselective beta-blocker use on acute kidney injury after living donor liver transplantation: Propensity score analysis.

INTRODUCTION AND OBJECTIVES: Acute kidney injury (AKI) is prevalent and has deleterious effects on postoperative outcomes following liver transplantation (LT). The impact of nonselective beta-blockers (NSBBs) in patients with liver cirrhosis remains controversial. This study investigated the association between preoperative NSBB use and AKI after living donor LT (LDLT). PATIENTS AND METHODS: We evaluated 2,972 adult LDLT recipients between January 2012 and July 2022. The patients were divided into two groups based on the preoperative NSBB use. Propensity score matched (PSM) and inverse probability of treatment weighting (IPTW) analyses were performed to evaluate the association between preoperative NSBB use and postoperative AKI. Multiple logistic regression analyses were also used to identify the risk factors for AKI. RESULTS: The overall incidence of AKI was 1,721 (57.9%) cases. The NSBB group showed a higher incidence of AKI than the non-NSBB group (62.4% vs. 56.7%; P = 0.011). After PSM and IPTW analyses, no significant difference in the incidence of AKI was found between the two groups (Odds ratio, OR 1.13, 95% confidence interval, CI 0.93-1.37, P = 0.230, PSM analysis; OR 1.20, 95% CI 0.99-1.44, P = 0.059, IPTW analysis). In addition, preoperative NSBB use was not associated with AKI after multivariate logistic regression analysis (OR 1.16, 95% CI 0.96-1.40, P = 0.118). CONCLUSIONS: Preoperative NSBB use was not associated with AKI after LDLT. Further studies are needed to validate our results.

Transcriptomic and metabolomic analysis unveils nanoplastic-induced gut barrier dysfunction via STAT1/6 and ERK pathways.

The widespread prevalence of micro and nanoplastics in the environment raises concerns about their potential impact on human health. Recent evidence demonstrates the presence of nanoplastics in human blood and tissues following ingestion and inhalation, yet the specific risks and mechanisms of nanoplastic toxicity remain inadequately understood. In this study, we aimed to explore the molecular mechanisms underlying the toxicity of nanoplastics at both systemic and molecular levels by analyzing the transcriptomic/metabolomic responses and signaling pathways in the intestines of mice after oral administration of nanoplastics. Transcriptome analysis in nanoplastic-administered mice revealed a notable upregulation of genes involved in pro-inflammatory immune responses. In addition, nanoplastics substantially reduced the expression of tight junction proteins, including occludin, zonula occluden-1, and tricellulin, which are crucial for maintaining gut barrier integrity and function. Importantly, nanoplastic administration increased gut permeability and exacerbated dextran sulfate sodium-induced colitis. Further investigation into the underlying molecular mechanisms highlighted significant activation of signaling transsducer and activator of transcription (STAT)1 and STAT6 by nanoplastic administration, which was in line with the elevation of interferon and JAK-STAT pathway signatures identified through transcriptome enrichment analysis. Additionally, the consumption of nanoplastics specifically induced nuclear factor kappa-B (NF-κB) and extracellular signal-regulated kinase (ERK)1/2 signaling pathways in the intestines. Collectively, this study identifies molecular mechanisms contributing to adverse effects mediated by nanoplastics in the intestine, providing novel insights into the pathophysiological consequences of nanoplastic exposure.

A transcriptomic analysis of skeletal muscle tissues reveals promising candidate genes and pathways accountable for different daily weight gain in Hanwoo cattle.

Cattle traits like average daily weight gain (ADG) greatly impact profitability. Selecting based on ADG considering genetic variability can lead to economic and genetic advancements in cattle breeding. This study aimed to unravel genetic influences on ADG variation in Hanwoo cattle at the skeletal muscle transcriptomic level. RNA sequencing was conducted on longissimus dorsi (LD), semimembranosus (SB), and psoas major (PM) muscles of 14 steers assigned to same feed, grouped by low (≤ 0.71 kg) and high (≥ 0.77 kg) ADG. At P ≤ 0.05 and log2fold > 1.5, the distinct pattern of gene expression was identified with 184, 172, and 210 differentially expressed genes in LD, SB, and PM muscles, respectively. Tissue-specific responses to ADG variation were evident, with myogenesis and differentiation associated JAK-STAT signaling pathway and prolactin signaling pathways enriched in LD and SB muscles, while adipogenesis-related PPAR signaling pathways were enriched in PM muscle. Key hub genes (AXIN2, CDKN1A, MYC, PTGS2, FZD5, SPP1) were upregulated and functionally significant in muscle growth and differentiation. Notably, DPP6, CDKN1A, and FZD5 emerged as possible candidate genes linked to ADG variation. These findings enhance our understanding of genetic factors behind ADG variation in Hanwoo cattle, illuminating skeletal muscle mechanisms influencing ADG.

Effect of Nefopam on Dysesthesia, Postoperative Pain, and Satisfaction in Patients with Lumbar Spinal Stenosis Undergoing Spine Surgery: A Double-Blind, Randomized Study.

Postoperative residual pain and dysesthesia in patients with lumbar spinal stenosis (LSS) can reduce patient satisfaction. We investigated the effects of nefopam on dysesthesia, postoperative pain, and satisfaction in patients with LSS who underwent spine surgery. A total of 73 patients were randomly assigned to two groups: the nefopam group (n = 35), receiving a 20 mL normal saline-based solution containing nefopam 20 mg, and the control group (n = 38), which received 20 mL of normal saline 1 h before the end of the operation. Postoperative incisional pain, dysesthesia scores, and overall satisfaction with postoperative pain management were evaluated. The severity of dysesthesia within 12 and 24 h in the nefopam group was significantly lower than that in the control group (2.3 ± 1.9 and 1.7 ± 1.6 vs. 3.3 ± 2.1, and 2.6 ± 1.9, respectively; p = 0.029 and p = 0.048). Satisfaction scores for postoperative pain management were significantly higher in the nefopam group (3.7 ± 0.6 vs. 3.1 ± 1.0, respectively; p = 0.006). The administration of nefopam effectively reduced the severity of dysesthesia within 24 h of surgery in geriatric patients undergoing spine surgery and increased patient satisfaction with postoperative pain management.

Comparison of Fibrinogen Concentrate and Cryoprecipitate on Major Thromboembolic Events after Living Donor Liver Transplantation.

(1) Background: Liver transplantation (LT) is associated with significant hemorrhage and massive transfusions. Fibrinogen replacement has a key role in treating massive bleeding during LT and hypofibrinogenemia is treated by fibrinogen concentrate or cryoprecipitate. However, these two products are known to be associated with major thromboembolism events (MTEs). We aimed to compare the effect of fibrinogen concentrate and cryoprecipitate on MTEs in living donor LT (LDLT) recipients. (2) Methods: We analyzed 206 patients who underwent LDLT between January 2021 and March 2022. The patients were divided into two groups according to fibrinogen concentrate or cryoprecipitate use. We compared the incidence of MTEs between the two groups. In addition, we performed multiple logistic regression analyses to identify the risk factors for MTEs. (3) Results: There was no significant difference in the incidence of MTEs (16 [14.7%] vs. 14 [14.4%], p = 1.000) between the cryoprecipitate group and fibrinogen concentrate group. In the multivariate analysis, cryoprecipitate (OR 2.09, 95%CI 0.85-5.11, p = 0.107) and fibrinogen concentrate (OR 2.05, 95%CI 0.82-5.12, p = 0.126) were not significantly associated with MTEs. (4) Conclusions: there was no significant difference in the incidence of MTEs between cryoprecipitate and fibrinogen concentrate in LDLT recipients.

Investigating preoperative myoglobin level as predictive factor for acute kidney injury following cardiac surgery with cardiopulmonary bypass: a retrospective observational study

Abstract Background: Early identification of patients at risk of AKI after cardiac surgery is of critical importance for optimizing perioperative management and improving outcomes. This study aimed to identify the association between preoperative myoglobin levels and postoperative acute kidney injury (AKI) in patients undergoing valve surgery or coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass. Methods: This retrospective study included 293 patients aged over 17 years who underwent valve surgery or CABG with cardiopulmonary bypass. We excluded 87 patients as they met the exclusion criteria. Therefore, 206 patients were included in the final analysis. The patients' demographics as well as intraoperative and postoperative data were collected from electronic medical records. AKI was defined according to the Acute Kidney Injury Network classification system. Results: Of the 206 patients included in this study, 77 developed AKI. The patients who developed AKI were older, had a history of hypertension, underwent valve surgery with concomitant CABG, had lower preoperative hemoglobin levels, and experienced prolonged extracorporeal circulation (ECC) times. Multivariate logistic regression analysis revealed that preoperative myoglobin levels and ECC time were correlated with the development of AKI. A higher preoperative myoglobin level was an independent risk factor for the development of cardiac surgery-associated AKI. Conclusions: Higher preoperative myoglobin levels may enable physicians to identify patients at risk of developing AKI and optimize management accordingly.

Early Colonization of the Intestinal Microbiome of Neonatal Piglets Is Influenced by the Maternal Microbiome.

The intestinal microbiome plays a crucial role in animal health and growth by interacting with the host, inhibiting pathogenic microbial colonization, and regulating immunity. This study investigated dynamic changes in the fecal microbial composition of piglets from birth through weaning and the relationship between the piglet fecal microbiome and sows. Feces, skin, neonatal oral cavity, and vaginal samples were collected from eight sows and sixty-three piglets, and 16S genome sequencing was performed. The results revealed that Firmicutes, Bacteroidetes, and Proteobacteria dominated the piglet microbiome in the early stages, and Firmicutes and Bacteroidetes were crucial for maintaining a balance in the intestinal microbiome during nursing. The abundance of Christensenellaceae_R-7_group, Succinivibrio, and Prevotella increased in weaned piglets fed solid feed. Analysis of the microbiome from sows to piglets indicated a shift in the microbiome colonizing piglet intestines, which became a significant constituent of the piglet intestinal microbiome. This study supports the theory that the neonatal intestinal microbiome is vertically transmitted from the mother. Further research is required to integrate factors related to sows, piglets, and their environments to gain a better understanding of the early establishment of the intestinal microbiome in piglets.

Application of genomic big data to analyze the genetic diversity and population structure of Korean domestic chickens.

Genetic diversity analysis is crucial for maintaining and managing genetic resources. Several studies have examined the genetic diversity of Korean domestic chicken (KDC) populations using microsatellite markers, but it is difficult to capture the characteristics of the whole genome in this manner. Hence, this study analyzed the genetic diversity of several KDC populations using high-density single nucleotide polymorphism (SNP) genotype data. We examined 935 birds from 21 KDC populations, including indigenous and adapted Korean native chicken (KNC), Hyunin and Jeju KDC, and Hanhyup commercial KDC populations. A total of 212,420 SNPs of 21 KDC populations were used for calculating genetic distances and fixation index, and for ADMIXTURE analysis. As a result of the analysis, the indigenous KNC groups were genetically closer and more fixed than the other groups. Furthermore, Hyunin and Jeju KDC were similar to the indigenous KNC. In comparison, adapted KNC and Hanhyup KDC populations derived from the same original species were genetically close to each other, but had different genetic structures from the others. In conclusion, this study suggests that continuous evaluation and management are required to prevent a loss of genetic diversity in each group. Basic genetic information is provided that can be used to improve breeds quickly by utilizing the various characteristics of native chickens.

Neutrophilia is more predictive than increased white blood cell counts for short-term mortality after liver transplantation in patients with acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a life-threatening disease that requires urgent liver transplantation (LT). Accurate identification of high-risk patients is essential for predicting post-LT survival. The chronic liver failure consortium ACLF score is a widely accepted risk-stratification score that includes total white blood cell (WBC) counts as a component. This study aimed to evaluate the predictive value of total and differential WBC counts for short-term mortality following LT in patients with ACLF. METHODS: A total of 685 patients with ACLF who underwent LT between January 2008 and February 2019 were analyzed. Total and differential WBC counts were examined as a function of the model for end-stage liver disease for sodium (MELD-Na) score. The association between total and differential WBC counts and 90-day post-LT mortality was assessed using multivariable Cox proportional hazards regression analysis. RESULTS: The total WBC counts and neutrophil ratio were higher in patients with ACLF than in those without ACLF. The neutrophil ratio was significantly associated with 90-day post-LT mortality after adjustment (hazard ratio [HR], 1.04; P = 0.001), whereas total WBC counts were not significantly associated with 90-day post-LT mortality in either univariate or multivariate Cox analyses. The neutrophil ratio demonstrated a relatively linear trend with an increasing MELD-Na score and HR for 90-day post-LT mortality, whereas the total WBC counts exhibited a plateaued pattern. CONCLUSIONS: Neutrophilia, rather than total WBC counts, is a better prognostic indicator for short-term post-LT mortality in patients with ACLF.

The Influence of Cardiac Arrest Floor-Level Location within a Building on Survival Outcomes.

This nationwide, population-based observational study investigated the association between the floor level of out-of-hospital cardiac arrest (OHCA) incidence and survival outcomes in South Korea, notable for its significant high-rise apartment living. Data were collected retrospectively from OHCA patients through the South Korean Out-of-Hospital Cardiac Arrest Surveillance database. The study incorporated cases that included the OHCA's building floor information. The primary outcome assessed was survival to discharge, analyzed using multivariate logistic regression, and the secondary outcome was favorable neurological outcome. Among 36,977 patients, a total of 29,729 patients were included, and 1680 patients were survivors. A weak yet significant correlation between floor level and hospital arrival time was observed. Interestingly, elevated survival rates were noted among patients from higher floors despite extended emergency medical service response times. Multivariate analysis identified age, witnessed OHCA, shockable rhythm, and prehospital return of spontaneous circulation (ROSC) as primary determinants of survival to discharge. The floor level's impact on survival was less substantial than anticipated, suggesting residential emergency response enhancements should prioritize witness interventions, shockable rhythm management, and prehospital ROSC rates. The study underscores the importance of bespoke emergency response strategies in high-rise buildings, particularly in urban areas, and the potential of digital technologies to optimize response times and survival outcomes.

Characterizing Heart Failure With Preserved Ejection Fraction in End-Stage Liver Disease and Liver Transplant Outcomes.

Background: Heart failure with preserved ejection fraction (HFpEF) and its risk factors are increasingly recognized in patients with end-stage liver disease (ESLD). Objectives: The aim of this study was to characterize HFpEF and identify relevant risk factors in patients with ESLD. Additionally, the prognostic impact of high-probability HFpEF on post-liver transplantation (LT) mortality was investigated. Methods: Patients with ESLD prospectively enrolled from the Asan LT Registry between 2008 and 2019 were divided into groups with low (scores of 0 and 1), intermediate (scores of 2-4), and high (scores of 5 and 6) probability using the Heart Failure Association-PEFF diagnostic score for HFpEF. Gradient-boosted modeling in machine learning was further used to appraise the apparent importance of risk factors. Finally, post-LT all-cause mortality was followed for 12.8 years (median 5.3 years); there were 498 deaths after LT. Results: Among the 3,244 patients, 215 belonged to the high-probability group, commonly those with advanced age, female sex, anemia, dyslipidemia, renal dysfunction, and hypertension. The highest risk factors for the high-probability group, according to gradient-boosted modeling, were female sex, anemia, hypertension, dyslipidemia, and age >65 years. Among patients with Model for End-Stage Liver Disease scores of >30, those with high, intermediate, and low probability had cumulative overall survival rates of 71.6%, 82.2%, and 88.9% at 1 year and 54.8%, 72.1%, and 88.9% at 12 years after LT (log-rank P = 0.026), respectively. Conclusions: High-probability HFpEF was found in 6.6% of patients with ESLD with poorer long-term post-LT survival, especially those with advanced stages of liver disease. Therefore, identifying HFpEF using the Heart Failure Association-PEFF score and addressing modifiable risk factors can improve post-LT survival.

Genome-wide association study revealed the genomic regions associated with skin pigmentation in an Ogye x White Leghorn F2 chicken population.

Skin color in chickens is an economically important trait that determines the first impression of a consumer toward a broiler and can ultimately affect consumer choice in the market. Therefore, identification of genomic regions associated with skin color is crucial for increasing the sales value of chickens. Although previous studies have attempted to reveal the genetic markers associated with the skin coloration in chickens, most were limited to investigations of candidate genes, such as melanin-related genes, and focused on case/control studies based on a single or small population. In this study, we performed a genome-wide association study (GWAS) on 770 F2 intercrosses produced by an experimental population of 2 chicken breeds, namely Ogye and White Leghorns, with different skin colors. The GWAS demonstrated that the L* value among the 3 skin color traits is highly heritable, and the genomic regions located on 2 chromosomes (20 and Z) were detected to harbor SNPs significantly associated with the skin color trait, accounting for most of the total genetic variance. Particular genomic regions spanning a ∼2.94 Mb region on GGA Z and a ∼3.58 Mb region on GGA 20 were significantly associated with skin color traits, and in these regions, certain candidate genes, including MTAP, FEM1C, GNAS, and EDN3, were found. Our findings could help elucidate the genetic mechanisms underlying chicken skin pigmentation. Furthermore, the candidate genes can be used to provide a valuable breeding strategy for the selection of specific chicken breeds with ideal skin coloration.

Comparison of out-of-hospital cardiac arrests during the COVID-19 pandemic with those before the pandemic: an updated systematic review and meta-analysis.

The coronavirus disease of 2019 (COVID-19) pandemic, directly and indirectly, affected the emergency medical care system and resulted in worse out-of-hospital cardiac arrest (OHCA) outcomes and epidemiological features compared with those before the pandemic. This review compares the regional and temporal features of OHCA prognosis and epidemiological characteristics. Various databases were searched to compare the OHCA outcomes and epidemiological characteristics during the COVID-19 pandemic with before the pandemic. During the COVID-19 pandemic, survival and favorable neurological outcome rates were significantly lower than before. Survival to hospitalization, return of spontaneous circulation, endotracheal intubation, and use of an automated external defibrillator (AED) decreased significantly, whereas the use of a supraglottic airway device, the incidence of cardiac arrest at home, and response time of emergency medical service (EMS) increased significantly. Bystander CPR, unwitnessed cardiac arrest, EMS transfer time, use of mechanical CPR, and in-hospital target temperature management did not differ significantly. A subgroup analysis of the studies that included only the first wave with those that included the subsequent waves revealed the overall outcomes in which the epidemiological features of OHCA exhibited similar patterns. No significant regional differences between the OHCA survival rates in Asia before and during the pandemic were observed, although other variables varied by region. The COVID-19 pandemic altered the epidemiologic characteristics, survival rates, and neurological prognosis of OHCA patients. Review registration: PROSPERO (CRD42022339435).

Transient decrease in B-type natriuretic peptide level after liver transplantation does not ensure favorable post-transplant 30-day outcomes.

BACKGROUND: High B-type natriuretic peptide (BNP) levels within the first 3 postoperative days (postBNPPOD3) after liver transplantation (LT) are greatly predictive of the 30-day mortality. We evaluated clinical impact of transient decrease in postBNPPOD3 compared to pretransplant BNP (preBNP) level on mortality and major adverse cardiac event (MACE) within 30 days after LT. METHODS: We retrospectively evaluated 3,811 LT patients who measured delta BNP (deltaBNP), defined by serial postBNPPOD3 minus preBNP. Thirty-day all-cause mortality and MACE were estimated in patients with deltaBNP < 0 (n = 594, 15.6%) and > 0 (n = 3,217, 84.4%), respectively. Kaplan-Meier survival and multivariable Cox regression analysis were used. RESULTS: Within 30 days, 100 (2.6%) of all patients died. Unexpectedly, 30-day mortality rate (6.1% [95% CI: 4.2-8.4%] vs. 2.0% [95% CI: 1.5-2.5%], P < 0.001) and MACE (24.2% [95% CI: 20.4-28.5%] vs. 15.3% [95% CI: 14.0-16.7%], P < 0.001) were higher in patients with deltaBNP < 0 compared to those with deltaBNP > 0, respectively. Patients with deltaBNP < 0 had higher preBNP level (median [interquartile range], 251 [118, 586] vs. 43 [21, 92] pg/ml, P < 0.001) and model for end-stage liver disease score (26 [14, 37] vs. 14 [9, 23], P < 0.001) and more transfused intraoperatively. DeltaBNP < 0 remained significant after adjustments for potential confounders in multivariable analysis of 30-day mortality and MACE. CONCLUSIONS: DeltaBNP < 0 within the first 3 postoperative days is mainly attributed to pre-LT severe liver and cardiac disease status, therefore, transient decrease in BNP level after LT does not ensure favorable post-LT 30-day outcomes.