Effectiveness and intention to use a COVID-19 self-management app for epidemiological investigation: a web-based survey study.

Introduction: Numerous COVID-19-related apps were widely used during the COVID-19 pandemic. Among them, those supporting epidemiological investigations were particularly useful. This study explored the effectiveness of apps that support epidemiological investigations, factors influencing users' intention to use them, and ways to encourage their use. Methods: We developed and evaluated the KODARI app to demonstrate its importance in epidemiological investigations. After adapting a questionnaire based on an existing evaluation framework for COVID-19-related apps, we collected data from 276 participants through an online survey conducted between April 28 and May 25, 2023. We conducted two independent sample t-tests to determine the differences between each variable according to demographic characteristics and a multiple regression analysis to identify factors affecting intention to use. Results: Users were generally satisfied with the KODARI. We observed differences in sex, age, marital status, occupational characteristics, and experience with epidemiological investigation. Females rated the app's information accuracy higher than males. Males had a higher intention to use than females. Participants aged under 35 years rated information accuracy and transparency highly, whereas single participants rated information accuracy higher than married participants. Occupational groups with frequent interactions with others evaluated their self-determination regarding the application. The app's self-determination was highly valued among participants with experience in epidemiological investigations. By investigating the factors affecting the intention to use the app, we confirmed that effectiveness, self-determination, and usability significantly affected the intention to use. Discussion: This study demonstrated the effectiveness of app supporting epidemiological investigations, identified meaningful factors that influence intention to use, and confirmed the applicability of our new framework by considering the specificity of infectious disease situations such as COVID-19. This study provides a new basis for future epidemiological studies.

Korea4K: whole genome sequences of 4,157 Koreans with 107 phenotypes derived from extensive health check-ups.

BACKGROUND: Phenome-wide association studies (PheWASs) have been conducted on Asian populations, including Koreans, but many were based on chip or exome genotyping data. Such studies have limitations regarding whole genome-wide association analysis, making it crucial to have genome-to-phenome association information with the largest possible whole genome and matched phenome data to conduct further population-genome studies and develop health care services based on population genomics. RESULTS: Here, we present 4,157 whole genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest genomic resource of the Korean Genome Project. It encompasses most of the variants with allele frequency >0.001 in Koreans, indicating that it sufficiently covered most of the common and rare genetic variants with commonly measured phenotypes for Koreans. Korea4K provides 45,537,252 variants, and half of them were not present in Korea1K (1,094 samples). We also identified 1,356 new genotype-phenotype associations that were not found by the Korea1K dataset. Phenomics analyses further revealed 24 significant genetic correlations, 14 pleiotropic associations, and 127 causal relationships based on Mendelian randomization among 37 traits. In addition, the Korea4K imputation reference panel, the largest Korean variants reference to date, showed a superior imputation performance to Korea1K across all allele frequency categories. CONCLUSIONS: Collectively, Korea4K provides not only the largest Korean genome data but also corresponding health check-up parameters and novel genome-phenome associations. The large-scale pathological whole genome-wide omics data will become a powerful set for genome-phenome level association studies to discover causal markers for the prediction and diagnosis of health conditions in future studies.

Cell Type- and Age-Specific Expression of lncRNAs across Kidney Cell Types.

BACKGROUND: Accumulated evidence demonstrates that long non-coding RNAs (lncRNAs) regulate cell differentiation and homeostasis, influencing kidney aging and disease. Despite their versatility, the function of lncRNA remains poorly understood due to the lack of a reference map of lncRNA transcriptome in various cell types. METHODS: In this study, we employed a targeted single-cell RNA sequencing (scRNA-seq) method to enrich and characterize lncRNAs in individual cells. We applied this method to various mouse tissues, including normal and aged kidneys. RESULTS: Through tissue-specific clustering analysis, we identified cell type-specific lncRNAs that showed a high correlation with known cell-type marker genes. Furthermore, we constructed gene regulatory networks (GRNs) to explore the functional roles of differentially expressed lncRNAs in each cell type. In the kidney, we observed dynamic expression changes of lncRNAs during aging, with specific changes in glomerular cells. These cell type- and age-specific expression patterns of lncRNAs provide insights into their potential roles in regulating cellular processes, such as immune response and energy metabolism, during kidney aging. CONCLUSIONS: Our study sheds light on the comprehensive landscape of lncRNA expression and function and provides a valuable resource for future analysis of lncRNAs (https://gist-fgl.github.io/sc-lncrna-atlas/).

Single-cell lineage tracing approaches to track kidney cell development and maintenance.

The kidney is a complex organ consisting of various cell types. Previous studies have aimed to elucidate the cellular relationships among these cell types in developing and mature kidneys using Cre-loxP-based lineage tracing. However, this methodology falls short of fully capturing the heterogeneous nature of the kidney, making it less than ideal for comprehensively tracing cellular progression during kidney development and maintenance. Recent technological advancements in single-cell genomics have revolutionized lineage tracing methodologies. Single-cell lineage tracing enables the simultaneous tracing of multiple cell types within complex tissues and their transcriptomic profiles, thereby allowing the reconstruction of their lineage tree with cell state information. Although single-cell lineage tracing has been successfully applied to investigate cellular hierarchies in various organs and tissues, its application in kidney research is currently lacking. This review comprehensively consolidates the single-cell lineage tracing methodologies, divided into 4 categories (clustered regularly interspaced short palindromic repeat [CRISPR]/Cas9-based, transposon-based, Polylox-based, and native barcoding methods), and outlines their technical advantages and disadvantages. Furthermore, we propose potential future research topics in kidney research that could benefit from single-cell lineage tracing and suggest suitable technical strategies to apply to these topics.

Early-onset vasomotor symptoms and development of depressive symptoms among premenopausal women.

BACKGROUND: We investigated the association between vasomotor symptoms (VMSs) and the onset of depressive symptoms among premenopausal women. METHODS: This cross-sectional study included 4376 premenopausal women aged 42-52 years, and the cohort study included 2832 women without clinically relevant depressive symptoms at baseline. VMSs included the symptoms of hot flashes and night sweats. Depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale; a score of ≥16 was considered to define clinically relevant depressive symptoms. RESULTS: Premenopausal Women with VMSs at baseline exhibited a higher prevalence of depressive symptoms compared with women without VMSs at baseline (multivariable-adjusted prevalence ratio 1.76, 95 % confidence interval [CI] 1.47-2.11). Among the 2832 women followed up (median, 6.1 years), 406 developed clinically relevant depressive symptoms. Women with versus without VMSs had a significantly higher risk of developing clinically relevant depressive symptoms (multivariable-adjusted hazard ratio, 1.72; 95 % CI 1.39-2.14). VMS severity exhibited a dose-response relationship with depressive symptoms (P for trend <0.05). LIMITATIONS: Self-reported questionnaires were only used to obtain VMSs and depressive symptoms, which could have led to misclassification. We also could not directly measure sex hormone levels. CONCLUSIONS: Even in the premenopausal stage, women who experience hot flashes or night sweats have an increased risk of present and developed clinically relevant depressive symptoms. It is important to conduct mental health screenings and provide appropriate support to middle-aged women who experience early-onset VMSs.

Comparison of structural variant callers for massive whole-genome sequence data.

BACKGROUND: Detecting structural variations (SVs) at the population level using next-generation sequencing (NGS) requires substantial computational resources and processing time. Here, we compared the performances of 11 SV callers: Delly, Manta, GridSS, Wham, Sniffles, Lumpy, SvABA, Canvas, CNVnator, MELT, and INSurVeyor. These SV callers have been recently published and have been widely employed for processing massive whole-genome sequencing datasets. We evaluated the accuracy, sequence depth, running time, and memory usage of the SV callers. RESULTS: Notably, several callers exhibited better calling performance for deletions than for duplications, inversions, and insertions. Among the SV callers, Manta identified deletion SVs with better performance and efficient computing resources, and both Manta and MELT demonstrated relatively good precision regarding calling insertions. We confirmed that the copy number variation callers, Canvas and CNVnator, exhibited better performance in identifying long duplications as they employ the read-depth approach. Finally, we also verified the genotypes inferred from each SV caller using a phased long-read assembly dataset, and Manta showed the highest concordance in terms of the deletions and insertions. CONCLUSIONS: Our findings provide a comprehensive understanding of the accuracy and computational efficiency of SV callers, thereby facilitating integrative analysis of SV profiles in diverse large-scale genomic datasets.

Comprehensive RNA-sequencing analysis of colorectal cancer in a Korean cohort.

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.

Dynamics of The Γδtcr Repertoires During The Dedifferentiation Process and Pilot Implications for Immunotherapy of Thyroid Cancer.

γδ T cells are evolutionarily conserved T lymphocytes that manifest unique antitumor efficacy independent of tumor mutation burden (TMB) and conventional human leukocyte antigen (HLA) recognition. However, the dynamic changes in their T cell receptor (TCR) repertoire during cancer progression and treatment courses remain unclear. Here, a comprehensive characterization of γδTCR repertoires are performed in thyroid cancers with divergent differentiation states through cross-sectional studies. The findings revealed a significant correlation between the differentiation states and TCR repertoire diversity. Notably, highly expanded clones are prominently enriched in γδ T cell compartment of dedifferentiated patients. Moreover, by longitudinal investigations of the γδ T cell response to various antitumor therapies, it is found that the emergence and expansion of the Vδ2neg subset may be potentially associated with favorable clinical outcomes after post-radiotherapeutic immunotherapy. These findings are further validated at single-cell resolution in both advanced thyroid cancer patients and a murine model, underlining the importance of further investigations into the role of γδTCR in cancer immunity and therapeutic strategies.

Hedgehog signalling is involved in acquired resistance to KRASG12C inhibitors in lung cancer cells.

Although KRASG12C inhibitors have shown promising activity in lung adenocarcinomas harbouring KRASG12C, acquired resistance to these therapies eventually occurs in most patients. Re-expression of KRAS is thought to be one of the main causes of acquired resistance. However, the mechanism through which cancer cells re-express KRAS is not fully understood. Here, we report that the Hedgehog signal is induced by KRASG12C inhibitors and mediates KRAS re-expression in cancer cells treated with a KRASG12C inhibitor. Further, KRASG12C inhibitors induced the formation of primary cilia and activated the Hedgehog-GLI-1 pathway. GLI-1 binds to the KRAS promoter region, enhancing KRAS promoter activity and KRAS expression. Inhibition of GLI using siRNA or the smoothened (Smo) inhibitor suppressed re-expression of KRAS in cells treated with a KRASG12C inhibitor. In addition, we demonstrate that KRASG12C inhibitors decreased Aurora kinase A (AURKA) levels in cancer cells, and inhibition of AURKA using siRNA or inhibitors led to increased expression levels of GLI-1 and KRAS even in the absence of KRAS inhibitor. Ectopic expression of AURKA attenuated the effect of KRASG12C inhibitors on the expression of GLI-1 and re-expression of KRAS. Together, these findings demonstrate the important role of AURKA, primary cilia, and Hedgehog signals in the re-expression of KRAS and therefore the induction of acquired resistance to KRASG12C inhibitors, and provide a rationale for targeting Hedgehog signalling to overcome acquired resistance to KRASG12C inhibitors.

Chromatin accessibility analysis and architectural profiling of human kidneys reveal key cell types and a regulator of diabetic kidney disease.

Diabetes is the leading cause of kidney disease that progresses to kidney failure. However, the key molecular and cellular pathways involved in diabetic kidney disease (DKD) pathogenesis are largely unknown. Here, we performed a comparative analysis of adult human kidneys by examining cell type-specific chromatin accessibility by single-nucleus ATAC-seq (snATAC-seq) and analyzing three-dimensional chromatin architecture via high-throughput chromosome conformation capture (Hi-C method) of paired samples. We mapped the cell type-specific and DKD-specific open chromatin landscape and found that genetic variants associated with kidney diseases were significantly enriched in the proximal tubule- (PT) and injured PT-specific open chromatin regions in samples from patients with DKD. BACH1 was identified as a core transcription factor of injured PT cells; its binding target genes were highly associated with fibrosis and inflammation, which were also key features of injured PT cells. Additionally, Hi-C analysis revealed global chromatin architectural changes in DKD, accompanied by changes in local open chromatin patterns. Combining the snATAC-seq and Hi-C data identified direct target genes of BACH1, and indicated that BACH1 binding regions showed increased chromatin contact frequency with promoters of their target genes in DKD. Thus, our multi-omics analysis revealed BACH1 target genes in injured PTs and highlighted the role of BACH1 as a novel regulator of tubular inflammation and fibrosis.

CD40 is expressed in the subsets of endothelial cells undergoing partial endothelial-mesenchymal transition in tumor microenvironment.

Tumor progression and metastasis are regulated by endothelial cells undergoing endothelial-mesenchymal transition (EndoMT), a cellular differentiation process in which endothelial cells lose their properties and differentiate into mesenchymal cells. The cells undergoing EndoMT differentiate through a spectrum of intermediate phases, suggesting that some cells remain in a partial EndoMT state and exhibit an endothelial/mesenchymal phenotype. However, detailed analysis of partial EndoMT has been hampered by the lack of specific markers. Transforming growth factor-ß (TGF-ß) plays a central role in the induction of EndoMT. Here, we showed that inhibition of TGF-ß signaling suppressed EndoMT in a human oral cancer cell xenograft mouse model. By using genetic labeling of endothelial cell lineage, we also established a novel EndoMT reporter cell system, the EndoMT reporter endothelial cells (EMRECs), which allow visualization of sequential changes during TGF-ß-induced EndoMT. Using EMRECs, we characterized the gene profiles of multiple EndoMT stages and identified CD40 as a novel partial EndoMT-specific marker. CD40 expression was upregulated in the cells undergoing partial EndoMT, but decreased in the full EndoMT cells. Furthermore, single-cell RNA sequencing analysis of human tumors revealed that CD40 expression was enriched in the population of cells expressing both endothelial and mesenchymal cell markers. Moreover, decreased expression of CD40 in EMRECs enhanced TGF-ß-induced EndoMT, suggesting that CD40 expressed during partial EndoMT inhibits transition to full EndoMT. The present findings provide a better understanding of the mechanisms underlying TGF-ß-induced EndoMT and will facilitate the development of novel therapeutic strategies targeting EndoMT-driven cancer progression and metastasis.

Predictors of surgical outcomes for limited palatal muscle resection in patients with obstructive sleep apnea.

OBJECTIVE: Limited palatal muscle resection (LPMR) is a modified palatal surgical technique to correct retropalatal obstruction without complications. This study aims to determine the associated factors affecting the success and cure rate of LPMR in patients with obstructive sleep apnea (OSA), thus guiding patient selection and improving surgical outcome. METHODS: Thirty-five OSA patients underwent LPMR were enrolled. All patients received routine physical examination, preoperative drug-induced sleep endoscopy (DISE), and polysomnography (PSG). Clinical, polysomnographic, cephalometric variables, and DISE findings were evaluated. These measurements were compared between the surgical success and failure group based on the results of preoperative and postoperative PSG. Furthermore, we compared the cured and non-cured groups in the surgical success group. RESULTS: Among 35 patients, the overall success rate was 57 % with a cure rate of 31.4 %. Patients with Friedman stage II had a significantly higher success rate (p = 0.032). According to DISE results, tongue base obstruction affected the surgical outcome (p < 0.001). The success rate was 100 % in the no tongue base obstruction during DISE, 72.2 % in the partial obstruction, and 9.1 % in the total obstruction. Tonsil size is also helpful in predicting surgical success rate (p = 0.041). Furthermore, patients with mild AHI were more likely to be surgical cures. when compared with patients with severe AHI (p = 0.044). CONCLUSION: Patients with larger tonsil size and no tongue base obstruction during DISE may have a higher chance of surgical success with LPMR. The lower AHI may be predictors of surgical cure after LPMR.

Sleep time on back as a predictor of adherence to positive airway pressure therapy.

Upper airway collapse can be effectively dealt with positive airway pressure (PAP), and patient adherence is considered as a major determining factor for success of PAP therapy. This study was performed to determine the potential factors affecting the adherence to PAP in patients with OSA by using polysomnography (PSG) parameters recorded for diagnosis of OSA. The data of 158 patients between December 2018 and July 2021 were collected. They were prescribed with PAP and used the device during the adaptation period for 90 days. They were categorized into adherent and non-adherent group according to the criteria of good adherence as use of PAP ≥ 4 h per night on 70% of nights. Demographic, clinical characteristics, and PSG results were reviewed. Among 158 patients engaged in PAP therapy, 121 patients (76.6%) met the criteria of good adherence. No significant differences were found in good adherence rate regarding demographic and clinical characteristics. None of the polysomnographic factors showed significant differences between adherent and non-adherent groups. However, the percentage of sleep time on back in the adherent group was significantly higher than non-adherent group (p = 0.041). The cut-off value was determined to be 41.45% (95% confidence interval 0.43 to 0.79) by receiver operating characteristic curve analysis and the odds ratio was calculated as 2.97. Only the percentage of sleep time on back appeared to be polysomnographic predictor for identifying good adherence to PAP therapy in OSA patients. However, the conclusions may be limited in generalization due to the small sample size.

Ambient particulate matter exposure and urologic cancer: a longitudinal nationwide cohort study.

Increased particulate matter (PM) exposure is positively associated with increased incidence and mortality of many human malignancies. However, evidence of urologic cancer is limited. We aimed to evaluate the association between PM10 exposure and the relative risk of urologic cancer. This nationwide longitudinal cohort study included 231,997 participants who underwent a baseline health examination in 2008 from the National Health Information Database of Korea. The primary endpoint was newly diagnosed urologic cancer according to PM10 exposure. Of the total 231,99 participants, 50,677 developed urologic cancer during a median follow-up of 6.7 years. After controlling for confounding factors, participants in the high PM10 exposure group had a higher risk of kidney cancer (hazard ratio [HR] 1.111, 95% confidence interval [CI] 1.068-1.157) and prostate cancer (HR 1.083, 95% CI 1.058-1.109) than those in the low PM10 exposure group. However, in urothelial cell carcinoma, there was no significant increase in the HRs in the high PM10 exposure group. For kidney cancer, participants with the following characteristics were more susceptible: age < 65 years, female sex, decreased regular physical activity, current smoking, no diabetes, no hypertension, normal body mass index, and desirable total cholesterol level. For prostate cancer, participants with the following characteristics were more susceptible: decreased regular physical activity, current smoking, and no hypertension. High PM10 exposure is associated with an increased risk of overall urologic cancers, especially kidney and prostate cancer.

Factors Influencing the Acceptance of Distributed Research Networks in Korea: Data Accessibility and Data Security Risk.

OBJECTIVES: Distributed research networks (DRNs) facilitate multicenter research by enabling the use of multicenter data; therefore, they are increasingly utilized in healthcare fields. Despite the numerous advantages of DRNs, it is crucial to understand researchers' acceptance of these networks to ensure their effective application in multicenter research. In this study, we sought to identify the factors influencing the adoption of DRNs among researchers in Korea. METHODS: We used snowball sampling to collect data from 149 researchers between July 7 and August 28, 2020. Five factors were used to formulate the hypotheses and research model: data accessibility, usefulness, ease of use, data security risk, and intention to use DRNs. We applied a structural equation model to identify relationships within the research model. RESULTS: Data accessibility and data security were critical to the acceptance and use of DRNs. The usefulness of DRNs partially mediated the relationship between data accessibility and the intention to use DRNs. Interestingly, ease of use did not influence the intention to use DRNs, but it was affected by data accessibility. Furthermore, ease of use impacted the perceived usefulness of DRNs. CONCLUSIONS: This study highlighted major factors that can promote the broader adoption and utilization of DRNs. Consequently, these findings can contribute to the expansion of active multicenter research using DRNs in the field of healthcare research.

Exploring the DNA methylome of Korean patients with colorectal cancer consolidates the clinical implications of cancer-associated methylation markers.

Aberrant DNA methylation plays a critical role in the development and progression of colorectal cancer (CRC), which has high incidence and mortality rates in Korea. A variety of CRCassociated methylation markers for cancer diagnosis and prognosis have been developed; however, those markers have not been validated for Korean patients because of the lack of comprehensive clinical and methylome data. Here, we obtained reliable methylation profiles of 228 tumor, 103 adjacent normal, and two unmatched normal colon tissues from Korean patients with CRC using an Illumina Infinium EPIC array, and the data were corrected for biological and experiment biases. A comparative methylome analysis confirmed the previous findings that hypermethylated positions in the tumor were highly enriched in CpG island and promoter, 5' untranslated, and first exon regions, whereas hypomethylated positions were enriched in open-sea regions that are considerably distant from CpG islands. After applying a CpG island methylator phenotype (CIMP) to the methylome data of tumor samples to stratify the CRC patients, we consolidated the previously established clinicopathological findings that the tumors with high CIMP signatures were significantly enriched in the right colon and showed a higher prevalence of microsatellite instability status and MLH1 methylation than the tumors with low or non-CIMP signatures. Therefore, our methylome analysis and dataset can provide insights into the application of the CRC-associated methylation markers for Korean patients, regarding cancer diagnosis and prognosis.

Integrative single-cell transcriptome analysis provides new insights into post-COVID-19 pulmonary fibrosis and potential therapeutic targets.

The global COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 virus has resulted in a significant number of patients experiencing persistent symptoms, including post-COVID pulmonary fibrosis (PCPF). This study aimed to identify novel therapeutic targets for PCPF using single-cell RNA-sequencing data from lung tissues of COVID-19 patients, idiopathic pulmonary fibrosis (IPF) patients, and a rat transforming growth factor beta-1-induced fibrosis model treated with antifibrotic drugs. Patients with COVID-19 had lower alveolar macrophage counts than healthy controls, whereas patients with COVID-19 and IPF presented with elevated monocyte-derived macrophage counts. A comparative transcriptome analysis showed that macrophages play a crucial role in IPF and COVID-19 development and progression, and fibrosis- and inflammation-associated genes were upregulated in both conditions. Functional enrichment analysis revealed the upregulation of inflammation and proteolysis and the downregulation of ribosome biogenesis. Cholesterol efflux and glycolysis were augmented in both macrophage types. The study suggests that antifibrotic drugs may reverse critical lung fibrosis mediators in COVID-19. The results help clarify the molecular mechanisms underlying pulmonary fibrosis in patients with severe COVID-19 and IPF and highlight the potential efficacy of antifibrotic drugs in COVID-19 therapy. Collectively, all these findings may have significant implications for the development of new treatment strategies for PCPF.

DRG2 in macrophages is crucial for initial inflammatory response and protection against Listeria monocytogenes infection.

Innate immune response is critical for the control of Listeria monocytogenes infection. Here, we identified developmentally regulated GTP-binding protein 2 (DRG2) in macrophages as a major regulator of the innate immune response against L. monocytogenes infection. Both whole-body DRG2 knockout (KO) mice and macrophage-specific DRG2 KO mice had low levels of IL-6 during early infection and increased susceptibility to L. monocytogenes infection. Following an initial impaired inflammatory response of macrophages upon i.p. L. monocytogenes infection, DRG2-/- mice showed delayed recruitment of neutrophils and monocytes into the peritoneal cavity, which led to elevated bacterial burden, inflammatory cytokine production at a late infection time point, and liver micro-abscesses. DRG2 deficiency decreased the transcriptional activity of NF-κB and impaired the inflammatory response of both bone marrow-derived and peritoneal macrophages upon L. monocytogenes stimulation. Our findings reveal that DRG2 in macrophages is critical for the initial inflammatory response and protection against L. monocytogenes infection.

Safety and efficacy of remimazolam for general anesthesia in elderly patients undergoing laparoscopic cholecystectomy: a randomized controlled trial.

Introduction: There is insufficient evidence regarding the efficacy and safety of remimazolam in elderly patients. Therefore, this study evaluated the differences in the anesthesia characteristics and perioperative hemodynamic profiles of elderly patients receiving total intravenous anesthesia with remimazolam or propofol. Methods: Eighty-four patients aged >65 years with an American Society of Anesthesiologists physical status of I-III were randomly assigned to Group R (receiving remimazolam, n = 42) or Group P (receiving propofol, n = 42). In Group R, remimazolam was initiated at a rate of 6 mg/kg/h until loss of consciousness (LOC) was achieved and maintained at 1 mg/kg/h subsequently. In Group P, 1.0-1.5 mg/kg of propofol was injected for 1 min and maintained at 100 µg/kg/min subsequently. The maintenance infusion rate was adjusted to maintain an appropriate depth of anesthesia until the end of the surgery. The primary outcome was the time to LOC. The depth of anesthesia scores and hemodynamic profiles were recorded perioperatively. Results: The time to LOC was significantly longer in Group R (120 s) than in Group P (60 s) (p < 0.001). The time to eye-opening (Group R, 10 min; Group P, 10 min; p = 0.056), the incidence of maintenance of hemodynamic changes within 20% of the peri-anesthetic values, and treatments for hemodynamic instability did not differ significantly between the groups. The depth of anesthesia scores did not differ significantly between the groups; however, the scores were higher in Group R than those in Group P before endotracheal intubation. The hemodynamic parameters did not differ significantly at any time point. The time to extubation was longer in Group R (12 min) than that in Group P (10 min) (p = 0.007). Similarly, the time to discharge from the operating room was significantly longer in Group R (15 min) compared to Group P (12 min) (p = 0.018). Conclusion: Remimazolam does not exhibit a comparable effect to propofol in terms of anesthesia induction and recovery. However, it demonstrates a similar effect to propofol regarding intraoperative anesthesia depth and hemodynamic profile in elderly patients undergoing remifentanil-based total intravenous anesthesia.