Background: Residents and nurses who activate rapid response teams (RRTs) are well positioned to offer insights on its effectiveness. Here, we assess such evaluation of RRTs and identify barriers to activation in a 1,400-bed teaching hospital. Methods: We conducted a 24-item Likert-scale survey from January to May 2017 among residents and ward nurses with RRT experience. Factor analysis was used to identify the barriers. Results: This study comprised 305 nurses and 53 residents, most of whom were satisfied with their RRT experiences. Factor analysis showed that lack of awareness of activation criteria was a major barrier, with only 21.4% and 22.2% participants, respectively, confident about their knowledge of activation protocols. Of the survey respondents, 85.7% reported first contacting the doctor before activating the RRT. Despite the protocol, 66.7% first discussed the decision with other staff, and 71.5% called the RRT when the patient’s condition worsened despite management. Conclusions Nurses and residents value RRTs but face barriers in initiation, primarily due to a lack of confidence in applying the activation criteria. Many prefer to consult a doctor or manage the patient before calling the RRT.

Background: Primary cutaneous CD30+ lymphoproliferative disorders (pcCD30-LPDs) are a diseases with various clinical and prognostic characteristics. Objective: Increasing our knowledge of the clinical characteristics of pcCD30-LPDs and identifying potential prognostic variables in an Asian population. Methods: Clinicopathological features and survival data of pcCD30-LPD cases obtained from 22 hospitals in South Korea were examined. Results: A total of 413 cases of pcCD30-LPDs (lymphomatoid papulosis [LYP], n=237; primary cutaneous anaplastic large cell lymphoma [C-ALCL], n=176) were included. Ninety percent of LYP patients and roughly 50% of C-ALCL patients presented with multiple skin lesions. Both LYP and C-ALCL affected the lower limbs most frequently. Multiplicity and advanced T stage of LYP lesions were associated with a chronic course longer than 6 months. Clinical morphology with patch lesions and elevated serum lactate dehydrogenase were significantly associated with LPDs during follow-up in LYP patients. Extracutaneous involvement of C-ALCL occurred in 13.2% of patients. Lesions larger than 5 cm and increased serum lactate dehydrogenase were associated with a poor prognosis in C-ALCL. The survival of patients with C-ALCL was unaffected by the anatomical locations of skin lesions or other pathological factors. Conclusion The multiplicity or size of skin lesions was associated with a chronic course of LYP and survival among patients with C-ALCL.

Background: The exposome encompasses all factors people encounter through life, with the skin constantly exposed. While particulate matter (PM) and sleep deprivation are known to contribute to barrier dysfunction, their combined effects remain unclear. Objective: To evaluate the independent and combined effects of PM exposure and short-term sleep deprivation on skin barrier function. Methods: Forty healthy Korean women (aged 24–58 years) were enrolled in this study. Forearms were divided into 4 sites: control, PM exposure, sleep deprivation, and PM plus sleep deprivation. Parameters such as trans-epidermal water loss (TEWL), hydration, elasticity, roughness, and redness were measured at baseline and post-exposure. RNA sequencing and reverse transcription-polymerase chain reaction were conducted on tape-stripped skin samples. Results: PM exposure significantly increased TEWL (+25.59%, p<0.01), roughness (+21.9%, p<0.01), and redness (+13.7%, p<0.0001) while reducing elasticity (−3.98%, p<0.01). Sleep deprivation modestly reduced elasticity (−1.39%, p<0.05) without affecting other parameters.Combined PM and sleep deprivation did not further exacerbate barrier dysfunction compared to PM alone. RNA sequencing revealed reduced FLG and LORICRIN expression and upregulated endoplasmic reticulum (ER) stress markers (HSP90B1, CANX) in both PM and sleep deprivation conditions. Conclusion PM exposure impaired skin barrier function, while short-term sleep deprivation alone did not significantly affect the barrier, either independently or in combination with PM.However, it was observed that the sleep deprivation-only, while not directly causing barrier damage, induced changes in ER stress-related gene expression in tape-stripped skin samples, like the PM exposure-only. This suggests that such signaling pathways could potentially exacerbate skin barrier deterioration.

Background: MUTYH-associated polyposis is an autosomal recessive disorder associated with an increased lifetime risk of colorectal cancer and a moderately increased risk of ovarian, bladder, breast, and endometrial cancers. We analyzed the carrier frequency and estimated the incidence of MUTYH-associated polyposis in East Asian and Korean populations, for which limited data were previously available. Methods: We examined 125,748 exomes from the gnomAD database, including 9,197 East Asians, and additional data from 5,305 individuals in the Korean Variant Archive and 1,722 in the Korean Reference Genome Database. All MUTYH variants were interpreted according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines and the Sequence Variant Interpretation guidelines from ClinGen. Results: The global carrier frequency of MUTYH-associated polyposis was 1.29%, with Europeans (non-Finnish) having the highest frequency of 1.86% and Ashkenazi Jews the lowest at 0.06%. East Asians and Koreans had a carrier frequency of 0.35% and 0.37% and an estimated incidence of 1 in 330,409 and 1 in 293,304 in Koreans, respectively, which were substantially lower than the global average of 1 in 24,160 and the European (nonFinnish) incidence of 1 in 11,520. Conclusions This was the first study to investigate the frequency of carriers of MUTYH-associated polyposis in East Asians, including specific subgroups, utilizing gnomAD and a Korean genome database. Our data provide valuable reference information for future investigations of MUTYH-associated polyposis to understand the genetic diversity and specific variants associated with this condition in East Asian populations.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and lacks clinical biomarkers. Exosomes are extracellular vesicles that facilitate cell–cell communication by distributing macromolecules, such as small RNAs (smRNAs). We assessed the potential of exosome-derived small RNAs (Ex-smRNAs) as PDAC biomarkers. Methods: Peripheral blood was collected from 51 patients with PDAC and 15 control individuals. Exosomes were isolated using an aqueous two-phase system. Ex-smRNAs were analyzed using smRNA sequencing. smRNA-mediated target gene regulation was verified via The Cancer Genome Atlas analysis and in vitro transfection and wound-healing assays using PDAC organoids. Results: The total Ex-smRNA count was substantially reduced in patients with PDAC compared with that in control individuals. The levels of microRNAs (miRNAs) miR-125a-5p, miR-30e-5p, miR-16-2-3p, miR-98-5p, and the let-7 family were significantly suppressed, whereas that of miR-6731-5p was significantly elevated. Let-7c-5p and miR-98-5p were found to interact with the long non-coding RNA OLMALINC to regulate their common target genes, BACH1 and CCND1, thus controlling PDAC proliferation and migration. The expressions of CARS1-AS1 and miR-142-5p were upregulated in treatment-responsive patients.Multivariable Cox regression analyses, adjusting for potential prognostic factors such as sex, Eastern Cooperative Oncology Group performance status, and tumor size and stage, revealed that CARS1-AS1 (adjusted hazard ratio [HR] 0.33; 95% confidence interval [CI], 0.15–0.73; P = 0.0061) and miR-142-5p (adjusted HR 0.79; 95% CI, 0.61–1.01; P = 0.0581) were associated with improved overall survival. Conclusions We identified potential Ex-smRNA biomarkers involved in PDAC progression and prognosis that reflect key molecular alterations in PDAC and may serve as clinically relevant biomarkers for disease monitoring.

Background: Citrin deficiency is an autosomal recessive disorder caused by pathogenic variants in SLC25A13, presenting with various age-dependent clinical phenotypes and a broad spectrum of severity. However, few studies have examined the frequency and prevalence of citrin deficiency. We aimed to analyze the carrier frequency and disease prevalence in East Asian populations and Koreans. Methods: We comprehensively reviewed the literature and conducted a cross-sectional study to analyze genomic databases, including the Genome Aggregation Database (gnomAD), Korean Variant Archive (KOVA), and Tohoku Medical Megabank Organization (ToMMo), to identify pathogenic SLC25A13 variants in East Asian populations. A founder 3-kilobase (kb) insertion in intron 16 of SLC25A13 was investigated using whole-genome sequencing data from 681 Koreans with the Linux grep command. Results: Twenty-three pathogenic SLC25A13 variants were identified, with c.852_855del being the most common. Analysis of data from 17,501 East Asian individuals in the gnomAD and ToMMo databases revealed a carrier frequency of 1 in 62 people. Analysis of data from 7,214 individuals in the gnomAD and KOVA databases revealed a carrier frequency of 1 in 86, corresponding to an estimated disease prevalence of 1 in 29,502.c.1177+1G > A was identified as the most prevalent pathogenic variant in Koreans. The 3 kb insertion in intron 16 was detected in three out of 681 individuals, indicating a carrier frequency of 1 in 228. Conclusions The high carrier frequency of citrin deficiency in East Asians highlights the need for enhanced genetic screening and counseling, particularly in Korea, providing a valuable reference for future studies on genetic diversity and pathogenic variants in this population.

Background: The Clauss assay is widely used to quantify blood fibrinogen levels in clinical laboratories. However, by relying on thrombin as the main reagent, the Clauss assay is susceptible to interference from thrombin inhibitors, such as heparin or direct thrombin inhibitors. Here, we developed an innovative fibrinogen assay utilizing both recombinant batroxobin (rBat) and carboxymethyl chitosan (CMCS). Methods: Various biopolymers were tested to identify a suitable candidate that could enhance rBat-induced fibrin clot formation. Chromogenic substrate hydrolysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that CMCS potentiated rBat activity. Consequently, we formulated a novel fibrinogen assay reagent, ANYFIB.C, comprising rBat and CMCS. We compared ANYFIB.C fibrinogen with an established reagent (HemosIL fibrinogen-C) with 96 clinical samples using an ACL-TOP 700 coagulation analyzer. We also evaluated the interfering effects of thrombin inhibitors on fibrinogen measurements. Results: CMCS significantly enhanced the enzymatic activity of rBat and dose-dependently reduced plasma clotting times. ANYFIB.C fibrinogen levels were comparable with those of HemosIL fibrinogen-C, with the 95% confidence intervals of the Passing–Bablok regres-sion intercept and slope being −7.4797 to 6.0185 and 0.9581 to 1.0116, respectively. Nosignificant interference was observed with heparin concentrations up to 10 U/mL or dabigatran concentrations up to 600 µg/L in the ANYFIB.C fibrinogen assays. In contrast, the HemosIL fibrinogen-C reagent demonstrated inhibitory interference at dabigatran concentrations as low as 150 µg/L. Conclusions Our results suggest that ANYFIB.C (a mixture of CMCS and rBat) can be used to measure blood fibrinogen levels effectively and protect from thrombin inhibitor interference.

Background: Because of the low prevalence of inherited retinal diseases, reports on the distribution of retinitis pigmentosa (RP)-related genes in Korean patients are scarce. The aim of this study was to determine the mutation spectrum and allele frequency and observe the final diagnoses in a Korean cohort clinically diagnosed with RP. Methods: We used whole-exome sequencing (WES) to analyze a Korean cohort of 100 unrelated patients clinically diagnosed with RP. The possible pathogenicity of each variant was assessed based on the guidelines of the American College of Medical Genetics and Genomics and Association for Molecular Pathology, in-silico prediction tools, known clinical phenotypes, and inheritance patterns. Results: Definite causative genes were detected in 60/100 patients (60.0%). Of these 60 cases, USH2A was the most common causative gene (14/60, 23.3%), followed by EYS (13/60, 21.7%) and RP1 (6/60, 10.0%). The clinical diagnosis was redefined in 9 of the 60 probands (15.0%) with causative genes after WES. Five of the 60 patients (8.3%) carried a causative variant in CHM, and the clinical diagnosis was redefined as choroideremia. Leber congenital amaurosis was diagnosed in 2/60 probands (3.3%), and RDH12 and RPGRIP1 were the causative genes in each patient. One patient (1/60, 1.7%) was diagnosed with Bietti’s crystalline dystrophy, with CYP4V2 identified as the causative gene. In another patient (1/60, 1.7%), ABCA4 variants were detected with clinical findings suggestive of cone-rod dystrophy. Conclusion This study reports the mutational spectrum of a cohort of Korean patients with a clinical diagnosis of RP who were referred for genetic testing. This study adds valuable data regarding the frequency of genes as well as their relation to the age of symptom onset and relation to other inherited retinal degenerations.

Background: With growing elderly populations, management of patients with acute stroke is increasingly important. In South Korea, the Acute Stroke Quality Assessment Program (ASQAP) has contributed to improving the quality of stroke care and practice behavior in healthcare institutions. While the mortality of hemorrhagic stroke remains high, there are only a few assessment indices associated with hemorrhagic stroke. Considering the need to develop assessment indices to improve the actual quality of care in the field of acute stroke treatment, this study aims to investigate the current status of human resources and practices related to the treatment of patients with acute stroke through a nationwide survey. Methods: For the healthcare institutions included in the Ninth ASQAP of the Health Insurance Review and Assessment Service (HIRA), data from January 2022 to December 2022 were collected through a survey on the current status and practice of healthcare providers related to the treatment of patients with acute stroke. The questionnaire consisted of 19 items, including six items on healthcare providers involved in stroke care and 10 items on the care of patients with acute stroke. Results: In the treatment of patients with hemorrhagic stroke among patients with acute stroke, neurosurgeons were the most common providers. The contribution of neurosurgeons in the treatment of ischemic stroke has also been found to be equivalent to that of neurologists. However, a number of institutions were found to be devoid of healthcare providers who perform definitive treatments, such as intra-arterial thrombectomy for patients with ischemic stroke or cerebral aneurysm clipping for subarachnoid hemorrhage. The intensity of the workload of healthcare providers involved in the care of patients with acute stroke, especially those involved in definitive treatment, was also found to be quite high. Conclusion Currently, there are almost no assessment indices specific to hemorrhagic stroke in the ASQAP for acute stroke. Furthermore, it does not reflect the reality of the healthcare providers and practices that provide definitive treatment for acute stroke. The findings of this study suggest the need for the development of appropriate assessment indices that reflect the realities of acute stroke care.