Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor β (TGF-β) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-β1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-β pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-β1. Finally, TGF-β1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.

Background: and Purpose Despite the growing demands and challenges faced by patients with amyotrophic lateral sclerosis (ALS) in accessing healthcare services, our understanding of this access remains poor. This study aimed to investigate the healthcare utilization patterns and timing of nutritional and respiration support in patients with ALS in South Korea. Methods: A retrospective cohort study was conducted on patients diagnosed with ALS at a single tertiary hospital between 2016 and 2019 and followed up for 2 years. We evaluated patient characteristics, healthcare utilization (hospital admissions, outpatient visits, and emergency department [ED] visits), and the timing of nutritional and respiration support (noninvasive positive pressure ventilation [NIPPV], tracheostomy, gastrostomy, and nasogastric tube) at 6-month intervals from the first outpatient visit. Results: Among the 143 included patients, 73.4% were admitted at least once, 18.9% experienced unplanned admissions, and 30.1% visited the ED at least once during the study period.The most-common reason for ED visits was neurological symptoms during the first 6 months (59.1%), followed by respiratory symptoms. One fifth of patients who visited the ED underwent tracheostomy (20.9%) or NIPPV (20.9%). Two years after the first visit, 32.2% used a ventilator, and 13.3%, 26.6%, and 6.3% had undergone tracheostomy, gastrostomy, and nasogastric tube insertion, respectively. Conclusions During the 2 years following their first outpatient visit, 20% of patients with ALS experienced unplanned admissions and 30% visited the ED. An active and prompt supportivecare program should be implemented to ensure timely functional support in order to reduce these risks of unplanned admissions.

Background: Clinical ethics support is a form of preventive ethics aimed at mediating ethicsrelated conflicts and managing ethical issues arising in the healthcare setting. However, limited evidence exists regarding the specific ethical issues in clinical practice. This study aimed to explore the diverse ethical issues of cases referred to clinical ethics support after the new legislation on hospice palliative care and end-of-life decision-making was implemented in Korea in 2018. Methods: A retrospective study of cases referred to clinical ethics support at a university hospital in Korea from February 2018 to February 2021 was conducted. The ethical issues at the time of referral were analyzed via qualitative content analysis of the ethics consultationrelated documents. Results: A total of 60 cases of 57 patients were included in the study, of whom 52.6% were men and 56.1% were older than 60 years of age. The majority of cases (80%) comprised patients from the intensive care unit. One-third of the patients were judged as being at the end-of-life stage. The most frequent ethical categories were identified as goals of care/ treatment (78.3%), decision-making (75%), relationship (41.7%), and end-of-life issues (31.7%). More specifically, best interests (71.7%), benefits and burdens/harms (61.7%), refusal (53.3%), and surrogate decision-making (33.3%), followed by withholding or withdrawal (28.3%) were the most frequent ethical issues reported, which became diversified by year. In addition, the ethical issues appeared to differ by age group and judgment of the end-of-life stage. Conclusion The findings of this study expand the current understanding of the diverse ethical issues including decision-making and goals of care/treatment that have been referred to clinical ethics support since the enforcement of the new legislation in Korea. This study suggests a need for further research on the longitudinal exploration of ethical issues and implementation of clinical ethics support in multiple healthcare centers.

Purpose: Social distancing and strict visitor restrictions at hospitals have been national policies since the onset of the coronavirus disease 2019 (COVID-19) pandemic. This has challenged the concept of a good death in comfort with the opportunity to say goodbye.Little is known about how these measures have influenced end-of-life (EOL) care among cancer patients who die in acute care hospitals. This study examined changes in the EOL care of cancer patients during the COVID-19 pandemic. Methods: We retrospectively analyzed 1,456 adult cancer patients who died in 2019 (n=752) and 2020 (n=704) at a tertiary hospital. Data on EOL care—symptom control and comfort care in an imminently dying state, preparation for death, place of death, and aggressive care in the last month— were reviewed. Results: The 1,456 patients had a median age of 67 years, and 62.5% were men. Patients who died in 2020 were more likely to experience agitation or delirium before death (17.2% vs. 10.9%), to use inotropes/vasopressors near death (59.2% vs. 52.3%), and to receive cardiopulmonary resuscitation in their last months (16.3% vs. 12.5%) than those who died in 2019. Additionally, the number of deaths in the emergency room doubled in 2020 compared to 2019 (from 7.1% to 14.1%). Conclusion This study suggests that EOL care for cancer patients who died in a tertiary hospital deteriorated during the COVID-19 pandemic. The implementation of medical care at the EOL and the preferred place of death should be discussed carefully in advance for high-quality EOL care.

The dental high-speed air turbine handpiece operates by rotating the impeller inside the handpiece with compressed air. However, even if the inflow of the powered compressed air is stopped, the impeller rotates due to inertial rotation and creates negative pressure inside the handpiece (backflow suction, commonly known as suck-back). Organic matter and microorganisms in the patient’s oral cavity flow into not only the inside of the handpiece but also other parts connected to the handpiece, causing contamination. In this study, the Zero Suck-back Control Box (ZSCB) device, which was developed to prevent the reverse suction of the handpiece, was applied to five different handpieces and tested. After driving the five different handpieces with or without ZSCB in the air, the presence or absence of suck-back was observed when they were stopped. In addition, when the handpiece was driven using the fluorescent solution to imitate the oral environment, the fluorescent solution flowing into the inside due to the reverse suction phenomenon was observed. It was evident that operating different handpieces with the ZSCB is effective in preventing the inhalation of external contaminants. In two different experiments conducted in this study, the use of ZSCB was shown to be effective in preventing regurgitation in both atmospheric and immersion conditions.

BACKGROUND: The lack of medical personnel has led to the employment of hospitalists in Korean hospitals to provide high-quality medical care. However, whether hospitalists' care can improve patients' outcomes remains unclear. We aimed to analyze the outcome in patients cared for by hospitalists. METHODS: A retrospective review was conducted in 1,015 patients diagnosed with pneumonia or urinary tract infection from March 2017 to July 2018. After excluding 306 patients, 709 in the general ward who were admitted via the emergency department were enrolled, including 169 and 540 who were cared for by hospitalists (HGs) and non-hospitalists (NHGs), respectively. We compared the length of hospital stay (LOS), in-hospital mortality, readmission rate, comorbidity, and disease severity between the two groups. Comorbidities were analyzed using Charlson comorbidity index (CCI). RESULTS: HG LOS (median, interquartile range [IQR], 8 [5–12] days) was lower than NHG LOS (median [IQR], 10 [7–15] days), (P < 0.001). Of the 30 (4.2%) patients who died during their hospital stay, a lower percentage of HG patients (2.4%) than that of NHG patients (4.8%) died, but the difference between the two groups was not significant (P = 0.170). In a subgroup analysis, HG LOS was shorter than NHG LOS (median [IQR], 8 [5–12] vs. 10 [7–16] days, respectively, P < 0.001) with CCI of ≥ 5 points. CONCLUSION: Hospitalist care can improve the LOS of patients, especially those with multiple comorbidities. Further studies are warranted to evaluate the impact of hospitalist care in Korea.
Comorbidity ; Emergency Service, Hospital ; Employment ; Hospital Mortality ; Hospitalists ; Humans ; Korea ; Length of Stay ; Patients' Rooms ; Pneumonia ; Retrospective Studies ; Urinary Tract Infections

Melanin is a pigment produced from tyrosine in melanocytes. Although melanin has a protective role against UVB radiation-induced damage, it is also associated with the development of melanoma and darker skin tone. Tyrosinase is a key enzyme in melanin synthesis, which regulates the rate-limiting step during conversion of tyrosine into DOPA and dopaquinone. To develop effective RNA interference therapeutics, we designed a melanin siRNA pool by applying multiple prediction programs to reduce human tyrosinase levels. First, 272 siRNAs passed the target accessibility evaluation using the RNAxs program. Then we selected 34 siRNA sequences with ΔG ≥−34.6 kcal/mol, i-Score value ≥65, and siRNA scales score ≤30. siRNAs were designed as 19-bp RNA duplexes with an asymmetric 3′ overhang at the 3′ end of the antisense strand. We tested if these siRNAs effectively reduced tyrosinase gene expression using qRT-PCR and found that 17 siRNA sequences were more effective than commercially available siRNA. Three siRNAs further tested showed an effective visual color change in MNT-1 human cells without cytotoxic effects, indicating these sequences are anti-melanogenic. Our study revealed that human tyrosinase siRNAs could be efficiently designed using multiple prediction algorithms.
Dihydroxyphenylalanine ; Gene Expression ; Humans ; Melanins ; Melanocytes ; Melanoma ; Monophenol Monooxygenase* ; RNA ; RNA Interference ; RNA, Small Interfering* ; Skin Pigmentation ; Tyrosine ; Weights and Measures

A 41-year-old female presented with complaint of left hip and buttock pain. Magnetic resonance imaging (MRI) showed multi-focal bone marrow signal intensity changes in left iliac bone, sacrum and femur with an area of necrosis. The primary radiological differential diagnosis was multi-focal tuberculous osteomyelitis. Subsequent pelvic bone biopsy and bone marrow biopsy confirmed the diagnosis of B-cell precursor acute lymphoblastic leukemia with extensive necrosis, which is infrequent in leukemia. When musculoskeletal symptoms precede peripheral blood abnormalities and MRI scanning reveals multi-focal necrotic lesions rather than diffuse signal change, it can be difficult to identify and/or advance leukemia as differential diagnosis.

PURPOSE: In Korea, registration of paraquat-containing herbicides was canceled in November 2011, and sales thereof were completely banned in November 2012. We evaluated the effect of the paraquat ban on the epidemiology and mortality of herbicide-induced poisoning. MATERIALS AND METHODS: This retrospective study analyzed patients treated for herbicide poisoning at 17 emergency departments in South Korea between January 2010 and December 2014. The overall and paraquat mortality rates were compared pre- and post-ban. Factors associated with herbicide mortality were evaluated using logistic analysis. To determine if there were any changes in the mortality rates before and after the paraquat sales ban and the time point of any such significant changes in mortality, R software, version 3.0.3 (package, bcp) was used to perform a Bayesian change point analysis. RESULTS: We enrolled 2257 patients treated for herbicide poisoning (paraquat=46.8%). The overall and paraquat poisoning mortality rates were 40.6% and 73.0%, respectively. The decreased paraquat poisoning mortality rate (before, 75% vs. after, 67%, p=0.014) might be associated with increased intentionality. The multivariable logistic analysis revealed the paraquat ban as an independent predictor that decreased herbicide poisoning mortality (p=0.035). There were two major change points in herbicide mortality rates, approximately 3 months after the initial paraquat ban and 1 year after complete sales ban. CONCLUSION: This study suggests that the paraquat ban decreased intentional herbicide ingestion and contributed to lowering herbicide poisoning-associated mortality. The change point analysis suggests a certain timeframe was required for the manifestation of regulatory measures outcomes.
Commerce ; Eating ; Emergency Service, Hospital ; Epidemiology ; Herbicides ; Humans ; Intention ; Korea ; Mortality* ; Paraquat* ; Poisoning ; Retrospective Studies

This retrospective observational case series study was conducted to describe the clinical feature of acute type II pyrethroid poisoning, and to investigate whether hyperglycemia at presentation can predict the outcome in patients with type II pyrethroid poisoning. This study included 104 type II pyrethroid poisoned patients. The complication rate and mortality rate was 26.9% and 2.9% in type II pyrethroid poisoned patients. The most common complication was respiratory failure followed by acidosis and hypotension. In non-diabetic type II pyrethroid poisoned patients, patients with complications showed a higher frequency of hyperglycemia, abnormalities on the initial X ray, depressed mentality, lower PaCO2 and HCO3- levels, and a higher WBC and AST levels at the time of admission compared to patients without complication. Hyperglycemia was an independent factor for predicting complications in non-diabetic patients. Diabetic patients had a significantly higher incidence of complications than non-diabetic patients. However, there was no significant predictive factor for complications in patients with diabetes mellitus probably because of small number of diabetes mellitus. In contrast to the relatively low toxicity of pyrethroids in mammals, type II pyrethroid poisoning is not a mild disease. Hyperglycemia at presentation may be useful to predict the critical complications in non-diabetic patients.
Acute Disease ; Aged ; Blood Glucose/analysis ; Female ; Humans ; Hyperglycemia/*chemically induced ; Insecticides/*poisoning ; Male ; Middle Aged ; Pyrethrins/*poisoning