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Background@#A total of 8,303 individuals (4.3%) with adverse reactions (n=191,860) after vaccination developed serious conditions or died. Such health developments could cause people not vaccinated yet or waiting for a booster shot to become fearful of the vaccination. @*Methods@#The 3-month (July–September 2021) clinical data of 41 patients from the family medicine department of a single medical center were analyzed retrospectively to determine risk factors and to investigate the clinical course to identify the cause of symptoms in detail. @*Results@#A significant number of older adults aged over 50 years reported experiencing general weakness (P=0.026) but fewer incidences of fever than patients aged 50 years or younger (P=0.011). Eighteen of the 41 patients were requested to visit more than twice or consult a specialist. In 14 patients, the symptoms were explained by other medical causes. @*Conclusion@#The primary physician has a pivotal role in thoroughly evaluating patients who complain of adverseeffects after vaccination, considering the broad multitude of symptoms and medical conditions presented. To thoroughlyevaluate and appropriately advise patients with adverse reactions to their chosen vaccine, taking detailedmedical history and nutritional counseling are required to identify possible underlying causes, resolve symptoms,and educate them on self-care and regarding vaccines.
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The Korean National Health Information Database (NHID) contains big data combining information obtained from the National Health Insurance Service and health examinations. Data are provided in the form of a cohort, and the NHID can be used to conduct longitudinal studies and research on rare diseases. Moreover, data on the cause and date of death are provided by Statistics Korea. Research and publications based on the NHID have increased explosively in the field of endocrine disorders. However, because the data were not collected for research purposes, studies using the NHID have limitations, particularly the need for the operational definition of diseases. In this review, we describe the characteristics of the Korean NHID, operational definitions of endocrine diseases used for research, and an overview of recent studies in endocrinology using the Korean NHID.
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Objectives@#. Obesity, which induces chronic low-grade systemic inflammation in the human body, is a known risk factor for various diseases. Recent studies have shown associations between various otorhinolaryngological diseases and obesity. In particular, inflammatory sinonasal diseases have been found to be strongly associated with obesity-related proinflammatory mediators. Many studies have been conducted to identify therapeutic agents for controlling obesity-related inflammatory airway diseases. Ghrelin, an endogenous peptide from the stomach, has anti-inflammatory and antioxidative effects in a wide range of tissues. However, the effect of ghrelin on the regulation of mucus secretion has not yet been studied in the human nasal mucosa. Therefore, we investigated the effects of ghrelin on lipopolysaccharide (LPS)/leptin-mediated MUC5AC expression and mechanisms involved in human nasal epithelial cells (HNEpCs). @*Methods@#. In HNEpCs, the effect and signaling pathways of ghrelin on LPS/leptin-induced MUC5AC expression were examined using reverse transcription polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassays, Western blotting, and immunofluorescence staining. @*Results@#. Growth hormone secretagogue receptor 1a (GHSR1a) was expressed in the HNEpCs. Ghrelin downregulated LPS/leptin-induced MUC5AC expression, which was abolished by D-Lys-3-growth hormone-releasing peptide 6 (D-Lys-3-GHRP-6). Ghrelin significantly inhibited LPS/leptin-activated extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs). These ghrelin-mediated changes in MAPK activation were abolished by D-Lys-3-GHRP-6. These results showed that ghrelin inhibits LPS/leptin-induced MUC5AC overexpression by modulating the ERK1/2 and p38 MAPK pathways in HNEpCs. @*Conclusion@#. These findings suggest that ghrelin is a potential therapeutic agent for treating obesity-related inflammatory sinonasal diseases.
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Purpose@#Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. @*Materials and Methods@#We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. @*Results@#Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). @*Conclusion@#In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.
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Pancreatic cancer is one of the most fatal cancers with a poor prognosis. Standard chemotherapies have proven largely ineffective because of their toxicity and the development of resistance. Therefore, there is an urgent need to develop novel therapies. In this study, we investigated the antitumor activity of MS-5, a naphthalene derivative, on BxPC-3, a human pancreatic cancer cell line. We observed that MS-5 was cytotoxic to BxPC-3 cells, as well as inhibited the growth of cells in a concentration- and time- dependent manner. Flow cytometry analysis revealed that the percentage of annexin V-positive cells increased after MS-5 treatment. We also observed cleavage of caspases and poly (ADP-ribose) polymerase, and downregulation of Bcl-xL protein. Flow cytometry analysis of intracellular levels of reactive oxygen species (ROS) and mitochondrial superoxide suggested that MS-5 induced the generation of mitochondrial superoxide while lowering the overall intracellular ROS levels. Thus, MS-5 may be potential candidate for pancreatic cancer treatment.
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Allergic rhinitis (AR) is a type of rhinitis accompanied by sensitization to allergens. One of the most clinically important allergens is pollen. Recently, due to climate change and CO 2 air pollution, the flowering period starts earlier and persists longer. In addition, antigenicity due to environmental pollution is also being strengthened. As a result, the sensitization rate to pollen antigens is on the rise. It is known that the prevalence of AR especially caused by pollen is rapidly escalating. Although the causal relationship between pollen exposure and the severity of rhinitis is not precisely established, an association of rhinitis symptoms with the time of pollen scattering exists. In addition, the mixed effect of environmental pollution and pollen may play a role in the development of rhinitis symptoms. Therefore, in order to avoid pollen, it is necessary to constantly improve pollen forecast and minimize the contact with pollen indoors and outdoors. Treatment of AR should be performed according to guidelines. Also, continuous efforts to solve the environmental problems affecting the ecology of pollen are needed.
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Purpose@#We aimed to evaluate the time and cost of developing prompts using large language model (LLM), tailored to extract clinical factors in breast cancer patients and their accuracy. @*Materials and Methods@#We collected data from reports of surgical pathology and ultrasound from breast cancer patients who underwent radiotherapy from 2020 to 2022. We extracted the information using the Generative Pre-trained Transformer (GPT) for Sheets and Docs extension plugin and termed this the “LLM” method. The time and cost of developing the prompts with LLM methods were assessed and compared with those spent on collecting information with “full manual” and “LLM-assisted manual” methods. To assess accuracy, 340 patients were randomly selected, and the extracted information by LLM method were compared with those collected by “full manual” method. @*Results@#Data from 2,931 patients were collected. We developed 12 prompts for Extract function and 12 for Format function to extract and standardize the information. The overall accuracy was 87.7%. For lymphovascular invasion, it was 98.2%. Developing and processing the prompts took 3.5 hours and 15 minutes, respectively. Utilizing the ChatGPT application programming interface cost US $65.8 and when factoring in the estimated wage, the total cost was US $95.4. In an estimated comparison, “LLM-assisted manual” and “LLM” methods were time- and cost-efficient compared to the “full manual” method. @*Conclusion@#Developing and facilitating prompts for LLM to derive clinical factors was efficient to extract crucial information from huge medical records. This study demonstrated the potential of the application of natural language processing using LLM model in breast cancer patients. Prompts from the current study can be re-used for other research to collect clinical information.
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Acute fracture-related infection (FRI) is a common and serious complication of fracture treatment. The clinical symptoms of the patient and the results of the serological, radiological, and histopathologi-cal examinations can be divided into ‘Confirmatory’ criteria and ‘Suggestive’ criteria, allowing for the diagnosis of FRI. Treatment principles can be broadly categorized into (1) the DAIR (Debridement, Antimicrobial therapy, Implant Retention) method and (2) the staged reconstruction method. The choice of treatment depends on factors such as the time elapsed after infection, stability of the internal fixation device, reduction status, host physiology, and virulence of the pathogens. Thorough surgical debridement and irrigation, ensuring stability at the fracture site, reconstruction of bone defects, and appropriate soft tissue coverage, along with antibiotic therapy, are essential to suppress or eradicate the infection. The restoration of limb function should be promoted through proper soft tissue coverage and bone union at the fracture site.
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Background/Aims@#This study aimed to investigate whether pretransplant frailty can predict postoperative morbidity and mortality after liver transplantation (LT) in patients with cirrhosis. @*Methods@#We retrospectively reviewed 242 patients who underwent LT between 2018 and 2020 at a tertiary hospital in Korea. @*Results@#Among them, 189 patients (78.1%) received LT from a living donor. Physical frailty at baseline was assessed by the Short Physical Performance Battery (SPPB), by which patientswere categorized into two groups: frail (SPPB <10) and non-frail (SPPB ≥10). Among the whole cohort (age, 55.0±9.2 years; male, 165 [68.2%]), 182 patients were classified as non-frail and 60 patients were classified as frail. Posttransplant survival was shorter in the frail group than the non-frail group (9.3 months vs 11.6 months). Postoperative intensive care unit stay was longer in the frail group than in the non-frail group (median, 6 days vs 4 days), and the 30-day complication rate was higher in the frail group than in the non-frail group (78.3% vs 59.3%). Frailty was an independent risk factor for posttransplant mortality (adjusted hazard ratio, 2.38; 95% confidence interval, 1.02 to 5.57). In subgroup analysis, frail patients showed lower posttransplant survival regardless of history of hepatocellular carcinoma and donor type. @*Conclusions@#Assessment of pretransplant frailty, as measured by SPPB, provides important prognostic information for clinical outcomes in cirrhotic patients undergoing LT.
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Background/Aims@#The ursodeoxycholic acid (UDCA) response score (URS) was developed to identify poor responders to UDCA before treatment, in order to offer timely and proactive intervention. However, validation of the URS in Asian population is warranted. @*Methods@#A total of 173 Asian patients diagnosed with primary biliary cholangitis (PBC) between 2007 and 2016 at seven academic institutions in Korea who started UDCA treatment were analyzed to validate the performance of URS. UDCA response was defined as an alkaline phosphatase level less than 1.67 times the upper limit of normal after 1-year of UDCA treatment. In addition, prognostic performance of URS for liver-related events, defined as newly developed hepatic decompensation or hepatocellular carcinoma was evaluated. @*Results@#After 1 year of UDCA treatment, 133 patients (76.9%) achieved UDCA response. UDCAresponse rate was 98.7% for those with URS ≥1.41 (n=76) and 58.8% for those with URS <1.41(n=97). The area under the receiver operating characteristic curve of URS in predicting UDCAresponse was 0.84 (95% confidence interval, 0.78 to 0.88). During a median follow-up of 6.5years, liver-related events developed in 18 patients (10.4%). Among 117 patients with PBC stage I-III by histological evaluation, the 5-year liver-related event-free survival rate differed accordingto the URS; 100% for URS ≥1.41 and 86.5% for URS <1.41 (p=0.005). @*Conclusions@#URS demonstrated good performance in predicting a UDCA treatment response in Asian PBC patients. In addition, the risk of liver-related events differed according to the URS for the PBC stage. Thus, URS can be used to predict the response and clinical outcome in patients with PBC.
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Background@#Diabetic kidney disease (DKD) is a risk factor for hospitalization for heart failure (HHF). DKD could be classified into four phenotypes by estimated glomerular filtration rate (eGFR, normal vs. low) and proteinuria (PU, negative vs. positive). Also, the phenotype often changes dynamically. This study examined HHF risk according to the DKD phenotype changes across 2-year assessments. @*Methods@#The study included 1,343,116 patients with type 2 diabetes mellitus (T2DM) from the Korean National Health Insurance Service database after excluding a very high-risk phenotype (eGFR <30 mL/min/1.73 m2) at baseline, who underwent two cycles of medical checkups between 2009 and 2014. From the baseline and 2-year eGFR and PU results, participants were divided into 10 DKD phenotypic change categories. @*Results@#During an average of 6.5 years of follow-up, 7,874 subjects developed HHF. The cumulative incidence of HHF from index date was highest in the eGFRlowPU– phenotype, followed by eGFRnorPU+ and eGFRnorPU–. Changes in DKD phenotype differently affect HHF risk. When the persistent eGFRnorPU– category was the reference, hazard ratios for HHF were 3.10 (95% confidence interval [CI], 2.73 to 3.52) in persistent eGFRnorPU+ and 1.86 (95% CI, 1.73 to 1.99) in persistent eGFRlowPU–. Among altered phenotypes, the category converted to eGFRlowPU+ showed the highest risk. In the normal eGFR category at the second examination, those who converted from PU– to PU+ showed a higher risk of HHF than those who converted from PU+ to PU–. @*Conclusion@#Changes in DKD phenotype, particularly with the presence of PU, are more likely to reflect the risk of HHF, compared with DKD phenotype based on a single time point in patients with T2DM.
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Coronavirus disease 2019 (COVID-19) has multiple negative impacts on the psychiatric health of both those previously infected and not infected with severe acute respiratory syndrome coronavirus 2. Moreover, the negative impacts of COVID-19 are closely associated with geographical region, culture, medical system, and ethnic background. We summarized the evidence of the impact of COVID-19 on the psychiatric health of the Korean population. This narrative review included thirteen research articles, which investigated the impact of COVID-19 on the psychiatric health of Koreans. COVID-19 survivors were reported to have a 2.4 times greater risk of developing psychiatric disorders compared to members of a control group, and anxiety and stress-related disorders were the most common newly diagnosed psychiatric illnesses. Studies also reported that COVID-19 survivors had a 3.33-fold higher prevalence of insomnia, a 2.72-fold higher prevalence of mild cognitive impairment, and a 3.09-fold higher prevalence of dementia compared to the control group. In addition, more than four studies have highlighted that the medical staff members, including nurses and medical students, exhibit a greater negative psychiatric impact of COVID-19. However, none of the articles investigated the biological pathophysiology or mechanism linking COVID-19 and the risk of diverse psychiatric disorders. Moreover, none of the studies were actual prospective studies. Thus, longitudinal studies are needed to more clearly elucidate the effect of COVID-19 on the psychiatric health of the Korean population. Lastly, studies focusing on preventing and treating COVID-19–associated psychiatric problems are needed to provide a benefit in real clinical settings.
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Hepatocellular carcinoma (HCC) is a major cause of death in many countries, including South Korea. To provide useful and sensible advice for clinical management of patients with HCC, the Korean Liver Cancer Association and National Cancer Center Korea Practice Guideline Revision Committee have recently revised the practice guidelines for HCC management. However, there are some differences between practice guidelines and real-life clinical practice. In this review, we describe some key recommendations of the 2022 version of practice guidelines and the real-life clinical situation in South Korea, together with discussion about efforts needed to reduce the difference between guidelines and real-life clinical practice.
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The lack of molecular targets hampers the treatment of triple-negative breast cancer (TNBC). In this study, we determined the cytotoxicity of domperidone, a dopamine D2 receptor (DRD2) antagonist in human TNBC BT-549 and CAL-51 cells. Domperidone inhibited cell growth in a dose- and time-dependent manner. The annexin V/propidium iodide staining showed that domperidone induced apoptosis. The domperidone-induced apoptosis was accompanied by the generation of mitochondrial superoxide and the down-regulation of cyclins and CDKs. The apoptotic effect of domperidone on TNBC cells was prevented by pre-treatment with Mito-TEMPO, a mitochondria-specific antioxidant. The prevention of apoptosis with Mito-TEMPO even at concentrations as low as 100 nM, implies that the generation of mitochondrial ROS mediated the domperidone-induced apoptosis. Immunoblot analysis showed that domperidone-induced apoptosis occurred through the down-regulation of the phosphorylation of JAK2 and STAT3.Moreover, domperidone downregulated the levels of D2-like dopamine receptors including DRD2, regardless of their mRNA levels. Our results support further development of DRD2 antagonists as potential therapeutic strategy treating TNBC.
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Purpose@#This study aimed to investigate the quality of medical care in North Korea using data from North Korean medical research. @*Materials and Methods@#This study included publications containing the keyword “medical” among North Korea’s consecutive publications and selected 415 papers related to heart disease, brain disease, and emergency medical care published at The North Korean Data Center of the Ministry of Unification (https://unibook.unikorea.go.kr). Among 40 research articles, we reviewed ten with representative epidemiological data for cardiovascular treatment, and the latest medical materials were selected and analyzed in detail. @*Results@#Few studies reported the experience of large-scale medical facilities or verified professional performance. Proof of the efficacy of the latest drugs was rare, although the treatment results of interventional therapy and conventional heart surgery were reported. Efforts to improve emergency medical care and innovation of treatment materials using new technologies were being actively studied. However, careful interpretation is required due to the lack of objectivity in research data and some deviation in the composition of patients included in the data. @*Conclusion@#Research of cardiovascular disease in North Korea is conducted at a very limited scope, although treatment results appear to be recorded. The management of cardiovascular disease and the establishment of an emergency medical system warrant global attention and cooperation for further improvement.
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Purpose@#The proper implantable collamer lens (ICL) size affects ICL stability. This study compared device efficacy using white-to-white diameter (WTW) measurements with Orbscan II and IOL Master 700. @*Methods@#We retrospectively studied 90 eyes (45 patients) who underwent toric ICL implantation from January 2019 to February 2020 and were followed for 1 year. The correlation between WTW and anterior chamber depth (ACD) for each measuring device was analyzed. @*Results@#The mean WTW measured by IOL Master 700 and Orbscan II was 12.2 ± 0.3 and 11.6 ± 0.3 mm, respectively, while the mean ACD was 3.28 ± 0.16 and 3.20 ± 0.15 mm. The WTW and ACD measured with IOL Master 700 averaged 0.57 ± 0.12 and 0.08 ± 0.04 mm larger than with Orbscan II. The differences were significant and the regression analysis had high correlations (R2 = 0.875 and R2 = 0.913, respectively; both p < 0.001). @*Conclusions@#WTW measured by the IOL Master 700 can be used as a reference either alone or together with the Orbscan II value to determine ICL size.
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Purpose@#A patient with heterozygous granular corneal dystrophy type 2 (GCD2) underwent phacoemulsification with multifocal intraocular lens insertion, and complained of visual discomfort. We investigated the cause of the discomfort and visual function in this case.Case summary: A 59-year-old woman with granular opacity had slit lamp photographs taken 5 years earlier. Two years later, she underwent phacoemulsification with multifocal intraocular lens (Trifocal AT Lisa tri toric 839MP®, Carl Zeiss Meditec AG, Inc., Jena, Germany) insertion in both eyes at a local clinic. She felt very uncomfortable after the surgery, but the granular and lattice opacities due to GCD2 of her corneas remained stationary for 5 years. Her visual acuity decreased from preoperatively (preoperative: right 0.5, left 0.6; last visit: right 0.3, left 0.4). Her contrast sensitivity was also decreased and the total higher order aberration was increased (right 1.590 μm, left 1.194 μm), compared to normal range. @*Conclusions@#Multifocal intraocular lens insertion in cataract surgery can lead to severe declines in contrast sensitivity and visual acuity and increased higher-order aberration in a GCD2 patient. It may not be advisable to use multifocal intraocular lenses in a GCD2 patient.
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Velopharyngeal insufficiency (VPI) is a phenomenon that can occur due to anatomical or neurological causes of the soft palate. VPI can make the patient difficult to articulate through hypernasality and nasal emission. There has been needed the customized treatment, as VPI can occur for many causes. We present the case of 21-year-old male who took palate plastic surgery 20 years ago for congenital submucosal cleft palate. As he had poor contraction of both lateral side of velopharynx, he was diagnosed with coronal type VPI. Through sphincter pharyngoplasty, he can obtain improvement of articulation accuracy. We would like to share this challenged case.
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Till date, researchers have been developing animal models of Alzheimer’s disease (AD) in various species to understand the pathological characterization and molecular mechanistic pathways associated with this condition in humans to identify potential therapeutic treatments. A widely recognized AD model that mimics the pathology of human AD involves the intracerebroventricular (ICV) injection with streptozotocin (STZ).However, ICV injection as an invasive approach has several limitations related to complicated surgical procedures. Therefore, in the present study, we created a customized stereotaxic frame using the XperCT-guided system for injecting STZ in cynomolgus monkeys, aiming to establish an AD model. The anatomical structures surrounding the cisterna magna (CM) were confirmed using CT/MRI fusion images of monkey brain with XperCT, the c-arm cone beam computed tomography. XperCT was used to determine the appropriate direction in which the needle tip should be inserted within the CM region. Cerebrospinal fluid (CSF) was collected to confirm the accurate target site when STZ was injected into the CM.Cynomolgus monkeys were administered STZ dissolved in artificial CSF once every week for 4 weeks via intracisterna magna (ICM) injection using XperCT-guided stereotactic system. The molecular mechanisms underlying the progression of STZ-induced AD pathology were analyzed two weeks after the final injection. The monkeys subjected to XperCT-based STZ injection via the ICM route showed features of AD pathology, including markedly enhanced neuronal loss, synaptic impairment, and tau phosphorylation in the hippocampus. These findings suggest a new approach for the construction of neurodegenerative disease models and development of therapeutic strategies.
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Among allergic diseases of the Korean pediatric population, allergic rhinitis shows the most rapidly increasing prevalence. Its economic burden is substantial in many Asian countries including South Korea. This investigation of its risk factors aims to reduce the socioeconomic burden by blocking exposure of susceptible individuals to identified causes. However, the risk factors of allergic rhinitis varied considerably depending on the seasons, geographical locations, and populations involved. This review article primarily deals with studies on the risk factors for allergic rhinitis in Korean children that were published during the last 10 years and additionally investigates associated large scale international studies. Our investigation identified several single-nucleotide polymorphisms, inhalant allergens, pollution, tobacco smoke, chemicals, and family affluence as risk factors for allergic rhinitis. In contrast, breastfeeding, older sibling, and microbial diversity were protective factors against allergic rhinitis. This suggests that various genetic and environmental factors might affect the manifestation and presentation of allergic rhinitis complexly. These findings are beneficial as they can provide insights into modifiable risk factors that may hinder the development of allergic rhinitis.