Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients. Methods: Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927). Results: The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]). Conclusions In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.

Pancreatic metastasis from papillary thyroid cancer (PTC) is extremely rare; only 18 cases have been reported in the literature. However, several reviews have highlighted similar characteristics between metastatic and primary pancreatic tumors. The patient was a 51-year-old male with a history of total thyroidectomy, modified radical neck dissection, and radioactive iodine ablation for PTC in 2014. Nodules suspected of metastasis were found in both lungs on chest computed tomography (CT). However, after 6 months, a follow-up chest CT showed no increase in size; thus, a follow-up observation was planned. Six years after his initial diagnosis, abdominal CT and pancreas magnetic resonance imaging revealed a 4.7 cm cystic mass with a 2.5 cm enhancing mural nodule in the pancreas tail. We diagnosed the pancreatic lesion as either metastatic cancer or primary pancreas cancer. The patient underwent distal pancreato-splenectomy. After surgery, the pathological report revealed that the mass was metastatic PTC. Pancreatic metastasis from PTC indicates an advanced tumor stage and poor prognosis. However, pancreatectomy can increase the survival rate when the lesion is completely resectable. Therefore, surgical resection should be considered as a treatment for pancreatic metastasis from PTC.

Background: Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells.Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. Methods: Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. Results: In our study, 3,798 eligible patients were included. Mean age of patients was 42.7(19–88) years and mean BMI was 22.5 (16.9–34.1) kg/m2 . The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475–3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367–0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385–2.469). Conclusion Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

Background: Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells.Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. Methods: Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. Results: In our study, 3,798 eligible patients were included. Mean age of patients was 42.7(19–88) years and mean BMI was 22.5 (16.9–34.1) kg/m2 . The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475–3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367–0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385–2.469). Conclusion Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

Background: The current Korean Blood Inventory Monitoring System (BMS) has several drawbacks. It does not provide real-time data and only monitors 211 of the more than 2500 institutes that performed blood transfusions.This survey study investigated the status of BMS use and the preparation status of the data input system of medical institutions to help in the revision of BMS in preparation for the full surveillance of BMS. Methods: A survey questionnaire was given to 200 hospitals participating in the current BMS, along with another set of questionnaires to 150 non-participating hospitals. The questionnaire consisted of the method of data registry to BMS, the current status of electronic medical records (EMR) and order communication system (OCS), perception, and readiness of adaptation of an open application programming interface system (API). Results: Two hundred and one BMS participating hospitals responded to the survey. Approximately 75% entered data with a comma-separated value (CSV) or Excel spreadsheet (xls) files, and approximately half had an in-house developed EMR and OCS. The majority showed enthusiasm for the introduction to an open API. Among the non-participating hospitals, 138 responded. Approximately 70% counted the blood inventory daily, but approximately half did not use electronic methods for this process. The response to the introduction to an open API was positive, but the readiness for a prompt introduction was low at 15.9%. Conclusion These results will help revise the current BMS. On the other hand, full surveillance of BMS is anticipated to be hindered by the ready state of each medical institute. Moreover, the encouragement of participation would require supportive government administrative measures.

Background: The current Korean Blood Inventory Monitoring System (BMS) has several drawbacks. It does not provide real-time data and only monitors 211 of the more than 2500 institutes that performed blood transfusions.This survey study investigated the status of BMS use and the preparation status of the data input system of medical institutions to help in the revision of BMS in preparation for the full surveillance of BMS. Methods: A survey questionnaire was given to 200 hospitals participating in the current BMS, along with another set of questionnaires to 150 non-participating hospitals. The questionnaire consisted of the method of data registry to BMS, the current status of electronic medical records (EMR) and order communication system (OCS), perception, and readiness of adaptation of an open application programming interface system (API). Results: Two hundred and one BMS participating hospitals responded to the survey. Approximately 75% entered data with a comma-separated value (CSV) or Excel spreadsheet (xls) files, and approximately half had an in-house developed EMR and OCS. The majority showed enthusiasm for the introduction to an open API. Among the non-participating hospitals, 138 responded. Approximately 70% counted the blood inventory daily, but approximately half did not use electronic methods for this process. The response to the introduction to an open API was positive, but the readiness for a prompt introduction was low at 15.9%. Conclusion These results will help revise the current BMS. On the other hand, full surveillance of BMS is anticipated to be hindered by the ready state of each medical institute. Moreover, the encouragement of participation would require supportive government administrative measures.

OBJECTIVE: Knowledge regarding the prevalence and distribution of human papillomavirus (HPV) genotyping in healthy women is important in establishing strategies for cervical cancer screening and HPV vaccination. METHODS: A total of 18,170 women who visited a Korean Medical Institute for health check-ups were recruited retrospectively; they underwent HPV genotyping and conventional cervical cytology. An HPV DNA test was performed using the Anyplex™ II HPV 28 detection system (Seegene) or HPV Liquid Bead Microarray (Osang Healthcare). The distribution of HPV genotypes was assessed according to cervical cytology and age. RESULTS: HPV was detected in 3,037 (16.71%) of the 18,170 women enrolled, and 2,268 (12.48%) were positive for high-risk (HR) HPV. In total, HPV 53 (9.69% of all detected HPV viruses) was the most common type; HPV 58 (7.90%) and 52 (7.81%) were also common. HPV 54 (6.99%) was common in low-risk subjects. Overall and in the normal cytology group, the most common HPV genotype was HPV 53, whereas HPV 58 was more common in women who had atypical squamous cells of undetermined significance or low-grade squamous intraepithelial neoplasia cervical cytology. In addition, HPV 16 was the most common type in cases with high-grade squamous intraepithelial neoplasia (HSIL)/atypical squamous cells-cannot exclude HSIL. Among women with normal cytology, 76 of 231 (32.9%) women under 24 years of age were positive for HR HPV, whereas 84 of 852 (9.9%) women aged 55–59 years were positive. CONCLUSION: HPV 53 was the most prevalent genotype in healthy women. Distribution of HPV genotypes varied with cervical cytology and age. Our study provides important baseline data for the recently implemented national HPV vaccination program.
Atypical Squamous Cells of the Cervix ; Cervical Intraepithelial Neoplasia ; Female ; Genotype ; Human papillomavirus 16 ; Human Papillomavirus DNA Tests ; Humans ; Mass Screening ; Papanicolaou Test ; Papillomaviridae ; Prevalence ; Republic of Korea ; Retrospective Studies ; Uterine Cervical Neoplasms ; Vaccination

PURPOSE: Despite new treatment strategies, anemia remains the most prevalent complication in patients with end-stage renal disease (ESRD). We investigated whether 25-hydroxyvitamin D [25(OH)D3] deficiency was associated with anemia in ESRD patients. MATERIALS AND METHODS: We reviewed the medical records of 410 ESRD patients who had undergone renal transplantation (RTx) at Yonsei University Health System and who had 25(OH)D3 levels measured at the time of RTx. Patients were divided into two groups based on baseline 25(OH)D3 concentrations: group 1, 25(OH)D3 levels <10 ng/mL; and group 2, 25(OH)D3 levels ≥10 ng/mL. RESULTS: Using multivariate regression models, 25(OH)D3, age, and erythrocyte-stimulating agent (ESA) dose were found to be significantly associated with hemoglobin (Hb) levels [25(OH)D3: β=0.263, p<0.001; age: β=0.122, p=0.010; ESA dose: β=-0.069, p=0.005]. In addition, logistic regression analysis revealed that patients in group 1 had a significantly higher risk for developing anemia (Hb level <10 g/dL) compared to group 2 patients, even after adjusting for potential risk factors for anemia (odds ratio=3.857; confidence interval=1.091-13.632; p=0.036). CONCLUSION: 25(OH)D3 deficiency was significantly associated with anemia in patients with ESRD. Randomized controlled trials are needed to determine whether vitamin D supplementation can improve anemia in these patients.
Adult ; Aged ; Anemia/blood/*etiology ; Calcifediol ; Cross-Sectional Studies ; Female ; Hemoglobin A/analysis ; Humans ; Kidney Failure, Chronic/*complications ; Kidney Transplantation ; Male ; Middle Aged ; Odds Ratio ; Prevalence ; Regression Analysis ; Risk Factors ; Vitamin D/analogs & derivatives/blood ; Vitamin D Deficiency/blood/*complications

PURPOSE: CKD-516 is a newly developed vascular disrupting agent. This phase I dose-escalation study of CKD-516 was conducted to determine maximum-tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor efficacy in patients with advanced solid tumors. MATERIALS AND METHODS: Patients received CKD-516 intravenously on D1 and D8 every 3 weeks, in a standard 3+3 design. Safety was evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.02 and response was assessed by Response Evaluation Criteria in Solid Tumor ver. 1.1. RESULTS: Twenty-three patients were treated with CKD-516 at seven dosing levels: 1 mg/m2/day (n=3), 2 mg/m2/day (n=3), 3.3 mg/m2/day (n=3), 5 mg/m2/day (n=3), 7 mg/m2/day (n=3), 9 mg/m2/day (n=6), and 12 mg/m2/day (n=2). Mean age was 54 and 56.5% of patients were male. Two dose-limiting toxicities, which were both grade 3 hypertension, were observed in two patients at 12 mg/m2/day. The MTD was determined as 12 mg/m2/day. Most common adverse events were gastrointestinal adverse events (diarrhea, 34.8% [30.4% grade 1/2, 13.0% grade 3]; nausea, 21.7% [all grade 1/2]; vomiting, 21.7% [all grade 1/2]), myalgia (17.4%, all grade 1/2), and abdominal pain (21.7% [21.7% grade 1/2, 4.3% grade 3]). The pharmacokinetic study showed the dose-linearity of all dosing levels. Among 23 patients, six patients (26.1%) showed stable disease. Median progression-free survival was 39 days (95% confidence interval, 37 to 41 days). CONCLUSION: This study demonstrates feasibility of CKD-516, novel vascular disrupting agent, in patients with advanced solid tumor. MTD of CKD-516 was defined as 12 mg/m2/day on D1 and D8 every 3 weeks.
Abdominal Pain ; Disease-Free Survival ; Humans ; Hypertension ; Male ; Myalgia ; National Cancer Institute (U.S.) ; Nausea ; Pharmacokinetics ; Vomiting