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.

Purpose: Immune checkpoint inhibitors (ICIs) have been shown significant oncological improvements in several cancers.However, ICIs are still in their infancy in hepatocellular carcinoma (HCC). Programmed cell death-ligand 1 (PD-L1), tumorinfiltrating lymphocytes (TILs), and epithelial-mesenchymal transition (EMT) have been known as prognostic factors in HCC. Therefore, we have focused on identifying the molecular mechanisms between each marker to evaluate a predictive role. Methods: Formalin-fixed paraffin-embedded samples were obtained from 166 patients with HCC who underwent surgery. The expression of PD-L1 and TILs and EMT marker were evaluated by immunohistochemical analysis. Results: The multivariate analysis showed that TIL expression (hazard ratio [HR], 0.483; 95% confidence interval [CI], 0.269–0.866; P = 0.015) were independent prognostic factors for overall survival. The prognostic factors for disease-free survival were EMT marker expression (HR, 1.565; 95% CI, 1.019–2.403; P = 0.005). Patients with high expression of TILs had significantly better survival compared to patients with low expression (P = 0.023). Patients who were TIL+/EMT– showed a significantly better prognosis than those who were TIL–/EMT+ (P = 0.049). Conclusion This study demonstrates that PD-L1 expression of TILs is closely associated with EMT marker expression in HCC. Clinical investigations using anti–PD-1/PD-L1 inhibitors in patients with EMT-associated PD-L1 upregulation are warranted.

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.

Purpose: This study examined the effect of lag screw insertion on proximal fragments by separating the right and left sides of intertrochanteric fractures in elderly patients that underwent intramedullary nailing. Materials and Methods: Patients aged ≥65 years that underwent intramedullary nailing after a diag-nosis of intertrochanteric fractures during the period February 2012 to May 2016 were included in the study. The subjects were divided into right and left side groups. The effect of the clockwise rotational force generated when a lag screw was inserted on the proximal fragment was evaluated in both groups. Results: In the right and left groups, most proximal fragments were located in the intramedullary canal after surgery (45 cases [75.0%] and 67 cases [73.6%], respectively). Clockwise rotation due to lag screw placement in the right group occurred in two cases (3.3%), which both showed internal rotation, and in four cases (4.4%) in the left group, all of which showed external rotation. Conclusion After intramedullary nailing of intertrochanteric fractures in elderly patients, proximal fragments were mostly located in the intramedullary cavity. The results obtained confirmed that the clockwise rotational force generated by lag screw insertion did not affect left or right sides.

Purpose: This study examined the effect of lag screw insertion on proximal fragments by separating the right and left sides of intertrochanteric fractures in elderly patients that underwent intramedullary nailing. Materials and Methods: Patients aged ≥65 years that underwent intramedullary nailing after a diag-nosis of intertrochanteric fractures during the period February 2012 to May 2016 were included in the study. The subjects were divided into right and left side groups. The effect of the clockwise rotational force generated when a lag screw was inserted on the proximal fragment was evaluated in both groups. Results: In the right and left groups, most proximal fragments were located in the intramedullary canal after surgery (45 cases [75.0%] and 67 cases [73.6%], respectively). Clockwise rotation due to lag screw placement in the right group occurred in two cases (3.3%), which both showed internal rotation, and in four cases (4.4%) in the left group, all of which showed external rotation. Conclusion After intramedullary nailing of intertrochanteric fractures in elderly patients, proximal fragments were mostly located in the intramedullary cavity. The results obtained confirmed that the clockwise rotational force generated by lag screw insertion did not affect left or right sides.

Purpose: This study examined the effects of the postoperative administration of parathyroid hormone (PTH) on fracture healing in intertrochanteric fractures accompanied by osteoporosis in elderly females. Materials and Methods: Female patients aged 65 years and more who underwent surgery after a diagnosis of intertrochanteric fractures and osteoporosis during the period from July 2013 to December 2017 were included as subjects. The subjects were divided into two groups: PTH-treated group and non-PTH-treated group. The formation time of the first callus, timing of the bridging callus, and time of bony union for both groups were evaluated. Results: In the PTH-treated group, the mean time of the first callus formation, average time of bridging callus, and the average time of bony union were 32, 58, 83 days, respectively, which were significantly shorter than that of the untreated group. Conclusion PTH, a treatment for osteoporosis, promotes callus formation and the healing process. Therefore it will be helpful in intertrochanteric fractures accompanied by osteoporosis in elderly females.

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

No abstract available.
Fingers*

BACKGROUND/AIMS: Because there is a lack of effective biomarkers, we aimed to discover proteomic candidate markers for hepatocellular carcinoma (HCC) in cirrhotic patients at the highest-risk of HCC, and to validate the markers. METHODS: We collected tumor tissue from 5 cirrhotics with HCC, and from 5 cirrhotics without HCC, who underwent liver resection or transplantation. These tissue samples were analyzed by 2-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and potential markers were validated at the transcriptional and translational levels. We also performed western blot assays using other blood samples from 10 cirrhotics with HCC and 10 without HCC. RESULTS: Among the 66 distinguishable spots on 2-D gel images, we identified 15 proteins overexpressed more than 1.5 fold in terms of volume ratio in the tumors. Ten of the over-expressed proteins were identified by MALDI-TOF MS; of those, only methionine adenosyltransferase 1 (MAT1), a protein specific for liver, and acyl-CoA dehydrogenase were significantly up-regulated in tumors in further immunoblotting analyses (Ps<0.05). There was no between-pair difference in MAT1 mRNA measured by real-time polymerase chain reaction (P=0.96). However, in western blots of serum samples, distinct MAT1 bands were observed in all 10 HCC patients, but in only 2 of the non-HCC patients. CONCLUSIONS: MAT1 is a potential marker for surveillance in cirrhotic patients with and without prior HCC.
Acyl-CoA Dehydrogenase ; Biomarkers ; Blotting, Western ; Carcinoma, Hepatocellular ; Humans ; Immunoblotting ; Liver ; Liver Cirrhosis ; Mass Spectrometry ; Methionine Adenosyltransferase ; Methionine ; Proteomics ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Two-Dimensional Difference Gel Electrophoresis