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.

Primary pneumatization of the frontal bone occurs in the first year of life, but further pneumatization continues until 18 years of age. Elongation of the ethmoidal infundibulum and frontal recess, or upwards migration of the anterior ethmoidal cells has been proposed as a mechanism of frontal sinus development. The frontal sinus drainage pathway is displaced in the anterior or posterior direction depending on the pneumatization pattern of the frontoethmoidal cells. Also, frontal sinuses can be connected to the infundibulum or directly to the middle meatus depending on the superior attachment pattern of the uncinate process. Bilateral frontal sinuses are separated by their bony septum, and thus have their own drainage pathways. Contrary to this general rule, we experienced two cases of frontal sinuses that were connected to each other, showing a single drainage pathway from both frontal sinuses. We report these two cases along with a literature review.

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.

Extra-pulmonary tuberculosis usually progresses as a secondary infection from pulmonary tuberculosis, and tuberculosis of the head and neck region. Tuberculosis of ocular and periocular areas, however, is a rare disease. Among ocular tuberculosis involving the adnexal structures, a few lacrimal sac tuberculosis has been reported. We recently experienced a case of lacrimal sac tuberculosis presenting as epiphora. Examination revealed bilateral nasolacrimal duct obstruction and the patient underwent endoscopic endonasal dacryocystorhinostomy. During the operation, a biopsy taken from the unhealthy looking lacrimal sac filled with caseous necrotic tissue was suggestive of tuberculosis. Histopathological features and further systemic evaluation confirmed tuberculosis. She was treated medically with anti-tubercular agents. The new opening of the lacrimal sac was patent and epiphora was resolved successfully at a year follow up. This report highlights the requirement of high suspicion of tuberculosis, even in the nasolacrimal drainage system.

Purpose: We sought to establish normative ranges of the ganglion cell-inner plexiform layer (GCIPL) thickness using spectral-domain optical coherence tomography in Korean elderly individuals and to identify factors that influence GCIPL thickness. Methods:  We conducted a retrospective, observational study of 114 healthy subjects (75 years old or older) who underwent comprehensive ophthalmic examinations at a single institution. GCIPL thickness was measured with the Cirrus spectral-domain optical coherence tomography system and automatic segmentation. Subjects were divided into two age groups: those younger than 80 years and those 80 years or older, respectively. A cross-sectional analysis was adopted to evaluate associations of GCIPL thickness with sex, age, intraocular pressure, optic disc rim area, axial length, spherical equivalent (SE) refractive errors, astigmatism, and body mass index. Results: The average and minimum GCIPL thicknesses were 80.3 ± 5.6 µm and 76.3 ± 5.9 µm, respectively. The GCIPL thickness was significantly lower in the older group than in the younger group in the inferior, inferonasal, and inferotemporal segments (all p < 0.01). A thinner average GCIPL thickness was strongly associated with increasing age (β = -2.87, p = 0.021) and thinner circumpapillary retinal nerve fiber layer thickness (β = 2.87, p < 0.001) in all segments. Conclusions GCIPL thickness decreased with age globally and in all segments, even after 75 years of age. Thinner GCIPL was associated with older age and thinner circumpapillary retinal nerve fiber layer. Age-related changes should be considered when using GCIPL thickness to assess glaucoma and other optic neuropathies characterized by retinal ganglion cell loss.

Objective: This study aimed to investigate the clinicopathologic risk factors for type-specific persistence of high-risk human papillomavirus (hrHPV) and residual/recurrent cervical intraepithelial neoplasia (CIN) after surgical treatment. Methods: Patients with CIN-2/3 who underwent conization or loop electrosurgical excision procedure (LEEP) at Korea University Hospital were enrolled. All patients underwent hrHPV testing and genotyping before conization or LEEP followed by both hrHPV genotyping and cytology. The significance of associations between patient characteristics and persistence of infection were assessed by multivariate logistic regression analyses. Results: Among 398 women with pathologically confirmed CIN-2/3, 154 (38.7%) patients showed hrHPV persistence after surgical treatment. In multivariate analysis, high preoperative hrHPV load (P<0.05; odds ratio [OR], 2.063), presence of CIN-2 at treatment (P<0.01; OR, 2.732), and multiple hrHPV infections (P<0.001; OR, 4.752) were associated with hrHPV persistence. HPV 53 was the most likely to persist after treatment (24/43, 55.8%). The risk of residual/recurrent CIN-2/3 was higher in persistent infection with HPV 16 than other types (P<0.05). Menopause (P<0.001; OR, 3.969), preoperative and postoperative hrHPV load (P<0.05; OR, 2.430; P<0.05; OR, 5.351), and infection with multiple hrHPV types (P<0.05; OR, 2.345) were significantly related to residual/recurrent CIN following surgical treatment. Conclusion HPV load before treatment and infection with multiple hrHPV types were predictors of postoperative hrHPV persistence. HPV 53 was the type most likely to persist, but HPV 16 was the type that was most closely associated with residual/recurrent CIN-2/3.

Objective: This study aimed to investigate the clinicopathologic risk factors for type-specific persistence of high-risk human papillomavirus (hrHPV) and residual/recurrent cervical intraepithelial neoplasia (CIN) after surgical treatment. Methods: Patients with CIN-2/3 who underwent conization or loop electrosurgical excision procedure (LEEP) at Korea University Hospital were enrolled. All patients underwent hrHPV testing and genotyping before conization or LEEP followed by both hrHPV genotyping and cytology. The significance of associations between patient characteristics and persistence of infection were assessed by multivariate logistic regression analyses. Results: Among 398 women with pathologically confirmed CIN-2/3, 154 (38.7%) patients showed hrHPV persistence after surgical treatment. In multivariate analysis, high preoperative hrHPV load (P<0.05; odds ratio [OR], 2.063), presence of CIN-2 at treatment (P<0.01; OR, 2.732), and multiple hrHPV infections (P<0.001; OR, 4.752) were associated with hrHPV persistence. HPV 53 was the most likely to persist after treatment (24/43, 55.8%). The risk of residual/recurrent CIN-2/3 was higher in persistent infection with HPV 16 than other types (P<0.05). Menopause (P<0.001; OR, 3.969), preoperative and postoperative hrHPV load (P<0.05; OR, 2.430; P<0.05; OR, 5.351), and infection with multiple hrHPV types (P<0.05; OR, 2.345) were significantly related to residual/recurrent CIN following surgical treatment. Conclusion HPV load before treatment and infection with multiple hrHPV types were predictors of postoperative hrHPV persistence. HPV 53 was the type most likely to persist, but HPV 16 was the type that was most closely associated with residual/recurrent CIN-2/3.

Acute isolated sphenoid sinusitis is a rare disease, and accounts for less than 3% of all sinusitis, especially in young children. Delayed diagnosis or misdiagnosis can occur frequently due to atypical clinical presentations. This can lead to serious complications because of the involvement of anatomically related intracranial structures. Therefore, nasal endoscopy, computed tomography (CT), and magnetic resonance imaging (MRI) are important diagnostic tools to confirm the diagnosis. We report two cases of a previously healthy 6-year-old girl and a 13-year-old boy, whose chief complaints were uncontrolled headache and high fever over 38°C. Physical examination and initial laboratory test results of blood, urine, and cerebrospinal fluid were normal. The diagnosis was made after a brain MRI revealed isolated sphenoid sinusitis. The girl was treated with third generation cephalosporins intravenously. The boy, however, had to undergo an emergent endoscopic sinus surgery as his headache and eyeball-pain symptoms did not resolve by medical treatment alone. Both cases had good outcomes, without neurological sequelae.

BACKGROUND: Cell division cycle 6 (CDC6) is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle. CDC6 has been associated with oncogenic activities in human cancers; however, the clinical significance of CDC6 in prostate cancer (PCa) remains unclear. Therefore, we investigated whether the CDC6 mRNA expression level is a diagnostic and prognostic marker in PCa. METHODS: The study subjects included 121 PCa patients and 66 age-matched benign prostatic hyperplasia (BPH) patients. CDC6 expression was evaluated using real-time polymerase chain reaction and immunohistochemical (IH) staining, and then compared according to the clinicopathological characteristics of PCa. RESULTS: CDC6 mRNA expression was significantly higher in PCa tissues than in BPH control tissues (P = 0.005). In addition, CDC6 expression was significantly higher in patients with elevated prostate-specific antigen (PSA) levels (> 20 ng/mL), a high Gleason score, and advanced stage than in those with low PSA levels, a low Gleason score, and earlier stage, respectively. Multivariate logistic regression analysis showed that high expression of CDC6 was significantly associated with advanced stage (≥ T3b) (odds ratio [OR], 3.005; confidence interval [CI], 1.212–7.450; P = 0.018) and metastasis (OR, 4.192; CI, 1.079–16.286; P = 0.038). Intense IH staining for CDC6 was significantly associated with a high Gleason score and advanced tumor stage including lymph node metastasis stage (linear-by-linear association, P = 0.044 and P = 0.003, respectively). CONCLUSION: CDC6 expression is associated with aggressive clinicopathological characteristics in PCa. CDC6 may be a potential diagnostic and prognostic marker in PCa patients.
Cell Cycle ; DNA Replication ; Gene Expression ; Humans ; Logistic Models ; Lymph Nodes ; Neoplasm Grading ; Neoplasm Metastasis ; Passive Cutaneous Anaphylaxis ; Prostate* ; Prostate-Specific Antigen ; Prostatic Hyperplasia ; Prostatic Neoplasms* ; Real-Time Polymerase Chain Reaction ; RNA, Messenger*

Atypical femoral fracture related to a long-term bisphosphonate therapy has commonly been reported; however, a fracture at the site other than the femur has rarely been reported to date. Herein, we report a case of a patient on long-term bisphosphonate therapy who presented atypical tibial insufficiency fracture at the anterolateral aspect of diaphysis, without trauma. We, for the first time in Korea, present this case with a literature review.
Diaphyses ; Femoral Fractures ; Femur ; Fractures, Stress* ; Humans ; Korea ; Tibia*