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: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Purpose: To report a case of secondary Descemet membrane endothelial keratoplasty (DMEK) for graft failure after primary DMEK.Case summary: A 47-year-old female underwent primary DMEK in her left eye with a diagnosis of Fuchs’ endothelial dystrophy. At 6 weeks later, corneal stromal edema with epithelial and subepithelial bullae was first observed. From that point on, the condition of the cornea and the visual acuity continued to degrade. After 7 months, a second DMEK procedure (i.e., a repeat DMEK) for graft failure was performed successfully without any complications. Since the second procedure, the cornea has been clear, and the best-corrected visual acuity has remained at 0.6 for 8 months. Conclusions To manage graft failure after primary DMEK, we performed a second DMEK procedure. The removal of the previous graft was easy, and there were no complications. Thus, repeat DMEK may be a feasible procedure.

Objective: External beam radiation therapy (EBRT) with concurrent chemotherapy followed by intracavitary brachytherapy is the standard treatment in locally advanced cervical cancer. This study examined the brachytherapy utilization rate and evaluated the effect of brachytherapy on survival in cervical cancer patients in Korea. Methods: In this study, data from the Korea Central Cancer Registry and Korean National Health Insurance Service and data on mortality from Statistics Korea were linked and used. Patients with other cancers, distant metastasis at diagnosis, or unknown stage or who underwent hysterectomy were excluded. A total of 12,721 cervical cancer patients were analyzed in this study. Results: The brachytherapy utilization rate (%) was calculated as the proportion of patients who received brachytherapy among those who received curative EBRT. The brachytherapy utilization rate decreased from 84% in 2005 to 78% in 2013 (p<0.001). Brachytherapy utilization rates varied by region, ranging from 72% to 100% except for in Jeju Island, where the rate was 56%. The brachytherapy utilization rate was lower in patients older than 80 years; patients with localized disease, non-squamous cell carcinoma, or Charlson comorbidity index 3 or more; patients diagnosed after 2010; patients from certain regions; patients receiving medical aid; and patients who underwent gynecologic procedures. Multivariable Cox regression analysis showed that brachytherapy when added to curative EBRT was independently associated with better cancer-specific survival (CSS) and overall survival (OS) than curative EBRT only. Conclusion The brachytherapy utilization rate decreased from 2005 to 2013 and varied by region in Korea. Brachytherapy use is independently associated with significantly higher CSS and OS in cervical cancer.

Purpose: To report a case of secondary Descemet membrane endothelial keratoplasty (DMEK) for graft failure after primary DMEK.Case summary: A 47-year-old female underwent primary DMEK in her left eye with a diagnosis of Fuchs’ endothelial dystrophy. At 6 weeks later, corneal stromal edema with epithelial and subepithelial bullae was first observed. From that point on, the condition of the cornea and the visual acuity continued to degrade. After 7 months, a second DMEK procedure (i.e., a repeat DMEK) for graft failure was performed successfully without any complications. Since the second procedure, the cornea has been clear, and the best-corrected visual acuity has remained at 0.6 for 8 months. Conclusions To manage graft failure after primary DMEK, we performed a second DMEK procedure. The removal of the previous graft was easy, and there were no complications. Thus, repeat DMEK may be a feasible procedure.

Objective: Burr hole trephination is a common treatment for chronic subdural hematoma, intracranial hematoma, and intraventricular hematoma due to its effective drainage of hematoma, minimal invasiveness and short operation time. However, cosmetic complications such as scalp depression can occur. The aim of this study was to evaluate the usefulness of an allogenic acellular dermal matrix (ADM) to prevent scalp depression at the burr hole site. Methods: A retrospective analysis was performed with 75 cases in 66 patients who were treated with burr hole trephination from January 2018 to December 2019. These cases divided into 2 groups; based on the method used to cover the burr hole site: Gelfoam packing only (GPO) and ADM. The degree of the scalp depression was measured from the more recent follow-up brain computed tomography scan. Results: There was a significant difference in the degree of scalp depression between GPO and ADM groups (p=0.003). No significant correlation between patient's age and the degree of scalp depression (GPO: p=0.419, ADM: p=0.790). There were no wound infection complication in either group. Conclusion ADM is a suitable material to prevent scalp depression after burr hole trephination.

A 69-year-old male presented with a week of worsening headache, mild dizziness and left side weakness,and the radiological work-up of his brain displayed an enhancing mass on the right frontal lobe.The tumor was totally resected. The patient was initially diagnosed with glioblastoma multiforme. Hisneurologic symptoms recovered after surgery. He underwent adjuvant radiotherapy with concurrent temozolomide.Approximately 7 months after surgery, the patient complained of epigastric pains. AbdominalCT scan showed multiple hepatic metastasis and multiple lymphadenopathy. Chest CT andTorso positron emission tomography-CT scans for additional metastasis study revealed multiple metastaticlesions in the right lung, left pleura, liver, lymph nodes, bones, and muscles. Percutaneous liverbiopsy was performed, and associated pathology was consistent with sarcomatous component. Afterliver biopsy, brain tumor pathology was reviewed, which revealed typical gliomatous and sarcomatouscomponents. The patient was therefore diagnosed with metastatic gliosarcoma. The patient was in aseptic condition with aggravated pleural effusion. The patient died 9 months after the diagnosis of primarygliosarcoma.

Supratentorial extraventricular anaplastic ependymoma (SEAE) in adults is a relatively rare intracranial tumor. Because of the very low prevalence, only a few cases have been reported. According to a recent study, SEAE is associated with a poor prognosis and there is no definite consensus on optimal treatment. We report a case of an adult SEAE patient who had no recurrence until seven years after a gross total resection (GTR) followed by conventional radiotherapy. A 42-year-old male had a persistent mild headache, left facial palsy, dysarthria, and left hemiparesis. Preoperative neuroimaging revealed an anaplastic astrocytoma or supratentorial ependymoma in the right frontal lobe. A GTR was performed, followed by adjuvant radiotherapy. Histologic and immunohistochemical results revealed anaplastic ependymoma. After seven years of initial therapy, a regular follow-up MRI showed a 3-cm-sized partially cystic mass in the same area as the initial tumor. The patient underwent a craniotomy, and a GTR was performed. Histopathologic examination revealed recurrence of the SEAE. External radiotherapy was performed. The patient has been stable without any disease progression or complications for 12 months since the surgery for recurrent SEAE.
Adult ; Astrocytoma ; Consensus ; Craniotomy ; Disease Progression ; Dysarthria ; Ependymoma ; Facial Paralysis ; Follow-Up Studies ; Frontal Lobe ; Headache ; Humans ; Magnetic Resonance Imaging ; Male ; Neuroimaging ; Paresis ; Prevalence ; Prognosis ; Radiotherapy ; Radiotherapy, Adjuvant ; Recurrence ; Supratentorial Neoplasms

OBJECTIVE: Patients with traumatic acute subdural hematoma (ASDH) often require surgical treatment. Among patients who primarily underwent craniotomy for the removal of hematoma, some consequently developed aggressive intracranial hypertension and brain edema, and required secondary decompressive craniectomy (DC). To avoid reoperation, we investigated factors which predict the requirement of DC by comparing groups of ASDH patients who did and did not require DC after craniotomy. METHODS: The 129 patients with ASDH who underwent craniotomy from September 2007 to September 2017 were reviewed. Among these patients, 19 patients who needed additional DC (group A) and 105 patients who underwent primary craniotomy only without reoperation (group B) were evaluated. A total of 17 preoperative and intraoperative factors were analyzed and compared statistically. Univariate and multivariate analyses were used to compare these factors. RESULTS: Five factors showed significant differences between the two groups. They were the length of midline shifting to maximal subdural hematoma thickness ratio (magnetization transfer [MT] ratio) greater than 1 (p < 0.001), coexistence of intraventricular hemorrhage (IVH) (p < 0.001), traumatic intracerebral hemorrhage (TICH) (p=0.001), intraoperative findings showing intracranial hypertension combined with brain edema (p < 0.001), and bleeding tendency (p=0.02). An average value of 2.74±1.52 was obtained for these factors for group A, which was significantly different from that for group B (p < 0.001). CONCLUSION: An MT ratio >1, IVH, and TICH on preoperative brain computed tomography images, intraoperative signs of intracranial hypertension, brain edema, and bleeding tendency were identified as factors indicating that DC would be required. The necessity for preemptive DC must be carefully considered in patients with such risk factors.
Brain ; Brain Edema ; Cerebral Hemorrhage, Traumatic ; Craniotomy* ; Decompressive Craniectomy* ; Hematoma ; Hematoma, Subdural ; Hematoma, Subdural, Acute* ; Hemorrhage ; Humans ; Intracranial Hypertension ; Multivariate Analysis ; Reoperation ; Risk Factors

Dural arteriovenous fistula (D-AVF) at the foramen magnum is an extremely rare disease entity. It produces venous hypertension, and can lead to progressive cervical myelopathy thereafter. On the other hand, the venous hypertension may lead to formation of a venous varix, and it can rarely result in an abrupt onset of subarachnoid hemorrhage (SAH) when the venous varix is ruptured. The diagnosis of D-AVF at the foramen magnum as a cause of SAH may be difficult due to its low incidence. Furthermore, when the D-AVF is fed solely by the ascending pharyngeal artery (APA), it may be missed if the external carotid angiography is not performed. The outcome could be fatal if the fistula is unrecognized. Herein, we report on a rare case of SAH caused by ruptured venous varix due to D-AVF at the foramen magnum fed solely by the APA. A review of relevant literatures is provided, and the treatment modalities and outcomes are also discussed.
Angiography ; Arteries* ; Central Nervous System Vascular Malformations* ; Diagnosis ; Fistula ; Foramen Magnum* ; Hand ; Hypertension ; Incidence ; Rare Diseases ; Spinal Cord Diseases ; Subarachnoid Hemorrhage* ; Varicose Veins*