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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.
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Background@#Helicobacter pylori infection, prevalent in more than half of the global population, is associated with various gastrointestinal diseases, including peptic ulcers and gastric cancer. The effectiveness of early diagnosis and treatment in preventing gastric cancer highlights the need for improved diagnostic methods. This study aimed to develop a simple scoring system based on endoscopic findings to predict H. pylori infection. @*Methods@#A retrospective analysis was conducted on 1,007 patients who underwent upper gastrointestinal endoscopy at Asan Medical Center from January 2019 to December 2021. Exclusion criteria included prior H. pylori treatment, gastric surgery, or gastric malignancies. Diagnostic techniques included rapid urease and 13C-urea breath tests, H. pylori culture, and assessment of endoscopic features following the Kyoto gastritis classification. A new scoring system based on endoscopic findings including regular arrangement of collecting venules (RAC), nodularity, and diffuse or spotty redness was developed for predicting H. pylori infection, utilizing logistic regression analysis in the development set. @*Results@#The scoring system demonstrated high predictive accuracy for H. pylori infection in the validation set. Scores of 2 and 3 were associated with 96% and 99% infection risk, respectively. Additionally, there was a higher prevalence of diffuse redness and sticky mucus in cases where the initial H. pylori eradication treatment failed. @*Conclusions@#Our scoring system showed potential for improving diagnostic accuracy in H. pylori infection. H. pylori testing should be considered upon spotty redness, diffuse redness, nodularity, and RAC absence on endoscopic findings as determined by the predictive scoring system.
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Small bowel variceal bleeding is a rare cause of gastrointestinal hemorrhage, with clinical manifestations ranging from asymptomatic incidental findings to life-threatening conditions. The diagnosis and management of small bowel bleeding are challenging because of the localization of the lesion and the difficulty of the procedure. Trans-arterial embolization (TAE) is a secure and straightforward method for treating ectopic varices. On the other hand, there have been limited local studies on the outcomes of TAE for patients with small bowel variceal hemorrhage. This paper reports patients diagnosed with small bowel variceal bleeding and treated with TAE.
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Pancreatic pseudoaneurysm is a potentially life-threatening complication often associated with pancreatitis or pancreatic surgery. As the rupture of pancreatic pseudoaneurysms can lead to catastrophic bleeding and is associated with high mortality rates, clinical suspicion and early diagnosis are essential to improve patient outcomes. In the management of pseudoaneurysms, transarterial embolization (TAE) could be effective; however, there have been limited local studies on the outcomes of TAE for patients with pseudoaneurysm rupture associated with pancreatitis. Here, we describe patients who were diagnosed with pseudoaneruysm rupture associated with pancreatitis and treated with TAE.
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Background@#The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. @*Results@#K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. @*Conclusion@#Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.
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Background/Aims@#Identification of Helicobacter pylori infection status is necessary as H. pylori is associated with gastric malignancy. Recently, a red linear scrape-like appearance on the gastric mucosa, called the “scratch sign,” was reported to be associated with H. pylori-negative gastric mucosal status. Herein, we aimed to validate the association between the scratch sign and H. pylori infection status. @*Methods@#The data of patients who underwent screening endoscopy at Bundang Jesaeng General Hospital between March 2023 and April 2023 were reviewed. Patients were classified as having an H. pylori current infection or non-infection status based on the results of rapid urease tests. Patients who had undergone H. pylori eradication therapy were excluded. Endoscopic features of the gastric mucosa were assessed using the Kyoto classification of gastritis. @*Results@#The scratch sign appeared more frequently in patients with non-infection than in those with current infection status (32.7% vs. 10.6%, respectively; P<0.001). Multivariate analysis showed that only the presence of sticky mucus was significantly associated with the presence of the scratch sign. Patient without the scratch sign had a higher prevalence of open-type atrophy, intestinal metaplasia, enlarged folds, and diffuse redness, which reflected a higher Kyoto score. @*Conclusions@#Presence of the gastric mucosal scratch sign, a novel endoscopic marker, is indicative of H. pylori-negative status and appears to be inversely correlated with the presence of sticky mucus. In addition to the Kyoto classification of gastritis, detection of the scratch sign may facilitate identification of the H. pylori infection status.
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Background/Aims@#The treatment for gastric mucosa-associated lymphoid tissue lymphoma (MALToma) generally involves eradication of Helicobacter pylori. However, MALToma lesions may recur even without H. pylori re-infection. Furthermore, the remission rate of H. pylori-negative MALToma after eradication is low. Therefore, herein, we report on endoscopic submucosal dissection (ESD) as a treatment strategy for gastric MALToma. @*Methods@#We retrospectively reviewed the data of all patients of gastric MALToma who underwent endoscopic resection at our institution between January 2000 and December 2021. Clinical remission was defined as complete histological remission or probable minimal residual disease according to the GELA grading system for post-treatment evaluation of gastric MALToma. @*Results@#Six patients with gastric MALToma underwent ESD. Two patients were diagnosed with gastric MALToma, which improved after eradication treatment and relapsed approximately 36 and 41 months later, respectively. These patients had singular lesions localized to the mucosa and did not experience H. pylori re-infection. The lesions were successfully removed via ESD. The remaining four patients had H. pylori-negative gastric MALToma. These patients also had single, localized lesions that were removed via ESD. All the patients remained in clinical remission until the final follow-up. @*Conclusions@#ESD is a safe and effective intervention for H. pylori-negative gastric MALToma when the lesion is single and confined to the mucosal layer.
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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.
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Viperin is an IFN-stimulated gene (ISG)-encoded protein that was identified in human primary macrophages treated with IFN-γ and in human primary fibroblasts infected with cytomegalovirus (CMV). This protein plays multiple roles in various cell types. It inhibits viral replication, mediates signaling pathways, and regulates cellular metabolism. Recent studies have shown that viperin inhibits IFN expression in macrophages, while it enhances TLR7 and TLR9-mediated IFN production in plasmacytoid dendritic cells, suggesting that viperin can play different roles in activation of the same pathway in different cell types. Viperin also controls induction of ISGs in macrophages. However, the effect of viperin on induction of ISGs in cell types other than macrophages is unknown. Here, we show that viperin differentially induces ISGs in 2 distinct cell types, macrophages and fibroblasts isolated from wild type and viperin knockout mice. Unlike in bone marrow-derived macrophages (BMDMs), viperin downregulates the expression levels of ISGs such as bone marrow stromal cell antigen-2, Isg15, Isg54, myxovirus resistance dynamin like GTPase 2, and guanylate binding protein 2 in murine embryonic fibroblasts (MEFs) treated with type I or II IFN. However, viperin upregulates expression of these ISGs in both BMDMs and MEFs stimulated with polyinosinic-polycytidylic acid or CpG DNA and infected with murine CMV. The efficiency of viral entry is inversely proportional to the expression levels of ISGs in both cell types. The data indicate that viperin differentially regulates induction of ISGs in a cell type-dependent manner, which might provide different innate immune responses in distinct cell types against infections.
Subject(s)
Animals , Humans , Mice , Carrier Proteins , Cytomegalovirus , Dendritic Cells , DNA , Dynamins , Fibroblasts , GTP Phosphohydrolases , Immunity, Innate , Interferons , Macrophages , Mesenchymal Stem Cells , Metabolism , Mice, Knockout , Orthomyxoviridae , Poly I-CABSTRACT
Viperin is a multifunctional protein that was first identified in human primary macrophages treated with interferon-γ and in human fibroblasts infected with human cytomegalovirus. This protein plays a role as an anti-viral protein and a regulator of cell signaling pathways or cellular metabolism when induced in a variety of cells such as fibroblasts, hepatocytes and immune cells including T cells and dendritic cells. However, the role of viperin in macrophages is unknown. Here, we show that viperin is basally expressed in murine bone marrow cells including monocytes. Its expression is maintained in bone marrow monocyte-derived macrophages (BMDMs) depending on macrophage colony-stimulating factor (M-CSF) treatment but not on granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment. In wild type (WT) and viperin knockout (KO) BMDMs differentiated with M-CSF or G-MCSF, there are little differences at the gene expression levels of M1 and M2 macrophage markers such as inducible nitric oxide synthase (iNOS) and arginase-1, and cytokines such as IL-6 and IL-10, indicating that viperin expression in BMDMs does not affect the basal gene expression of macrophage markers and cytokines. However, when BMDMs are completely polarized, the levels of expression of macrophage markers and secretion of cytokines in viperin KO M1 and M2 macrophages are significantly higher than those in WT M1 and M2 macrophages. The data suggest that viperin plays a role as a regulator in polarization of macrophages and secretion of M1 and M2 cytokines.
Subject(s)
Humans , Bone Marrow , Bone Marrow Cells , Cytokines , Cytomegalovirus , Dendritic Cells , Fibroblasts , Gene Expression , Granulocyte-Macrophage Colony-Stimulating Factor , Hepatocytes , Interleukin-10 , Interleukin-6 , Macrophage Colony-Stimulating Factor , Macrophages , Metabolism , Monocytes , Nitric Oxide Synthase Type II , T-LymphocytesABSTRACT
Although calcaneal fracture is relatively common in ankle injury, open intraarticular calcaneal fracture with dorsal dislocation of the navicular from talus is extremely rare and severe injury. There are few data which are available concerning the injury mechanism and treatment options. The purpose of this report is to describe a case with bilateral open transcalcaneal fracture with talonavicular dislocation and to discuss the prevalence, mechanism of this injury, and treatment options.
Subject(s)
Ankle Injuries , Calcaneus , Joint Dislocations , Prevalence , TalusABSTRACT
Spontaneous bilateral rupture of the quadriceps tendons without a significant history of trauma is an uncommon disease. It is generally associated with mechanical factors and coexisting systemic and local factors are taken into consideration in the pathogenesis of these ruptures. In patients with some chronic systemic diseases, simultaneous rupture can occur spontaneously or with minor trauma. We present a case of patient with chronic renal failure on hemodialysis for the past 9 years, who sustained this injury, and subsequently had surgical repair of both tendons. We performed a preoperative magnetic resonance imaging to confirm the diagnosis, then we repaired the ruptured quadriceps tendons and performing MRI postoperatively 1 yr later. He regained his normal knee joint functions 1 yr after the operation.
Subject(s)
Humans , Kidney Failure, Chronic , Knee Joint , Magnetic Resonance Imaging , Quadriceps Muscle , Renal Dialysis , Rupture , Rupture, Spontaneous , TendonsABSTRACT
PURPOSE: To evaluate the clinical outcomes of the vertebroplasty in the treatment of osteoporotic vertebral compression fracture and Kummell's disease. MATERIALS AND METHODS: The clinical and the radiological results of 54 vertebrae in 47 patients, who were followed for more than one year after vertebroplasty for 46 painful osteoporotic compression fractures (group 1) and 8 Kummell's disease (group 2) were analyzed. Clinically, the Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) were analyzed prospectively. Radiologically, kyphotic deformity, vertebral height, cement leakage and bone resorption around cement were analyzed retrospectively at preoperative, postoperative and last follow-up. RESULTS: The ODI and VAS at each group were lowered after vertebroplasty and the pain relief of vertebroplasty was significant (p<0.001). However the mean ODI and VAS of group 2 were higher than those of group 1 at preoperative and postoperative (p=0.02 (ODI), p=0.02 (VAS)). The kyphotic deformity was more severe at group 2 than at group 1 but it was not statistically significant. The loss of vertebral height was also not statistically significant at each group. The cement leakage was found in 21 vertebrae among 54 vertebrae (38.8%). Group 2 had 75% (6/8) of cement leakage and most of them were type C leakage. Group 1 had 32.6% (15/46) of cement leakage and most of them were type B leakage. Bone resorption around cement was found at 2 vertebrae of group 2 and 1 vertebra of group 1. There were adjacent vertebral fractures in one case of group 2, four cases of group 1 and reoperation was needed in one case of group 2. CONCLUSION: The vertebropasty is an excellent method as a treatment of osteoporotic compression fracture and Kummell's disease, providing pain relief and early mobility in appropriate patients. However it must be kept in mind that higher rates of complications are related to cement in Kummell's disease.
Subject(s)
Humans , Bone Resorption , Congenital Abnormalities , Follow-Up Studies , Fractures, Compression , Osteoporosis , Prospective Studies , Reoperation , Retrospective Studies , Spine , VertebroplastyABSTRACT
The development of primary squamous cell carcinoma in the endometrium is extremely rare. In 1928 Fluhmann proposed three criteria to establish the diagnosis: (1) no coexisting endometrial adenocarcinoma, (2) no connection between the endometrial tumor and the squamous epithelium of the cervix and (3) no squamous cell carcinoma of the cervix present. More recently, the World Health Organization (WHO) updated Fluhmann's criteria by adding that the tumor must contain clear evidence of squamous differentiation, such as the presence of intercellular bridges and/or keratin. We have experienced a case of primary endometrial squamous cell carcinoma which fulfills Fluhmann's criteria and WHO's. In this report, we present the clinical and pathological findings of a case of a primary endometrial squamous cell carcinoma of a 62-year-old patient with a review of the concerned literatures.
Subject(s)
Female , Humans , Middle Aged , Adenocarcinoma , Carcinoma, Squamous Cell , Cervix Uteri , Diagnosis , Endometrium , Epithelium , World Health OrganizationABSTRACT
Hypermesis gravidarum is a complication defined as vomiting severe enough to require hospital admission during early pregnancy. Thiamine deficiency is known to lead to certain neurological seguelae including Wernicke-Korsakoff syndrome. Wernicke's encephalopathy is an illness of acute onset characterized by global confusion, paralysis of eye ball movements, and gate ataxia due to a deficiency of thiamine. The immediate administration of thiamine prevents progression of the disease and reverses brain lesions that have not yet progressed to the point of fixed structural change. We have experienced a case of Wernicke-Korsakoff syndrome associated with hyperemesis gravidarum, which seemed to be developed by prolonged thiamine-free fluid therapy. We emphasize the need for thiamine supplementation in hyperemesis gravidarum patients.
Subject(s)
Female , Humans , Pregnancy , Ataxia , Brain , Fluid Therapy , Hyperemesis Gravidarum , Korsakoff Syndrome , Paralysis , Thiamine , Thiamine Deficiency , Vomiting , Wernicke EncephalopathyABSTRACT
Acardiac twinning affects 1 in 100 monozygotic twin pregnancies and 1 in 35,000 pregnancies overall. This condition is characterized by the absence or rudimentary development of fetal heart, and associated with various anomaly. The presence of an acardiac twin requires the normal (or "pump") twin to provide circulation for itself, as well as the acardiac sibling. The acardiac malformations are uniformly fatal in the affected twin, and mortality in the co-twin is as high as 55%. The principal perinatal problems associated with acardiac twinning are pump-twin congestive heart failure, maternal hydramnios, and preterm delivery. We recently experienced a case of acardius anceps associated with a normal male infant, so present with a brief review of the literature.
Subject(s)
Humans , Infant , Male , Pregnancy , Fetal Heart , Heart Failure , Mortality , Polyhydramnios , Siblings , Twins, MonozygoticABSTRACT
Mucocele of the sphenoid sinus is a rare disease, and its signs and symptoms are different depending on multiple contiguous neurologic and vascular structures. So it is occasionally misdiagnosed as pituitary tumors. But careful radiologic evaluation including CT scan, helps in the correct assessment of this lesion. We have recently experienced one case of sphenoid sinus mucocele which presented with subtle nasal symptom. The mucocele was removed by endoscopic intranasal sphenoethmoidectomy.