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.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces excessive pro-inflammatory cytokine release and cell death, leading to organ damage and mortality.High-mobility group box 1 (HMGB1) is one of the damage-associated molecular patterns that can be secreted by pro-inflammatory stimuli, including viral infections, and its excessive secretion levels are related to a variety of inflammatory diseases. Here, the aim of the study was to show that SARS-CoV-2 infection induced HMGB1 secretion via active and passive release. Active HMGB1 secretion was mediated by post-translational modifications, such as acetylation, phosphorylation, and oxidation in HEK293E/ACE2-C-GFP and Calu-3 cells during SARS-CoV-2 infection. Passive release of HMGB1 has been linked to various types of cell death; however, we demonstrated for the first time that PANoptosis, which integrates other cell death pathways, including pyroptosis, apoptosis, and necroptosis, is related to passive HMGB1 release during SARS-CoV-2 infection. In addition, cytoplasmic translocation and extracellular secretion or release of HMGB1 were confirmed via immunohistochemistry and immunofluorescence in the lung tissues of humans and angiotensin-converting enzyme 2-overexpressing mice infected with SARS-CoV-2.

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: The Act on Hospice and Palliative Care and Decisions on Life-Sustaining Treatment for Patients at the End of Life came into force in February 2018 in Korea. This study reviews the practices of end-of-life care for patients who withdrew or withheld lifesustaining treatment at a tertiary care hospital, addresses the limitations of the law, and discusses necessary steps to promote patient-centered self-determination. Methods: We retrospectively analyzed the medical records of patients who died after agreeing to withhold lifesustaining treatment in 2018 at our university hospital. The cause of death, the intensity of end-of-life care, and other characteristics were reviewed and statistically analyzed. Results: Of a total of 334 patients, 231 (69%) died from cancer. The decision to stop life-sustaining treatment was made by family members for 178 patients overall (53.3%) and for 101 (43.7%) cancer patients, regardless of the patient’s wishes. When the patient decided to stop lifesustaining treatment, the time from the authorization to withhold life-sustaining treatment to death was longer than when the decision was made by family members (28.7±41.3 vs 10.5±23.2 days, P＜0.001). Conclusion In many cases, the decision to discontinue lifesustaining treatment was made by the family, not by the patient. In order to protect human dignity based on the patients’ self-determination, it is necessary for patients to understand their disease based on careful explanations from physicians. Ongoing survey-based research will be necessary in the future.

Diverticulosis of the vermiform appendix is an uncommon entity with incidence of 0.2~2.0% in surgical pathologic specimens. Inflammation, perforation, and hemorrhage will be complications of appendiceal diverticulum. Without these complications, appendiceal diverticulum is asymptomatic. Authors experienced intussusception combined with appendiceal diverticulum.
Adult* ; Appendix ; Diverticulum* ; Hemorrhage ; Humans ; Incidence ; Inflammation ; Intussusception*

Performing laparoscopic surgery for colorectal cancer and early gastric caner has recently been rapidally increasing. We report here on our experiences of 3 cases of laparoscopic combined resection for synchronous colorectal cancer with early gastric cancer. Case 1) An 87-year-old male had synchronous right colon cancer along with early gastric cancer, and he underwent laparoscopic right colectomy with laparoscopic assisted distal gastrectomy. Case 2) A 49-year-old male had synchronous rectal cancer with early gastric cancer, and he underwent laparoscopic abdominoperineal resection and totally laparoscopic distal gastrectomy with delta anastomosis. Case 3) A 76-year-old female had synchronous sigmoid colon cancer with early gastric cancer, and she underwent laparoscopic low anterior resection with laparoscopic assisted distal gastrectomy. The laparoscopic approach for synchronous cancer can be a treatment option for selected cases.
Aged ; Aged, 80 and over ; Colectomy ; Colonic Neoplasms ; Colorectal Neoplasms* ; Female ; Gastrectomy ; Humans ; Laparoscopy ; Male ; Middle Aged ; Rectal Neoplasms ; Sigmoid Neoplasms ; Stomach Neoplasms*

PURPOSE: To evaluate the effectiveness of iliosacral screw fixation with anterior plating in the management of an unstable pelvic ring injury. MATERIALS AND METHODS: Nineteen patients with an unstable pelvic ring injury were enrolled in this retrospective study. All patients were followed up for at least 1 year. The mean age of the patients was 43 years. According to the AO-OTA classification, there were five B2 injuries, 11 C1 injuries, and 3 C2 injuries. After anterior fixation by plating, ilio-sacral screw fixation was performed percutaneously under the C-arm guide. RESULTS: All cases united except for 1 case of nonunion at the pubic ramus. The radiology results showed 9, 7, 2 and 1 case of anatomic, nearly anatomic, moderate and poor reduction, respectively. Sixteen out of 19 patients had a good or excellent functional result. Two moderate and one poor result were from an unsatisfactory reduction in a type C injury with the residual neurological signs. Screw misplacement with neurological compromise occurred in one patient but there were no adverse sequelae after its removal. Regarding the complications, there were two cases of screw loosening, two cases of anterior metal failures, and 1 case of a deep infection. CONCLUSION: Percutaneous ilio-sacral screwing with anterior plating may be a useful method for treating unstable pelvic ring injuries, and the reduction quality and neurological signs are important.
Classification ; Humans ; Retrospective Studies

PURPOSE: Splenic flexure mobilization in an anterior resection is a subject of controversy, but a tension-free anastomosis is needed in case of a low anterior resection or a coloanal anastomosis. Classical splenic flexure mobilization by means of the lesser sac opening is technically difficult in the laparoscopic era. METHODS: This study retrospectively analyzed the medical records and operation videos of 16 patients who underwent laparoscopic splenic flexure mobilization in Our Lady of Mercy Hospital, The Catholic University of Korea by using a medial approach. The operation procedure is as follows: Under general anesthesia, the patient was placed in the Trendelenburg position, after making pneumoperitoneum, the inferior mesenteric artery (IMA) and the inferior mesenteric vein (IMV) were ligated and divided. A medial-to-lateral mesocolon dissection was done, and the pancreas was dissected from the mesocolon of the transverse colon; then, the greater omentum was dissected. RESULTS: The mean age was 60 years old, and the male- to-female sex ratio was 9:7. The mean operation time was 293 minutes. The mean distal margin was 5.3 cm, and the mean number of harvested lymph nodes was 15. An anterior resection was done in 2 cases, a low anterior resection is 10 cases, and a coloanal anastomosis in 4 cases. The mean time from ligation of the IMA to splenic flexure mobilization was 45 minutes. There was no mortality or morbidity. CONCLUSIONS: Laparoscopic medial splenic flexure mobilization is a technically feasible and safe method.
Anesthesia, General ; Colon, Transverse* ; Head-Down Tilt ; Humans ; Korea ; Laparoscopy ; Ligation ; Lymph Nodes ; Medical Records ; Mesenteric Artery, Inferior ; Mesenteric Veins ; Mesocolon ; Middle Aged ; Mortality ; Omentum ; Pancreas ; Peritoneal Cavity ; Pneumoperitoneum ; Retrospective Studies ; Sex Ratio

Crohn's disease is a chronic and insidious condition characterized by an inflammatory process that may extend across all layers of the entire gastrointestinal tract. The common sites involved by Crohn's disease are the terminal ileum and ascending colon. Crohn's disease limited to the appendix is uncommon. Since its first report in 1953 by Meyerding and Bertram, 156 cases of appendiceal Crohn's disease have been documented in the world literature. We experienced a case of Crohn's disease limited to the appendix in a-35year-old female who were performed an ileocecectomy.
Appendix* ; Colon, Ascending ; Crohn Disease* ; Female ; Gastrointestinal Tract ; Humans ; Ileum

Peutz-Jeghers syndrome is a disease entity consisting of gastrointestinal hamartoma, mucocutaneous pigmentation, and autosomal dominant inheritance. From a surgical standpoint, the syndrome is of significance because the hamartoma may lead to intussusception, gastrointestinal bleeding, abdominal pain, and a fifteen-times-increased risk of malignancy in the GI tract, pancreas, breast, ovarles, and testes. Recent reports indicate the STK11 (LKB1) gene, located on region 13.3 of the short arm of chromosome 19, as being the locus of autosomal dominant indentify. The case of a 21-year-old female who required a partial jejunal resection due to intussusception and bleeding from a jejunal hamartoma twice in five years is presented.
Abdominal Pain ; Anemia* ; Arm ; Breast ; Chromosomes, Human, Pair 19 ; Female ; Gastrointestinal Tract ; Hamartoma ; Hemorrhage ; Humans ; Intussusception* ; Pancreas ; Peutz-Jeghers Syndrome* ; Pigmentation ; Testis ; Wills ; Young Adult