Pre-existing Immunity to Endemic Human Coronaviruses Does Not Affect the Immune Response to SARS-CoV-2 Spike in a Murine Vaccination Model

Endemic human coronaviruses (HCoVs) have been evidenced to be cross-reactive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a correlation exists between the immunological memory to HCoVs and coronavirus disease 2019 (COVID-19) severity, there is little experimental evidence for the effects of HCoV memory on the efficacy of COVID-19 vaccines. Here, we investigated the Ag-specific immune response to COVID-19 vaccines in the presence or absence of immunological memory against HCoV spike Ags in a mouse model.Pre-existing immunity against HCoV did not affect the COVID-19 vaccine-mediated humoral response with regard to Ag-specific total IgG and neutralizing Ab levels. The specific T cell response to the COVID-19 vaccine Ag was also unaltered, regardless of pre-exposure to HCoV spike Ags. Taken together, our data suggest that COVID-19 vaccines elicit comparable immunity regardless of immunological memory to spike of endemic HCoVs in a mouse model.

Current Status of COVID-19 Vaccine Development: Focusing on Antigen Design and Clinical Trials on Later Stages

The global outbreak of coronavirus disease 2019 (COVID-19) is still threatening human health, economy, and social life worldwide. As a counteraction for this devastating disease, a number of vaccines are being developed with unprecedented speed combined with new technologies. As COVID-19 vaccines are being developed in the absence of a licensed human coronavirus vaccine, there remain further questions regarding the long-term efficacy and safety of the vaccines, as well as immunological mechanisms in depth. This review article discusses the current status of COVID-19 vaccine development, mainly focusing on antigen design, clinical trials in later stages, and immunological considerations for further study.

Newly Emerging Human Coronaviruses:Animal Models and Vaccine Research for SARS, MERS, and COVID-19

The recent emergence of the novel coronavirus (CoV) or severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a global threat to human health and economy. As of June 26, 2020, over 9.4 million cases of infection, including 482,730 deaths, had been confirmed across 216 countries. To combat a devastating virus pandemic, numerous studies on vaccine development are urgently being accelerated. In this review article, we take a brief look at the characteristics of SARS-CoV-2 in comparison to SARS and Middle East respiratory syndrome (MERS)-CoVs and discuss recent approaches to coronavirus disease-2019 (COVID-19) vaccine development.

Two base pair deletion in IL2 receptor γ gene in NOD/SCID mice induces a highly severe immunodeficiency / 한국실험동물학회지

Genome editing has recently emerged as a powerful tool for generating mutant mice. Small deletions of nucleotides in the target genes are frequently found in CRISPR/Cas9 mediated mutant mice. However, there are very few reports analyzing the phenotypes in small deleted mutant mice generated by CRISPR/Cas9. In this study, we generated a mutant by microinjecting sgRNAs targeting the IL2 receptor γ gene and Cas9 protein, into the cytoplasm of IVF-derived NOD.CB17/Prkdcscid/JKrb (NOD/SCID) mice embryos, and further investigated whether a 2 bp deletion of the IL2 receptor γ gene affects severe deficiency of immune cells as seen in NOD/LtSz-scid IL2 receptor γ−/− (NSG) mice. Our results show that the thymus weight of mutant mice is significantly less than that of NOD/SCID mice, whereas the spleen weight was marginally less. T and B cells in the mutant mice were severely deficient, and NK cells were almost absent. In addition, tumor growth was exceedingly increased in the mutant mice transplanted with HepG2, Raji and A549 cells, but not in nude and NOD/SCID mice. These results suggest that the NOD/SCID mice with deletion of 2 bp in the IL2 receptor γ gene shows same phenotype as NSG mice. Taken together, our data indicates that small deletions by genome editing is sufficient to generate null mutant mice.

Clinical usefulness of transarterial chemoembolization response prior to liver transplantation as predictor of optimal timing for living donor liver transplantation

PURPOSE: Response to preoperative transarterial chemoembolization (TACE) has been recommended as a biological selection criterion for liver transplantation (LT). The aim of our study was to identify optimal timing of living donor liver transplantation (LDLT) after TACE based on the TACE response. METHODS: We performed a retrospective study to assess recurrence in 128 hepatocellular carcinoma (HCC) patients who underwent LDLT following sequential TACE from January 2002 to March 2015 at a single institute. Cox proportional hazard models and Kaplan-Meier analysis were utilized to estimate HCC recurrence and find optimal timing for LDLT. RESULTS: Seventy-three and 61 patients were divided as the responder and nonresponder, respectively. Multivariate analysis showed independent pre-liver transplantation (pre-LT) predictors of recurrence were larger sized tumor (>3 cm, P = 0.024), nonresponse to TACE (P = 0.031), vascular invasion (P = 0.002), and extrahepatic nodal involvement (P = 0.001). In the 3-month time difference between last pre-LT TACE and LDLT subgroup, TACE responders showed significantly higher adjusted hazard ratio (aHR) of recurrence free survival (aHR, 6.284; P = 0.007), cancer specific survival (aHR, 7.033; P = 0.016), and overall survival (aHR, 7.055; P = 0.005). Moreover, for overall patients and responder groups, the significant time difference between last pre-LT TACE and LDLT was 2 months in the minimum P-value approach. CONCLUSION: In selected patients who showed good response to pre-LT TACE, a shorter time interval between TACE and LDLT may be associated with higher recurrence free survival, cancer specific survival, and overall survival.

Simultaneous pancreas-kidney transplantation: lessons learned from the initial experience of a single center in Korea

PURPOSE: The purpose of this study is to report the results of simultaneous pancreas-kidney (SPK) transplantations and describe the lessons learned from the early experiences of a single center. METHODS: Between January 2002 and June 2013, a total of 8 patients underwent SPK transplantation. Clinical and radiologic data were reviewed retrospectively. RESULTS: Seven patients were diagnosed with type I diabetes mellitus and one patient became insulin-dependent after undergoing a total pancreatectomy because of trauma. Pancreas exocrine drainage was performed by enteric drainage in 4 patients and bladder drainage in 4 patients. Three patients required conversion from initial bladder drainage to enteric drainage due to urinary symptoms and duodenal leakage. Four patients required a relaparotomy due to hemorrhage, ureteral stricture, duodenal leakage, and venous thrombosis. There was no kidney graft loss, and 2 patients had pancreas graft loss because of venous thrombosis and new onset of type II diabetes mellitus. With a median follow-up of 76 months (range, 2-147 months), the death-censored graft survival rates for the pancreas were 85.7% at 1, 3, and 5 years and 42.9% at 10 years. The patient survival rate was 87.5% at 1, 3, 5, and 10 years. CONCLUSION: The long-term grafts and patient survival in the current series are comparable to previous studies. A successful pancreas transplant program can be established in a single small-volume institute. A meticulous surgical technique and early anticoagulation therapy are required for further improvement in the outcomes.

Prolonged shedding of the canine influenza H3N2 virus in nasal swabs of experimentally immunocompromised dogs

PURPOSE: The avian origin canine influenza virus H3N2 has been recently isolated and found to be currently in dog population in South Korea and China. The purpose of this study was to clarify the relationship between immunosuppressive glucocorticoids used in veterinary clinical practice and viral shedding pattern of influenza in dogs. MATERIALS AND METHODS: Eight conventional beagle dogs were divided into control infection group and immunocompromised group. Dogs of both groups were infected with H3N2 canine influenza virus (2x106.0 EID50/0.1 mL). Dogs in immunocompromised group were given orally 3.0 mg/kg prednisolone for 7 days. Virus shedding was monitored using real-time polymerase chain reaction. After necropsy, histopathologic lesions were compared. RESULTS: We found that immunocompromised dogs exhibited more prolonged (8 days vs. 13 days) and higher magnitude viral shedding than control group (peak titer of viral shedding 4.6 vs. 5.5 EID50). CONCLUSION: Restricted use of immunosuppressive drugs in the clinical setting might help control the rapid spread of H3N2 through local dog populations.

Prognostic significance of computed tomography defined ascites in advanced gastric cancer / 대한외과학회지

PURPOSE: The aim of this study was to investigate the clinicopathologic features and prognosis in patients with computed tomography (CT) findings of ascites, with a focus on the correlation with peritoneal carcinomatosis. METHODS: This study included a total of 157 patients who underwent surgery for advanced gastric cancer from 2003 to 2008 at the Department of Surgery, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea, which were analyzed retrospectively. RESULTS: Fourteen patients (8.9%) presented ascites on their CT scan. Among them, 10 patients had peritoneal carcinomatosis, and showed significant difference with CT ascites positive group in the incidence of peritoneal carcinomatosis. The presence of CT ascites was significantly correlated with pathologic T stage, tumor size, histologic type, CT T and N stages, CT peritoneal nodularity and curability of surgery, statistically. The prognosis of CT ascites positive group was much poorer in the total advanced gastric cancer patients (P < 0.001), as well as in patients with pathologic T4 (P = 0.002). Also in patients without peritoneal carcinomatosis, CT ascites positive subgroup tended to have a worse prognosis than CT ascites negative subgroup (P = 0.086). Tumor size, CT T and N stages and the presence of CT peritoneal nodularity and ascites influenced the prognosis significantly; among which, if a tumor size larger than 5 cm, CT T4 stage and the presence of CT ascites were identified as independent prognostic factors. CONCLUSION: The presence of ascites was closely associated with peritoneal metastasis, and was the most significant independent prognostic factor in advanced gastric cancer in the present study.

Relationship between the risk of bile duct injury during laparoscopic cholecystectomy and the types of preoperative magnetic resonance cholangiopancreatiocography (MRCP)

BACKGROUNDS/AIMS: Bile duct injury is one of the potential severe complications that can occur during laparoscopic cholecystectomy, which can be cause by anatomic variations in the confluence of the bile duct. Recently magnetic resonance cholangiopancreatiocography (MRCP) has become a helpful tool to detect bile duct variation on a preoperative basis and to prevent bile duct injury during laparoscopic cholecystectomy, as well other hepatic surgeries. This study aimed to clarify the types of bile duct on MRCP and to search for a method of avoiding injury during laparoscopic cholecystectomy. METHODS: Between January 2009 and December 2010, 277 patients underwent laparoscopic cholecystectomy with preoperative MRCP in our institution. On a retrospective basis, the bile ducts were categorized into 5 types according to the Couinaud classification system. RESULTS: The proportion of types was revealed type A (70.4%), type B (8.7%), type C (19.5%), type D (0.7%), type E (0%), and type F (0.7%), respectively. Bile duct injury occurred in 4 cases (1.4%) during laparoscopic cholecystectomy. In particular, the possibility of aberrant extrahepatic confluence (Type C and F) represented the highest risk of duct injury (OR=11.89 [CI: 1.21-116.53]). CONCLUSIONS: Preoperative evaluation of the bile duct anatomy is important to avoid injury of duct during laparoscopic cholecystectomy. Specific types of bile duct variation should be considered as a high risk group for bile duct injury.

Cavo-caval intervention stent insertion after deceased-donor liver transplantation using side-to-side piggyback technique: report of a case

Liver transplantation with preservation of the recipient vena cava (piggyback technique) has been performed as an alternative to the conventional method. Outflow disturbance or obstruction of the vena cava in the early period after liver transplantation is associated with high morbidity and mortality. We used side-to-side cavo-caval anastomosis (modified piggyback technique) in a deceased-donor liver transplantation (DDLT) for venous outflow reconstruction. On postoperative day 9, the patient developed abdominal discomfort, and abnormal liver function showing serum total bilirubin of 6.2 mg/dl and serum AST/ALT of 297/597 IU/L. Doppler ultrasound showed mono-phasic wave forms of the hepatic vein. Computed tomography showed focal narrowing of 9.5 mmx12 mm in diameter at the cavo-caval anastomosis site. Liver biopsy was showed that there was no evidence of acute allograft rejection. Direct venogram showed stenosis of the cavo-caval anastomosis with a pressure gradient of 12 mmHg. An interventional stent was inserted in the stenotic site of the inferior vena cava, and the pressure gradient decreased to 2 mmHg. He was discharged from hospital on postoperative day 23 without any other complications. Herein we report a case of deceased-donor liver transplantation using the modified piggyback technique, who received an inferior vena cava stent due to stricture of the reconstructed orifice of the vena cava.

Laparoscopic Resection of an Asymptomatic Intra-Abdominal Lymphangioma / 대한내시경복강경외과학회지

An intra-abdominal cystic lymphangioma is a benign neoplasm that rarely occurs within the abdominal cavity. Intra-abdominal cystic lymphangioma is treated by a resection performed through a radical procedure. We report a case of a 37-year-old woman who had an asymptomatic mesenteric cyst that was discovered incidentally during a routine physical check-up. Treatment was completed without complications using a laparoscope.

A case of pedunculated hepatic hemangioma mimicking submucosal tumor of the stomach / 대한간학회지

Hepatic hemangioma is the most common benign tumor of the liver. Most such hemangiomas are small, asymptomatic, and have an excellent prognosis. Giant hepatic hemangioma has been reported in the literature, but the exophytic and pedunculated forms of hepatic hemangioma are rare. A 56-year-old woman was referred to our hospital under the suspicion of having a gastric submucosal tumor. Abdominal computer tomography (CT) scans showed a pedunculated mass from the left lateral segment of the liver into the gastric fundus, exhibiting the atypical CT findings of hepatic hemangioma. We therefore decided to perform laparoscopic resection based on the symptoms, relatively large diameter, inability to exclude malignancy, and risk of rupture of the exophytic lesion. The pathology indicated it to be a cavernous hemangioma of the liver. Herein we report a case of pedunculated hepatic hemangioma mimicking a submucosal tumor of the stomach due to extrinsic compression of the gastric fundus.

Laparoscopic vs Transumbilical Single-Port Laparoscopic Appendectomy; Results of Prospective Randomized Trial

PURPOSE: Conventional three-port laparoscopic appendectomy (LA) is more commonly performed than transumbilical single port laparoscopic appendectomy (TUSPLA). In this report, we performed a prospective randomized study comparing the outcomes of LA and TUSPLA. METHODS: Between April 14, 2009 and June 10, 2009, 40 patients who required laparoscopic appendectomies were randomly selected to receive either a TUSPLA or a LA. None of these patients had perforation or abscess. Twenty of the patients received a LA and the other 20 received a TUSPLA. The clinical outcomes and visual analog pain scores (VAS) were compared between the groups. RESULTS: The TUSPLA procedures were performed successfully in every indicated patient. Clinical outcomes were similar in both study groups. The TUSPLA group showed a significantly higher VAS score 24 hours postoperatively than the LA group. CONCLUSION: Compared with LA, TUSPLA was technically feasible and safe in patients with non-complicated appendicitis. However, the patients in the TUSPLA group reported more postoperative pain than those in the LA group.

Expression of E-cadherin, Heat Shock Protein 47, Transforming Growth Factor beta1 and C4d in Chronic Allograft Nephropathy / 대한이식학회지

BACKGROUND: Chronic allograft nephropathy (CAN), which causes graft failure, is related to tubular atrophy and interstitial fibrosis. E-cadherin is a well-known epithelial marker and heat shock protein (HSP)-47 is a collagen-specific molecular chaperone that regulates collagen synthesis. Transforming growth factor (TGF)-beta1, a profibrotic cytokine, downregulates E-cadherin and induces expression of mesenchymal markers in an in vitro model. C4d expression is considered a poor prognostic marker for graft survival. This study evaluated the relationship between the expression of E-cadherin, HSP47, TGF-beta1, and C4d with the prognosis for CAN. METHODS: Between March 1991 and August 2007, we performed renal allograft biopsies on 42 recipients with deteriorating renal function. CAN was diagnosed according to the chronic allograft damage index (Banff classification). Renal allograft biopsies were examined for the expression of E-cadherin, HSP47, TGF-beta1, or C4d by immunohistochemistry. The HSP47, TGF-beta1, and E-cadherin staining was scored semiquantitatively by analyzing ten different fields of cortical interstitium and tubules. Biopsies with endothelial C4d staining in peri-tubular capillaries (> or =25%) were designated as C4d-positive. RESULTS: Of 42 recipients, 17 (40.5%) were in the graft survival group (GS) and 25 (59.5%) were in the graft failure group (GF). E-cadherin expression in tubular cells of the GS was much higher than that of the GF (94.1% vs 52%, P=0.04). HSP47 expression in tubular cells and interstitium in the GF was much higher than that in the GS (84% vs 35.3%, P=0.001). TGF-beta1 expression in tubular cells and interstitium in the GF was much higher than that in the GS (72% vs 23.5%, P=0.02). CONCLUSIONS: E-cadherin, HSP47, and TGF-beta1 expression was strongly correlated with the CAN prognosis.

A Case of Paraduodenal Pancreatitis and Immunohistochemical Analysis

Paraduodenal pancreatitis (PP) is a rare, distinct form of chronic pancreatitis, and it is related to alcohol abuse in middle-aged men. A 36-year-old man with a history of chronic recurrent pancreatitis for 4 years and alcohol abuse for 15 years presented with abdominal pain. Computed tomography revealed a multilocular cystic mass 3.2 x 3 x 3 cm in size and it was located within the muscular layer of the duodenal wall. The cysts were lined by a single layer of eosinophilic cuboidal epithelial cells that stained positively for mucin (MUC)1, MUC6, cytokeratin (CK)7 and CK19 and they stained negatively for MUC2, MUC5AC and CK5/6. Mild, chronic inflammatory reaction around the cystic wall, Brunner's gland hyperplasia and several clusters of heterotopic pancreatic tissue were noted. We report here on a case of PP and we demonstrated that the pancreatitis was of pancreatic ductal cell origin according to the MUC and CK expression patterns we observed on the immunohistochemical analysis.

Comparison of New Onset Diabetes according to the Time of Onset in Kidney Transplant Recipients / 대한이식학회지

BACKGROUND: New onset diabetes is a common complication after kidney transplantation. However, the clinical course of post-transplant diabetes mellitus (PTDM) remains unclear. The aim of the present study is to analyze the natural courses and risk factors of PTDM according to the time of onset. METHODS: A total of 216 consecutive kidney transplant recipients were enrolled and patient medical records were investigated retrospectively. PTDM was defined as glucose > or =126mg without previous diabetic history. Patients were classified according to the onset (12 months): early PTDM (E-PTDM) and late PTDM (L-PTDM). RESULTS: PTDM was observed in 34 (17.4%) patients. The number of E-PTDM and L-PTDM patients was 17 and 17. Compared with normoglycemic patients, the PTDM group was older and showed higher pre-transplant HbA1c level. The use of tacrolimus was associated with the development of E-PTDM (OR=4.87, 1.71~13.8 in 95% CI) but not L-PTDM (OR=0.34, 0.04~2.70 in 95% CI) CONCLUSIONS: The development of E-PTDM and L-PTDM may have different risk factors. It will be important to choose different therapeutic strategy according to the onset of PTDM.

Feasibility of Laparoscopic Appendectomy for Complicated Appendicitis / 대한내시경복강경외과학회지

PURPOSE: Laparoscopic appendectomy (LA) is now widely practiced in most medical centers, yet there is no consensus regarding the indications and advantages of LA over the conventional technique. Various reports have demonstrated conflicting results about the merit of LA. Especially, complicated appendicitis was initially considered as a contraindication for LA. However, with the improvements of laparoscopic instruments and the technical proficiency, the choice of the operative approach mostly depends on the surgeon's experience or the patient's preference. Here we compared the outcome of LA versus open appendectomy (OA) overall and specifically in the patients with complicated appendicitis. METHODS: From January 2007 to December 2007, the records of 495 patients with the diagnosis of appendicitis were retrieved from the computer database for analysis. All the patients had given informed consent for LA or the OA technique and the patients chose the operative method. The two groups were compared with respect to the patients' demographic data, the clinical outcomes, the cost and the type of pathology RESULTS: During the study period, 195 patients (39.4%) underwent LA and 300 patients (60.6%) underwent OA. There were 53 cases (27.1%) of complicated appendicitis and 105 cases each (35%) in the LA and OA groups, respectively. The patients of the LA group revealed a significant female prevalence, a shorter hospital stay, less use of analgesics, a lower complication rate and a higher cost (p<0.005), and also a comparable operation time to the OA group. As for the complicated appendicitis, there was benefit for only the hospital stay. CONCLUSION: Usually LA has more advantage than OA except cost. Even in complicated appendicitis, LA is feasible without increase of complication.

Microsatellite Instability and p53 Gene Loss of Heterozygosity in Hepatocellular Carcinoma

PURPOSE: Hepatocellular carcinoma (HCC) shows various molecular and genetic alterations in its development and progression. Recently, microsatellite instability (MSI) and the loss of heterozygosity (LOH), have been postulated as useful prognostic factors in many malignant tumors. LOH is related to the allelic loss of various tumor suppressor genes, however, MSI has been found to be the result of a mismatched DNA pairing. Our objectives were to evaluate MSI and p53 gene LOH and to correlate this to clinicopathological factors. METHODS: MSI analysis was performed by using polymerase chain reaction with 5 microsatellite markers (BAT25, BAT26, D2S123, D5S346 and D17S250 recommended in the 1998 NCI International Workshop) on 50 surgically resected tumors. p53 LOH was detected with 4 markers (D17S796, TP53, D17S5, D17S513). RESULTS: MSI and p53 LOH were detected in 30% and 66%, respectively. 18% of HCCs exhibited MSI in 5 NCI-recommended markers and 18% of HCCs demonstrated MSI in 4 p53 markers. MSI was mostly detected in BAT25 and BAT26 markers. MSI was more frequently detected in tumor grade I, small HCC, and non-lymphovascular group. For the most part, p53 LOH was detected by D17S513 marker (38.1%). p53 LOH results were correlated with higher tumor grade and invasiveness. LOH-High group showed a significant correlation with advanced HCCs and lymphovascular invasion. There was no demonstrated correlation between MSI and p53 LOH was not demonstrated. CONCLUSION: These results suggest that MSI may be involved to some extent in hepatocarcinogenesis and tumor invasion. Also MSI and p53 gene LOH may be a useful clinical indicator in determining the prognosis among patients with HCC.

The Effect of Compliance, Family Support and Graft Function on Quality of Life in Kidney Transplant Recipients / 대한이식학회지

BACKGROUND: Previous studies have shown that kidney transplant recipients' quality of life depend on compliance of treatment, family support, socioeconomic status. The purpose of this study was to determine whether estimated glomerular filtration rate (GFR) by Modification of Diet in Renal Disease (MDRD) study as a index of graft function influence recipients' quality of life including above mentioned factors. METHODS: One hundred and ten patients who visited out-patient department at least 3 months after kidney transplantation were included in this study. A structured questionnaire was used to collect data. This tool included; quality of life, compliance and family support scale as well as medical record review. The analysing of data was performed with SPSS version 11.5 (SPSS Inc. Chicago, IL, USA). RESULTS: The mean score of the recipients' quality of life (3.59/5), compliance (3.81/5), the support of family (4.02/5) and GFR (63 ml/min/1.73 m2) were revealed respectively. The quality of life was correlated with compliance (r=.260, P<.001) and family support (r=.377, P<.001) statistically. and compliance and family support also revealed correlation (r=.452, P<.001). Family support was the most explainable factor for the quality of life (R2=.142). however, the quality of life was not correlated with recipients' GFR (r=.013 P=0.819). CONCLUSIONS: Results of this study showed that kidney transplant recipients had a moderate quality of life. These findings suggest that emotional aspect like family support is as important as clinical factors such as GFR or compliance for recipients' quality of life. To optimize post-transplant quality of life, implication for interventional programming should be focused on family support.

Simultaneous Pancreas-kidney Transplantation from Pediatric Donor: A Case Report / 대한이식학회지

Simultaneous pancreas-kidney (SPK) transplantation is a well-established treatment for patients with insulin-dependent DM complicated by ESRD. The current shortage of cadaver donors and the increasing number of diabetic patients on the transplant waiting list has prompted the use of cadaveric organ from pediatric donors. But the lower age limit of the pancreatic donors has not yet been established. We report the successful result using a 10 years old donor for a 36-year-old SPK transplant recipient.