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.

Objective: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Methods: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Results: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Conclusion Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

BACKGROUND/AIMS: Previous studies have reported a high rate of sustained virologic response (SVR) and a low rate of serious adverse events with the use of daclatasvir (DCV) and asunaprevir (ASV) combination therapy. We evaluated the efficacy and safety of DCV and ASV combination therapy for patients with chronic hepatitis C virus (HCV) genotype 1b infection in real world. METHODS: We enrolled 278 patients (184 treatment-naïve patients) from five hospitals in Daegu and Gyeongsangbuk-do. We evaluated the rates of rapid virologic response (RVR), end-of-treatment response (ETR), and SVR at 12 weeks after completion of treatment (SVR12). Furthermore, we investigated the rate of adverse events and predictive factors of SVR12 failure. RESULTS: The mean age of patients was 59.5 ± 10.6 years, and 140 patients (50.2%) were men. Seventy-seven patients had cirrhosis. Baseline information regarding nonstructural protein 5A (NS5A) sequences was available in 268 patients. Six patients presented with pretreatment NS5A resistance-associated variants. The RVR and the ETR rates were 96.6% (258/267) and 95.2% (223/232), respectively. The overall SVR12 rate was 91.6% (197/215). Adverse events occurred in 17 patients (7.9%). Six patients discontinued treatment because of liver enzyme elevation (n = 4) and severe nausea (n = 2). Among these, four achieved SVR12. Other adverse events observed were fatigue, headache, diarrhea, dizziness, loss of appetite, skin rash, and dyspnea. Univariate analysis did not show significant predictive factors of SVR12 failure. CONCLUSIONS DCV and ASV combination therapy showed high rates of RVR, ETR, and SVR12 in chronic HCV genotype 1b-infected patients in real world and was well tolerated without serious adverse events.

PURPOSE: Colostomy creation is an essential procedure for colorectal surgeons, but the preferred method of colostomy varies by surgeon. We compared the outcomes of trephine colostomy creation with open those for the (laparotomy) and laparoscopic methods and evaluated appropriate indications for a trephine colostomy and the advantages of the technique. METHODS: We retrospectively evaluated 263 patients who had undergone colostomy creation by trephine, open and laparoscopic approaches between April 2006 and March 2016. We compared the clinical features and the operative and postoperative outcomes according to the approach used for stoma creation. RESULTS: One hundred sixty-three patients (62%) underwent colostomy surgery for obstructive causes and 100 (38%) for fistulous problems. The mean operative time was significantly shorter with the trephine approach (trephine, 46.0 ± 1.9 minutes; open, 78.7 ± 3.9 minutes; laparoscopic, 63.5 ± 5.0 minutes; P < 0.001), as was the time to flatus (1.8 ± 0.1 days, 2.1 ± 0.1 days, 2.2 ± 0.3 days, P = 0.025). Postoperative complications (<30 days) were not different among the 3 approaches (trephine, 4.3%; open, 1.2%; laparoscopic, 0%; P = 0.828). In patients who underwent rectal surgery, a trephine colostomy was feasible for a diversion colostomy (P < 0.001). CONCLUSION: The trephine colostomy is safe and can be implemented quickly in various situations, and compared to other colostomy procedures, the patient's recovery is faster. Previous laparotomy history was not a contraindication for a trephine colostomy, and a trephine transverse colostomy is feasible for patients who have undergone previous rectal surgery.
Colostomy* ; Flatulence ; Humans ; Laparotomy ; Methods ; Operative Time ; Postoperative Complications ; Retrospective Studies ; Surgeons

PURPOSE: This study investigated the role of the education level (EL) as a prognostic factor for breast cancer and analyzed the relationship between the EL and various confounding factors. MATERIALS AND METHODS: The data for 64,129 primary breast cancer patients from the Korean Breast Cancer Registry were analyzed. The EL was classified into two groups according to the education period; the high EL group (≥ 12 years) and low EL group (< 12 years). Survival analyses were performed with respect to the overall survival between the two groups. RESULTS: A high EL conferred a superior prognosis compared to a low EL in the subgroup aged > 50 years (hazard ratio, 0.626; 95% confidence interval [CI], 0.577 to 0.678) but not in the subgroup aged ≤ 50 years (hazard ratio, 0.941; 95% CI, 0.865 to 1.024). The EL was a significant independent factor in the subgroup aged > 50 years according to multivariate analyses. The high EL group showed more favorable clinicopathologic features and a higher proportion of patients in this group received lumpectomy, radiation therapy, and endocrine therapy. In the high EL group, a higher proportion of patients received chemotherapy in the subgroups with unfavorable clinicopathologic features. The EL was a significant prognosticator across all molecular subtypes of breast cancer. CONCLUSION: The EL is a strong independent prognostic factor for breast cancer in the subgroup aged > 50 years regardless of the molecular subtype, but not in the subgroup aged ≤ 50 years. Favorable clinicopathologic features and active treatments can explain the main causality of the superior prognosis in the high EL group.
Breast Neoplasms* ; Breast* ; Drug Therapy ; Education* ; Educational Status ; Humans ; Mastectomy, Segmental ; Multivariate Analysis ; Prognosis ; Survival Analysis

Idiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia. Minimal change nephrotic syndrome (MCNS) is the most common form of INS in children. The pathogenesis of MCNS still remains unclear, however, several hypotheses have been recently proposed. For several decades, MCNS has been considered a T-cell disorder, which causes the impairment of the glomerular filtration barrier with the release of different circulating factors. Increased levels of several cytokines are also suggested. Recently, a "two-hit" theory was proposed that included the induction of CD80 (B7-1) and regulatory T-cell (Treg) dysfunction, with or without impaired autoregulatory functions of the podocyte. In contrast to the well-established involvement of T cells, the role of B cells has not been clearly identified. However, B-cell biology has recently gained more attention, because rituximab (a monoclonal antibody directed against CD20-bearing cells) demonstrated a very good therapeutic response in the treatment of childhood and adult MCNS. Here, we discuss recent insights into the pathogenesis of MCNS in children.
Adult ; B-Lymphocytes ; Biology ; Child ; Cytokines ; Glomerular Filtration Barrier ; Humans ; Hypoalbuminemia ; Nephrosis, Lipoid* ; Nephrotic Syndrome ; Podocytes ; Proteinuria ; Rituximab ; T-Lymphocytes

PURPOSE: Colorectal obstruction develops most frequently by carcinoma, and 7%–30% of these colorectal carcinomas are acute cases. The oncologic safety of self-expanding metal stent (SEMS) insertion as a bridge to surgery has not yet been established. Thus, we investigated the oncologic safety of SEMS insertion as a bridge to surgery in patients with obstructive colorectal cancer.METHODS: This retrospective had 56 patients enrolled requiring emergency management for obstructive colorectal cancer at stage II or III, who had undergone curative surgery between July 2008 and June 2011. These subjects were divided into two groups: patients who had undergone emergency surgery without SEMS insertion (non-stent group) and those who had undergone elective surgery after preoperative decompression with SEMS insertion (stent group). The two groups were compared for clinicopathologic characteristics, postoperative complications, and survival rate.RESULTS: Enterostomy was performed in 25 patients (100.0%) in the non-stent group and 1 patient (3.2%) in the stent group; laparoscopic surgery was carried out in 7 patients (28.0%) in the non-stent group and 19 patients (61.29%) in the stent group, each showing statistically significant differences. There was no statistically significant difference in postoperative complications and 5-year disease-free survival rate (72% vs. 74.19%, P=0.87, respectively).CONCLUSION: In treatment of malignant colorectal obstruction, elective operation after stent insertion had similar oncologic outcomes compared with emergency operation. Preoperative stent insertion not only lowers the incidence of enterostomy but also makes laparoscopic surgery possible, thereby enhancing patients' quality of life. Therefore, preoperative stent insertion is a useful method that may replace emergency surgery in treatment of malignant colorectal obstruction.
Colorectal Neoplasms ; Decompression ; Disease-Free Survival ; Emergencies ; Enterostomy ; Humans ; Incidence ; Intestinal Obstruction ; Laparoscopy ; Methods ; Postoperative Complications ; Quality of Life ; Retrospective Studies ; Stents ; Survival Rate

No abstract available.
Blood Glucose* ; Glucose*