Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

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.

Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are associated with the risk of metachronous advanced neoplasia. Postpolypectomy surveillance is the most important method for managing advanced metachronous neoplasia. A more efficient and evidence-based guideline for postpolypectomy surveillance is required because of the limited medical resources and concerns regarding colonoscopy complications. In these consensus guidelines, an analytic approach was used to address all reliable evidence to interpret the predictors of CRC or advanced neoplasia during surveillance colonoscopy. The key recommendations state that the high-risk findings for metachronous CRC following polypectomy are as follows: adenoma ≥10 mm in size; 3 to 5 (or more) adenomas; tubulovillous or villous adenoma; adenoma containing high-grade dysplasia; traditional serrated adenoma; sessile serrated lesion containing any grade of dysplasia; serrated polyp of at least 10 mm in size; and 3 to 5 (or more) sessile serrated lesions. More studies are needed to fully comprehend the patients who are most likely to benefit from surveillance colonoscopy and the ideal surveillance interval to prevent metachronous CRC.

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.

Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are associated with the risk of metachronous advanced neoplasia. Postpolypectomy surveillance is the most important method for managing advanced metachronous neoplasia. A more efficient and evidence-based guideline for postpolypectomy surveillance is required because of the limited medical resources and concerns regarding colonoscopy complications. In these consensus guidelines, an analytic approach was used to address all reliable evidence to interpret the predictors of CRC or advanced neoplasia during surveillance colonoscopy. The key recommendations state that the high-risk findings for metachronous CRC following polypectomy are as follows: 1) adenoma ≥10 mm in size; 2) 3-5 (or more) adenomas; 3) tubulovillous or villous adenoma; 4) adenoma containing high-grade dysplasia; 5) traditional serrated adenoma; 6) sessile serrated lesion (SSL) containing any grade of dysplasia; 7) serrated polyp of at least 10 mm in size; and 8) 3-5 (or more) SSLs. More studies are needed to fully comprehend the patients who are most likely to benefit from surveillance colonoscopy and the ideal surveillance interval to prevent metachronous CRC.

Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are associated with the risk of metachronous advanced neoplasia. Postpolypectomy surveillance is the most important method for the management of advanced metachronous neoplasia. A more efficient and evidence-based guideline for postpolypectomy surveillance is required because of limited medical resources and concerns regarding colonoscopy complications. In these consensus guidelines, an analytic approach was used to address all reliable evidence to interpret the predictors of CRC or advanced neoplasia during surveillance colonoscopy. The key recommendations state that the high-risk findings for metachronous CRC following polypectomy are as follows: (1) adenoma ≥10 mm in size; (2) 3 to 5 (or more) adenomas; (3) tubulovillous or villous adenoma; (4) adenoma containing high-grade dysplasia; (5) traditional serrated adenoma; (6) sessile serrated lesion (SSL) containing any grade of dysplasia; (7) serrated polyp of at least 10 mm in size; and (8) 3 to 5 (or more) SSLs. More studies are needed to fully comprehend the patients most likely to benefit from surveillance colonoscopy and the ideal surveillance interval to prevent metachronous CRC.

Background: Antineutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AAGN) is a common cause of rapidly progressive glomerulonephritis and requires prompt and proper immunosuppressive therapy to improve renal prognosis. This study aimed to evaluate the predictive value of two different classifications for renal outcomes in Korean AAGN patients. Methods: Ninety-two patients who were diagnosed with AAGN at two tertiary hospitals between 2004 and 2018 were retrospectively analyzed retrospectively. The histopathologic classification according to glomerular pathology and the clinicopathologic classification according to normal glomeruli ratio, degree of interstitial fibrosis/tubular atrophy, and baseline renal function were evaluated using the Cox proportional hazards model. Results: Forty-five patients (48.9%) progressed to end-stage kidney disease (ESKD) during the observation period. The mean age was 61.0 ± 15.3 years, and most patients had myeloperoxidase-ANCA (93.5%). In the histopathologic classification, the best renal survival occurred in the focal class, whereas the sclerotic class had the worst renal survival (sclerotic class vs. focal class; adjusted hazard ratio [aHR], 5.05; 95% confidence interval [CI], 1.32–19.31; p = 0.018). The mixed class had intermediate renal outcomes (mixed class vs. focal class; aHR, 4.23; 95% CI, 1.23–14.58; p = 0.022). In the clinicopathologic classification, the high-risk group had poor renal outcomes compared with the low-risk group (aHR, 6.56; 95% CI, 1.25–34.26; p = 0.026), but renal outcomes did not differ between the low- and medium-risk groups. Conclusion In Korean AAGN patients, histopathologic and clinicopathologic classifications had predictive value for renal outcomes, especially in the sclerotic class or the high-risk group with higher risk of progression to ESRD despite treatment.

Background: Antineutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AAGN) is a common cause of rapidly progressive glomerulonephritis and requires prompt and proper immunosuppressive therapy to improve renal prognosis. This study aimed to evaluate the predictive value of two different classifications for renal outcomes in Korean AAGN patients. Methods: Ninety-two patients who were diagnosed with AAGN at two tertiary hospitals between 2004 and 2018 were retrospectively analyzed retrospectively. The histopathologic classification according to glomerular pathology and the clinicopathologic classification according to normal glomeruli ratio, degree of interstitial fibrosis/tubular atrophy, and baseline renal function were evaluated using the Cox proportional hazards model. Results: Forty-five patients (48.9%) progressed to end-stage kidney disease (ESKD) during the observation period. The mean age was 61.0 ± 15.3 years, and most patients had myeloperoxidase-ANCA (93.5%). In the histopathologic classification, the best renal survival occurred in the focal class, whereas the sclerotic class had the worst renal survival (sclerotic class vs. focal class; adjusted hazard ratio [aHR], 5.05; 95% confidence interval [CI], 1.32–19.31; p = 0.018). The mixed class had intermediate renal outcomes (mixed class vs. focal class; aHR, 4.23; 95% CI, 1.23–14.58; p = 0.022). In the clinicopathologic classification, the high-risk group had poor renal outcomes compared with the low-risk group (aHR, 6.56; 95% CI, 1.25–34.26; p = 0.026), but renal outcomes did not differ between the low- and medium-risk groups. Conclusion In Korean AAGN patients, histopathologic and clinicopathologic classifications had predictive value for renal outcomes, especially in the sclerotic class or the high-risk group with higher risk of progression to ESRD despite treatment.

Background: We investigated the changing patterns of insulin secretion and resistance and risk factors contributing to the development of post-transplant diabetes mellitus (PTDM) in kidney recipients under tacrolimus-based immunosuppression regimen during 1 year after transplantation. Methods: This was a multicenter prospective cohort study. Of the 168 subjects enrolled in this study, we analyzed a total 87 kidney transplant recipients without diabetes which was assessed by oral glucose tolerance test before transplantation. We evaluated the incidence of PTDM and followed up the index of insulin secretion (insulinogenic index [IGI]) and resistance (homeostatic model assessment for insulin resistance [HOMA-IR]) at 3, 6, 9 months, and 1 year after transplantation by oral glucose tolerance test and diabetes treatment. We also assessed the risk factors for incident PTDM. Results: PTDM developed in 23 of 87 subjects (26.4%) during 1 year after transplantation. More than half of total PTDM (56.5%) occurred in the first 3 months after transplantation. During 1 year after transplantation, insulin resistance (HOMA-IR) was increased in both PTDM and no PTDM group. In no PTDM group, the increase in insulin secretory function to overcome insulin resistance was also observed. However, PTDM group showed no increase in insulin secretion function (IGI). Old age, status of prediabetes and episode of acute rejection were significantly associated with the development of PTDM. Conclusion In tacrolimus-based immunosuppressive drugs regimen, impaired insulin secretory function for reduced insulin sensitivity contributed to the development of PTDM than insulin resistance during 1 year after transplantation.