Background: Given the dual potential of statins to act as both carcinogenic and antineoplastic agents, evidence from previous investigations into statin use and the risk of nonmelanoma skin cancer (NMSC) remains inconclusive. Objective: To demonstrate the impact of statin exposure on the NMSC risk in Korean patients. Methods: We carried out a multicenter cohort study based on electronic health record data aggregated from 11 Korean hospitals. Patients with hyperlipidemia who had been taking antilipidemic agents, including statins were included in this study. We applied 1:1 propensity score matching to create balanced cohorts and used Cox regression to assess the hazard ratio (HR) for NMSC. Results: A total of 18,579 statin users and a matched number of non-users were included across 11 databases. Statin use showed no significant association with an increased risk of NMSC (HR, 1.03; 95% confidence interval, 0.75–1.43). Subgroup analyses of drug exposure, age, and sex depicted no significant HR trends. Conclusion Statin exposure demonstrated no significant association with NMSC development in Korean patients with hyperlipidemia.

Background: Hydrochlorothiazide (HCTZ) has carcinogenic effects owing to its photosensitizing properties. Recent studies have reported inconsistent results regarding the association between HCTZ and skin cancer. Objective: This study aimed to clarify the effects of HCTZ on the risk of developing nonmelanoma skin cancer (NMSC) in Korean patients with hypertension. Methods: This multicenter, retrospective cohort study was conducted using clinical data from 11 hospitals in Korea, and converted to the Observational Medical Outcomes Partnership-Common Data Model. Large-scale 1:1 propensity score-matching was conducted to balance the target and comparator cohorts. Cox regression analysis was used to examine the hazard ratio (HR) for NMSC in HCTZ users compared to HCTZ never-users. Results: 8,821 patients and same number of controls were pooled from 11 databases. HCTZ use was not associated with a decreased risk of NMSC (HR, 1.01; 95% confidence interval [CI], 0.70–1.47). In the dose-response analysis, no significant correlation was found between NMSC risk and HCTZ dose for <1 year (HR, 1.17; 95% CI, 0.64–2.17) and ≥1 year (HR, 1.02; 95% CI, 0.64–1.61). No significant increase in the risk of NMSC was observed in the subgroup analyses for either age or sex. Conclusion HCTZ was not associated with the development of NMSC in a Korean hypertensive population, regardless of the duration of drug exposure.

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.

Background: We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients. Methods: A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001–2008) and the post-intervention (2009–2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patientdays, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ2 . Results: The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = −16.5; 95% confidence interval [CI], −30.6 to −2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881). Conclusion The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.

Background: and Purpose Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke. Methods: This randomized, open-label, controlled trial assigned patients with recent ischemic stroke <90 days to rosuvastatin/ezetimibe 10/10 mg once daily (ROS10/EZT10) or to rosuvastatin 20 mg once daily (ROS20). The primary endpoint was LDL-C reduction ≥50% from baseline at 90 days. Key secondary endpoints were LDL-C <70 mg/dL and multiple lipid goal achievement, and composite of major vascular events. Results: Of 584 randomized, 530 were included in the modified intention-to-treat analysis. The baseline LDL-C level was 130.2±34.7 mg/dL in the ROS10/EZT10 group and 131.0±33.9 mg/dL in the ROS20 group. The primary endpoint was achieved in 198 patients (72.5%) in the ROS10/EZT10 group and 148 (57.6%) in the ROS20 group (odds ratio [95% confidence interval], 1.944 [1.352–2.795]; P= 0.0003). LDL-C level <70 mg/dL was achieved in 80.2% and 65.4% in the ROS10/EZT10 and ROS20 groups (P=0.0001). Multiple lipid goal achievement rate was 71.1% and 53.7% in the ROS10/EZT10 and ROS20 groups (P<0.0001). Major vascular events occurred in 1 patient in the ROS10/EZT10 group and 9 in the ROS20 group (P=0.0091). The adverse event rates did not differ between the two groups. Conclusion Moderate-intensity rosuvastatin plus ezetimibe was superior to high-intensity rosuvastatin alone for intensive LDL-C reduction in patients with recent ischemic stroke. With the combination therapy, more than 70% of patients achieved LDL-C reduction ≥50% and 80% had an LDL-C <70 mg/dL at 90 days.