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.

Background: Respiratory syncytial virus (RSV), a highly transmissible virus, is the leading cause of lower respiratory tract infections. We examined molecular changes in the RSV genome before and after the coronavirus disease 2019 (COVID-19) pandemic in Korea, and investigated whether drug-resistant mutations were present. Methods: In this prospective, single-center study, RSV-positive respiratory samples were collected between September 2019 and December 2022. Long-read whole-genome sequencing (WGS) was performed, and the presence of known drug-resistant substitutions for palivizumab, nirsevimab, and suptavumab was investigated. Results: Overall, 288 respiratory samples were collected from 276 children. WGS data were available for 133 samples (71 and 62 samples from the pre- and post-pandemic periods, respectively). All RSV-A strains (n = 56) belonged to the GA2.3.5 (ON1) genotype, whereas all RSV-B strains (n = 77) belonged to the GB5.0.5a (BA) genotype. No significant differences in genotypes were observed between the pre- and post-pandemic periods. In addition, no notable mutations related to nirsevimab or palivizumab resistance were detected in the F gene. However, the L172Q and S173L substitutions, which are known to confer resistance to suptavumab, were present in all RSV-B samples. Conclusion Despite the unprecedented interruption of RSV seasonality, there were no significant molecular changes in circulating RSV strains in Korea related to nirsevimab or palivizumab resistance before and after the COVID-19 pandemic. However, RSV-specific drug-resistance substitutions for suptavumab were identified.

The effectiveness of corticosteroids in preventing immune reconstitution inflammatory syndrome in non-human immunodeficiency viruses Pneumocystis carinii pneumonia (PCP) patients, such as severe combined immunodeficiency (SCID) patients, is controversial. We experienced a paradoxical reaction during severe PCP treatment in a SCID infant, which responded well to adjuvant corticosteroids.

Background/Aims: It remains unclear which maintenance treatment modality is most appropriate for mild gastroesophageal reflux disease (GERD).We aimed to compare on-demand treatment with continuous treatment using a proton pump inhibitor (PPI) in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis. Methods: Patients whose GERD symptoms improved after 4 weeks of standard dose PPI treatment were prospectively enrolled at 25 hospitals.Subsequently, the enrolled patients were randomly assigned to either an on-demand or a continuous maintenance treatment group, and followed in an 8-week interval for up to 24 weeks. Results: A total of 304 patients were randomized to maintenance treatment (continuous, n = 151 vs on-demand, n = 153). The primary outcome, the overall proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the noninferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%). Compared with the on-demand group, the GERD symptom and health-related quality of life scores significantly more improved and the overall satisfaction score was significantly higher in the continuous treatment group, particularly at week 8 and week 16 of maintenance treatment. Work impairment scores were not different in the 2 groups, but the prescription cost was less in the on-demand group. Serum gastrin levels significantly elevated in the continuous treatment group, but not in the on-demand group. Conclusions Continuous treatment seems to be more appropriate for the initial maintenance treatment of non-erosive GERD or mild erosive esophagitis than on-demand treatment. Stepping down to on-demand treatment needs to be considered after a sufficient period of continuous treatment.

Severely worn dentition causes various complications such as loss of tooth structure, discoloration, pulp complications and loss of function and aesthetics. In this case, the patient showed particularly severe attrition in the anterior teeth and lack of space for restoration. The amount of vertical dimension was determined based on the diagnostic wax up, and the patient’s adaptation was evaluated by using a removable occlusal splint for 6 weeks. Thereafter, the coordination of the muscular nervous system, aesthetics, temporomandibular joint were re-evaluated for 3 months by restoring the fixed provisional restoration. Through the above treatment process, the final restoration was completed with full mouth fixed prosthesis using monolithic zirconia, and functionally and aesthetically stable results were obtained.

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.

Background: Interscalene brachial plexus block (ISBPB) is commonly used with general anesthesia for postoperative pain management in shoulder surgery. This study investigated the incidence of hypothermia and changes in the body temperature in patients undergoing arthroscopic shoulder surgery under ISBPB with propofol sedation. Methods: This retrospective study enrolled 220 patients who underwent arthroscopic shoulder surgery. Patients were divided into general anesthesia (n = 34) and ISBPB with propofol sedation (n = 186) groups, and medical records were retrospectively compared. In addition, patients from the ISBPB group were further divided according to age (elderly, [≥ 65 years]; n = 98 vs. young, [< 65 years]; n = 88), and the incidence of hypothermia and changes in the body temperature were compared. Results: Twenty-seven patients (12.3%) experienced perioperative hypothermia (range; 35.3–35.9℃). The incidence of perioperative hypothermia was 29.4% and 9.1% in the general anesthesia and ISBPB groups, respectively, and there was a significant difference between the two groups (P = 0.002). The incidence of perioperative hypothermia according to age in the ISBPB group was 9.2% and 9.1% in the elderly and young groups, respectively, and there was no significant difference between the two groups (P = 0.983). Conclusions The incidence of perioperative hypothermia during arthroscopic shoulder surgery under ISBPB with propofol sedation is lower than that under general anesthesia. Furthermore, when using ISBPB with propofol sedation, the incidence of perioperative hypothermia in elderly patients is similar to that in younger patients.

Enterocytozoon bieneusi is a microsporidian pathogen. Recently, the equestrian population is increasing in Korea. The horse-related zoonotic pathogens, including E. bieneusi, are concerns of public health. A total of 1,200 horse fecal samples were collected from riding centers and breeding farms in Jeju Island and inland areas. Of the fecal samples 15 (1.3%) were PCR positive for E. bieneusi. Interestingly, all positive samples came from Jeju Island. Diarrhea and infection in foals were related. Two genotypes (horse1, horse2) were identified as possible zoonotic groups requiring continuous monitoring.

Background: Oocyte retrieval is the most important procedure in in vitro fertilization (IVF). Various anesthetic methods are used to control a patient’s anxiety and pain during IVF; however, there are no recommended anesthetic methods at present. In this study, we retrospectively investigated chemical pregnancy rates according to the anesthetic method used for oocyte retrieval. Methods: We reviewed records of patients who underwent oocyte retrieval between January 1, 2012 and December 31, 2017. Patients were divided into the spinal anesthesia (SA) and monitored anesthesia care (MAC) groups. The primary outcome was chemical pregnancy rate after IVF. Results: The study included 95 patients. SA was administered in 77 (81%) and MAC in 18 (19%). The overall chemical pregnancy rate was 32.6% (31/95). According to the anesthetic method, the pregnancy rate was 32.5% (25/77) in the SA group and 33.3% (6/18) in the MAC group. There was no statistical difference in the pregnancy rate between the groups (P = 0.575). The procedural time was significantly shorter in the SA group than in the MAC group (P < 0.001). Conclusions Chemical pregnancy rates were not significantly different between the SA and MAC groups. However, the procedure duration was shorter in the SA group than in the MAC group.