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.

An arachnoid cyst is a rare cerebrospinal fluid–filled non-neoplastic cystic lesion. Most arachnoid cysts are asymptomatic; however, depending on their location and size, they may show various clinical symptoms and rarely can cause serious complications. We report a case of an arachnoid cyst incidentally found in a 25-year-old male soldier, which was not the cause of death. A 2.3×1.7 cm unilocular cystic lesion filled with colorless serous fluid was observed near the interpeduncular fossa of the brain. Microscopy revealed the cyst membrane to be lined by a single layer of meningothelial cells with no edema or inflammatory reaction in the surrounding structures. Considering the medical history, circumstances of death, and autopsy findings, the cause of death was determined to be sudden cardiac death, and the cyst found in the brain was consistent with an arachnoid cyst. Reviewing this case and related literature would help to determine the cause and manner of death if an arachnoid cyst is incidentally found during an autopsy.

Calcific aortic valve disease (CAVD) is an uncommon disease in young adults, unless there is a congenital anomaly in the aortic valve. We report a case of CAVD identified during the autopsy of a 26-year-old male soldier who died in his room while sitting on a chair. Macroscopic examination revealed multiple nodules in the semilunar cusps of the aortic valve, and that the commissure of semilunar valve cusps was slightly fused. Under microscopic examination, fibrotic nodules with neovascularization were identified in the fibrosa layer of the aortic valve, although neither calcification nor chronic inflammation were identified in the fibrotic nodule. Mitral valve prolapse and left ventricular hypertrophy with interstitial fibrosis were also identified. Microscopic examination of CAVD typically shows calcified nodules in the fibrosa layer of the valve, but fibrosis alone, without calcification, can be observed in the early stage of the disease. Death from CAVD is rare in young adults, so careful examination must be taken not to misdiagnose this condition with rheumatic valvular disease, which is relatively common in this population.

Background/Aims: Long-term use of acid suppressants such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonist (H2RA) has been associated with the risk of osteoporotic fracture. Acid suppressants and muco-protective agents (MPAs) are often used together as anti-ulcer agents. We evaluated the association between the risk of osteoporotic fracture and the combined use of these anti-peptic agents. Methods: A population-based case-control study was conducted by analyzing the Korean National Health Insurance Data from 2014 to 2020. Patients who had been prescribed anti-peptic agents, such as PPI, H2RA, or MPA, were included. Considering the incidence of osteoporotic fractures, the case group (n = 14,704) and control group (n = 58,816) were classified by 1:4 matching based on age and sex. Results: The use of all types of anti-peptic agents was associated with an increased risk of osteoporotic fractures (PPI: hazard osteoratio [HR], 1.31; H2RA: HR, 1.44; and MPA: HR, 1.33; all p < 0.001). Compared to PPI alone, the combined use of “PPI and H2RA” (HR, 1.58; p = 0.010) as well as “PPI, H2RA, and MPA” (HR, 1.71; p = 0.001) was associated with an increased risk of osteoporotic fracture. However, compared with PPI alone, “MPA and PPI or H2RA” was not associated with an increased risk of osteoporotic fracture. Conclusions This study found that the combined use of “PPI and H2RA” was associated with a higher risk of osteoporotic fractures. In cases where deemed necessary, the physicians may initially consider prescribing the combination use of MPA.

Background/Aims: Mucoprotective agents, such as eupatilin, are often prescribed to prevent gastrointestinal (GI) bleeding in addition to an acid suppressant despite the absence of a large-scale study. We evaluated the additional effect of eupatilin on the prevention of GI bleeding in both the upper and lower GI tract in concomitant aspirin and acid suppressant users using the nationwide database of national claims data from the Korean National Health Insurance Service (NHIS). Methods: An aspirin cohort was constructed using the NHIS claims data from 2013 to 2020. Patients who manifested with hematemesis, melena, or hematochezia were considered to have GI bleeding. A Cox proportional hazards regression model was used to determine the risk factors for GI bleeding associated with the concomitant use of GI drugs and other covariates among aspirin users. Results: Overall, a total of 432,208 aspirin users were included. The concurrent use of an acid suppressant and eupatilin (hazard ratio [HR] = 0.85, p = 0.016, vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Moreover, a more than 3-month duration (HR = 0.88, p = 0.030) of acid suppressant and eupatilin prescription (vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Conclusions Eupatilin administration for ≥ 3 months showed additional preventive effect on GI bleeding in concomitant aspirin and acid suppressant users. Thus, cotreatment with eupatilin with a duration of 3 months or longer is recommended for reducing GI bleeding among aspirin plus acid suppressant users.

Although most cerebral aneurysms are considered as acquired degenerative lesions, diverse anatomical variations in the circle of Willis have been encountered, some of which may play an important role in lesion hemodynamics and pathogenesis. The coalescence of the small vascular plexus to form the anterior communicating artery at the 6-7-week embryological stage may lead to developmental variations, such as fenestration and duplication. Herein, we report a rare anatomical variant of the anterior communicating artery that was concomitantly identified with a ruptured aneurysm. Both the right and left anterior cerebral arteries were connected by three anterior communicating arteries. A vertical segmental artery was present and connected the two anterior communicating arteries, forming an H-shape or plexiform structure. Furthermore, a 0.6×0.4 cm-sized saccular aneurysm with antero-inferior projection was present in the middle anterior communicating artery. The combination of triplication and H-shape in the present case was compared to previously reported anatomical variants.

Background/Aims: We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. Methods: A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)–28– erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). Results: Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. Conclusions Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

We present an autopsy case of a 19-year-old man with a history of epilepsy whose unwitnessed sudden death occurred unexpectedly in the night. About 4 years before death, he was diagnosed with unilateral optic neuritis (ON). Demyelinating disease was suspected, but he was lost to follow up after the recovery. Six months before death, he received a second dose of mRNA coronavirus disease 2019 (COVID-19) vaccine. Three months before death, he experienced epileptic seizures for the first time. Seventeen days before death, he was infected with COVID-19, which showed self-limited course under home isolation. Several days before death, he complained of seizures again at night. Autopsy revealed multifocal gray-tan discoloration in the cerebrum. Histologically, the lesions consisted of active and inactive demyelinated plaques in the perivenous area of the white matter. Perivascular lymphocytic infiltration and microglial cell proliferation were observed in both white matter and cortex. The other major organs including heart and lung were unremarkable. Based on the antemortem history and postmortem findings, the cause of death was determined to be multiple sclerosis with suspected exacerbation. The direct or indirect involvement of cortex and deep gray matter by exacerbated multiple sclerosis may explain the occurrence of seizures. Considering the absence of other structural abnormalities except the inflammatory demyelination of the cerebrum, fatal arrhythmia or laryngospasm in the terminal epileptic seizure may explain his sudden unexpected death in the benign circumstances. In this case, the onset of seizure was preceded by COVID-19 vaccination, and the exacerbation of seizure was preceded by COVID-19 infection, respectively. Literature reporting first manifestation or relapse of multiple sclerosis temporally associated with COVID-19 vaccination or infection are reviewed.

Shallow water blackout (SWB) is defined as loss of consciousness due to hypoxia during underwater swimming or breath-holding, usually in shallow waters. To date, no cases of SWB-induced drowning have been reported in the Republic of Korea. Here, we report two cases of SWB, followed by drowning, with autopsy findings. Two men, aged 20 (case 1) and 25 (case 2) years, suddenly lost their consciousness during underwater swimming and escape training, respectively. Postmortem examination revealed foamy fluid within trachea and bronchus, pulmonary edema, and sphenoid sinus fluid, which are commonly observed findings in drowning cases. None of the organs in either case showed pathologic alterations, except for hypoplastic coronary artery disease incidentally found in case 2. Pathologists should be aware of this distinct pathologic entity to avoid misdiagnosing the cause or manner of death.

Hypoplastic coronary artery disease (HCAD) is a rare congenital abnormality characterized by underdevelopment of one or more major branches of the coronary arteries, which may lead to myocardial infarction and sudden death. We report a case of HCAD that was incidentally detected during autopsy in a 25-year-old male soldier who died during underwater escape training. On macroscopic examination, the right coronary artery measured 1 mm in diameter, which was significantly smaller than that of other coronary arteries. We observed no anomalies in addition to HCAD. Death was attributed to drowning, which was consistent with autopsy findings and the circumstances of death. Although extremely rare, if sudden cardiac death is suspected in children and young adults, it must be confirmed through careful evaluation.