Objective: As the demand for community mental health services continues to grow, the need for well-equipped and organized services has become apparent. This study aimed to optimize the roles and infrastructure of mental health services, by establishing, among other initiatives, standardized operating models. Methods: The study was conducted in multiple phases from May 12, 2021, to December 29, 2021. Stakeholders within South Korea and metropolitan mental health welfare centers were targeted, but addiction management support centers, including officials, patients, and their families, were integrated as well. A literature review and survey, focus group interviews, a Delphi survey, and expert consultation contributed to comprehensive revisions and improvements of the mental health service model. Results: The proposed model for community mental health welfare centers emphasizes the expansion of personnel and infrastructure, with a focus on severe mental illnesses and suicide prevention. The model for metropolitan mental health welfare centers delineates essential tasks in areas such as project planning and establishment, community research, and education about severe mental illnesses. The establishment of a 24-hour emergency intervention center was a crucial feature. In the integrated addiction support center model, the need to promote addiction management is defined as an essential task and the establishment of national governance for addiction policies is recommended. Conclusion This study proposed standard operating models for three types of mental health service centers. To meet the increasing need for community care, robust mental health service delivery systems are of primary importance.

Patients with ectodermal dysplasia often have atrophied alveolar bone and an inadequate maxillomandibular relationship owing to congenital edentulism.Accurate implant placement that can overcomes anatomical limitations and orthognathic surgery to improve the maxillomandibular relationship is necessary for creating implant-supported prosthesis for these patients. Implant placement and provisional prosthesis fabrication before orthognathic surgery can provide critical fixed reference points and ensure accuracy during orthognathic surgery.In our patient, a digital system was used to design a surgical guide that considered the predictable position of the definitive prosthesis, allowing the placement of implants to overcome anatomical limitations and the creation of fixed reference points via the delivery of a provisional prosthesis for effective orthognathic surgery. The lack of compensation during orthognathic surgery was considered in the definitive prosthesis. As a result, a prosthesis with a minimal anterior cantilever was fabricated. This study aimed to determine the appropriate sequence of multidisciplinary collaborations that would, result in the best functional and aesthetic outcomes.

Background/Aims: Cytomegalovirus (CMV) disease in the upper gastrointestinal (UGI) tract frequently occurs in immunocompromised patients. However, data regarding UGI CMV disease in non-transplant patients compared with those in transplant recipients are limited. Therefore, we compared the clinical characteristics, endoscopic findings, and outcomes of UGI CMV disease in non-transplant patients with those in transplant recipients. Methods: We reviewed the medical records of patients diagnosed with UGI CMV disease between May 1999 and January 2022. UGI CMV disease was defined as symptoms or signs of gastrointestinal disease with typical findings of CMV inclusion body and positive immunochemistry stain or CMV polymerase chain reaction from the endoscopic biopsy specimen. Results: Among the 219 eligible patients, 132 (60.3%) were transplant patients. Age, male sex, and Charlson Comorbidity Index were significantly higher in the non-transplant group than in the transplant group. The most common symptoms were pain and odynophagia (43.8%). Transplant recipients more frequently experienced UGI CMV disease in the stomach than non-transplant patients, typically presenting as erosions or mucosal hyperemia. However, non-transplant patients more commonly experienced UGI CMV disease in the esophagus than transplant recipients, typically presenting as ulcers. The transplant group had a significantly higher clinical response than the non-transplant group. Conclusions UGI CMV disease in transplant patients can be present in the stomach in various forms, including ulcers or erosions. In transplant patients suspected of UGI CMV disease, conducting an esophagogastroduodenoscopy with tissue biopsy in any area where even the slightest mucosal abnormality is observed is essential to facilitate a prompt diagnosis.

Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs—E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine—on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses.Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Background: Although an appropriate weight management strategy is essential for obese individuals, weight loss can have adverse effects on bone mineral density (BMD). We conducted a systematic review of randomized controlled trials to evaluate changes in BMD after the implementation of various weight loss strategies. Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched to find articles published from database inception until June 2023. Randomized controlled trials of various treatments for obese patients that reported changes in BMD were selected. The primary outcome was BMD of the whole body, lumbar spine, and total hip, measured using dual X-ray absorptiometry. Results: Eighteen randomized controlled trials involving 2,510 participants with obesity were included in the analysis. At follow-up examination, the BMD of the lumbar spine decreased significantly after metabolic surgery (mean difference [MD]= –0.40 g/cm2 ; 95% confidence interval [CI], –0.73 to –0.07; I2 = 0%); lifestyle and pharmacological interventions did not result in a significant decrease in BMD at any location. Metabolic surgery also produced the most substantial difference in weight, with an MD of –3.14 (95% CI, –3.82 to –2.47). Conclusion This meta-analysis is the first to examine the effects of all categories of anti-obesity strategies, including the use of anti-obesity medications, on BMD. Bariatric metabolic surgery can have adverse effects on BMD. Moreover, medications can be used as a treatment for weight loss without compromising bone quality.

Background: Epidermal growth factor receptor (EGFR) gene mutation testing is crucial for the administration of tyrosine kinase inhibitors to treat non–small cell lung cancer. In addition to traditional tissue-based tests, liquid biopsies using plasma are increasingly utilized, particularly for detecting T790M mutations. This study compared tissue- and plasma-based EGFR testing methods. Methods: A total of 248 patients were tested for EGFR mutations using tissue and plasma samples from 2018 to 2023 at Pusan National University Yangsan Hospital. Tissue tests were performed using PANAmutyper, and plasma tests were performed using the Cobas EGFR Mutation Test v2. Results: All 248 patients underwent tissue-based EGFR testing, and 245 (98.8%) showed positive results. Of the 408 plasma tests, 237 (58.1%) were positive. For the T790M mutation, tissue biopsies were performed 87 times in 69 patients, and 30 positive cases (38.6%) were detected. Plasma testing for the T790M mutation was conducted 333 times in 207 patients, yielding 62 positive results (18.6%). Of these, 57 (27.5%) were confirmed to have the mutation via plasma testing. Combined tissue and plasma tests for the T790M mutation were positive in nine patients (13.4%), while 17 (25.4%) were positive in tissue only and 12 (17.9%) in plasma only. This mutation was not detected in 28 patients (43.3%). Conclusions Although the tissue- and plasma-based tests showed a sensitivity of 37.3% and 32.8%, respectively, combined testing increased the detection rate to 56.7%. Thus, neither test demonstrated superiority, rather, they were complementary.

Background: Remimazolam is a novel short-acting benzodiazepine. This study compared the effects of remimazolam and propofol on cognitive function in adult patients after surgery or other procedures. Methods: We searched electronic databases, including PubMed, Embase, CENTRAL, Web of Science, and Scopus, for relevant studies. The primary outcome was the proportion of participants who experienced delirium or impaired cognitive function postoperatively. Secondary outcomes included the incidence of hypotension, bradycardia, and postoperative nausea and vomiting. We estimated the odds ratios (OR) and mean differences (MD) with 95% CIs using a random-effects model. Results: In total, 1295 patients from 11 randomized controlled trials were included. The incidence of postoperative delirium was 8.0% in the remimazolam group and 10.4% in the propofol group that was not significantly different (OR: 0.74, 95% CI [0.39–1.42], P = 0.369, I2 = 32%). More favorable cognitive function, as assessed using the Mini-Mental State Examination, was observed in the remimazolam group compared to the propofol group (MD: 1.06, 95% CI [0.32–1.80], P = 0.005, I2 = 89%). Remimazolam lowered the incidence of hypotension (OR: 0.28, 95% CI [0.21–0.37], P = 0.000, I2 = 0%) compared to propofol. Conclusions Remimazolam did not increase the risk of postoperative delirium and maintained cognitive function well, providing hemodynamic stability during surgery compared to propofol.

Background: Remimazolam is a novel short-acting benzodiazepine that has recently been used for general anesthesia. This study compared the safety and efficacy of remimazolam-based total intravenous anesthesia (TIVA) and volatile agent-based anesthesia in adults undergoing general anesthesia. Methods: We searched electronic databases including PubMed, Embase, CENTRAL, and Scopus for relevant studies. The primary outcome was the proportion of patients who experienced hypotension during surgery. Secondary outcomes included incidence of bradycardia, extubation time, duration in the post-anesthesia care unit hospital stay, and incidence of postoperative nausea and/or vomiting (PONV). We estimated the relative risk (RR) and mean difference with 95% CIs using a random-effects model. Results: A total of 969 patients from 12 randomized controlled trials were included. The incidence of hypotension was 14% and 34% in the remimazolam and volatile agent groups, respectively. Remimazolam significantly lowered the incidence of hypotension (RR: 0.43, 95% CI [0.29–0.63], P = 0.0000, I2 = 26%). The remimazolam group had a PONV incidence of 13%, compared to 28% in the volatile agent group, indicating a significant difference (RR: 0.51, 95% CI [0.37–0.72], P = 0.0001, I2 = 15%). No significant differences were observed in the other outcomes. Conclusions Remimazolam-based TIVA demonstrated favorable hemodynamic effects, with a lower incidence of hypotension and similar bradycardia rates, compared to volatile agent-based anesthesia. Furthermore, the reduction in PONV supports the use of remimazolam-based TIVA as a valuable method for general anesthesia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection contribute to platelet activation and thrombus formation. Severe coronavirus disease 2019 (COVID-19) is characterized by an increased risk of thromboembolic events that can lead to adverse outcomes in patients with severe disease manifestations. We present the case of a 41-year-old man who died from a pulmonary embolism and review the connection between SARS-CoV-2 infection, increased platelet counts, and the resulting fatal thrombosis. Total knee replacement surgery was performed and the patient was able to ambulate for a few days postoperatively. The platelet count exceeded the upper limit between postoperative days six and nine, reaching 708,000/μL on day 20. SARS-CoV-2 was confirmed 14 days after surgery, and the patient died 23 days after surgery while hospitalized. Autopsy revealed a fatal pulmonary embolism and deep vein thrombosis. If blood clots are caused by increased platelet counts due to COVID-19, it is essential to understand this relationship and prepare for complications that may arise after infection. Several recent studies have shown a link between COVID-19 and coagulation. We propose several considerations for autopsies of unexpected fatal pulmonary embolism during the SARS-CoV-2 endemic period.