Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.

Purpose: Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Objective: We aimed to investigate the effectiveness of buspirone as an adjunctive therapy for alleviating anxiety symptoms in patients with depressive disorders who are already taking antidepressants. Methods: This was an open-label prospective multicenter non-interventional observational study conducted over 12 weeks. We enrolled 180 patients diagnosed with depressive disorders according to DSM-5 criteria and Hamilton Anxiety Rating Scale (HAMA) scores ≥ 18. Participants were already taking selective serotonin reuptake inhibitors or serotoninnorepinephrine reuptake inhibitors and were prescribed adjunctive buspirone. Efficacy was assessed using HAMA, Hamilton Depression Rating Scale (HAMD), Clinical Global Impression Scale-Improvement, Clinical Global Impression Scale-Severity, Sheehan Disability Scale (SDS), and WHO-5 Well-Being Index. Results: The efficacy analysis included 161 patients. HAMA scores decreased significantly from 25.2 ± 6.7 at baseline to 15.4 ± 8.6 at 12 weeks (p ＜ 0.001), whereas HAMD scores decreased from 19.4 ± 4.6 to 12.7 ± 5.7 (p ＜ 0.001).WHO-5 and SDS scores showed significant improvements. The HAMA response rate was 39.1% and the remission rate was 13.7% at 12 weeks. Adverse drug reactions were reported in 3.7% of participants. Subgroup analyses showed no significant differences in treatment response based on buspirone dosage, baseline anxiety/depression severity, or benzodiazepine use. Conclusion Adjunctive buspirone therapy effectively improved anxiety symptoms in depressed patients taking antidepressants, regardless of baseline symptom severity or buspirone dosage. The treatment was well-tolerated with few adverse events. Future studies using a control group are needed.

Objective: Multiple cohort studies have investigated the potential link between anesthesia and dementia. However, mixed findings necessitate closer examination. This study aimed to investigate the association between anesthesia exposure and the incidence of dementia, considering different anesthesia types and anesthetic agents. Methods: This nationwide cohort study utilized data from the South Korean Health Insurance Review and Assessment Service database, covering 62,541 participants, to investigate the correlation between anesthesia exposure and dementia incidence. Results: Results revealed an increased risk of dementia in individuals who underwent general (hazard ratio [HR], 1.318;95% confidence interval [CI], 1.061−1.637) or regional/local anesthesia (HR, 2.097; 95% CI, 1.887−2.329) compared to those who did not. However, combined general and regional/local anesthesia did not significantly increase dementia risk (HR, 1.097; 95% CI, 0.937−1.284). Notably, individual anesthetic agents exhibited varying risks; desflurane and midazolam showed increased risks, whereas propofol showed no significant difference. Conclusion This study provides unique insights into the nuanced relationship between anesthesia, individual anesthetic agents, and the incidence of dementia. While confirming a general association between anesthesia exposure and dementia risk, this study also emphasizes the importance of considering specific agents. These findings under-score the need for careful evaluation and long-term cognitive monitoring after anesthesia.

Background: The treatment of Kümmell disease (KD) is controversial. Corpectomy and reconstruction or osteotomy with long-level fusion was traditionally performed for the advanced KD. However, these procedures can be disadvantageous for elderly patients.Several alternative surgical procedures including transpedicular intravertebral cage augmentation (TPICA) or vertebroplasty (VP) combined with short-segment fixation (SSF) have been suggested to minimize the surgical burden. This study aimed to compare the outcomes of percutaneous TPICA plus SSF with VP plus SSF for advanced thoracolumbar (T11–L2) KD and to introduce our novel percutaneous TPICA technique using specially designed cannulated cage trials. Methods: We devised specially designed cannulated cage trials to make the TPICA procedure safer and more reproducible, minimizing the risk of the pedicle medial wall violation. All consecutive patients who underwent percutaneous TPICA or VP combined with SSF for advanced thoracolumbar KD, from January 2021 to June 2022, with ≥ 1-year follow-up at a single institution, were included. Perioperative details, clinical outcomes (visual analog scale and Oswestry Disability Index), and radiological outcomes (anterior vertebral body compression percentage and vertebral kyphotic angle [VKA] of the fractured vertebra, and local Cobb angle [LCA]) were collected and compared between the groups. Results: A total of 42 patients were enrolled, with 21 patients in each group. There were no patients with pedicle medial wall fracture in the TPICA group. Both procedures provided significantly favorable radiological outcomes compared to those preoperatively. No significant differences were observed in the changes over time in all radiological parameters between the groups. Loss of correction during the follow-up period was significantly smaller in patients with TPICA than in those with VP in VKA (median [interquartile range], 2.15 [0.30–2.80] vs. 2.90 [0.90–6.53]; p = 0.030) and LCA (2.70 ± 2.90 vs. 5.17 ± 4.40, p = 0.037). Conclusions Both procedures are minimally invasive and useful options for advanced KD, especially for elderly patients with high comorbidity. Our novel percutaneous TPICA technique using cannulated cage trials, being safer and more reproducible, may allow spine surgeons to easily perform TPICA.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Background/Aims: The Korean guidelines for Helicobacter pylori treatment were revised in 2020, however, the extent of adherence to these guidelines in clinical practice remains unclear. Herein, we initiated a prospective, nationwide, multicenter registry study in 2021 to evaluate the current management of H.pylori infection in Korea. Methods: This interim report describes the adherence to the revised guidelines and their impact on firstline eradication rates. Data on patient demographics, diagnoses, treatments, and eradication outcomes were collected using a web-based electronic case report form. Results: A total of 7,261 patients from 66 hospitals who received first-line treatment were analyzed.The modified intention-to-treat eradication rate for first-line treatment was 81.0%, with 80.4% of the prescriptions adhering to the revised guidelines. The most commonly prescribed regimen was the 14-day clarithromycin-based triple therapy (CTT; 42.0%), followed by tailored therapy (TT; 21.2%), 7-day CTT (14.1%), and 10-day concomitant therapy (CT; 10.1%). Time-trend analysis demonstrated significant increases in guideline adherence and the use of 10-day CT and TT, along with a decrease in the use of 7-day CTT (all p<0.001). Multivariate logistic regression analysis revealed that guideline adherence was significantly associated with first-line eradication success (odds ratio, 2.03; 95% confidence interval, 1.61 to 2.56; p<0.001). Conclusions The revised guidelines for the treatment of H. pylori infection have been increasingly adopted in routine clinical practice in Korea, which may have contributed to improved first-line eradication rates. Notably, the 14-day CTT, 10-day CT, and TT regimens are emerging as the preferred first-line treatment options among Korean physicians.

Background: The World Health Organization has declared the end of the coronavirus disease 2019 (COVID-19) public health emergency. However, this did not indicate the end of COVID-19. Several months after the infection, numerous patients complain of respiratory or nonspecific symptoms; this condition is called long COVID. Even patients with mild COVID-19 can experience long COVID, thus the burden of long COVID remains considerable. Therefore, we conducted this study to comprehensively analyze the effects of long COVID using multi-faceted assessments. Materials and Methods: We conducted a prospective cohort study involving patients diagnosed with COVID-19 between February 2020 and September 2021 in six tertiary hospitals in Korea. Patients were followed up at 1, 3, 6, 12, 18, and 24 months after discharge. Long COVID was defined as the persistence of three or more COVID-19-related symptoms. The primary outcome of this study was the prevalence of long COVID after the period of COVID-19. Results: During the study period, 290 patients were enrolled. Among them, 54.5 and 34.6% experienced long COVID within 6 months and after more than 18 months, respectively. Several patients showed abnormal results when tested for post-traumatic stress disorder (17.4%) and anxiety (31.9%) after 18 months. In patients who underwent follow-up chest computed tomography 18 months after COVID-19, abnormal findings remained at 51.9%. Males (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.05–0.53; P=0.004) and elderly (OR, 1.04; 95% CI, 1.00–1.09; P=0.04) showed a significant association with long COVID after 12–18 months in a multivariable logistic regression analysis. Conclusion Many patients still showed long COVID after 18 months post SARS-CoV-2 infection. When managing these patients, the assessment of multiple aspects is necessary.