Neuron type-specific optogenetic stimulation for differential stroke recovery in chronic capsular infarct.

Cortical neuromodulation (CNM) is widely used to promote recovery after stroke. Despite the beneficial results of CNM, the roles played by different neuron types in the effects of current CNM techniques are unable to be differentiated. Our aim was to use selective optogenetic cortical stimulation to explore how different subpopulations of neuronal cells contribute to poststroke recovery. We transduced the sensory-parietal cortex (SPC) of rats with CamKII-ChR2 (pyramidal neurons), PV-ChR2 (parvalbumin-expressing inhibitory neurons), or hSyn-ChR2 (pan-neuronal population) before inducing photothrombotic capsular infarct lesions. We found that selective stimulation of inhibitory neurons resulted in significantly greater motor recovery than stimulation of excitatory neurons or the pan-neuronal population. Furthermore, 2-deoxy-2-[18F] fluoro-D-glucose microPET (FDG-microPET) imaging revealed a significant reduction in cortical diaschisis and activation of the corticostriatal neural circuit, which were correlated with behavioral recovery in the PV-ChR2 group. The spatial pattern of brain-derived neurotrophic factor (BDNF) expression was evident in the stimulated cortex and underlying cortico-subcortical circuit. Our results indicate that the plasticity of inhibitory neurons is crucial for functional recovery after capsular infarct. Modifying CNM parameters to potentiate the stimulation of inhibitory neurons could improve poststroke outcomes.

Expert Consensus on the Structure, Role, and Procedures of the Korea Expert Committee on Immunization Practices.

BACKGROUND: The Korea Expert Committee on Immunization Practices (KECIP) is a key advisory body the government to develop guidelines and provide technical advisory activities on immunization policies in Korea. A recent policy study, inspired by global best practices, aims to enhance KECIP's functionality for providing timely and transparent recommendations in the face of evolving vaccine science and emerging infectious diseases like COVID-19. METHODS: This study reviewed the current status of KECIP and collected expert opinions through surveys and consultations. Among the 40 panel members who were surveyed, 19 responded to a questionnaire specifically designed to assess the potential areas of improvement within KECIP. RESULTS: The majority of respondents favored maintaining the current member count and emphasized the need for a subcommittee. Opinions varied on issues such as the length of KECIP's term, the representation of vaccine manufacturers' perspectives, and the chairperson's role. However, there was a consensus on the importance of expertise, transparency, and fair proceedings within the committee. CONCLUSION: This study underscores the pivotal role of KECIP in shaping national immunization policies, emphasizing the necessity for informed guidance amidst evolving vaccine science and emerging infectious diseases. Furthermore, it stressed the importance of enhancing KECIP's capacity to effectively address evolving public health challenges and maintain successful immunization programs in South Korea.

Pharmacokinetics of a Fixed-Dose Combination Product of Amlodipine, Losartan, Ezetimibe, and Rosuvastatin and Its Comparison with Co-administration of Four Individual Components in Healthy Participants.

BACKGROUND AND OBJECTIVE: This study aimed to assess and compare the pharmacokinetics, safety, and tolerability of a fixed-dose combination product (FDCP) comprising four different drugs (two antihypertensive drugs, amlodipine and losartan, and two lipid-lowering agents, ezetimibe and rosuvastatin) with their separate tablets. METHODS: A total of 60 participants were enrolled in this open-label, randomized, single-dose crossover study. Each participant received a single dose of FDCP and individual tablets during each period, with a 14-day washout period between the periods. The pharmacokinetic parameters of amlodipine, losartan, EXP3174 (an active metabolite of losartan), rosuvastatin, free ezetimibe, and total ezetimibe were evaluated and compared. RESULTS: The pharmacokinetic profiles of amlodipine, losartan, rosuvastatin, and ezetimibe after administration of the individual products were similar to those of FDCP. The geometric mean ratios and 90% confidence intervals for maximum concentration (Cmax) and area under the curve (AUC) of FDCP to individual tablets were within 0.8-1.25 for all six analytes. No clinically relevant changes were observed in the vital signs or physical, biochemical, hematological, electrocardiographic, or urinalysis findings during the study, and no serious adverse events were reported. CONCLUSION: This study demonstrated that a newly developed FDCP containing amlodipine, losartan, ezetimibe, and rosuvastatin exhibited pharmacokinetic equivalence with the individual products and met the regulatory criteria. Both formulations were well tolerated. CLINICAL TRIAL REGISTRATION: This trial (NCT04322266) was retrospectively registered on 9 September 2019.

Interferon-Gamma Release Assay Combined with Renal Indicators to Reduce the False-Negativity of Latent Tuberculosis Infection in End-Stage Renal Disease with Hemodialysis Patients.

BACKGROUND: Tuberculosis (TB) is still the main cause of mortality due to a single transfectant, Mycobacterium tuberculosis (MTB). Latent tuberculosis infection (LTBI) is a condition characterized by the presence of tuberculosis (TB) that is not clinically apparent but nonetheless shows a sustained response to MTB. Presently, tuberculin skin test (TST) and interferon gamma (IFN-γ) release assays (IGRAs) are mainly used to detect LTBI via cell-mediated immunity of T-cells. For people with end-stage renal disease (ESRD), the diagnosis of patients infected with MTB is difficult because of T-cell dysfunction. To get more accurate diagnosis results of LTBI, it must compensate for the deficiency of IGRA tests. METHODS: Sixty-seven hemodialysis (HD) patients and 96 non-HD patients were enrolled in this study and the study population is continuously included. IFN-γ levels were measured by the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. Kidney function indicators, blood urea nitrogen (BUN), serum creatinine (Cr), and estimated glomerular filtration rate (eGFR) were used to compensate for the declined IFN-γ levels in the IGRA test. RESULTS: In individuals who were previously undetected, the results of compensation with serum Cr increased by 10.81%, allowing for about 28% more detection, and compensation with eGFR increased by 5.41%, allowing for approximately 14% more detectable potential among them and employing both of them could enhance the prior shortcomings of IGRA tests. when both are used, the maximum compensation results show a sensitivity increase rate of 8.81%, and approximately 23% of patients who were previously undetectable may be found. CONCLUSION: Therefore, the renal function markers which are routine tests for HD patients to compensate for the deficiency of IGRA tests could increase the accuracy of LTBI diagnosis.

Tonic excitation by astrocytic GABA causes neuropathic pain by augmenting neuronal activity and glucose metabolism.

Neuropathic pain is a debilitating condition caused by the hyperexcitability of spinal dorsal horn neurons and is often characterized by allodynia. Although neuron-independent mechanisms of hyperexcitability have been investigated, the contribution of astrocyte-neuron interactions remains unclear. Here, we show evidence of reactive astrocytes and their excessive GABA release in the spinal dorsal horn, which paradoxically leads to the tonic excitation of neighboring neurons in a neuropathic pain model. Using multiple electrophysiological methods, we demonstrated that neuronal hyperexcitability is attributed to both increased astrocytic GABA synthesis via monoamine oxidase B (MAOB) and the depolarized reversal potential of GABA-mediated currents (EGABA) via the downregulation of the neuronal K+/Cl- cotransporter KCC2. Furthermore, longitudinal 2-deoxy-2-[18F]-fluoro-D-glucose microPET imaging demonstrated increased regional glucose metabolism in the ipsilateral dorsal horn, reflecting neuronal hyperexcitability. Importantly, inhibiting MAOB restored the entire astrocytic GABA-mediated cascade and abrogated the increased glucose metabolism and mechanical allodynia. Overall, astrocytic GABA-mediated tonic excitation is critical for neuronal hyperexcitability, leading to mechanical allodynia and neuropathic pain.

A low-endotoxic Salmonella enterica Gallinarum serovar delivers infectious bronchitis virus immunogens via a dual-promoter vector system that drives protective immune responses through MHC class-I and -II activation in chickens.

An effective vaccine strategy is indispensable against infectious bronchitis virus (IBV) and fowl typhoid (FT), both of which threaten the poultry industry. This study demonstrates a vector system, pJHL270, designed to express antigens in prokaryotic and eukaryotic cells. The vector system stimulates immune responses via synchronized antigen presentation to MHC class-I and -II molecules to produce balanced Th1/Th2 responses. The vaccine antigens were crafted by selecting the consensus sequence of the N-terminal domain of the spike protein (S1-NTD) and a conserved immunogenic region of the nucleocapsid protein (N321-406 aa) from IBV strains circulating in South Korea. The vaccine antigen was cloned and transformed into a live-attenuated Salmonella Gallinarum (SG) strain, JOL2854 (∆lon, ∆cpxR, ∆rfaL, ∆pagL, ∆asd). Western blot analysis confirmed concurrent antigen expression in Salmonella and eukaryotic cells. Oral immunization with the SG-based IBV vaccine construct JOL2918 induced IBV antigen and Salmonella-specific humoral and cell-mediated immune responses in chickens. PBMCs collected from immunized chickens revealed that MHC class-I and -II expression had increased 3.3-fold and 2.5-fold, respectively, confirming MHC activation via bilateral antigen expression and presentation. Immunization induced neutralizing antibodies (NAbs) and reduced the viral load by 2-fold and 2.5-fold in the trachea and lungs, respectively. The immunized chickens exhibited multifaceted humoral, mucosal, and cell-mediated responses via parallel MHC class-I and -II activation as proof of a balanced Th1/Th2 immune response. The level of NAbs, viral load, and gross and histological analyses provide clear evidence that the construct provides protection against IBV and FT.

Primary Invasive Ductal Carcinoma Arising in Axillary Accessory Breast: A Case Report.

Ectopic breast tissue can develop along the mammary ridge from the axilla to the groin, and the most common site is the axillae. Primary carcinoma of ectopic breast tissue is extremely rare. We report a rare case of a 61-year-old woman with a palpable mass in her left axilla who had a history of surgical excision of accessory breast tissue in the same area. Mammography (MMG), including axillary tail view, ultrasound (US), and breast MRI were performed. We evaluated the extent and characteristics of the microcalcifications in the axillary tail view. A US-guided biopsy was done, and histopathology revealed an invasive ductal carcinoma. Enhanced abdominal CT revealed multiple hepatic masses consistent with metastases, and the patient received palliative chemotherapy. Herein, we present a rare case of breast cancer arising from accessory breast tissue in the axilla, best appreciated on the axillary tail view of the patient's MMG.

Long non-coding RNA SOX2OT in tamoxifen-resistant breast cancer.

Hormone receptor (HR)-positive breast cancer can become aggressive after developing hormone-treatment resistance. This study elucidated the role of long non-coding RNA (lncRNA) SOX2OT in tamoxifen-resistant (TAMR) breast cancer and its potential interplay with the tumor microenvironment (TME). TAMR breast cancer cell lines TAMR-V and TAMR-H were compared with the luminal type A cell line (MCF-7). LncRNA expression was assessed via next-generation sequencing, RNA extraction, lncRNA profiling, and quantitative RT-qPCR. SOX2OT overexpression effects on cell proliferation, migration, and invasion were evaluated using various assays. SOX2OT was consistently downregulated in TAMR cell lines and TAMR breast cancer tissue. Overexpression of SOX2OT in TAMR cells increased cell proliferation and cell invasion. However, SOX2OT overexpression did not significantly alter SOX2 levels, suggesting an independent interaction within TAMR cells. Kaplan-Meier plot analysis revealed an inverse relationship between SOX2OT expression and prognosis in luminal A and B breast cancers. Our findings highlight the potential role of SOX2OT in TAMR breast cancer progression. The downregulation of SOX2OT in TAMR breast cancer indicates its involvement in resistance mechanisms. Further studies should explore the intricate interactions between SOX2OT, SOX2, and TME in breast cancer subtypes.

Iridium oxide-based non-enzymatic glucose sensor: Superior electro-catalytic performance in biological environmental media.

Nanostructured inorganic materials have potential advantages as glucose-sensing elements in diabetes care, thereby circumventing the need for expensive enzymatic agents. However, many nonenzymatic sensors face challenges related to selectivity and reliability, reducing their efficacy in body fluids. In this study, we introduce an Iridium oxide (IrO2)-based non-enzymatic glucose sensor. This sensor demonstrates exceptional electro-catalytic properties in human serum, characterized by high sensitivity (638 µA µM-1cm2) and a consistent recovery rate (∼104%) across 15 cycles in saline. Furthermore, its impressive performance in human serum, as evidenced by a low relative standard deviation (RSD <1.57%), underscores its applicability in biological matrices such as interstitial fluids. Overall, the IrO2 sensor is a promising, highly reversible, economical, and simple method for detecting glucose in continuous monitoring systems.

National Level Cross-Sectional Study on Antibiotic Use in Children during the Pre- and Early COVID-19 Eras.

This study aimed to investigate national data for a quantitative evaluation of antibiotic usage in Korean children during the pre- and early COVID-19 period. This was a cross-sectional study from 2016 to 2021 of children <18 years, grouped by age (0, 1, 2-4, 5-11, and 12-17 years) and city/province. Systemic antibiotic prescriptions, days of administration, and population by age and region were collected. Days of therapy (DOT)/1000 pediatric inhabitant per day (PID) was used for antibiotic quantitative monitoring. A total of 257,088,265 antibiotic doses were prescribed to 170,309,944 children during the 6-year period. The highest DOT during the entire study period was observed in the 1-year age group, followed by the 2-4- and 0-year age groups. The highest DOT was observed in 2019, with 72.8 DOT/1000 PID in the 1-year age group, which fell to 34.7 DOT/1000 PID in 2020, however, DOT soon increased at similar rates to that in the pre-COVID-19 period. A higher DOT/1000 PID was observed for third-generation cephalosporins in 58.8% of the regions compared to beta-lactam/beta-lactamase inhibitors. To conclude, reductions in antibiotic use during the early COVID-19 pandemic period were not maintained. Further interventions are needed to decrease antibiotic overuse and misuse.

A phase 3, single-arm, open-label study to evaluate the safety, tolerability, and immunogenicity of a 15-valent pneumococcal conjugate vaccine, V114, in a 3+1 regimen in healthy infants in South Korea (PNEU-PED-KOR).

There is an ongoing burden of pneumococcal disease in children despite the use of pneumococcal conjugate vaccines (PCVs). This phase 3, open-label, single-arm, multisite, descriptive study was designed to evaluate the safety and immunogenicity of a 3 + 1 regimen of V114 (VAXNEUVANCE™), a 15-valent PCV, in South Korean infants and toddlers. Adverse events (AEs) were reported for 14 d following any vaccination, and throughout the study period for serious AEs. Serotype-specific immunoglobulin G (IgG) response rates (proportion of participants meeting an IgG threshold value of ≥0.35 µg/mL) and geometric mean concentrations (GMCs) for the 15 serotypes at 30 d postdose 3 (PD3) and at 30 d postdose 4 (PD4) were evaluated as endpoints. Healthy infants enrolled at 42-90 d after birth were vaccinated with V114 (N = 57). The most commonly reported AEs were those solicited in the trial. The majority of reported AEs were transient and of mild or moderate intensity. Few serious AEs were reported; none were vaccine related. No participants died nor discontinued the study vaccine because of an AE. V114 was immunogenic for all 15 serotypes contained in the vaccine, as assessed by IgG response rates at 30 d PD3 and IgG GMCs at 30 d PD3 and at 30 d PD4. V114 was well tolerated and immunogenic when administered as a 3 + 1 regimen in healthy South Korean infants and toddlers.

Despite the use of pneumococcal vaccines, the burden of pneumococcal disease in children persists. V114, a 15-valent pneumococcal conjugate vaccine, was immunogenic and well-tolerated in healthy South Korean infants and toddlers.

Impact of exercise training and diet therapy on the physical fitness, quality of life, and immune response of people living with HIV/AIDS: a randomized controlled trial.

BACKGROUND: Exercise and dietary nutrition are considered crucial in human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) treatment protocols and people living with HIV/AIDS (PLWHA) rehabilitation care. However, there is no well-studied research evaluating the effects of combined interventions on the fitness and immune systems of PLWHA. Therefore, this study aimed to analyze the effects of exercise and dietary intervention on physical fitness, quality of life and immune response in PLWHA. METHODS: This was an experimental study, with a sample of 25 male PLWHA divided into two groups: the intervention group (IG: 12 participants) and the control group (CG: 13 participants). All participants have not had any exercise habits and nutritional supplements in the past six months. The participants in the IG completed 45 min of exercise (60-80% HRmax) 4 times per week for 4 weeks. The exercise was in the form of brisk walking or running. They were also given a nutritional dietary supplement 3 times a day for 4 weeks. The 13 individuals in the CG continued their normal daily life (physical activity and diet). The following parameters were evaluated before and after the intervention: body composition, physical fitness, immune response, quality of life (QoL), stress, dietary behavior, dietary habits, exercise motivation, and physical self-efficacy. RESULTS: The significant changes were observed in burnout of stress variables and physical efficiency index (PEI) of physical fitness in the IG (p =.023). Moreover, in the saliva samples, sal-T levels significantly increased only after the intervention in the IG (p =.012). Additionally, regarding the analysis of the interaction (group × time), there was a significant improvement in the reaction speed (p =.001) and grip strength (left: p =.002, right: p =.030) and a significant difference in physical satisfaction in QoL (p =.001), stress burnout (p =.043), self-confidence in physical efficacy (p =.045), external display (p =.008), and fulfillment (p =.047) in exercise motivation. Moreover, the significant effect of the intervention on emotional eating in dietary behavior was shown in the comparison of the IG before and after intervention (p =.001) and in the comparison of the IG group with the CG after the experiment (p =.013). However, there was no significant effect of time or interaction between the condition and time on body composition. CONCLUSIONS: In conclusion, exercise training and diet therapy caused changes in physical fitness and Sal-T levels, which had positive effects on the health promotion of PLWHA.

Predictors of sleep quality components in patients undergoing transarterial chemoembolisation: a cross-sectional study.

PURPOSE: Patients undergoing transarterial chemoembolisation experience postembolisation symptoms and interferences affecting sleep quality, which require intervention. The study aimed to identify the predictors of sleep quality components in patients undergoing transarterial chemoembolisation. METHODS: This study included two groups of participants: 50 patients undergoing transarterial chemoembolisation and 45 nurses caring for them. Data were collected from September to November 2022 using a structured questionnaire, and analysed using descriptive statistics, the t-test, analysis of variance, Spearman's rank correlation, and multiple regression analysis using the SPSS 27.0 program (IBM Corp., Armonk, NY, USA). RESULTS: The mean sleep quality score was 40.28±14.10. Heat sensation (t=-2.08, p=.043) and fatigue (t=-4.47, p<.001) predicted sleep fragmentation in 38.6% of the patients. Abdominal pain (t=-2.54, p=.014), vomiting (t=-2.21, p=.032), and the expected fatigue by the nurses (t=2.68, p=.014) predicted sleep length in 41.7% of patients. Abdominal pain (t=-2.05, p=.046) explained 42.9% of sleep depth. CONCLUSION: Based on the predictors of sleep quality components obtained in this study, strategies to improve sleep quality tailored to patients undergoing transarterial chemoembolisation should be developed. This study highlighted the need to bridge the gap between patients' and nurses' expected fatigue and its contribution to sleep fragmentation and sleep length. It also highlighted the importance of noncontact temperature measurement, controlling vomiting, and pain relief for improving sleep length in patients undergoing transarterial chemoembolisation.

Tuberculous Pericarditis Mimicking a Malignant Pericardial Tumor: A Case Report.

Tuberculous pericarditis is an extrapulmonary manifestation of tuberculosis that is most commonly associated with pericardial thickening, effusion, and calcification. We present a case of tuberculous pericarditis mimicking a malignant pericardial tumor in a 77-year-old male. CT revealed an irregular and nodular pericardial thickening. MRI revealed high signal intensity on T1-weighted fat-suppressed images and peripheral rim enhancement after gadolinium administration. MRI can be helpful in determining the differential diagnoses in cases of tuberculous pericarditis with nonspecific imaging findings.

Advanced Magnetic Actuation: Harnessing the Dynamics of Sm2Fe17-xCuxN3 Composites.

Recently, there has been an escalating demand for advanced materials with superior magnetic properties, especially in the actuator domain. High coercivity (Hci), an essential magnetic property, is pivotal for programmable shape changes in magnetic actuators and profoundly affects their performance. In this study, a new Sm2Fe17-xCuxN3 magnet with a high Hci was achieved by modifying the temperature of the reduction-diffusion process─lowering it from 900 to 700 °C through the introduction of Cu and finer control over the structure and morphology of the Sm2Fe17-xCuxN3 magnetic component within the actuator composite. Consequently, the Sm2Fe17-xCuxN3 magnet demonstrated a remarkable Hci of 11.5 kOe, eclipsing the value of 6.9 kOe attained by unalloyed Sm2Fe17N3 at reduced temperatures. By capitalizing on the enhanced magnetic properties of the Sm2Fe17-xCuxN3 composite and incorporating poly(ethylene glycol) into the elastomer matrix, we successfully fabricated a robust actuator. This innovative approach harnesses the strengths of hard magnets as actuators, offering stability under high-temperature conditions, precision control, longevity, wireless functionality, and energy efficiency, highlighting the vast potential of hard magnets for a range of applications.

Exploration of MELK as a downstream of Del-1 and druggable targets in triple-negative breast cancer.

PURPOSE: In our previous study, Developmental endothelial locus-1 (Del-1) was a promising predictive marker for breast cancer. However, the downstream targets of Del-1 remain unknown. Here, we sought to discover a druggable target downstream of Del-1 and investigate the mechanism by which it regulates the course of breast cancer. METHODS: To investigate Del-1 downregulation effect on breast cancer, we performed transcriptome analysis using RNA sequencing of Del-1 knockdowned MDA-MB-231 cell line Plus, to investigate the expression of Del-1 and Maternal embryonic leucine zipper kinase (MELK), mRNA levels in eight different triple-Negative Breast Cancer (TNBC) cell lines were analyzed. High-throughput sequencing was performed on total RNA isolated. OTS167 was used for MELK inhibition. The effects of MELK on cell proliferation and invasion were determined using the MTT and Matrigel transwell assays. Furthermore, we examined MELK expression in breast cancer tissue. RESULTS: Del-1 and MELK mRNA expression levels were significantly higher in the TNBC cell lines, MDA-MB-468, HCC-1806, and MBA-MB-231. Knocking down Del-1 with siRNA in HCC-1806 and MBA-MB-231 cells significantly decreased MELK expression and thus suggested a possible relationship between Del-1 and MELK. In MDA-MB-468 cells, a basal-like 1 TNBC cell line, OTS167 significantly inhibited breast cancer cell proliferation and promoted cell apoptosis. To further investigate the relationship between Del-1 and MELK, dual inhibition of both Del-1 and MELK was performed, which significantly reduced the viability of MDA-MB-468 and MBA-MB-231 cells. CONCLUSION: We found that MELK acts downstream of Del-1 and is a promising druggable target, especially in basal-like and mesenchymal stem-like subtype.

Evaluation of Physicochemical Changes in Hard-Boiled Eggs Stored at Different Temperatures.

Eggs that have been hard-boiled are frequently used as ready-to-eat food. Refrigerated and frozen storage of hard-boiled eggs causes issues, such as customer rejection owing to textural changes. The objective of this research is to ascertain how storage temperature affects hard-boiled eggs' alteration in texture over time. Medium-sized brown shell eggs were acquired from a local market, boiled at 100°C for 15 min, and then stored at room temperature (25°C), refrigeration (4°C), and freezing (-18°C) conditions for 0, 12, 24, and 48 h. Fourier transform infrared spectroscopy (FTIR), texture profile, visual observation using a gemological microscope, free amino acid content, and color were measured. Freezing had a substantial impact on the eggs' hardness, gumminess, chewiness, and cohesiveness (p<0.05). The FTIR spectrums confirmed the textural changes in bonds of amide A (3,271 cm-1), amide I (1,626.2 cm-1), amide II (1,539.0 cm-1), C=O stretch of COO- (1,397 cm-1), asymmetric PO2- stretch (1,240 cm-1). Microscopic images confirmed structural changes in eggs stored at -18°C. The free amino acid content was lower in fresh and frozen eggs than in the rest (p<0.05). However, there was no discernible variation in the egg white's color when eggs were kept at 4°C (p>0.05). Salmonella spp. was found exclusively in eggs kept at room temperature. In conclusion, hard-boiled eggs did not exhibit structural or chemical changes when stored at 4°C for up to 48 h compared to freezing and room temperature conditions.

Menopausal hormone therapy increases the risk of gallstones: Health Insurance Database in South Korea (HISK)-based cohort study.

OBJECTIVE: To determine whether menopausal hormone therapy (MHT) increases the risk of gallstones and gallbladder cancer. DESIGN: A retrospective cohort study. PATIENTS OR OTHER PARTICIPANTS: Data from the Korea National Health Insurance Corporation was obtained between January 1, 2002, and December 31, 2019. INTERVENTIONS: Participants were divided into MHT and non-MHT groups; the MHT group was analyzed in detail by dividing participants into tibolone, combined estrogen plus progestin by the manufacturer (CEPM) or physician (CEPP), oral estrogen alone, and topical estrogen subgroups. MAIN OUTCOME MEASURES: The incidence of gallstones and gallbladder cancer was compared between the two groups. RESULTS: This study enrolled 1,004,034 and 381,711 patients in the non-MHT and the MHT groups, respectively. The incidence of gallstones was 2.6% in the non-MHT group and 3.4%, 2.6%, 3.4%, 3.2%, and 4.4% in the tibolone, CEPM, oral estrogen alone, CEPP, and topical estrogen groups, respectively. Cox proportional hazard analysis revealed that all hormones increased the risk of gallstones ([tibolone] hazard ratio [HR]: 1.347, 95% confidence interval [CI]: 1.309-1.387, [CEPM] HR: 1.146, 95% CI: 1.1-1.19, [oral estrogen alone] HR: 1.241, 95% CI: 1.18-1.305, [CEPP] HR: 1.164, 95% CI: 1.01-1.341, [topical estrogen] HR: 1.602, 95% CI: 1.295-1.983). However, the risk of gallbladder cancer did not change with any hormone therapy. CONCLUSIONS: All types of MHT including tibolone, increased the risk of gallstones. This risk was the highest with topical estrogen, which may be a result of selection bias due to concerns regarding the adverse effects of CEE and MPA.

Real-world first-line afatinib for advanced EGFR mutation-positive non-small cell lung cancer in Korea: updated survival data.

Background: Data from clinical trials and real-world studies show that afatinib is effective in treating non-small cell lung cancer (NSCLC) harboring activating mutations in the epidermal growth factor receptor (EGFR) gene. A previous analysis of patients enrolled in the Korean Academy of Tuberculosis and Respiratory Disease (KATRD) EGFR cohort showed that first-line afatinib was well tolerated and effectiveness results were encouraging. At the time of the previous analysis, survival data were not mature. Here we briefly present updated survival data from the cohort. Methods: The study was a retrospective, multicenter (15 sites) review of electronic records of Korean adult patients (aged >20 years) with advanced EGFR mutation-positive NSCLC who initiated first-line afatinib (N=421). Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier survival curves. Results: Overall, median PFS was 20.2 months and median OS was 48.6 months. OS rates at 36 and 60 months were 60.1% and 42.3%, respectively. Presence vs. absence of baseline brain metastases was associated with significantly reduced median PFS (14.9 vs. 28.0 months; P<0.001) and median OS (32.2 vs. 65.6 months; P<0.001). The presence of common baseline EGFR mutations (Del19, L858R) was associated with significantly prolonged median OS (49.6 vs. 30.1 months; P=0.017). In patients stratified by the presence/absence of T790M EGFR mutation, the T790M mutation was associated with significantly reduced median PFS (P=0.0005) but there was no significant difference between groups in survival (P=0.263). There were no significant differences in PFS or OS for patients stratified by afatinib dose reduction or by age group (<70 vs. ≥70 years). Conclusions: Afatinib was effective in Korean patients with EGFR mutation-positive NSCLC with median OS over 4 years. The presence of baseline brain metastases and/or uncommon EGFR mutations were associated with reduced survival. In the absence of baseline brain metastases, median OS was more than 5 years.