Use of stepwise lung recruitment maneuver to predict fluid responsiveness under lung protective ventilation in the operating room.

Recent research has revealed that hemodynamic changes caused by lung recruitment maneuvers (LRM) with continuous positive airway pressure can be used to identify fluid responders. We investigated the usefulness of stepwise LRM with increasing positive end-expiratory pressure and constant driving pressure for predicting fluid responsiveness in patients under lung protective ventilation (LPV). Forty-one patients under LPV were enrolled when PPV values were in a priori considered gray zone (4% to 17%). The FloTrac-Vigileo device measured stroke volume variation (SVV) and stroke volume (SV), while the patient monitor measured pulse pressure variation (PPV) before and at the end of stepwise LRM and before and 5 min after fluid challenge (6 ml/kg). Fluid responsiveness was defined as a ≥ 15% increase in the SV or SV index. Seventeen were fluid responders. The areas under the curve for the augmented values of PPV and SVV, as well as the decrease in SV by stepwise LRM to identify fluid responders, were 0.76 (95% confidence interval, 0.61-0.88), 0.78 (0.62-0.89), and 0.69 (0.53-0.82), respectively. The optimal cut-offs for the augmented values of PPV and SVV were > 18% and > 13%, respectively. Stepwise LRM -generated augmented PPV and SVV predicted fluid responsiveness under LPV.

Implementation of Head of Bed Elevation Using Adjustable Bed and Its Effects on Sleep: A Pilot Randomized Trial.

Background: Although mild head of bed elevation (HBE) is a proven method to reduce obstructive sleep apnea, there is no study to apply mild HBE in daily life using an adjustable bed. Objective: We aimed to explore the applicability of mild HBE using an adjustable bed in daily life by investigating adverse events and discomforts induced by mild HBE. This pilot randomized trial additionally investigated the objective effects of mild HBE on sleep using polysomnography (PSG). Methods: Pilot randomized controlled trial. With a two-tailed alpha of 0.05 and a power of 0.95, the minimum number of participants for each group; control group slept on flat bed and study group slept on bed with mild HBE on follow-up PSG; was calculated to be 12. Considering a 20% follow-up loss, we enrolled a total of 32 participants (16 participants for each group). Setting: Dongguk University, Ilsan hospital. Participants: A total of 37 individuals complained of subjective sleep disturbance in the Republic of Korea, 32 of whom met the inclusion criteria between September 2021 to July 2022. 23 participants completed the study and participants were randomly assigned into two groups. Intervention: A mild HBE of 7.5 degrees using an adjustable bed was implemented. PSG results and questionnaires were evaluated. Results: There was no difference in the proportion of adverse events between groups after post-intervention which was adjusting mild HBE on study group. Changes in sleep satisfaction from baseline to post-intervention showed no significant difference between groups either. However, changes in respiratory distress index (RDI) (F = 6.088, 95% CI, 17.0% to 26.4%; P = .023) and apnea-hypopnea index (AHI) (F = 5.542, 95% CI, 13.6% to 23.5%; P = .029) were significantly different. Conclusions: Mild HBE is an implementable method for changing sleep posture without definitely causing discomfort or worsening sleep satisfaction. Since an easily applicable way to implement mild HBE using an adjustable bed in daily life reduces RDI and AHI in both subjects complaining of sleep disturbance and obstructive sleep apnea, it can be an alternative treatment for obstructive sleep apnea.

Clinical Outcomes of Secondary Duodenal Self-Expandable Metallic Stenting for Duodenal Stent Dysfunction in Patients with Malignant Duodenal Obstruction: A Retrospective Multicenter Study.

Background/Aims: Malignant duodenal obstruction has become more common with the development of palliative therapies.The outcomes of endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) are comparable to those of surgical gastrojejunostomy or duodenal stenting. However, EUS-GJ is technically challenging. Duodenal self-expandable metallic stent (SEMS) placement is popular; however, obstructions are common. Duodenal SEMS obstruction can be managed with the insertion of a second SEMS in a stent-in-stent manner. Therefore, we aimed to analyze the clinical outcomes of secondary duodenal SEMS placement in patients with malignant duodenal obstruction. Methods: We retrospectively analyzed the data of patients who underwent secondary duodenal stent insertion for duodenal stent dysfunction between January 2016 and December 2021. The primary outcome was stent patency. The secondary outcomes were clinical success, factors associated with dysfunction, patient survival, and adverse events. Results: A total of 109 patients were included. The mean age was 64.4±11.2 years, and 63 patients (57.8%) were male. Ninety-two patients (84.4%) had pancreaticobiliary cancer. Clinical success was achieved in 94 cases (86.2%). Twenty-three patients experienced stent dysfunction with 231 days of median stent patency (95% confidence interval [CI], 169 to not available). After a multivariable Cox hazard analysis of stent patency, the Eastern Cooperative Oncology Group performance status (hazard ratio [HR], 2.13; 95% CI, 1.20 to 3.81; p=0.010) and the first stent patency ≥6 months (HR, 0.33; 95% CI, 0.11 to 0.95; p=0.050) remained significant associated factors. Adverse events occurred in five patients (4.6%). Conclusions: Secondary duodenal stent insertion is a viable option for first duodenal stent obstruction. Further comparative studies involving surgery or EUS-GJ for obstructed duodenal stents are warranted.

Impact of Smoking and Alcohol Consumption on Early-Onset Gastric Cancer Development in Young Koreans: A Population-Based Study.

PURPOSE: Although smoking and alcohol consumption are known risk factors for gastric cancer (GC), studies assessing their effects on early-onset GC are limited. In this nationwide, population-based, prospective cohort study, we assessed the effects of smoking and alcohol consumption on early-onset GC in patients aged <50 years. MATERIALS AND METHODS: We analyzed data of patients aged 20-39 years who underwent cancer and general health screening in the Korean National Health Screening Program between 2009 and 2012. We calculated the adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for GC incidence until December 2020. RESULTS: We enrolled 6,793,699 individuals (men:women=4,077,292:2,716,407) in this cohort. The mean duration of follow-up was 9.4 years. During follow-up, 9,893 cases of GC (men:women=6,304:3,589) were reported. Compared with the aHRs (95% CI) of never-smokers, those of former and current-smokers were 1.121 (1.044-1.205) and 1.282 (1.212-1.355), respectively. Compared with the aHRs (95% CI) of non-consumers, those of low-moderate- and high-risk alcohol consumers were 1.095 (1.046-1.146) and 1.212 (1.113-1.321), respectively. GC risk was the highest in current-smokers and high-risk alcohol consumers (1.447 [1.297-1.615]). Interestingly, alcohol consumption and smoking additively increased the GC risk in men but not in women (Pinteraction=0.002). CONCLUSION: Smoking and alcohol consumption are significant risk factors for early-onset GC in young Koreans. Further studies are needed to investigate sex-based impact of alcohol consumption and smoking on GC incidence in young individuals.

Validation of Diagnostic Thresholds for Compensated Advanced Chronic Liver Disease Using Supersonic Shear Imaging.

Background The Society of Radiologists in Ultrasound (SRU) has proposed thresholds for acoustic radiation force impulse techniques to diagnose compensated advanced chronic liver disease (cACLD). However, the diagnostic performance of these thresholds has not been extensively validated. Purpose To validate the SRU thresholds in patients with chronic liver disease who underwent supersonic shear imaging and, if suboptimal diagnostic performance is observed, to identify optimal values for diagnosing cACLD. Materials and Methods This retrospective single-center study included high-risk patients with chronic liver disease who had liver stiffness (LS) measurements and had undergone endoscopy or liver biopsy between January 2018 and December 2021. Patients were randomly allocated to test and validation sets. cACLD was defined as varices at endoscopy and/or severe fibrosis or cirrhosis at liver biopsy. The diagnostic performance of the SRU guidelines was evaluated, and optimal threshold values were identified using receiver operating characteristic (ROC) curve analysis. Results A total of 1180 patients (median age, 57 years [IQR, 50-64 years]; 761 men), of whom 544 (46%) had cACLD, were included. With the SRU recommended thresholds of less than 9 kPa and greater than 13 kPa in the test set (n = 786), the sensitivity and specificity for ruling out and ruling in cACLD were 81% (303 of 374 patients; 95% CI: 77, 85) and 92% (380 of 412 patients; 95% CI: 89, 94), respectively. In ROC curve analysis, the identified optimal threshold values were less than 7 kPa and greater than 12 kPa, showing 91% sensitivity (340 of 374 patients; 95% CI: 88, 93) for ruling out cACLD and 91% specificity (373 of 412 patients; 95% CI: 87, 93) for ruling in cACLD, respectively. In the validation set (n = 394), the optimal thresholds showed 91% sensitivity (155 of 170 patients; 95% CI: 86, 95) and 92% specificity (206 of 224 patients; 95% CI: 88, 95). Conclusion Compared with the SRU guidelines, the dual LS threshold values of less than 7 kPa and greater than 12 kPa were better for diagnosing cACLD. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Barr in this issue.

Feasibility Study of Single-Photon Emission Computed Tomography with Iodine-123 Labeled Metaiodobenzylguanidine for Preclinical Evaluation of Labetalol as a ß-Adrenergic Receptor Blocker.

Among clinically used radiopharmaceuticals, iodine-123 labeled metaiodobenzylguanidine ([123I]mIBG) serves for diagnosing neuroendocrine tumors and obtaining images of myocardial sympathetic innervation. mIBG, a structural analogue of norepinephrine (NE), a neurotransmitter acting in peripheral and central nerves, follows a pathway similar to NE, transmitting signals through the NE transporter (NET) located at synaptic terminals. It moves through the body without decomposing, enabling noninvasive image evaluation. In this study, we aimed to quantify [123I]mIBG uptake in the adrenal glands using small animal single-photon emission computed tomography/computed tomography (SPECT/CT) images post [123I]mIBG administration. We investigated the possibility of assessing the effectiveness of ß-adrenergic receptor blockers by quantifying SPECT/CT images and biodistribution results to determine the degree of [123I]mIBG uptake in the adrenal glands treated with labetalol, a known ß-adrenergic receptor blocker. Upon intravenous administration of [123I]mIBG to mice, SPECT/CT images were acquired over time to confirm the in vivo distribution pattern, revealing a clear uptake in the adrenal glands. Labetalol inhibited the uptake of [123I]mIBG in cell lines expressing NET. A decrease in [123I]mIBG uptake in the adrenal glands was observed in the labetalol-treated group compared with the normal group through SPECT/CT imaging and biodistribution studies. These results demonstrate that SPECT/CT imaging with [123I]mIBG could be applicable for evaluating the preclinical efficacy of new antihypertensive drug candidates such as labetalol, a ß-adrenergic receptor blocker.

Development of a novel, high-efficacy oncolytic herpes simplex virus type 1 platform equipped with two distinct retargeting modalities.

To retarget oncolytic herpes simplex virus (oHSV) to cancer-specific antigens, we designed a novel, double-retargeted oHSV platform that uses single-chain antibodies (scFvs) incorporated into both glycoprotein H and a bispecific adapter expressed from the viral genome to mediate infection predominantly via tumor-associated antigens. Successful retargeting was achieved using a nectin-1-detargeted HSV that remains capable of interacting with herpesvirus entry mediator (HVEM), the second canonical HSV entry receptor, and is, therefore, recognized by the adapter consisting of the virus-binding N-terminal 82 residues of HVEM fused to the target-specific scFv. We tested both an epithelial cell adhesion molecule (EpCAM)- and a human epidermal growth factor receptor 2-specific scFv separately and together to target cells expressing one, the other, or both receptors. Our results show not only dose-dependent, target receptor-specific infection in vitro, but also enhanced virus spread compared with single-retargeted virus. In addition, we observed effective infection and spreading of the EpCAM double-retargeted virus in vivo. Remarkably, a single intravenous dose of the EpCAM-specific virus eliminated all detectable tumors in a subcutaneous xenograft model, and the same intravenous dose seemed to be harmless in immunocompetent FVB/N mice. Our findings suggest that our double-retargeted oHSV platform can provide a potent, versatile, and systemically deliverable class of anti-cancer therapeutics that specifically target cancer cells while ensuring safety.

Prevalence and risk factors of postoperative laryngeal edema in patients undergoing neck dissection.

PURPOSE: Postoperative laryngeal edema (PLE) is a common complication in patients undergoing head and neck surgery, leading to symptoms such as odynophagia, dysphagia, or potential airway obstruction. However, the prevalence and risk factors of PLE in patients undergoing neck dissection (ND) have not been well investigated. METHODS: A retrospective analysis was conducted in three steps. Initially, a pilot study of 50 consecutive ND patients revealed a preliminary PLE prevalence of 0.34. Then, the medical records of an additional 295 ND patients were reviewed to estimate the prevalence of PLE with a total width of 95% confidence interval (CI) of ± 5%. Finally, multivariable logistic regression analyses were performed to identify risk factors for PLE (n = 343). RESULTS: PLE occurred in 29.4% [95%CI 24.4-34.4%] of patients undergoing any type of ND, with the most common symptoms of odynophagia (75.0%) and dyspnea (11.1%). Hospital stay was just one day longer in PLE patients, responding well with short-term steroid treatment (p = 0.0057). In multivariable analyses, no significant association was found between PLE occurrence and airway management. However, body mass index and the American Society of Anesthesiologists classification correlated with PLE. More importantly, surgery for oro-hypopharynx or supraglottis tumors (odds ratio, OR = 3.019, [95%CI 1.166-7.815]) and lymph node level 2(3) ND (OR = 4.214 to 5.279, [95%CI 1.160-20.529]) were significant risk factors for PLE. CONCLUSIONS: PLE developed in approximately 30% of ND patients, causing uncomfortable symptoms. Early diagnosis and intervention of PLE in high-risk patients can improve patient care and outcomes.

Multidisciplinary approach for hepatocellular carcinoma patients: current evidence and future perspectives.

Management of hepatocellular carcinoma (HCC) is challenging due to the complex relationship between underlying liver disease, tumor burden, and liver function. HCC is also notorious for its high recurrence rate even after curative treatment for early-stage tumor. Liver transplantation can substantially alter patient prognosis, but donor availability varies by each patient which further complicates treatment decision. Recent advancements in HCC treatments have introduced numerous potentially efficacious treatment modalities. However, high level evidence comparing the risks and benefits of these options is limited. In this complex situation, multidisciplinary approach or multidisciplinary team care has been suggested as a valuable strategy to help cope with escalating complexity in HCC management. Multidisciplinary approach involves collaboration among medical and health care professionals from various academic disciplines to provide comprehensive care. Although evidence suggests that multidisciplinary care can enhance outcomes of HCC patients, robust data from randomized controlled trials are currently lacking. Moreover, the implementation of a multidisciplinary approach necessitates increased medical resources compared to conventional cancer care. This review summarizes the current evidence on the role of multidisciplinary approach in HCC management and explores potential future directions.

Predictors of Continuous Positive Airway Pressure Adherence and Comparison of Clinical Factors and Polysomnography Findings Between Compliant and Non-Compliant Korean Adults With Obstructive Sleep Apnea.

OBJECTIVE: Continuous positive airway pressure (CPAP) is the preferred treatment for obstructive sleep apnea (OSA). However, compliance with CPAP therapy varies among studies, and studies on its predictors are insufficient in Korea. This study aimed to identify factors that predict compliance with CPAP therapy in patients with OSA. METHODS: We retrospectively reviewed medical records, polysomnography (PSG) records, and self-report questionnaires of patients w ith OSA. Criteria for compliance was the use of CPAP devices for ≥4 h per night for ≥70% of the consecutive 30 nights (i.e., 21 days) during the first 3 months of treatment initiation. The patients were classified into two groups: compliant and non-compliant. Logistic regression analyses were performed to identify the clinical factors and PSG parameters associated with CPAP compliance. RESULTS: Of the 188 participants, 80 were classified into the compliant group and 108 into the non-compliant group. The ratios of stage N1 (p=0.011) and health insurance coverage (p=0.007) were significantly associated with compliance with CPAP, with an explanatory power of 18.6% (R2=0.186, p<0.001). CONCLUSION: Stage N1 ratio and health insurance coverage were significant predictors of CPAP compliance. It is necessary to confirm whether the relationship between a high stage N1 ratio and compliance can be reproduced in a larger sample and in individuals from other countries.

Ginsenoside Re protects rhinovirus-induced disruption of tight junction through inhibition of ROS-mediated phosphatases inactivation in human nasal epithelial cells.

Maintaining tight junction integrity significantly contributes to epithelial barrier function. If the barrier function is destroyed, the permeability of the cells increases, and the movement of the pathogens is promoted, thereby further increasing the susceptibility to secondary infection. Ginsenoside components have multiple biological activities, including antiviral effects. In this study, we examined the protective effects of ginsenoside Re against rhinovirus-induced tight junction disruption in primary human nasal epithelial cells (HNE). Incubation with human rhinovirus resulted in marked disruption of tight junction proteins (ZO-1, E-cadherin, claudin-1, and occludin) in human nasal epithelial cells. Rhinovirus-induced disruption of tight junction proteins was strongly inhibited by the treatment of cells with ginsenoside Re. Indeed, significant amounts of reactive oxygen species (ROS) have been detected in human nasal epithelial cells co-incubated with rhinovirus. Moreover, rhinovirus-induced ROS generation was markedly reduced by the ginsenoside Re. However, ginsenosides Rb1 and Rc did not inhibit tight junction disruption or ROS generation in nasal epithelial cells following incubation with rhinovirus. Furthermore, incubation with rhinovirus resulted in a marked decrease in protein phosphatase activity and an increase in protein tyrosine phosphorylation levels in nasal epithelial cells. Treatment of cells with ginsenoside Re inhibited rhinovirus-induced inactivation of phosphatases and phosphorylation of tyrosine. Our results identified ginsenoside Re as an effective compound that prevented rhinovirus-induced tight junction disruption in human nasal epithelial cells.

Influence of cosmetic foundation cream on skin condition during treadmill exercise.

BACKGROUND: There is a growing trend of individuals wearing cosmetics while participating in physical activities. Nonetheless, there remains a need for further understanding regarding the effects of makeup on the facial epidermis during exercise, given the existing knowledge gaps. PURPOSE: This study aimed to evaluate the effects of a cosmetic foundation cream on skin conditions during physical activity. METHODS: Forty-three healthy college students, 20 males (26.3 ± 1.5 years) and 23 females (23.1 ± 1.0 years), were enrolled in this study. Foundation cream was applied to participants on half of the face in two different areas (MT: makeup T zone and MU: makeup U zone). The other half of the face served as internal control (T: non-makeup T zone and U: non-makeup U zones). Skin levels of moisture, elasticity, pore, sebum, and oil were measured using a skin analysis device (Aramhuvis, Gyeonggi, Republic of Korea) before and after a 20-min treadmill exercise. Paired t-test and independent t-test were performed for skin condition measurements at pre- and postexercise. RESULTS: The skin moisture levels in both the T and MT significantly increased after exercise (p < 0.05) (pre-T: 24.5 ± 1.3, post-T: 38.5 ± 3.5 and pre-MT: 18.7 ± 0.7, post-MT: 40.4 ± 4.8). Elasticity also significantly improved in both the T and MT (p < 0.05) (pre-T: 25.6 ± 1.3, post-T: 41.5 ± 3.5 and pre-MT: 20.0 ± 0.9, post-MT: 41.7 ± 3.7). The size of the pores in the T zone observed a significant increase after exercise (p < 0.05) (pre-T: 41.7 ± 2.1, post-T: 47.8 ± 2.4). The sebum levels in the T zone exhibited a reduction following physical activity, whereas there was a notable increase in sebum levels in the makeup zones (p < 0.05) (pre-MT: 2.4 ± 0.7, post-MT:4.2 ± 0.8 and pre MU 1.8 ± 0.34, post MU 4.9 ± 0.9). The oil level was increased in the non-makeup zones (pre-T: 6.1 ± 1.4, post-T: 11.8 ± 2.0 and pre-U: 7.3 ± 1.5, post-U: 11.9 ± 1.9; p < 0.05) and decreased in the makeup zones (pre-MT: 13.3 ± 1.9, post-MT: 7.4 ± 2.3 and pre-MU: 22.1 ± 2.4, post-MU: 3.2 ± 1.0; p < 0.05). CONCLUSIONS: The findings suggest that using foundation cream during aerobic exercise can reduce skin oil, causing dryness. Additionally, makeup can clog pores and increase sebum production. Therefore, wearing makeup may not be recommended for people with dry skin conditions based on the results of the current study. This research offers important insights to the public, encouraging them to consider the possible consequences of using makeup while exercising.

Semi-supervised learning towards automated segmentation of PET images with limited annotations: application to lymphoma patients.

Manual segmentation poses a time-consuming challenge for disease quantification, therapy evaluation, treatment planning, and outcome prediction. Convolutional neural networks (CNNs) hold promise in accurately identifying tumor locations and boundaries in PET scans. However, a major hurdle is the extensive amount of supervised and annotated data necessary for training. To overcome this limitation, this study explores semi-supervised approaches utilizing unlabeled data, specifically focusing on PET images of diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) obtained from two centers. We considered 2-[18F]FDG PET images of 292 patients PMBCL (n = 104) and DLBCL (n = 188) (n = 232 for training and validation, and n = 60 for external testing). We harnessed classical wisdom embedded in traditional segmentation methods, such as the fuzzy clustering loss function (FCM), to tailor the training strategy for a 3D U-Net model, incorporating both supervised and unsupervised learning approaches. Various supervision levels were explored, including fully supervised methods with labeled FCM and unified focal/Dice loss, unsupervised methods with robust FCM (RFCM) and Mumford-Shah (MS) loss, and semi-supervised methods combining FCM with supervised Dice loss (MS + Dice) or labeled FCM (RFCM + FCM). The unified loss function yielded higher Dice scores (0.73 ± 0.11; 95% CI 0.67-0.8) than Dice loss (p value < 0.01). Among the semi-supervised approaches, RFCM + αFCM (α = 0.3) showed the best performance, with Dice score of 0.68 ± 0.10 (95% CI 0.45-0.77), outperforming MS + αDice for any supervision level (any α) (p < 0.01). Another semi-supervised approach with MS + αDice (α = 0.2) achieved Dice score of 0.59 ± 0.09 (95% CI 0.44-0.76) surpassing other supervision levels (p < 0.01). Given the time-consuming nature of manual delineations and the inconsistencies they may introduce, semi-supervised approaches hold promise for automating medical imaging segmentation workflows.

Challenges in the Therapeutic Targeting of KCa Channels: From Basic Physiology to Clinical Applications.

Calcium-activated potassium (KCa) channels are ubiquitously expressed throughout the body and are able to regulate membrane potential and intracellular calcium concentrations, thereby playing key roles in cellular physiology and signal transmission. Consequently, it is unsurprising that KCa channels have been implicated in various diseases, making them potential targets for pharmaceutical interventions. Over the past two decades, numerous studies have been conducted to develop KCa channel-targeting drugs, including those for disorders of the central and peripheral nervous, cardiovascular, and urinary systems and for cancer. In this review, we synthesize recent findings regarding the structure and activating mechanisms of KCa channels. We also discuss the role of KCa channel modulators in therapeutic medicine. Finally, we identify the major reasons behind the delay in bringing these modulators to the pharmaceutical market and propose new strategies to promote their application.

Reduced Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Receiving Long-Term Besifovir Therapy.

No information is available regarding the influence of besifovir (BSV), a new nucleotide analogue, on the occurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study evaluated the reduced risk of HCC in patients undergoing BSV treatment. A total of 188 patients with CHB were treated with BSV for up to 8 years. We prospectively assessed the incidence of HCC compared with the risk from prediction models. During the follow-up, 5 patients developed HCC: 1 of 139 patients with non-cirrhotic CHB, and 4 of 49 patients with liver cirrhosis. We compared the HCC incidence in non-cirrhotic and cirrhotic patients with the predicted number derived from the REACH-B (risk estimation for HCC in CHB) model and GAG-HCC (guide with age, gender, HBV DNA, core promotor mutation, and cirrhosis) model, respectively. The standardized incidence ratio (SIR) was 0.128 (p = 0.039) at 7 years in non-cirrhotic CHB patients, and the SIR was 0.371 (p = 0.047) at 7.5 years in cirrhotic patients, suggesting a significantly decreased HCC incidence in both groups. HCC prediction was available for BSV-treated patients using existing models. In conclusion, BSV decreased the risk of HCC in patients with CHB, and prediction models were applicable. Clinical trial registry website and trial number: ClinicalTrials.gov no: NCT01937806.

Assessing the New 2020 ESGO/ESTRO/ESP Endometrial Cancer Risk Molecular Categorization System for Predicting Survival and Recurrence.

This study aimed to evaluate the efficacy of the 2020 European Society of Gynecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) guidelines for endometrial cancer (EC). Additionally, a novel risk category incorporating clinicopathological and molecular factors was introduced. The predictive value of this new category for recurrence and survival in Korean patients with EC was assessed, and comparisons were made with the 2013 and 2016 European Society of Medical Oncology (ESMO) risk classifications. Patients with EC were categorized into the POLE-mutated (POLEmut), mismatch repair-deficient (MMRd), p53-aberrant (P53abn), and nonspecific molecular profile (NSMP) subtypes. Recurrence, survival, and adjuvant therapy were assessed according to each classification. Notably, patients with the POLEmut subtype showed no relapse, while patients with the P53abn subtype exhibited higher recurrence (31.8%) and mortality rates (31.8%). Regarding adjuvant therapy, 33.3% of low-risk patients were overtreated according to the 2020 ESGO/ESTRO/ESP guidelines. Overall and progression-free survival differed significantly across molecular classifications, with the POLEmut subtype showing the best and the P53abn subtype showing the worst outcomes. The 2020 ESGO molecular classification system demonstrated practical utility and significantly influenced survival outcomes. Immunohistochemistry for TP53 and MMR, along with POLE sequencing, facilitated substantial patient reclassification, underscoring the clinical relevance of molecular risk categories in EC management.

Association between Combustible Cigarettes and Noncombustible Nicotine or Tobacco Products and Generalized Anxiety Disorder Based on Data from the 8th Korea National Health and Nutrition Examination Survey 2021.

Background: Despite the increasing prevalence of anxiety disorders in Korea, there have been no nationwide studies on the association between tobacco status and generalized anxiety disorder (GAD). Furthermore, despite the increasing number of people using noncombustible nicotine or tobacco products (NNTPs), the association between NNTP use and GAD remains unclear. Therefore, this study investigated the association between tobacco use and GAD. Methods: This nationwide study used data from the 8th Korea National Health and Nutrition Examination Survey (2021) and included 5,454 adults aged ≥19 years who self-reported on the tobacco use and mental health sections. Multivariable logistic regression analysis was performed to investigate the odds ratios (ORs) of GAD (Generalized Anxiety Disorder-7 score ≥10) according to tobacco status among Korean adults. The severity of anxiety was assessed using the Generalized Anxiety Disorder-7 scale. Results: Compared to never tobacco users, the ORs of GAD for combustible cigarette smokers and NNTP users were 2.74 (95% confidence interval [CI], 1.66-4.50) and 2.11 (95% CI, 1.16-3.83), respectively. The OR of GAD for former tobacco users was 1.63 (95% CI, 0.98-2.72). Conclusion: Tobacco use (combustible cigarettes and NNTP) was positively associated with GAD. However, in former tobacco users, there was no significant association with GAD when compared with never tobacco users. Given the OR of GAD among tobacco users, it is crucial to pay attention to screening for GAD and implement appropriate early interventions.

Lysine demethylase LSD1 is associated with stemness in EBV-positive B cell lymphoma.

EBV-infected lymphoma has a poor prognosis and various treatment strategies are being explored. Reports suggesting that B cell lymphoma can be induced by epigenetic regulation have piqued interest in studying mechanisms targeting epigenetic regulation. Here, we set out to identify an epigenetic regulator drug that acts synergistically with doxorubicin in EBV-positive lymphoma. We expressed the major EBV protein, LMP1, in B-cell lymphoma cell lines and used them to screen 100 epigenetic modifiers in combination with doxorubicin. The screening results identified TCP, which is an inhibitor of LSD1. Further analyses revealed that LMP1 increased the activity of LSD1 to enhance stemness ability under doxorubicin treatment, as evidenced by colony-forming and ALDEFLUOR activity assays. Quantseq 3' mRNA sequencing analysis of potential targets regulated by LSD1 in modulating stemness revealed that the LMP1-induced upregulation of CHAC2 was decreased when LSD1 was inhibited by TCP or downregulated by siRNA. We further observed that SOX2 expression was altered in response to CHAC2 expression, suggesting that stemness is regulated. Collectively, these findings suggest that LSD1 inhibitors could serve as promising therapeutic candidates for EBV-positive lymphoma, potentially reducing stemness activity when combined with conventional drugs to offer an effective treatment approach.