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Enkyu Noh,1,&ast; Hyungmin Jeong,1,&ast; In-So Cho,2 Min-Seok Chang,2 Iseul Yu,2 Sunmin Park,2 Ji-Ho Lee,2 Seok Jeong Lee,2 Won-Yeon Lee,2 Suk Joong Yong,2 Sang-Ha Kim2 1Yonsei University Wonju College of Medicine, Wonju, 26426, Korea; 2Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, 26426, Korea&ast;These authors contributed equally to this workCorrespondence: Sang-Ha Kim, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Korea, 20 Ilsanro, Wonju, 26426, Korea, Tel +82-33-741-0926, Fax +82-33-746-4667, Email sanghakim@yonsei.ac.krPurpose: Chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) are among the most prevalent conditions that might predispose individuals to life-threatening events. We aimed to examine their associations with cardiovascular (CV) events and mortality using a large-scale population dataset from the National Health Information Database in Korea.Patients and Methods: This population-based cohort study enrolled adults aged ≥ 40 years who had undergone more than two health examinations between 2009 and 2011. They were divided into four groups based on the presence of COPD and MetS. Analysis of the outcomes and CV events or deaths was performed from 2014 to 2019. We compared CV event incidence and mortality rates using a multivariate Cox proportional hazards model and Kaplan–Meier curves.Results: Totally, 5,101,810 individuals were included, among whom 3,738,458 (73.3%) had neither COPD nor MetS, 1,193,014 (23.4%) had only MetS, 125,976 (2.5%) had only COPD, and 44,362 (0.9%) had both. The risk of CV events was significantly higher in individuals with both COPD and MetS than in those with either COPD or MetS alone (HRs: 2.4 vs 1.6 and 1.8, respectively; all P < 0.001). Similarly, among those with both COPD and MetS, all-cause and CV mortality risks were also elevated (HRs, 2.9 and 3.0, respectively) compared to the risks in those with either COPD (HRs, 2.6 and 2.1, respectively) or MetS (HRs, 1.7 and 2.1, respectively; all P < 0.001).Conclusion: The comorbidity of MetS in patients with COPD increases the incidence of CV events and all-cause and cardiovascular mortality rates.Keywords: cardiovascular event, chronic obstructive pulmonary disease, metabolic syndrome

Amal Kumar Ghimeray,1 Un Sun Jung,1,2 Ha Youn Lee,1 Young Hoon Kim,1 Eun Kyung Ryu,1 Moon Sik Chang11R&D Center, Natural Solution Co., Ltd, Gojan-dong, Namdong-gu, Incheon, Republic of Korea; 2Department of Horticultural Biotechnology, Kyung Hee University, Yongin, Republic of KoreaBackground: In phytotherapy, the therapeutic potential is based on the combined action of different herbal drugs. Our objective was to evaluate the antioxidant, anti-collagenase (in vitro), and anti-wrinkle (in vivo) effect of combined formulation containing Ginkgo biloba, Punica granatum, Ficus carica, and Morus alba fruits extract.Methods: Antioxidant evaluation was based on the scavenging activity of free radicals (1,1-diphenyl-2-picrylhydrazyl, H2O2, and O2-) and the anti-collagenase activity was based on the reduction of collagenase enzyme in vitro. In an in vivo study, 21 female subjects were examined in a placebo-controlled trail. Facial wrinkle, especially the crow's feet region of eyes, was treated with topical formulated 2% cream for 56 days and compared with the placebo.Results: In the in vitro study, the combination of fruits extract showed a higher antioxidant activity which was comparable with the positive standard (ascorbic acid, butylated hydroxyanisole, and Trolox). The data also showed a dose-dependent inhibition of collagenase. In the in vivo study, treatment with 2% formulated cream for 56 days significantly reduced the percentage of wrinkle depth, length, and area with 11.5, 10.07, and 29.55, respectively.Conclusion: The combined formulation of fruit extracts showed excellent antioxidative and anti-collagenase activity as well as a significant effect on anti-wrinkle activity on human skin.Keywords: antioxidant, anti-collagenase, anti-wrinkle, fruits, topical formulation

Objective:. To describe the long-term survival and clinical- and treatment-related variables that determine the outcome of repeat cytoreductive surgery (CRS) for mucinous appendiceal neoplasms with peritoneal dissemination. Summary Background:. After patients with peritoneal dissemination of an appendiceal mucinous neoplasm have a CRS, disease progression may require secondary cytoreductive surgery (SCRS) and other treatments performed in a timely manner to prolong survival and help preserve an optimal quality of life. Methods:. The clinical- and treatment-related variables associated with the index CRS and the SCRS were statistically assessed for their impact on survival. Results:. One hundred eighty-six of 687 complete CRS patients (27.1%) had SCRS. The median follow-up was 10 years and the median survival was 12 years. There were 95 males (51%) and the median age was 45.0 years. Survival benefit was associated with the index CRS by use of early postoperative intraperitoneal chemotherapy (EPIC) with 5-fluorouracil [Hazard ratio (HR), 0.4; P = 0.0004]. Also, survival of low-grade mucinous appendiceal neoplasms versus mucinous appendiceal adenocarcinoma (HR, 2.8; P < 0.0001) was improved. The interval between index CRS and SCRS was significant at ≤12 months versus 12–36 months versus >36 months (P < 0.0001). Change in peritoneal cancer index and disease distribution as focal or diffuse was significant by univariant and multivariant analyses. Conclusions:. If the CRS was complete, the use of EPIC 5-fluorouracil, the interval between the index CRS and the SCRS, the histologic grade of the mucinous neoplasm, and the extent of recurrent disease were prognostic variables that should be used to help select patients for SCRS.

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small-cell lung cancer (NSCLC). The aim of our study was to determine prognostic risk factors and establish a novel nomogram for lung adenocarcinoma patients. Methods: This retrospective cohort study is based on the Surveillance, Epidemiology, and End Results (SEER) database and the Chinese multicenter lung cancer database. We selected 22,368 eligible LUAD patients diagnosed between 2010 and 2015 from the SEER database and screened them based on the inclusion and exclusion criteria. Subsequently, the patients were randomly divided into the training cohort (n = 15,657) and the testing cohort (n = 6711), with a ratio of 7:3. Meanwhile, 736 eligible LUAD patients from the Chinese multicenter lung cancer database diagnosed between 2011 and 2021 were considered as the validation cohort. Results: We established a nomogram based on each independent prognostic factor analysis for 1-, 3-, and 5-year overall survival (OS) . For the training cohort, the area under the curves (AUCs) for predicting the 1-, 3-, and 5-year OS were 0.806, 0.856, and 0.886. For the testing cohort, AUCs for predicting the 1-, 3-, and 5-year OS were 0.804, 0.849, and 0.873. For the validation cohort, AUCs for predicting the 1-, 3-, and 5-year OS were 0.86, 0.874, and 0.861. The calibration curves were observed to be closer to the ideal 45° dotted line with regard to 1-, 3-, and 5-year OS in the training cohort, the testing cohort, and the validation cohort. The decision curve analysis (DCA) plots indicated that the established nomogram had greater net benefits in comparison with the Tumor-Node-Metastasis (TNM) staging system for predicting 1-, 3-, and 5-year OS of lung adenocarcinoma patients. The Kaplan–Meier curves indicated that patients’ survival in the low-risk group was better than that in the high-risk group ( P

Objective:. To determine causes of treatment failure of low-grade appendiceal mucinous neoplasms (LAMN). Background:. For 3 decades, LAMN have been treated by cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy. This combined treatment has resulted in a large change in the survival of these patients. Methods:. A retrospective review of a prospectively maintained database was performed. A restricted cohort of patients with only LAMN histology and complete CRS were included in the statistical analysis. Results:. Four hundred and fifty patients were available with a median follow-up of 15.3 years (range 10–35 years). The median age was 49.7 and there were 196 males (43.6%). The mean survival was 24.5 years. Extent of parietal peritonectomy, resection of uterus, ovaries and apex of vagina had no impact on survival. Variables that indicated an increased extent of disease on visceral peritoneal surfaces had a significant impact on survival. Early postoperative intraperitoneal chemotherapy with 5-fluorouracil did not augment hyperthermic intraperitoneal chemotherapy (HIPEC). Patients who required reoperation for recurrence or patients with class 4 adverse events had a reduced prognosis. Conclusions:. The mean survival of LAMN treated by complete CRS and perioperative chemotherapy was 24.5 years. Extent of disease quantitated on visceral peritoneal surfaces by the extent of visceral resections was the variable associated with treatment failure. Peritonectomy plus HIPEC was able to control disease on parietal peritoneal surfaces. Not only a larger extent of disease but also its location on visceral peritoneal surfaces controlled survival.

The incidence and mortality of prostate cancer (PCa) are gradually increasing. Traditional treatments for PCa may result numerous side effects and complications that affect patients’ quality of life. Furthermore, older patients frequently cannot tolerate conventional treatments, such as surgery, chemotherapy, and radiotherapy. Thus, minimally invasive and effective therapeutic approaches for PCa need to be developed for clinical practice. Focal ablation therapy, which uses high temperature to destroy tumors, holds promise as one such approach. It has been applied to PCa in several countries with gradual success and clinical practice This review briefly discusses the application of high-intensity focused ultrasound ablation (HIFU), cryoablation, laser ablation (LA), and radiofrequency and microwave ablation (RFA, MWA) for PCa, including the principles of treatment, clinical effects, and complications. The aim of this review is to provide a reliable reference for the application of focal ablation therapy to PCa.

The results from previous observational studies and clinical trials about the neuroprotective benefits of statins use for the prevention of dementia are contradictory. It is unclear whether the neuroprotective benefits are experienced in a specific group with a higher risk of dementia, such as patients with concurrent diabetes and hyperlipidemia. We aimed to examine the association between adherence to statins and the risk of dementia among patients with diabetes and comorbid hyperlipidemia. This was a retrospective study with a new user design. We used data from the Taiwan National Health Insurance Research Database to identify patients with diabetes and comorbid hyperlipidemia. The occurrence of dementia was the study outcome. The adherence to statins was the exposure, which was measured by the proportion of days covered (PDC) of statins. The good adherence included patients with ≥80% PDC of statins. Cox proportional hazards regression models were used to evaluate the association between adherence to statins and dementia. Among 18,125 included individuals with diabetes and comorbid hyperlipidemia, 33.5% had good adherence to statins. Compared to poor adherence to statins, good adherence to statins was not significantly associated with a reduced risk of dementia (hazard ratio = 0.94; 95%confidence interval = 0.70–1.24) among patients with diabetes and comorbid hyperlipidemia. Good adherence to statins was not found to be associated with the risk of dementia among patients with diabetes and comorbid hyperlipidemia in Taiwan. Future studies with a more diverse study population are needed to evaluate the neuroprotective effects of statins use on dementia prevention.

Summary:. Contour irregularities following pediatric craniofacial surgery are common. Hydroxyapatite cranioplasty is a successful technique for optimizing the aesthetic outcome in these patients. We describe a simple technique that can be carried out at the bedside to calculate the volume of hydroxyapatite needed and therefore optimize the preoperative planning for hydroxyapatite cranioplasty.

Objective . Numerous studies have investigated the efficacy of mindfulness meditation (MM) in managing quality of life (QoL) in cancer populations, yet only a few have studied the Asian population. The aim of this exploratory study is to evaluate the effect of a MM program on the QoL outcomes in Taiwanese cancer outpatients. Methods . Patients with various cancer diagnoses were enrolled and assigned to the MM group and usual care (UC) group. The meditation intervention consisted of 3 sessions held monthly. The outcomes of the whole intervention were measured using the World Health Organization Quality of Life (WHOQOL-BREF) instrument. Results . A total of 35 participants in the MM group and 34 in the UC group completed the study. The results showed that the postintervention scores were significantly higher than the preintervention scores in the MM group. In the UC group, there was no significant difference between preintervention and postintervention scores, except for the lower environment domain scores. There was no significant difference between the follow-up scores and postintervention scores in the MM group, indicating that improvement can be maintained for 3 months after completing the MM course. Conclusions . The present study provides preliminary outcomes of the effects on the QoL in Taiwanese cancer patients. The results suggest that MM may serve as an effective mind–body intervention for cancer patients to improve their QoL, and the benefits can persist over a 3-month follow-up period. This occurred in a diverse cancer population with various cancer diagnoses, strengthening the possibility of general use.

Toona sinensis (TS) is one of the most popular vegetarian dishes in Taiwan. It has been shown to exhibit antioxidant, antiangiogenic, antiatherosclerotic, and anticancer properties. In this study, we demonstrated the ability of aqueous leaf extracts from TS to promote immune responses in BALB/c mice and to exhibit anti-leukemia activity in murine WEHI-3 cells. BALB/c mice were injected intravenously with WEHI-3 cells and then treated orally with TS (50 mg/kg). In vivo study showed that TS treatment reduced liver and spleen enlargement in WEHI-3 bearing mice compared with the untreated group. Furthermore, TS also decreased white blood cells (WBC), indicating inhibition of differentiation of the precursor of macrophages in WEHI-3 bearing mice. Treatment of WEHI-3 cells with TS (0-75 μg/mL for 24 hours) significantly reduced cell viability. Furthermore, TS treatment–induced late apoptosis was confirmed by Annexin-V/PI staining. Western blot analyses revealed that treatment of WEHI-3 cells with TS statistically increased the protein expression level of cytochrome c in the cytoplasm and activates caspase-3. Notably, TS treatment caused a dramatic reduction in Bcl-2 and increase in Bax protein levels. TS may disturb the Bcl-2 and Bax protein ratio and induce apoptosis. This reports confirms the antitumor activity of this nutritious vegetable potentially against leukemia.

Study Objectives: To report the efficacy and findings of a large-scale preventive screening program for severe acute respiratory syndrome-associated coronavirus (SARS-CoV) using amplification of the virus from a nasopharyngeal swab (NPS) obtained from the health-care workers (HCWs).Design: A prospective observational study.Setting: A medical center in Taiwan.Participants: Two hundred thirty HCWs.Intervention: NPS examination for the presence of SARS-CoV by two nested reverse transcription-polymerase chain reaction (RT-PCR) assays.Measurements and Results: During the outbreak of severe acute respiratory syndrome (SARS), NPS polymerase chain reaction screening of HCWs for SARS-CoV was performed. SARS-CoV was examined by two nested RT-PCRs and a quantitative RT-PCR. Serum-specific antibodies were assessed by enzyme immunoassay and indirect immunofluorescence. We monitored 230 HCWs, including 217 first-line HCWs and 13 non-first-line HCWs. One hundred ninety first-line HCWs and 13 non-first-line HCWs had negative results in both nested RT-PCR assays. Two first-line HCWs who were positive on both nested RT-PCR assays had SARS. They had 16,900 +/- 7,920 copies (mean +/- SD) of RNA per milliliter in the NPS and had detectable anti-SARS antibodies. The remaining 25 first-line HCWs were negative for the first nested RT-PCR but positive for the second nested RT-PCR. Their corresponding titers were 338 +/- 227 copies of RNA per milliliter; antibodies developed in none of these 25 HCWs. The expression and function of angiotensin-converting enzyme-2 were not different among these HCWs. This study shows that colonization of SARS-CoV occurred in 25 of 217 well-protected first-line HCWs on a SARS-associated service, but they remained seronegative.Conclusion: With the second RT-PCR assay more sensitive than the first RT-PCR assay, we are able to show that approximately 11.5% of well-protected HCWs exposed to SARS patients or specimens may have colonization without seroconversion. Only those with significant clinical symptoms or disease would have active immunity. Thus, regular NPS screening for nested RT-PCR assays in conjunction with a daily recording of body temperature in all first-line HCWs may provide an effective way of early detection. [ABSTRACT FROM AUTHOR]

Introduction: Elimination of the initiating focus within the pulmonary vein (PV) using radiofrequency (RF) catheter ablation is a new treatment modality for treatment of drug-refractory atrial fibrillation. However, information on the long-term safety of RF ablation within the PV is limited. Methods and Results: In 102 patients with drug-refractory atrial fibrillation and at least one initiating focus from the PV, series transesophageal echocardiography was performed to monitor the effect of RF ablation on the PV. There were 66 foci in the right upper PV and 65 foci in the left upper PV. Within 3 days of ablation, 26 of the ablated right upper PVs (39%) had increased peak Doppler flow velocity (mean 130 ± 28 cm/sec, range 106 to 220), and 15 of the ablated left upper PVs (23%) had increased peak Doppler flow velocity (mean 140 ± 39 cm/sec, range 105 to 219). Seven patients had increased peak Doppler flow velocity in both upper PVs, No factor (including age, sex, site of ablation, number of RF pulses, pulse duration, and temperature) could predict PV stenosis after RF ablation. Three patients with stenosis of both upper PVs experienced mild dyspnea on exertion, but only one bad mild increase of pulmonary pressure. There was no significant change of peak and mean flow velocity and of PV diameter in sequential follow-up studies up to 16 (209 ± 94 days) months. Conclusion: Focal PV stenosis is observed frequently after RF catheter ablation applied within the vein, but usually is without clinical significance. However, ablation within multiple PVs might cause pulmonary hypertension and should be considered a limiting factor in this procedure. [ABSTRACT FROM AUTHOR]

Introduction: The characteristics of atrial tachycardia (AT) have varied widely among different reports. The anatomic locations of ATs may bias the results. We propose that septal ATs and free-wall ATs have different characteristics. Methods and Results: One hundred forty-one patients with AT underwent electropharmacologic study, endocardial mapping, and radiofrequency ablation. Forty-nine (34.7%) patients had septal AT originating from the anteroseptal, midseptal, and posteroseptal areas. Tachycardia cycle length was similar between septal AT and freewaIl AT(367 ± 46 msec vs 366 ± 58 msec, P> 0.05). More patients with septal AT required isoproterenol to facilitate induction (44.9% vs 31.5%, P < 0.05). Septal AT was more sensitive to adenosine than free-wall AT (84.4% vs 67.8%, p < 0.05). Only posteroseptal AT showed a positive P wave in lead V1 and negative P wave in all the inferior leads (II, III, aVF). Radiofrequency catheter ablation had a comparable success rate for septal AT and free-wall AT (96% vs 95%) without impairment of AV conduction. During follow-up of 49 ± 13 months (range 17 to 85), the recurrence rate was similar for septal AT and free-wall AT (3.2% vs 4.6%, P = 0.08). Conclusion: Septal AT has electrophysiologic characteristics that are distinct from those of free-wall AT. Catheter ablation of the septal AT is sale and effective. [ABSTRACT FROM AUTHOR]

Several atrial pacing modes have been reported to be effective in the prevention of atrial fibrillation (AF); they included biatrial pacing, dual site right atria! pacing. Bachmann 's bundle (BB) pacing, and coronary sinus pacing. However, the relative efficacy and electrophysioiogical mechanisms of these pacing modes in the prevention of AF are not clear. In 15 patients (age 54 :!: 14 years) with paroxysmal AF, P wave duration, effective refractory period, and atrial conduction time were determined with six different atria! drive pacings, that were right atrial appendage (BAA), BB, right posterior interatrial septum (EPS), distal coronary sinus (DCS), RAA plus BPS simultaneously (DSA), and BAA plus DCS simultaneously (BiA). All these patients consistently had AF induced with early BAA extrastimulation coupling to RAA drive pacing. No patient had AF induced with BAA extrastimulation coupled to BB. BPS. or DCS drive pacing, but seven and eight patients had AF induced with RAA extrastimulation coupled to DSA and BiA drive pacing, respectively. The P wave duration was longest during RAA pacing, and became shorter during other atrial pacing modes. Analysis of electrophysioiogical change showed that early RAA extrastimulation coupled to BAA drive pacing caused the longest atrial conduction delay among these atria! pacing modes; RR, HPS. and DCS drive pacing caused a greater reduction of this conduction delay than DSA and BiA drive pacing. In addition, the effective refractory periods of BAA determined with BB. RPS. and DCS drive pacing were similar and longer than that determined with DSA and BiA drive pacing. In patients with paroxysmal AF. this arrhythmia was readily induced with BAA extrastimuli coupled to BAA drive pacing. RB. BPS. and DCS pacing were similar and more effective than DSA and BiA pacing in preventing AF. [ABSTRACT FROM AUTHOR]

Ectopic beats from the pulmonary veins (PVs) have been demonstrated to initiate atrial fibrillation (AF). This article describes the conceptual approach to mapping, interpretation of different electrograms, and ablation of AF initiated by PV ectopic heats. [ABSTRACT FROM AUTHOR]

Introduction: Reports about the clinical and electrophysiologic characteristics of focal atrial tachycardia vary widely. Furthermore, the impact of age, gender, associated cardiac diseases, mechanism, location of atrial tachycardia, and the prediction of results of radiofrequency catheter ablation was not clear. The purpose of this study was to further understand the clinical and electrophyslologic characteristics of focal atrial tachycardia and the prediction of results of radiofrequency ablation. Methods and Results: We searched the literature published between January 1969 and July 1997 using the key word 'atrial tachycardia' from the MEDLINE and National Library of Medicine systems. The items analyzed were age, sex, cardiac disease, mechanism, attack pattern, cycle length, location, number of atrial tachycardias, results of ablation, and recurrence after ablation. Multivarlate analysis showed that age and paroxysmal type of tachycardia were independent predictors of nonautomatic mechanism; age and presence of other cardiac diseases were independent predictors of multiple atrial tachycardias, and age also was the independent predictor of right-sided atrial tachycardia. Atrial tachycardia located in the right atrium was the only significant predictor of successful radiofrequency catheter ablation. Other cardiac diseases and multiple atrial tachycardias were the significant predictors of recurrence after initial successful radiofrequency catheter ablation. Conclusion: Patient age is closely related to the clinical and electrophysiologic characteristics of atrial tachycardia based on our reanalysis, which found that patient age is an iidependent predictor of nonautomatic mechanism, right atrial location, existence of multiple atrial tachycardias, and recurrence of atrial tachycardia after initial successful ablation. [ABSTRACT FROM AUTHOR]

Introduction: There has been limited experience with radiofrequency catheter ablation in patients with dextrucardia. This report describes a 37-year-old man who had secundum type atrial septal defect, mirror-image dextrocardia, and drug-refractory atrial tachycardia, in whom catheter-mediated radiofrequency energy successfully eliminated the tachycardia without complication. Methods and Results: On electrophysiologic study, the atrial tachycardia could be induced and terminated by atrial extrastimulation or rapid atrial pacing. Mixed resetting response pattern and manifest entrainment were also demonstrated. These findings suggested that the mechanism of atrial tachycardia might be related to reentry with an excitable gap. Because of the mirror-image dextrocardia, biplane fluoroscopy was adjusted to the right anterior oblique (RAO) 60° and left anterior oblique (LAO) 30° positions. Inducibility of the tachycardia was completely abolished after the sixth application of radiofrequency current (30 W). It was noted that the successful electrogram preceded the onset of P wave during atrial tachycardia by about 40 msec. Conclusion: This report presents another case in which radiofrequency catheter ablation was used in a patient with dextrocardia. Atrial tachycardia in patients with congenital heart disease may be difficult to control pharmacologically; however, the use of radiofrequency catheter ablation could be recommended as an alternative to medication and surgery. [ABSTRACT FROM AUTHOR]

Purpose This study enhances the efficiency of predicting complications in lung cancer patients receiving proton therapy by utilizing large language models (LLMs) and meta-analytical techniques for literature quality assessment. Materials and Methods We integrated systematic reviews with LLM evaluations, sourcing studies from Web of Science, PubMed, and Scopus, managed via EndNote X20. Inclusion and exclusion criteria ensured literature relevance. Techniques included meta-analysis, heterogeneity assessment using Cochran’s Q test and I 2 statistics, and subgroup analyses for different complications. Quality and bias risk were assessed using the PROBAST tool and further analyzed with models such as ChatGPT-4, Llama2-13b, and Llama3-8b. Evaluation metrics included AUC, accuracy, precision, recall, F1 score, and time efficiency (WPM). Results The meta-analysis revealed an overall effect size of 0.78 for model predictions, with high heterogeneity observed (I 2 = 72.88%, P < 0.001). Subgroup analysis for radiation-induced esophagitis and pneumonitis revealed predictive effect sizes of 0.79 and 0.77, respectively, with a heterogeneity index (I 2 ) of 0%, indicating that there were no significant differences among the models in predicting these specific complications. A literature assessment using LLMs demonstrated that ChatGPT-4 achieved the highest accuracy at 90%, significantly outperforming the Llama3 and Llama2 models, which had accuracies ranging from 44% to 62%. Additionally, LLM evaluations were conducted 3229 times faster than manual assessments were, markedly enhancing both efficiency and accuracy. The risk assessment results identified nine studies as high risk, three as low risk, and one as unknown, confirming the robustness of the ChatGPT-4 across various evaluation metrics. Conclusion This study demonstrated that the integration of large language models with meta-analysis techniques can significantly increase the efficiency of literature evaluations and reduce the time required for assessments, confirming that there are no significant differences among models in predicting post proton therapy complications in lung cancer patients.

Purpose: Treatment burdens and toxicities related to palliative radiation therapy (RT) may lead to unplanned hospital admissions (UHAs). The likelihood for these toxicities may be related to treatment technique. We compared rates of UHA between patients receiving nonconformal (2-dimensional) and conformal (3-dimensional or higher) radiation treatments to bone metastases involving the vertebral column. Methods and materials: We retrospectively analyzed patients treated with RT for bone metastases at a single tertiary care center between 2010 and 2017. We compared rates of RT-related UHA within 90 days of receiving radiation using Cox competing risk regression models. Results: We identified 326 patients with bone metastases involving the vertebral column, 139 of whom received radiation by nonconformal technique and 187 by conformal technique. On multivariable analysis, conformal techniques were associated with a reduced risk of 90-day UHA (hazard ratio [HR]: 0.35; 95% confidence interval [CI], 0.14-0.88). Other significant factors include hematologic cancer (HR: 0.17; 95% CI, 0.03-0.82) and baseline Eastern Cooperative Oncology Group score ≥2 (HR: 3.02; 95% CI, 1.05-8.69). Conclusions: The utilization of conformal (non-2-dimensional) radiation treatment plans may help reduce treatment-related toxicities and consequently UHAs after palliation of bone metastases.

AIM OF THE STUDY: Cynomorium songaricum Ruprecht has been used in traditional Korean medicine to treat male infertility, including sexual dysfunction, by improving kidney function. Glial cell-derived neurotrophic factor (GDNF) produced by Sertoli cells induces the proliferation of undifferentiated spermatogonia. We investigated the effects of Cynomorium songaricum on sperm parameters and GDNF expression in rat testes. MATERIALS AND METHODS: Sperm analysis, RT-PCR, and Western blotting assays were performed after administration of CS to 8-week-old male Wistar rats for 56 consecutive days (1.0 g/kg/day, p.o.), the period of sperm formation in the rat. RESULTS AND CONCLUSIONS: The CS-treated animals showed significant increases in epididymal sperm count and absolute testes weights compared to the control group. CS also increased the expression of GDNF at both the mRNA and protein levels. These results suggest that CS may improve male fertility by enhancing spermatogenesis and GDNF expression. [ABSTRACT FROM AUTHOR]

Sustained androgen receptor (AR) signaling during relapse is a central driver of metastatic castration-resistant prostate cancer (mCRPC). Current AR antagonists, such as enzalutamide, fail to provide long-term benefit for the mCRPC patients who have dramatic increases in AR expression. Here, we report AR antagonists with efficacy in AR-overexpressing models. These molecules bind to the ligand-binding domain of the AR, promote AR localization to the nucleus, yet potently and selectively down-regulate AR-target genes. The molecules BG-15a and the pharmacokinetically optimized BG-15n elicit a decrease in cell and tumor growth in vitro and in vivo in models of mCRPC. BG-15a/n treatment causes the collapse of chromatin loops between enhancers and promoters at key genes in the AR-driven epigenome. AR binding in the promoter, as well as 3D chromatin clustering, is needed for genes to respond. BG-15a/n represent promising agents for treating patients with relapsed AR-driven mCRPC tumors., Competing Interests: Competing interests statement:E.C. received research funding under institutional SRA from Janssen Research and Development, Bayer Pharmaceuticals, KronosBio, Forma Pharmaceutics Foghorn, Gilead, Sanofi, AbbVie, MacrogGenics, Astra Zeneca, GSK, and K36. B.E.G., A.K.O., S.T., W.D.F., and J.S. are co-inventors on a patent covering this technology (WO2021150603A1). P.S.N. receives personal fees from Janssen, Bristol Myers Squibb, Pfizer, and Merck and grants from Janssen. The other authors declare no competing interests.

Despite a dramatic increase in ischemic stroke incidence worldwide, effective therapies for attenuating sequelae of cerebral infarction are lacking. This study investigates the use of human mesenchymal stem cells (hMSCs) induced toward glia-like cells (ghMSCs) to ameliorate chronic sequelae resulting from cerebral infarction. Transcriptome analysis demonstrated that ghMSCs exhibited astrocytic characteristics, and assessments conducted ex vivo using organotypic brain slice cultures demonstrated that ghMSCs exhibited superior neuroregenerative and neuroprotective activity against ischemic damage compared to hMSCs. The observed beneficial effects of ghMSCs were diminished by pre-treatment with a CXCR2 antagonist, indicating a direct role for CXCR2 signaling. Studies conducted in rats subjected to cerebral infarction demonstrated that ghMSCs restored neurobehavioral functions and reduced chronic brain infarction in a dose-dependent manner when transplanted at the subacute-to-chronic phase. These beneficial impacts were also inhibited by a CXCR2 antagonist. Molecular analyses confirmed that increased neuroplasticity contributed to ghMSCs' neuroregenerative effects. These data indicate that ghMSCs hold promise for treating refractory sequelae resulting from cerebral infarction by enhancing neuroplasticity and identify CXCR2 signaling as an important mediator of ghMSCs' mechanism of action., (Copyright © 2024. Published by Elsevier Inc.)

Background/aims: Combi-elastography is a B-mode ultrasound-based method in which two elastography modalities are utilized simultaneously to assess metabolic dysfunction-associated steatotic liver disease (MASLD). However, the performance of combi-elastography for diagnosing metabolic dysfunction-associated steatohepatitis (MASH) and determining fibrosis severity is unclear. This study compared the diagnostic performances of combi-elastography and vibration-controlled transient elastography (VCTE) for identifying hepatic steatosis, fibrosis, and high-risk MASH., Methods: Participants who underwent combi-elastography, VCTE, and liver biopsy were selected from a prospective cohort of patients with clinically suspected MASLD. Combi-elastography-related parameters were acquired, and their performances were evaluated using area under the receiver-operating characteristic curve (AUROC) analysis., Results: A total of 212 participants were included. The diagnostic performance for hepatic steatosis of the attenuation coefficient adjusted by covariates from combi-elastography was comparable to that of the controlled attenuation parameter measured by VCTE (AUROC, 0.85 vs 0.85; p=0.925). The performance of the combi-elastography-derived fibrosis index adjusted by covariates for diagnosing significant fibrosis was comparable to that of liver stiffness measured by VCTE (AUROC, 0.77 vs 0.80; p=0.573). The activity index from combi-elastography adjusted by covariates was equivalent to the FibroScan-aspartate aminotransferase score in diagnosing high-risk MASH among participants with MASLD (AUROC, 0.72 vs 0.74; p=0.792)., Conclusions: The performance of combi-elastography is similar to that of VCTE when evaluating histology of MASLD.

Background/aim: Predicting lymph node metastasis (LNM) in early gastric cancer (EGC) is crucial for making treatment decisions. This study aimed to confirm risk factors for LNM and identify novel auxiliary biomarkers for predicting LNM in EGC., Patients and Methods: We established a training set, comprising 63 patients with LNM-EGC and 274 patients with non-LNM EGC, and a test set, comprising 19 patients with LNM-EGC and 146 non-LNM EGC. Immunohistochemistry for lymphangiogenic and related pathway components (VEGF-C, TGF-β1, SMAD2/3, VEGF-D, pSTAT3, E-cadherin, CD44, c-MET, YAP, and HER2), in situ hybridization for Epstein-Barr virus-encoded small RNAs, and multiplex PCR for microsatellite instability were conducted., Results: In the training set, Lauren's diffuse/mixed classification, stromal desmoplasia, submucosal invasion ≥500 μm, lymphatic invasion, and high VEGF-C and SMAD2/3 expression were independent risk factors for LNM (p<0.05). A large tumor size, mixed histology, submucosal invasion, perineural invasion, and ulceration were determined as risk factors using univariate analysis (p<0.05). The tumor cutoff size for predicting LNM was 2.65 cm, based on a ROC analysis. The test set study verified that stromal desmoplasia, submucosal invasion, and high VEGF-C expression were independent risk factors for LNM (p<0.05). Moreover, mixed histology, lymphatic invasion, ulceration, and high SMAD 2/3 expression were identified as additional risk factors using univariate analysis (p<0.05)., Conclusion: Stromal desmoplasia, submucosal invasion, and high VEGF-C expression are potential biomarkers for LNM in EGC. VEGF-C expression might serve as an adjunct biomarker for predicting LNM on forceps-biopsy tissue at initial diagnosis., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To analyze and quantify the change in United States of America Medicare reimbursement rates for the 30 most commonly performed spinal imaging procedures., Materials and Methods: The Physician Fee Schedule Look-Up Tool from the Centers for Medicare & Medicaid Services was utilized to find and extract the 28 most billed spinal imaging procedures. All data was adjusted for inflation and listed in 2020 US dollars. Percent change in reimbursement and Relative Value Units between 2005 and 2020, both unadjusted and adjusted, were calculated and compared. Additionally, percent change per year and compound annual growth rate were calculated and compared., Results: After adjusting for inflation, the average reimbursement for all analyzed spinal imaging procedures between the years 2005 and 2020 decreased by 45.9%. The adjusted reimbursement rate for all procedures decreased at an average 4.3% per year and experienced an average compound annual growth rate (CAGR) of - 4.4%. Magnetic resonance imaging (MRI) had the most substantial adjusted decline of all imaging modalities at - 72.6%, whereas x-ray imaging had the smallest decline at - 27.33%. The average total RVUs per procedure decreased by 50.1%, from 7.96 to 3.97., Conclusion: From the years 2005 to 2020, Medicare reimbursement significantly decreased for all advanced imaging modalities involving the most common spinal imaging procedures. Among all practices, imaging procedures may be experiencing some of the largest decreases from Medicare reimbursement cutbacks., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Background: Three-column spinal osteotomies (3-CO) are powerful techniques used to correct spinal deformity. These surgeries are associated with an elevated risk of complications. While outcomes have been reported in the literature with 2 years follow-up, longer-term outcomes of three-column osteotomies remain understudied., Objectives: This study aims to examine patient reported outcomes and complications for three-column osteotomies at 5 years., Study Design: Retrospective review of a prospectively collected spinal deformity cases database., Patient Sample: All consecutive adult patients at a single spine surgery center treated with either a pedicle subtraction osteotomy (PSO) or vertebral column resection (VCR) for spinal deformity, and with a minimum 5-year follow-up were included., Outcome Measures: Visual-analog scale (VAS) for back pain score (0 to 10), Oswestry Disability Index (ODI) score (0 to 100), number of complications, revision rate, sagittal balance, lumbar lordosis at preoperative and at 5-year visit., Methods: Data was extracted from a prospectively collected spinal deformity surgery database continuously updated since 2002 with data from operative reports, patients' medical visit notes and patients' self-reported VAS and ODI questionnaires completed at each office visit. Radiographic measurements were performed on standing full-length spine radiographs taken at preop and 5-year visits. Descriptive statistics, comparison of means and proportions among groups, and a logistic regression analysis were conducted using the statistical software package SPSS version 28. Statistical significance was set at p<.05., Results: Of 127 consecutive adult patients with minimum of 5-year follow-up undergoing a 3-CO posterior spinal surgery for spinal deformity were identified and included in the study, 79 (62%) were treated with PSO, and 48 (38%) with VCR. Both PSO and VCR groups demonstrated significant improvements in VAS (PSO preop: 6.7, 5-year: 4.6, p<.001; VCR preop: 7.1, 5-year: 5.2, p<.001), and ODI (PSO preop: 52.9, 5-year: 45.4, p<.001; VCR preop: 57.5, 5-year 43.0, p<.001) that were maintained at 5 years. Major and minor complications occurring within 5 years were not statistically different between the PSO and VCR groups (major: 59.5% vs 56.3%, p=.85; minor: 45.6% vs 37.5%, p=.46). The rate of revision surgery within 5 years was 39.4% overall. Of the fifty patients requiring revision, 37.5% were for nonunion, 27.1% instrumentation failure, 14.6% proximal junctional kyphosis (PJK), 12.5% vertebral fracture, 6.3% motor weakness, and 2.1% infection. Improvements in lumbar lordosis were maintained at 5 years in both the PSO (29.9° vs 47.2°, p<.001) and VCR (34.6° vs 48.5°, p<.001) groups while sagittal balance maintained significant improvement in the VCR group (9.5 cm vs 6.3 cm, p=.008) but not the PSO (11.4 cm vs 9.3 cm, p=.065)., Conclusion: Patients undergoing three-column osteotomies had a major complication rate of 57.5% and a minor complication rate of 42.5% after 5 years. Improvements in lumbar lordosis were maintained at 5-year follow-up, but sagittal balance was only maintained in the VCR group. Despite these radiographic findings, both VCR and PSO groups maintained significant clinical improvements in both VAS and ODI scores at 5-year follow up., Competing Interests: Declaration of competing interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Previous studies have consistently reported a decrease in hospital admissions for respiratory diseases during the coronavirus disease 2019 (COVID-19) pandemic. However, the impact of the pandemic on idiopathic pulmonary fibrosis (IPF) admissions remains unknown., Methods: This study used data from the Korean National Health Insurance Service database. IPF was defined based on the International Classification of Diseases 10th Revision (ICD-10) and rare intractable disease (RID) codes. The rate of IPF admissions was calculated by dividing the number of IPF admissions by the prevalence of IPF. The rate of IPF admissions during the COVID-19 pandemic (2020-2021) was compared with the mean rate of admissions during the prepandemic period (2017-2019) and presented as the rate ratio (RR). A sensitivity analysis was conducted on patients treated with systemic corticosteroids during IPF admission., Results: In patients with IPF defined based on the ICD-10 (analysis 1), the RRs significantly decreased from March in 2020 to December 2021, except for June and September in 2020. Similarly, in patients with IPF defined based on the ICD-10 and RID (analysis 2), the RRs significantly decreased from March 2020 to December 2021, except for June and September 2020. In the sensitivity analysis of analysis 1, the RR significantly decreased in 2020 (0.93; 95%CI: 0.88-0.99; P = 0.029), whereas the RR in 2021 was not significantly different. The RRs in the sensitivity analysis of analysis 2 significantly decreased to 0.85 (0.79-0.92; P < 0.001) in 2020 and 0.82 (0.76-0.88; P < 0.001) in 2021. In the subgroup analysis, the rates of IPF admissions significantly decreased in 2020 and 2021 across both sexes, patients aged ≥ 60 years, and all household income groups., Conclusions: The rate of IPF admissions significantly decreased during the COVID-19 pandemic. This result indicates that preventive measures against COVID-19 may effectively mitigate IPF exacerbation. Therefore, it is assumed that there is a close relationship between respiratory viral infections and IPF exacerbations., (© 2024. The Author(s).)

Lappaconitine, a diterpene alkaloid isolated from Aconitum sinomontanum Nakai, exhibits a wide range of biological activities, making it a promising candidate for the development of novel derivatives with therapeutic potential. In our research, we executed a two-step transformation via oxidative cleavage of lappaconitine's vicinal diol using the hypervalent iodine reagent PhI(OAc) 2 , followed by strong alkaline hydrolysis. This approach yielded four new unanticipated compounds, whose structures were identified by spectroscopic methods and/or X-ray crystallography. Thus, we proposed plausible reaction mechanisms for their formations and particularly investigated the remarkable diastereoselectivity for the formation of single stereoisomer 8 observed during the alkaline hydrolysis step. Among them, compound 8 (code name: QG3030 ) demonstrated both enhanced osteogenic differentiation of human mesenchymal stem cells and significant osteogenic effect in an ovariectomized rat model with no acute oral toxicity.

Background/Objectives : Obstructive sleep apnea (OSA) impairs quality of life (QoL). However, its disease burden in the general population remains unknown. We aimed to investigate the association between OSA and health-related QoL in the general Korean population. Methods : This study analyzed cross-sectional datasets of adults (≥40 years) in the Korean National Health and Nutrition Examination Survey 2019-2021. QoL was assessed using the 3-level EuroQoL 5-dimension component (EQ-5D-3L). The high risk of OSA was determined using the STOP-Bang questionnaire (score ≥ 3). Demographic and clinical factors were included in linear regression analyses to identify the factors associated with EQ-5D-3L. Results : Of the 8966 total participants, 6792 (75.8%) and 2174 (24.2%) were classified as having a low risk and high risk of OSA, respectively. The high risk OSA group showed significantly lower QoL scores when compared with the low risk OSA group (0.939 ± 0.003 vs. 0.951 ± 0.002, p < 0.001). However, the mean difference was within the minimal clinically important difference (MCID) of EQ-5D-3L. Only females exceeded the MCID for the EQ-5D-3L. Elderly females with a high risk of OSA showed the lowest QoL. The regression coefficient of high risk OSA in the multivariate model was -0.018 (95% CI: -0.025--0.01, p < 0.001). Patient demographics and comorbidities also showed significant associations with the EQ-5D-3L. Their regression coefficient was higher than that of high risk OSA. Conclusions : The impact of high risk OSA on QoL manifested differently according to age and sex. The impact of comorbidities on QoL was greater than that of high risk OSA, highlighting the important role of comorbidities and the need for their adjustment in the assessment of QoL.