Feasibility of articulating laparoscopic instrument use in laparoscopic adnexectomy: a multicenter prospective observational study.

Background: Ovarian cysts, common in women of reproductive age, often require surgical intervention, with minimally invasive laparoscopic surgery becoming the preferred method due to its reduced complications and faster recovery. Despite its benefits, challenges such as instrument collisions and operational difficulties limit the use of single- or two-port approaches. The purpose of this study was to evaluate the feasibility of laparoscopic adnexa surgery using an articulating laparoscopic instrument, which offers flexible and ergonomic movements similar to robotic systems. Methods: This multicenter prospective observational study was conducted in South Korea and Taiwan. The electronic medical records of patients who underwent laparoscopic adnexectomy using the articulating laparoscopic instrument (ArtiSential®, LIVSMED Inc., Seongnam-si, South Korea) between October 2022 and September 2023 were analyzed. Data on patient demographics, operative and pathologic data were collected prospectively. Results: A total of 66 patients underwent laparoscopic adnexal surgery using the articulating instrument. The median age of the patients was 43 (range, 23-76) years, and the median body mass index (BMI) was 22.5 (range, 17.1-43.4) kg/m2. Thirty-five (53.0%) patients underwent oophorectomy or salpingectomy, while 31 (47.0%) underwent cystectomy of the ovary or fallopian tube. The final pathology after surgery was benign in 61 patients (92.4%), borderline in 3 patients (4.5%), and malignant in 2 patients (3.0%). During surgery, pelvic adhesions were found in 13 patients (19.7%) and adhesiolysis was performed. The median total operation time was 53.5 (range, 26-174) minutes, and median estimated blood loss (EBL) was 50 (range, 10-200) mL. Median length of hospital stay was 1 (range, 0-3) days. Only two patients experienced a postoperative complication, which was trocar site wound dehiscence in both cases. Conclusions: The results of this study demonstrated the feasibility of using the articulating laparoscopic instrument during laparoscopic adnexectomy.

Vitis vinifera seed extract versus micronized purified flavonoid fraction for patients with chronic venous disease: a randomized, non-inferiority trial.

BACKGROUND: Venoactive drugs (VADs) based on Vitis vinifera extract are widely used in Korea. However, studies on the clinical effects and head-to-head comparisons with other groups of VADs are limited. This trial aimed to evaluate whether Vitis vinifera seed extract was non-inferior to the micronized purified flavonoid fraction (MPFF) in relieving venous symptoms and improving quality of life in patients with chronic venous disease (CVD). METHODS: In this double-blind prospective randomized trial, patients from 13 hospitals, who were diagnosed with venous incompetence by duplex ultrasound and classified as clinical class 1, 2, or 3 in the Clinical, Etiological, Anatomical, and Pathophysiological classifications were enrolled. The primary outcome was the change in the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) score at 8 weeks from baseline. Secondary outcomes included changes in the Aberdeen Varicose Vein Questionnaire (AVVQ), visual analog scale (VAS), and Venous Clinical Severity Score (VCSS) at 4- and 8 weeks from baseline. Moreover, the change in leg circumferences was measured at 8 weeks and compared to baseline. RESULTS: In total, 303 patients were enrolled and randomly assigned to receive either Vitis vinifera seed extract (n = 154) or MPFF (n = 149). The CIVIQ-20 scores at 8 weeks were significantly reduced compared to those at baseline in both groups. No significant inter-group difference in the change of CIVIQ-20 at 8 weeks from baseline was observed (-8.31 ± 14.63 vs. -10.35 ± 14.38, P = 0.29, 95% confidence interval [CI] -1.65 to 5.72). The lower limit of the 95% CI was within the predefined noninferiority margin of 6.9. Furthermore, the AVVQ, VAS, and VCSS scores significantly decreased at 4- and 8 weeks after randomization compared with baseline in both groups. No significant differences were observed in the reduction of each score between groups. The calf circumference measured at 8 weeks was significantly reduced compared to that at baseline in patients receiving Vitis vinifera seed extract. CONCLUSIONS: Vitis vinifera seed extract was non-inferior to MPFF in relieving venous symptoms and improving the quality of life in patients with CVD.

A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC).

BACKGROUND: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. METHODS: Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. DISCUSSION: The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. TRIAL REGISTRATION: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Outcomes of extended progestin therapy in atypical endometrial hyperplasia patients without an initial response to progestin: a retrospective study from two tertiary centers in Korea and Taiwan.

OBJECTIVE: In this study, we evaluated the role of prolonged progestin treatment on atypical endometrial hyperplasia (AEH) patients who did not achieve complete regression (CR) after at least 3 months of progestin treatment. Possible prognostic factors predicting disease regression and recurrence were also assessed. METHODS: We retrospectively identified patients who had histologically confirmed persistent disease after at least 3 months of progestin treatment at two tertiary centers in Korea and Taiwan. Clinicopathologic factors and clinical outcomes were obtained from medical records. Logistic regression was used to analyze the relationship between covariates and the probability of CR and relapse. RESULTS: Fifty-two patients were included. Thirty-seven of 52 patients (71.2%) achieved CR after prolonged progestin treatment. Median time from starting progestin treatment to CR was 12.0 months. Daily administration of medroxyprogesterone acetate ≥200 mg or megestrol acetate ≥80 mg was associated with higher probability of regression. Nineteen of 37 patients (51.4%) experienced recurrence, with median time from CR to relapse of 15.0 months. Body mass index ≥27 was associated with higher relapse probability. Twelve of 16 patients with disease progression to endometrial carcinoma underwent surgery. The 12 cases had stage I tumors and lived without disease. CONCLUSION: Extension of progestin treatment course is feasible for AEH patients without an initial response to progestin. Higher daily progestin dosage was associated with higher probability of CR, and obesity was associated with higher risk of relapse. The patients without an initial response to progestins and whose AEH progressed to endometrial carcinoma had good prognoses.

Asparagine Dependency is a Targetable Metabolic Vulnerability in TP53-Altered Castration-Resistant Prostate Cancer.

The TP53 tumor suppressor is frequently altered in lethal, castration-resistant prostate cancer (CRPC). However, to date there are no effective treatments that specifically target TP53 alterations. Using transcriptomic and metabolomic analyses, we showed here that TP53-altered prostate cancer (PCa) exhibits an increased dependency on asparagine and overexpresses asparagine synthetase (ASNS), the enzyme catalyzing the synthesis of asparagine. Mechanistically, loss or mutation of TP53 transcriptionally activated ASNS expression, directly as well as via mTORC1-mediated ATF4 induction, driving de novo asparagine biosynthesis to support CRPC growth. TP53-altered CRPC cells were sensitive to asparagine restriction by knockdown of ASNS or L-asparaginase treatment to deplete the intracellular and extracellular sources of asparagine, respectively, and cell viability was rescued by asparagine addition. Notably, pharmacological inhibition of intracellular asparagine biosynthesis using a glutaminase inhibitor and depletion of extracellular asparagine with L-asparaginase significantly reduced asparagine production and effectively impaired CRPC growth. This study highlights the significance of ASNS-mediated metabolic adaptation as a synthetic vulnerability in CRPC with TP53 alterations, providing a rationale for targeting asparagine production to treat these lethal prostate cancers.

Comparison of Outcomes in Bowel Resections by Gynecologic Oncologists Versus General Surgeons During Maximal Cytoreductive Surgery for Advanced Ovarian Cancer: Gynecologic Oncology Research Investigators Collaboration Study (GORILLA-3006).

BACKGROUND: This report describes the oncologic outcomes for patients with advanced ovarian cancer who had bowel surgery performed by gynecologic oncologists (GOs) and compares the outcomes with those for bowel surgery performed by general surgeons (GSs) during maximal cytoreductive surgery. METHODS: Patients from six academic institutions who had FIGO stage III or IV ovarian cancer and underwent any bowel surgeries during maximal cytoreductive surgery were eligible for the study. The patients were divided into two groups according to whether bowel surgery was performed by a GO or a GS. In both groups, the GOs were mainly involved in extra bowel debulking procedures. Perioperative and survival outcomes were compared between the two groups. RESULTS: The 761 patients in this study included 113 patients who underwent bowel surgery by a GO and 648 who had bowel surgery by a GS. No discernible differences were observed in age, American Society of Anesthesiology (ASA) score, FIGO stage, histologic type, timing of cytoreductive surgery (primary or interval debulking surgery), or complications between the two groups. The GO group exhibited a shorter operation time than the GS group. Kaplan-Meier analysis showed no survival differences between the two groups. In the Cox analysis, non-serous cell types and gross residual diseases were associated with adverse effects on overall survival. However, performance of bowel surgery by a GO did not have an impact on survival. CONCLUSION: Performance of bowel surgery by a GO during maximal cytoreductive surgery is both feasible and safe. These results should be reflected in the training system for GOs regarding bowel surgery, and further research is needed to confirm that GOs can play a more leading role in performing extra-uterine procedures.

Comparison between intermittent claudication versus chronic limb-threatening ischemia in peripheral arterial disease: a retrospective multicenter cohort study.

Purpose: The anatomical distribution, characteristics of lesions, and treatment modalities for peripheral artery disease (PAD) are diverse. Endovascular intervention is popular for symptomatic PAD, for both intermittent claudication (IC) and chronic limb-threatening ischemia (CLTI). We aimed to investigate the endovascular devices used by comparing patients with PAD referred for endovascular revascularization with IC and CLTI. Methods: We identified 736 patients with PAD enrolled in the multicenter PAD registry in South Korea from 2019 to 2022. Of these patients, 636 received endovascular treatment at the time of this study. After excluding missing data, we analyzed 506 patients with IC or CLTI. Patients' characteristics, target lesions, and endovascular device data such as type, length, balloon diameter, and stent, were examined. Procedure outcomes of the aortoiliac, femoropopliteal, and below-the-knee lesions were analyzed. Results: Patients with CLTI were more likely to have diabetes mellitus, below-the-knee interventions, and multilevel PAD than the IC group. Patients with IC had more aortoiliac artery lesions and underwent atherectomies than the CLTI group (63.3% and 61.1% vs. 39.7% and 40.6%, respectively; P < 0.001). In patients with femoropopliteal lesions, those with CLTI were more revascularized with stents than the patients with IC, without significant differences (35.3% vs. 29.1%, P = 0.161). Compared to the IC group, the CLTI patients showed significantly worse rates of primary patency, amputation, and mortality (P = 0.029, P < 0.001, and P < 0.001, respectively). Conclusion: Among Korean patients with PAD, there is a significant difference in baseline and lesion characteristics, endovascular strategies, and short-term follow-up outcomes among those with IC and CLTI.

Development of Hsp90 inhibitor to regulate cytokine storms in excessive delayed- and acute inflammation.

BACKGROUND: The surplus cytokines remaining after use in the early stages of the inflammatory response stimulate immune cells even after the response is over, causing a secondary inflammatory response and ultimately damaging the host, which is called a cytokine storm. Inhibiting heat shock protein 90 (Hsp90), which has recently been shown to play an important role in regulating inflammation in various cell types, may help control excessive inflammatory responses and cytokine storms. METHODS: We discovered an anti-inflammatory compound by measuring the inhibitory effect of CD86 expression on spleen DCs (sDCs) using the chemical compounds library of Hsp90 inhibitors. Subsequently, to select the hit compound, the production of cytokines and expression of surface molecules were measured on the bone marrow-derived DCs (BMDCs) and peritoneal macrophages. Then, we analyzed the response of antigen-specific Th1 cells. Finally, we confirmed the effect of the compound using acute lung injury (ALI) and delayed-type hypersensitivity (DTH) models. RESULTS: We identified Be01 as the hit compound, which reduced CD86 expression the most in sDCs. Treatment with Be01 decreased the production of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1ß) in BMDC and peritoneal macrophages stimulated by LPS. Under the DTH model, Be01 treatment reduced ear swelling and pro-inflammatory cytokines in the spleen. Similarly, Be01 treatment in the ALI model decreased neutrophil infiltration and lower levels of secreted cytokines (IL-6, TNF-α). CONCLUSIONS: Reduction of CD80 and CD86 expression on DCs by Be01 indicates reduced secondary inflammatory response by Th1 cells, and reduced release of pro-inflammatory cytokines by peritoneal macrophages may initially control the cytokine storm.

Ten-year incidence of keratoconus in relation to sex, age, and thyroid gland dysfunction: a nationwide population-based cohort study (2009-2018).

Background: Keratoconus is a corneal ectatic disorder that often leads to visual impairment and may require corneal transplantation. However, its age and gender-based incidence and potential association with thyroid gland dysfunction (TGD) remain poorly understood. This study aims to clarify these aspects and investigate the possible connection between keratoconus and TGD. Methods: We conducted a nationwide population-based cohort study using data from the Korean National Health Insurance Service database. A retrospective chart review was conducted on 4,059,021 patients aged over 20 without underlying corneal diseases in 2009. The end of the review period was at ten years, or until the onset of keratoconus. To evaluate the association with TGD, multivariate Cox regression analysis was used with adjustment of confounding variables such as sex and age. Results: During the review period, 2,334 patients developed keratoconus before the 10-year mark. Females exhibited a higher keratoconus incidence (7.101 per 100,000 person-years) compared to males (5.559) (P<0.001). After adjusting for age, the hazard ratio (HR) for keratoconus was 1.295 times higher [95% confidence interval (CI): 1.193-1.406] in females compared to males. Age groups were stratified in 10-year intervals. The highest incidence of keratoconus was observed in the 20 to 29-year age group (10.695 per 100,000 person-years). All other age groups had significantly lower HR values, with the lowest at 50-59 years (0.508, 95% CI: 0.447-0.577). Keratoconus incidence per 100,000 person-years was 6.227 in subjects without TGD, 6.019 in the hypothyroidism group and 8.287 in the hyperthyroidism group, respectively. Although not statistically significant, individuals with hyperthyroidism showed a higher HR (1.290, 95% CI: 0.939-1.771) for keratoconus when compared to those without TGD, after adjusting for age and sex. Conclusions: This study emphasizes a female predominance in keratoconus incidence and suggests a possible connection between hyperthyroidism and keratoconus. Furthermore, it affirms a higher incidence of keratoconus among young individuals.

Knowledge, attitudes, and practices associated with influenza vaccine uptake among healthcare personnel in Israel during three influenza seasons, 2016-2019.

INTRODUCTION: Despite a longstanding Israel Ministry of Health recommendation that all healthcare personnel (HCP) receive a seasonal influenza vaccine, vaccine uptake among HCP remains below the country's target of 60% coverage. To understand factors related to vaccine hesitancy, we used data from a prospective three-year (2016-2019) influenza vaccine effectiveness study among Israeli HCP to examine knowledge, attitudes, and practices (KAP) about influenza vaccination and their association with vaccine uptake. METHODS: At the start of each influenza season, all participating HCP completed a questionnaire that included questions about socio-demographic and occupational characteristics, health status, and KAP related to seasonal influenza vaccination. We extracted vaccination history from electronic medical records and employee vaccination registries. We used logistic regression models to identify demographic and occupational factors, and KAP about influenza vaccination, associated with receipt of vaccination. RESULT: A total of 2,126 HCP were enrolled and had available data on vaccination history. Their median age was 42 years [IQR 35-52], and 73 % self-identified as female. Influenza vaccine uptake in 2016, 2017 and 2018 was 46 %, 48 % and 47 %, respectively. Overall, 36 % of HCP had received an influenza vaccine in ≥ 4 of the eight years prior. HCP aged 35-49 years were less likely to receive influenza vaccine compared to HCP aged ≥ 50 years (OR: 0.81 [95 % CI: 0.67-0.98]). Nurses and allied personnel were less likely to receive influenza vaccine compared to physicians (OR: 0.63 [95 % CI: 0.50-0.78] and OR: 0.53 [95 % CI: 0.40-0.70], respectively). The emotional benefit of vaccination (e.g., anticipating regret if not vaccinated) and the perception of vaccine safety were factors associated with vaccine uptake (OR: 7.60 [95 % CI: 6.27-9.22] and OR: 3.43 [95 % CI:2.91-4.03], respectively). CONCLUSION: Among HCP at two hospitals in Israel, less than half received an annual influenza vaccine. Older HCP, physicians, and those who reported the emotional benefit of vaccination or agreed that influenza vaccines are safe were more likely to be vaccinated. Future influenza vaccination campaigns could focus on these demographic groups and tailor messages emphasizing the emotional benefits of vaccination and vaccine safety to increase seasonal influenza vaccine uptake among HCP in Israel.

Switchable and conspicuous retroreflective sensors inspired by the wing scale of an emerald swallowtail.

Butterfly wings possess distinct micro/nanostructures that contribute to their vibrant coloration, light-trapping capabilities, and sensitivity to various stimuli. These complex features have inspired the creation of diverse devices and systems, such as sensors, photovoltaics, photocatalysis, and robotics. Specifically, the wing scales of the Emerald Swallowtail (Papilio palinurus) display iridescent, polarization-sensitive, and retroreflective colors due to their hierarchical structures. However, current technologies fail to mimic these natural designs fully, limiting their practical application in everyday life. In this study, we introduce a groundbreaking method for fabricating artificial wing scales that emulate the biological structure's functionality with a much simpler geometry. By integrating self-graded lossy media into metallic micro-concavity arrays, we achieve pronounced iridescent effects in both coaxial and non-coaxial arrangements, while preserving retroreflective properties. In particular, the simplified design allows for switchable color patterns based on the viewing angle. Demonstrating the concept, we successfully employ these conspicuous retroreflectors in hydrogen gas detection and the bi-directional/switchable recognition of patterned signals.

Humidity-tolerant porous polymer coating for passive daytime radiative cooling.

Coating building envelopes with a passive daytime radiative cooling (PDRC) material has attracted enormous attention as an alternative cooling technique with minimal energy consumption and carbon footprint. Despite the exceptional performance and scalability of porous polymer coating (PPC), achieving consistent performance over a wide range of drying environments remains a major challenge for its commercialization as a radiative cooling paint. Herein, we demonstrate the humidity vulnerability of PPC during the drying process and propose a simple strategy to greatly mitigate the issue. Specifically, we find that the solar reflectance of the PPC rapidly decreases with increasing humidity from 30% RH, and the PPC completely losses its PDRC ability at 45% RH and even become a solar-heating material at higher humidity. However, by adding a small amount of polymer reinforcement to the PPC, it maintains its PDRC performance up to 60% RH, resulting in a 950% increase in estimated areal coverage compared to PPC in the United States. This study sheds light on a crucial consistency issue that has thus far been rarely addressed, and offers engineering guidance to handle this fundamental threat to the development of dependable PDRC paint for industrial applications.

CTLA4 expression profiles and their association with clinical outcomes of breast cancer: a systemic review.

Purpose: The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. Methods: We assessed the effect of CTLA4 expression on BRCA using a variety of bioinformatics platforms, including Oncomine, GEPIA, UALCAN, PrognoScan database, Kaplan-Meier plotter, and R2: Kaplan-Meier scanner. Results: CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (P < 0.01). The CTLA4 messenger RNA levels in BRCA based on BRCA subtypes of Luminal, human epidermal growth factor receptor 2, and triple-negative BRCA were considerably higher than in normal tissues (P < 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P < 0.001) and was correlated with clinicopathological characteristics including age, T stage, estrogen receptors, progesterone receptors, and prediction analysis of microarray 50 (P < 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P < 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. Conclusion: This study provides suggestive evidence of the prognostic role of CTLA4 in BRCA, which may be a therapeutic target for BRCA. Furthermore, CTLA4 may influence BRCA prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in BRCA and set the stage for more research.

Effect of Therapeutic Gardening Program in Urban Gardens on the Mental Health of Children and Their Caregivers with Atopic Dermatitis.

This study was conducted to identify the physical and psychological difficulties of children with atopic dermatitis and their caregivers, and to investigate the effects of participation in a novel therapeutic gardening program based on psychological intervention on their physical and mental health. The program, consisting of 15 sessions, was conducted for approximately 4 months in urban gardens in Seoul and involved 30 children with atopic dermatitis and their caregivers. Additionally, a control group of 30 non-participating caregivers was recruited for comparative analysis. The psychological and emotional changes in caregivers were assessed using six self-report scales (depression, anxiety, stress, vitality, life satisfaction, parenting efficacy) before and after participation in the program. Additionally, the depression index (CDI) and atopic dermatitis index (SCORAD, TEWL) were measured for the children with atopic dermatitis. The research results indicate that the therapeutic gardening program utilizing psychological intervention had a positive impact on the physiological and psychological health of participants. These results are significant as they demonstrate the clinical application of the professionally developed therapeutic gardening program through active intervention and operation. This study suggests that this program can serve as an effective intervention in improving the mental health of both children with atopic dermatitis and their caregivers.

Evaluating the effect of a mobile-based symptom monitoring system for improving physical function in patients with cancer during chemotherapy: study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Symptoms due to chemotherapy are common in patients with cancer. Cancer-related symptoms are closely associated with the deterioration of physical function which can be associated with decreased quality of life and increased mortality. Thus, timely symptom identification is critical for improving cancer prognosis and survival. Recently, remote symptom monitoring system using digital technology has demonstrated its effects on symptom control or survival. However, few studies examined whether remote monitoring would contribute to retaining physical function among patients with cancer. Therefore, this study aimed to evaluate the effectiveness of mobile-based symptom monitoring in improving physical function among patients with cancer under chemotherapy. METHODS AND ANALYSIS: This study is a multicentre, open-label, parallel-group, randomised controlled trial. We will recruit 372 patients at three tertiary hospitals located in Seoul, South Korea. Study participants will be randomly assigned to either an intervention group receiving the ePRO-CTCAE app and a control group receiving routine clinical practice only. The primary outcome is changes in physical function from commencement to completion of planned chemotherapy. A linear mixed model will be performed under the intention-to-treat principle. The secondary outcomes include physical activity level; changes in pain interference; changes in depressive symptom; unplanned clinical visits; additional medical expenditure for symptom management; completion rate of planned chemotherapy; changes in symptom burden and health-related quality of life; and 1-year overall mortality. ETHICS AND DISSEMINATION: The study has been approved by the institutional review board and ethics committee at the three university hospitals involved in this trial. Written informed consent will be obtained from all the participants. The results of the trial will be submitted for publication in peer-reviewed academic journals and disseminated through relevant literatures. TRIAL REGISTRATION NUMBER: KCT0007220.

Efficacy and safety of biosimilar trastuzumab (CT-P6) in routine clinical practice in the Republic of Korea: a real-world post-marketing surveillance study.

BACKGROUND: The trastuzumab biosimilar CT-P6 is approved for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), metastatic breast cancer (MBC), and metastatic gastric cancer (MGC). The objective of this post-marketing surveillance (PMS) study was to evaluate the real-world safety and effectiveness of CT-P6 in patients with HER2-positive cancers. RESEARCH DESIGN AND METHODS: This open-label, observational, prospective, PMS study collected data via investigator surveys from 35 centers in the Republic of Korea (5 October 2018-4 October 2022). Eligible patients with HER2-positive EBC, MBC, or MGC started CT-P6 treatment during routine clinical practice, followed by 1-year observation. Evaluations included adverse events (AEs), adverse drug reactions (ADRs), and effectiveness. RESULTS: Safety was analyzed in 642 patients (494 EBC, 94 MBC, 54 MGC). Overall, 325 (50.6%) patients experienced 1316 AEs, and 550 ADRs occurred in 199 (31.0%) patients. Unexpected ADRs occurred in 62 (9.7%) patients. Unexpected ADRs and ADRs of special interest did not raise any new safety signals. Among trastuzumab-naïve patients, 34/106 (32.1%) with EBC achieved pathological complete response; 30/74 (40.5%) MBC and 24/49 (49.0%) MGC patients achieved complete or partial response. CONCLUSIONS: In a real-world setting, CT-P6 demonstrated safety and efficacy findings consistent with previous CT-P6 studies.

Anti-Proliferative Effects of Lidocaine as an Autophagy Inducer in Bladder Cancer via Intravesical Instillation: In Vitro and Xenograft Mouse Model Experiments.

Lidocaine exerts potential anti-tumor effects on various cancer cell lines, and its intravesical instillation is considered safer than intravenous administration for bladder cancer. However, the mechanisms underlying its anti-tumor effects have not been fully elucidated. Here, we aimed to elucidate the anti-tumor molecular mechanisms of lidocaine in bladder cancer cells and a xenograft model to substantiate the efficacy of its intravesical administration. We investigated the anti-proliferative and autophagyinducing activities of lidocaine in Nara Bladder Tumor No. 2 (NBT-II) rat bladder carcinoma cells using cell viability, flow cytometry, a wound healing assay, and western blotting. We also established a xenograft mouse model of bladder cancer, and cancer growth was examined using in vivo bioluminescence imaging. Lidocaine decreased cell viability, induced G0/G1 phase cell cycle arrest, and inhibited cell migration partially via glycogen synthase kinase (GSK) 3ß phosphorylation. Moreover, a combination of lidocaine and SB216763 (a GSK3ß inhibitor) suppressed autophagy-related protein expression. Bafilomycin-A1 with lidocaine significantly enhanced microtubule-associated protein 1A/1B-light chain (LC3B) expression; however, it decreased LC3B expression in combination with 3-methyladenine compared to lidocaine alone. In the xenograft mouse model, the bladder cancer volume was reduced by lidocaine. Overall, lidocaine exerts anti-proliferative effects on bladder cancer via an autophagy-inducing mechanism.

Determination of the Combined Effects of Asian Herbal Medicine with Calcium and/or Vitamin D Supplements on Bone Mineral Density in Primary Osteoporosis: A Systematic Review and Meta-Analysis.

Our review of 52 RCTs from 5 databases suggests a tendency for notable improvement in BMD when combining herbal medicine with supplements (calcium and vitamin D variants) compared to supplement monotherapy in primary osteoporosis. However, caution is needed in interpreting results due to substantial heterogeneity among included studies. PURPOSE: To conduct a systematic review and meta-analysis to determine whether herbal medicine (HM) plus supplements such as calcium (Ca) or vitamin D (Vit.D) improves bone mineral density (BMD) compared to supplements alone in primary osteoporosis (OP) patients. METHODS: We searched 5 databases for randomized controlled trials (RCTs) using HMs with supplements (Ca or Vit.D variants) as interventions for primary OP patients published until August 31, 2022. Meta-analysis using BMD score as the primary outcome was performed using RevMan 5.4 version. Risk of bias in the included studies was assessed useing RoB 2.0 tool. RESULTS: In total, 52 RCTs involving 4,889 participants (1,408 men, 3,481 women) were included, with average BMD scores of 0.690 ± 0.095 g/cm2 (lumbar) and 0.625 ± 0.090 g/cm2 (femoral neck). As a result of performing meta-analysis using BMD scores for all 52 RCTs included in this review, combination of HMs with Ca and Vit.D variants improved the BMD score by 0.08 g/cm2 (lumbar, 38 RCTs, 95% CI: 0.06-0.10, p < 0.001, I2 = 97%) and 0.06 g/cm2 (femoral neck, 19 RCTs, 95% CI: 0.04-0.08, p < 0.001, I2 = 92%)compared to controls. However, statistical significance of the lumbar BMD improvement disappeared after adjusting for potential publication bias. CONCLUSION: Our data suggest that combining of HM and supplements tends to be more effective in improving BMD in primary OP than supplements alone. However, caution is needed in interpretation due to the reporting bias and high heterogeneity among studies, and well-designed RCTs are required in the future.