Prognostic impact of erythropoietin-stimulating agent use during front-line chemotherapy in patients with ovarian cancer: A Korean multicenter cohort study.

OBJECTIVE: To evaluate whether treatment with erythropoiesis-stimulating agents (ESAs) for chemotherapy-induced anemia affects progression-free survival (PFS) in patients receiving front-line chemotherapy following surgery for ovarian cancer (OC). METHODS: We retrospectively reviewed all consecutive patients who received front-line chemotherapy after surgery between 2013 and 2019 at six institutions. The patients were divided according to the use of ESAs during front-line chemotherapy. The primary endpoint was PFS. The secondary endpoint was the occurrence of thromboembolism. Propensity score matching (PSM) analysis was used to compare survival between matched cohorts. RESULTS: Overall, 2147 patients (433 receiving ESA and 1714 for no-ESA) were identified, with a median follow-up of 44.0 months. The ESA group showed a significantly higher proportion of stage III/IV disease (81.8% vs 61.1%; P < 0.001) and postoperative gross residual disease (32.3% vs 21.2%; P < 0.001) than the no-ESA group. In the multivariable Cox regression analysis, the use of ESAs did not affect PFS (adjusted hazard ratio, 1.03; 95% confidence interval [CI]: 0.89-1.20; P = 0.661). The incidence of thromboembolism was 10.2% in the ESA group and 4.6% in the no-ESA group (adjusted odds ratio, 6.58; 95% CI: 3.26-13.28; P < 0.001). When comparing the well-matched cohorts after PSM, PFS did not differ between the ESA (median PFS 23.5 months) and no-ESA groups (median PFS 22.2 months) (P = 0.540, log-rank test). CONCLUSIONS: The use of ESAs during front-line chemotherapy did not negatively affect PFS in patients with OC after surgery but increased the risk of thromboembolism.

The Expression and Amplification of HER2 Has a Significant Impact on the Prognosis of Endometrial Carcinoma in Korean Patients.

Objective: The purpose of this study was to analyze the protein overexpression and gene amplification of HER2 in endometrial carcinoma (EC) and to evaluate its role as a prognostic factor in Korean women. Methods: A tissue microarray (TMA) was constructed from samples from 191 patients with diverse histologic types of EC. HER2 protein expression and gene amplification status were analyzed using immunohistochemistry (IHC) and silver in situ hybridization (SISH), respectively. All patients were treated and followed up at a single tertiary medical center in Seoul, Korea, between July 2009 and October 2020. Results: In terms of histological type, among the 191 EC patients, 157 had endometrioid carcinoma, nine had uterine serous papillary carcinoma (USPC), one had clear cell carcinoma, one had squamous cell carcinoma, eight had mixed carcinoma, and 15 had uterine carcinosarcoma (UC). HER2 protein overexpression was observed in eight of the 191 (4.2%) EC patients; of these patients, five had IHC scores of 2+, and three had IHC scores of 3+. The HER2 overexpression rates of USPC, UC, and endometrioid carcinomas were 33.3%, 26.6%, and 0.6%, respectively. HER2 protein overexpression was significant in USPC and UC tissues (p < 0.000) and was associated with poor overall survival (OS) (p < 0.001). HER2 gene amplification was confirmed in seven of 184 patients (3.8%), including three patients with USPC and four patients with UC. OS was significantly shorter in patients who had HER2 amplification (p < 0.001). On multivariate analysis, HER2 expression and HER2 amplification were statistically significantly associated with worse OS (p = 0.006). However, HER2 expression without amplification was not statistically associated with OS (p = 0.993). Conclusions: HER2 protein overexpression and gene amplification are significantly correlated with shorter OS in Korean women. HER2 can be considered an important predictor of survival outcomes in EC patients.

Major clinical research advances in gynecologic cancer in 2023: a tumultuous year for endometrial cancer.

In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.

Metabolomics Reveals Rubiadin Accumulation and the Effects of Methyl Jasmonate Elicitation in Damnacanthus major Calli.

Callus suspension techniques have been considered attractive for improving bioactive metabolite productivity; methyl jasmonate (MeJA) is a widely used elicitor for stimulating synthetic pathways. In this study, a multivariate analysis-based metabolomics approach was employed to investigate the primary and specialized metabolites in the leaves, unelicited calli, and 100 or 200 µM MeJA elicited calli of Damnacanthus major. Rubiadin, a powerful anthraquinone with various therapeutic properties, was only identified in D. major calli, accumulating in a MeJA elicitation concentration-dependent manner. Callus cultures also contained high levels of amino acids, sugars, and phenolic compounds, indicating energy metabolism and metabolic adaptation responses for proliferation and stabilization. Regarding MeJA application, elicited calli contained higher amounts of quinic acid, kaempferol, and glucose with lower amounts of sucrose and raffinose than those in the unelicited control, which were closely related to protective mechanisms against MeJA. Moreover, excessive elicitation increased the asparagine, fructose, and raffinose levels and decreased the glucose and sucrose levels, which was ascribed to increased activation of the aminoacyl-tRNA biosynthesis pathway and wider utilization of glucose than of fructose after sucrose degradation. These results will be useful for optimizing plant cell culture techniques to achieve high production rates for valuable specialized metabolites.

Impact of resident participation on surgical outcomes in laparoscopically assisted vaginal hysterectomy.

OBJECTIVE: To compare surgical outcomes in patients with benign diseases who underwent laparoscopically assisted vaginal hysterectomy (LAVH) to determine the association between surgical outcomes and resident participation in the gynecologic field. METHODS: A single-center retrospective study was conducted of patients diagnosed with benign gynecologic diseases who underwent LAVH between January 2010 and December 2015. Clinicopathologic characteristics and surgical outcomes were compared between the resident involvement and non-involvement groups. The primary endpoint was the 30-day postoperative morbidity. Observers were propensity matched for 17 covariates for resident involvement or non-involvement. RESULTS: Of the 683 patients involved in the study, 165 underwent LAVH with resident involvement and 518 underwent surgery without resident involvement. After propensity score matching (157 observations), 30-day postoperative morbidity occurred in 6 (3.8%) and 4 (2.5%) patients in the resident involvement and non-involvement groups, respectively (P = 0.501). The length of hospital stay differed significantly between the two groups: 5 days in the resident involvement group and 4 days in the non-involvement group (P < 0.001). On multivariate analysis, Charlson Comorbidity Index >2 (odds ratio [OR] 8.01, 95% confidence interval [CI] 2.68-23.96; P < 0.001), operative time (OR 1.02, 95% CI 1.01-1.03; P < 0.001), and estimated blood loss (OR 1.00, 95% CI 1.00-1.00; P < 0.001) were significantly associated with 30-day morbidity, but resident involvement was not statistically significant. CONCLUSION: There was no significant difference in the 30-day morbidity rate when residents participated in LAVH. These findings suggest that resident participation in LAVH may be a viable approach to ensure both residency education and patient safety.

Doping-Free Phosphorescent and Thermally Activated Delayed Fluorescent Organic Light-Emitting Diodes with an Ultra-Thin Emission Layer.

We report the electroluminescence (EL) characteristics of blue ultra-thin emissive layer (U-EML) phosphorescent (PH) organic light-emitting diodes (OLED) and thermally activated delayed fluorescence (TADF) OLED. A variety of transport layer (TL) materials were used in the fabricated OLEDs. The well-known FIrpic and DMAC-DPS were used with a thickness of 0.3 nm, which is relatively thicker than the optimal thickness (0.15 nm) of the blue phosphorescent ultra-thin emissive layer to ensure sufficient energy transfer. While FIrpic showed overall high efficiency in various TLs, DMAC-DPS exhibited three times lower efficiency in limited TLs. To clarify/identify low efficiency and to improve the EL, the thickness of DMAC-DPS was varied. A significantly higher and comparable efficiency was observed with a thickness of 4.5 nm, which is 15 times thicker. This thickness was oriented from the TADF itself, which reduces quenching in a triplet-triplet annihilation compared to the PH process. The thinner optimal thickness compared with ~30 nm of fluorescent OLEDs suggests that there still is quenching taking place. We expect that the efficiency of TADF U-EML OLEDs can be enhanced through further research on controlling the exciton quenching using multiple U-EMLs with spacers and a novel material with a high energy transfer rate (ΔES-T).

Risk of adverse obstetric outcomes in patients with a history of endometrial cancer: A nationwide population-based cohort study.

OBJECTIVE: To evaluate adverse obstetric outcomes in women with a history of endometrial cancer (EC). DESIGN: Population-based cohort study. SETTING: The Korean National Health Insurance (KNHI) claims database. POPULATION: Women who gave birth between 2009 and 2016, with a history of EC prior to pregnancy. METHODS: The KNHI database was used to compare obstetric outcomes of women with and without a history of EC, using the ICD-10 codes. Multivariable logistic regression models were used to determine the associations between a history of EC and adverse obstetric outcomes. MAIN OUTCOMES MEASURES: Adverse obstetric outcomes. RESULTS: Overall, 248 and 3 335 359 women with and without a history of EC, respectively, gave birth. When adjusted for age, primiparity and comorbidities, an increased risk of multiple gestations (odds ratio [OR] 4.925, 95% confidence interval [CI] 3.394-7.147), caesarean delivery (OR 2.005, 95% CI 1.535-2.62) and preterm birth (OR 1.941, 95% CI 1.107-3.404) was observed among women with a history of EC. We were unable to demonstrate significant differences in the risk of pre-eclampsia, gestational diabetes, vacuum delivery, placenta praevia, placenta accreta spectrum, placental abruption and postpartum haemorrhage between the groups. In the sensitivity analyses excluding multiple gestations, an increased risk of preterm birth was not observed among women with a history of EC (OR 1.276, 95% CI 0.565-2.881). CONCLUSIONS: There is no convincing evidence of an increased risk of adverse obstetric outcomes among women with a history of EC. Our findings would be useful in counselling of patients with EC who are undergoing fertility-sparing treatment.

Effect of α1D-adrenoceptor blocker for the reduction of ureteral contractions.

PURPOSE: Urolithiasis is a common urinary tract disease with growing prevalence. Alpha1-adrenoceptors (α1-ARs) are abundant in ureteral smooth muscle, distributed with different α1-AR subtypes. α1D-AR is the most widely distributed in the ureter. However, the effect of α1D-AR blockade on ureteric contraction remains unknown. MATERIALS AND METHODS: We dissected smooth muscle tissues (3 mm×3 mm) from the rat bladder and human ureter, tied silk strips on both tissue ends, and measured contraction in an organ bath chamber. Contraction activity in ureteral smooth muscle cells (USMCs) was immunocytochemically examined using primary rat and human USMC cultures. RESULTS: Using the organ bath system, we determined the inhibitory effects of silodosin, tamsulosin, and naftopidil. Naftopidil significantly decreased contractility of rat bladder tissue; similar results were observed in human ureteral tissue. To confirm ex vivo experimental results in vitro , we examined the phosphorylation of myosin light chain (MLC), a marker of contractility, in a primary human USMC culture. The examined drugs decreased phospho-MLC levels in human USMCs; however, naftopidil profoundly increased MLC dephosphorylation. CONCLUSIONS: We studied the effects of naftopidil, an α1D-AR inhibitor, on the ureter. Compared with alpha-blockers, naftopidil significantly relaxed ureteral smooth muscle. Therefore, naftopidil could be an effective therapy for patients with ureteral stones.

Therapeutic Efficacy of YM155 to Regulate an Epigenetic Enzyme in Major Subtypes of RCC.

Renal cell carcinoma (RCC) is the most common type of kidney cancer and includes more than 10 subtypes. Compared to the intensively investigated clear cell RCC (ccRCC), the underlying mechanisms and treatment options of other subtypes, including papillary RCC (pRCC) and chromogenic RCC (chRCC), are limited. In this study, we analyzed the public databases for ccRCC, pRCC, and chRCC and found that BIRC5 was commonly overexpressed in a large cohort of pRCC and chRCC patients as well as ccRCC and was closely related to the progression of RCCs. We investigated the potential of BIRC5 as a therapeutic target for these three types of RCCs. Loss and gain of function studies showed the critical role of BIRC5 in cancer growth. YM155, a BIRC5 inhibitor, induced a potent tumor-suppressive effect in the three types of RCC cells and xenograft models. To determine the mechanism underlying the anti-tumor effects of YM155, we examined epigenetic modifications in the BIRC5 promoter and found that histone H3 lysine 27 acetylation (H3K27Ac) was highly enriched on the promoter region of BIRC5. Chromatin-immunoprecipitation analysis revealed that H3K27Ac enrichment was significantly decreased by YM155. Immunohistochemistry of xenografted tissue showed that overexpression of BIRC5 plays an important role in malignancy in RCC. Furthermore, high expression of P300 was significantly associated with the progression of RCC. Our findings demonstrate the P300-H3K27Ac-BIRC5 cascade in three types of RCC and provide a therapeutic path for future research on RCC.

Proliferation and Metabolic Profiling of Cynanchum wilfordii Adventitious Roots Using Explants from Different Cultivation Methods.

Cynanchum wilfordii root is used in traditional herbal medicine owing to its various pharmacological activities. However, C. wilfordii roots are misused owing to their morphological similarities with C. auriculatum. Adventitious root (AR) culture can prevent such misuse, and the selection of plant materials is an important procedure for producing high-quality ARs. This study aimed to compare the proliferation and metabolic profiles of C. wilfordii ARs in two types of explants from different cultivation methods (either cultivated in open field (ECF) or cultivated on a heap of C. wilfordii (ECH)). After 4 weeks of culture, the proliferation rate and number and length of secondary ARs were determined, and 3/4 Murashige and Skoog (MS) salt medium, 4.92 µM indole-3-butyric acid (IBA), and 5% sucrose were suggested as the best proliferation conditions for ARs originating from both ECF and ECH. Through metabolic profiling, ARs from ECH were found to show higher accumulation patterns for flavonoids, polysaccharides, hydroxyacetophenones, aromatic amino acids, and mono-unsaturated fatty acids, which were ascribed to the activation of flavonoid biosynthesis, the phenylpropanoid pathway, and fatty acid desaturase, stimulated by abiotic stresses. In contrast, ARs from ECF had higher levels of TCA cycle intermediates, amino acids in the aspartate-glutamate pathway, and saturated and polyunsaturated fatty acids, indicating energy metabolism and plant development. Overall, the current study provided information on the optimal conditions for inducing C. wilfordii ARs with higher amounts of bioactive compounds.

A Simple Method for Fabricating an External Light Extraction Composite Layer with RNS to Improve the Optical Properties of OLEDs.

In this study, we fabricated a random nanostructure (RNS) external light extraction composite layer containing high-refractive-index nanoparticles through a simple and inexpensive solution process and a low-temperature mask-free process. We focused on varying the shape and density of the RNSs and adjusted the concentration of the high-refractive-index nanoparticles to control the optical properties. The RNSs fabricated using a low-temperature mask-free process can use the distance between the nanostructures and various forms to control the diffraction and scattering effects in the visible light wavelength range. Consequently, our film exhibited a direct transmittance of ~85% at a wavelength of 550 nm. Furthermore, when the RNSs' composite film, manufactured using the low-temperature mask-free process, was applied to organic light-emitting diodes (OLEDs), it exhibited an external quantum efficiency improvement of 32.2% compared with the OLEDs without the RNSs. Therefore, the randomly distributed high-refractive-index nanoparticles on the polymer film can reduce the waveguide mode and total reflection at the substrate/air interface. These films can be used as a scattering layer to reduce the loss of the OLED substrate mode.

Enhanced Light Extraction from Organic Light-Emitting Diodes with Micro-Nano Hybrid Structure.

In this study, an external light extraction layer with a micro-nano hybrid structure was applied to improve the external light extraction efficiency of organic light-emitting diodes (OLEDs). A reactive ion-etching (RIE) process, using O2 and CHF3 plasma, was performed on the surface of the micro-scale pattern to form micro-nano hybrid structures. According to the results of this study, the nanostructures formed by the treatment of O2 and CHF3 were different, and the efficiency according to the structures was analyzed experimentally and theoretically. As a result, the OLED, to which the micro-nano hybrid structure, manufactured through a simple process, is applied, improved the external light extraction efficiency by up to 38%, and an extended viewing angle profile was obtained. Additionally, an effective method for enhancing the out-coupling efficiency of OLEDs was presented by optimizing the micro-nano hybrid structure according to process conditions.

Indwelling urinary catheter assembled with lidocaine-loaded polymeric strand for local sustained alleviation of bladder discomfort.

Indwelling urinary catheters (IUCs) are used in clinical settings to assist detrusor contraction in hospitalized patients. However, an inserted IUC often causes catheter-related bladder discomfort. To resolve this, we propose an IUC coupled with local, sustained release of an anesthetic drug, lidocaine. For this, a thin strand composed of poly (lactic-co-glycolic acid) and lidocaine was separately prepared as a drug delivery carrier, which was then wound around the surface of the IUC to produce the drug-delivery IUC. Our results revealed that the drug-delivery IUC could exert the pain-relief effects for up to 7 days when placed in the bladder of living rats. Cystometrogram tests indicated that the drug-delivery IUC could significantly relieve bladder discomfort compared with the IUC without lidocaine. Furthermore, the expression of pain-related inflammatory markers, such as nerve growth factor, cyclooxygenase-2, and interleukin-6 in the biopsied bladder tissues was significantly lower when the drug-delivery IUC was used. Therefore, we conclude that an IUC simply assembled with a drug-loaded polymer strand can continuously release lidocaine to allow for the relief of bladder discomfort during the period of IUC insertion.

Management of isolated oligohydramnios in Korea: a questionnaire-based study of clinical practice patterns among the members of the Korean Society of Maternal Fetal Medicine.

OBJECTIVE: The aim of this survey was to investigate the recommendations and clinical practice patterns of the Korean Society of Maternal and Fetal Medicine (KSMFM) members, regarding management of isolated oligohydramnios (IO). METHODS: From December 2018 to February 2019, questionnaires were e-mailed to the KSMFM members at 257 institutes that are listed by the Korean Statistical Information Services (KOSIS) as suitable labor premises. Responses to the seven questions on the management of IO, from diagnosis to treatment, were evaluated. RESULTS: A total of 72 KSMFM members responded to this survey. Nearly all participants (90.1%) used the amniotic fluid index (AFI) as the primary method for estimating amniotic fluid volume. The majority of the participants (73.6%) believed that IO was a risk factor for adverse pregnancy outcomes, including abnormal fetal heart rate (73.6%), need for cesarean delivery (58.3%), intrauterine fetal demise (52.8%), and meconium aspiration syndrome (50%). Almost 70% of the participants believed that induction of labor might decrease perinatal morbidities, and that late-preterm to early-term period (36-38 gestational weeks) was a suitable timeframe for delivery, if the fetus was sufficiently grown and antenatal testing revealed reassuring results. Less than half of the participants (47.2%) believed that maternal oral or intravenous hydration was a useful intervention for IO management. CONCLUSIONS: KSMFM members preferred labor induction at late-preterm to early-term, to decrease perinatal morbidity in cases of IO, although it was still uncertain whether labor induction improved the outcomes. Further prospective studies are needed regarding IO management.

Catheter-Related Bladder Discomfort: How Can We Manage It?

The urethral catheter is used in various clinical situations such as diagnosing urologic disease, urine drainage in patients after surgery, and for patients who cannot urinate voluntarily. However, catheters can cause numerous adverse effects, such as catheter-associated infection, obstruction, bladder stones, urethral injury, and catheter-related bladder discomfort (CRBD). CRBD symptoms vary among patients from burning sensation and pain in the suprapubic and penile areas to urinary urgency. CRBD significantly reduces patient quality of life and can lead to several complications. CRBD is caused by catheter-induced bladder irritation due to muscarinic receptor-mediated involuntary contractions of bladder smooth muscle and also can be caused by mechanical stimulus of the urethral catheter. Various pharmacologic studies for managing CRBD, including antimuscarinic and antiepileptic agents and botulinum toxin injections have been reported. If urologists can reduce patients' CRBD, their quality of life and recovery can improve.