Optimizing Percutaneous Mitral Valvuloplasty for Rheumatic Mitral Stenosis　- Clinical Significance of Changes in Mitral Valve Area.

BACKGROUND: Percutaneous mitral valvuloplasty (PMV) is a standard treatment for severe rheumatic mitral stenosis (RMS). However, the prognostic significance of the change in mitral valve area (∆MVA) during PMV is not fully understood.Methods and Results: This study analyzed data from the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, which included 3,140 patients with severe RMS. We focused on patients with severe RMS undergoing their first PMV. Changes in echocardiographic parameters, including MVA quantified before and after PMV, and composite outcomes, including mitral valve reintervention, heart failure admission, stroke, and all-cause death, were evaluated. An optimal result was defined as a postprocedural MVA ≥1.5 cm2without mitral regurgitation greater than Grade II. Of the 308 patients included in the study, those with optimal results and ∆MVA >0.5 cm² had a better prognosis (log-rank P<0.001). Patients who achieved optimal results but with ∆MVA ≤0.5 cm² had a greater risk of composite outcomes than those with optimal outcomes and ∆MVA >0.5 cm² (nested Cox regression analysis, hazard ratio 2.27; 95% confidence interval 1.09-4.73; P=0.028). CONCLUSIONS: Achieving an increase in ∆MVA of >0.5 cm2was found to be correlated with improved outcomes. This suggests that, in addition to achieving traditional optimal results, targeting an increase in ∆MVA of >0.5 cm2could be a beneficial objective in PMV treatment for RMS.

A novel hydrogel-based moisturizing cream composed of hyaluronic acid for patients with xerosis: An intraindividual comparative analysis.

BACKGROUND: Hyaluronic acid (HA) is mainly used to treat xerosis. It also exerts wound-healing, moisturizing, and antiaging effects. Although HA is considered an effective and safe ingredient in cosmetics, there is a constant demand for a more money-saving and effective formulation. This study aimed to evaluate the safety and efficacy of a novel hydrogel-based moisturizer containing HA cross-linked with silicone polymers, produced solely through irradiation without the use of cross-linking agents. MATERIALS AND METHODS: A safety study enrolled 30 participants with healthy skin to perform patch and photopatch tests while recording adverse events. For the efficacy study, 30 participants with xerosis were compared before and after using the novel hydrogel, evaluating the cutaneous barrier function, xerosis severity scale (XSS) score, participant's satisfaction, and Investigator's Global Assessment (IGA). Furthermore, the efficacy of the novel hydrogel-based moisturizer was evaluated by comparing it with a conventional moisturizer, Physiogel, in another 30 participants with xerosis. RESULTS: In the safety study, no serious adverse events were observed. In the efficacy study before and after use, skin hydration and skin surface lipid increased (p < 0.05) whereas the XSS scores decreased (p < 0.05) with time. In the comparative efficacy study with Physiogel, skin hydration increased whereas the XSS scores decreased (p < 0.05) over time in both groups. Furthermore, IGA improved in 100% of participants in both groups. Also, 100% and 93% of participants were satisfied with the novel hydrogel-based moisturizer and Physiogel, respectively. CONCLUSIONS: The novel hydrogel-based moisturizer proved to be safe and effective for xerosis, showing comparable results to the conventional moisturizer.

Validation of Relationship between Patients' Descriptions of Pruritus and Patient-burden of Chronic Pruritus using Structural Equation Modelling.

Patients with chronic itch describe their pruritus in a wide variety of ways. However, these subjective descriptions are often not taken into consideration by physicians. This study aimed to validate patients' descriptions of pruritus, and to investigate the relationship between various descriptions of pruritus and the patient burden of chronic pruritus by examining the mediating effects of sleep disturbance and sexual dysfunction on patient's quality of life, as predicted by various descriptions of pruritus. Exploratory and confirmatory factor analyses were performed to identify the factor structure measured by 11 descriptions of pruritus. The study then analysed differences in the degree of sleep disturbance, sexual dysfunction, and quality of life deterioration factors using a structural equation modelling method. Using data from 419 patients with chronic pruritus, 11 descriptions of pruritus were classified into 2 groups: (i) sensory pruritus (i.e. stinging, stabbing, burning, painful, formication, throbbing, and cold) that are linked with descriptions of pruritus patterns; and (ii) affective pruritus (i.e. annoying, unbearable, worrisome, and warm) from patient reports of psychological or emotional distress. The study found that affective pruritus decreases patient's quality of life either directly or indirectly through sleep disturbance. In conclusion, clues about a patients' sleep disturbance or poor quality of life can be obtained through their descriptions of pruritus.

Robust analysis of angiotensin peptides in human plasma: Column switching-parallel LC/ESI-SRM/MS without adsorption or enzymatic decomposition.

Angiotensin (Ang) peptides are the main effectors of the renin-angiotensin system (RAS) regulating diverse physiological conditions and are involved in renal and vascular diseases. Currently, quantitative analyses of Ang peptides in human plasma mainly rely on radioimmunoassay-based methods whose reported levels are quite divergent. Analyses are further complicated by the potential of Ang peptides to bind to solid surfaces, to be enzymatically decomposed during sample preparation, and to undergo post-translational modifications. A column switching-parallel LC/ESI-SRM/MS method has been developed for seven Ang peptides (Ang I, Ang II, Ang III, Ang IV, Ang 1-9, Ang 1-7, and Ang A) in human plasma. Aqueous acetonitrile (5%) containing 50 mM arginine (Arg) as a dissolving solution and a combination of protease inhibitors with formic acid were used to prevent adsorption and enzymatic degradation, respectively. Plasma samples were simply deproteinized with acetonitrile followed by clean-up with an on-line trap column via column-switching. Stable isotope dilution with [13C5,15N1-Val]-Ang peptides as internal standards was employed for quantitative analysis. The current methodology has been successfully applied to determine the plasma levels of Ang peptides in healthy participants, suggesting future applicability to studies of various diseases related to RAS.

Screening of Chemical Modifications in Human Skin Keratins by Mass Spectrometry-Based Proteomic Analysis via Noninvasive Sampling and On-Tape Digestion.

Proteins are continuously exposed to diverse chemical stresses, and the resulting chemical modifications can provide significant information on biological events. Keratins are the main constituent of human skin and are the major target proteins of various chemical modifications. We have previously developed a mass spectrometry-based noninvasive proteomic methodology to screen oxidative modifications in human skin keratins. We have improved this methodology in terms of sample preparation time and amino acid sequence coverage using an on-tape digestion method. After sampling by tape stripping, skin proteins on the tape were subjected to reduction/alkylation, followed by trypsin digestion without a presolubilization step using detergents. To screen chemical modifications in keratins, target modifications and tryptic target peptides carrying the modification sites were determined from in vitro experiments with major reactive chemical species (4-hydroxy-2(E)-nonenal (HNE), 4-oxo-2(E)-nonenal, glucose, methylglyoxal, peroxynitrite, and hydrogen peroxide). The developed method was used to screen target modifications in controls and patients with a swollen red rash. Basal levels of lipid-derived modification, oxidation, nitration, and glycation in keratins were detected in controls. Principal component analysis based on the relative chemical modification resulted in a clear classification of both groups within a 95% confidence interval. Lipid-derived HNE modification increased most significantly in the patient group. This methodology can be easily applied to patients with other diseases, and the target modifications can be used as biomarkers of certain physiological conditions.

Angiotensin II-Induced Oxidative Stress in Human Endothelial Cells: Modification of Cellular Molecules through Lipid Peroxidation.

Angiotensin (Ang) II is a major bioactive peptide of the renin/angiotensin system and is involved in various cardiovascular functions and diseases. Ang II type 1 (AT1) receptor mediates most of the physiological effects of Ang II. Previous studies have revealed that the lipid peroxidation products 4-oxo-2(E)-nonenal (ONE) and 4-hydroxy-2(E)-nonenal (HNE) readily modify the N-terminus and Asp1, Arg2, and His6 residues of Ang II, and these modifications alter the biological activities of Ang II. Ang II is known to stimulate the formation of reactive oxygen species (ROS) that mediate cardiovascular remodeling. Another major consequence of ROS-derived damage is lipid peroxidation, which generates genotoxic aldehydes such as ONE and HNE. This study demonstrated that Ang II induced lipid peroxidation-derived modifications of cellular molecules in EA.hy926 cells, a human vascular endothelial cell line. Ang P (ONE- and ROS-derived N-terminal pyruvamide Ang II) and [His6(HNE)]-Ang II were detected in the medium of EA.hy926 cells incubated with Ang II, and their concentrations increased dose-dependently upon the addition of ascorbic acid (AscA) and CuSO4. Cells were then subjected to metabolic labeling using SILFAC (stable isotope labeling by fatty acids in cell culture) with [13C18]-linoleic acid. Analysis of cellular phospholipids indicated over 90% labeling. [13C9]-Thiadiazabicyclo-ONE-glutathione adduct as well as Ang P and [His6([13C9]-HNE)]-Ang II was detected in the labeled cells upon treatment with Ang II and their concentrations increased in an Ang II dose-dependent manner. Incubation of the labeled cells with losartan, an AT1 receptor blocker, inhibited the formation of modified Ang IIs in a dose-dependent manner. These results indicate that Ang II induces lipid peroxidation and modification of various cellular molecules and these reactions are mediated by the activation of AT1 receptor. Therefore, lipid peroxidation could be one mechanism by which Ang II contributes to cardiovascular dysfunction.

Imidazole dipeptides can quench toxic 4-oxo-2(E)-nonenal: Molecular mechanism and mass spectrometric characterization of the reaction products.

Imidazole dipeptides, such as carnosine (ß-alanyl-l-histidine) and anserine (ß-alanyl-Nπ -methyl-l-histidine), are highly localized in excitable tissues, including skeletal muscle and nervous tissue, and play important roles such as scavenging reactive oxygen species and quenching reactive aldehydes. We have demonstrated several reactions between imidazole dipeptides (namely, carnosine, and anserine) and a lipid peroxide-derived reactive aldehyde 4-oxo-2(E)-nonenal. Seven carnosine adducts and two anserine adducts were characterized using liquid chromatography/electrospray ionization-multiple-stage mass spectrometry. Adduct formation occurred between imidazole dipeptides and 4-oxo-2(E)-nonenal mainly through Michael addition, Schiff base formation, and/or Paal-Knorr reaction. The reactions were much more complicated than the reaction with a similar lipid peroxide-derived reactive aldehyde, 4-hydroxy-2(E)-nonenal.

Biomimetic trapping cocktail to screen reactive metabolites: use of an amino acid and DNA motif mixture as light/heavy isotope pairs differing in mass shift.

Candidate drugs that can be metabolically transformed into reactive electrophilic products, such as epoxides, quinones, and nitroso compounds, are of special concern because subsequent covalent binding to bio-macromolecules can cause adverse drug reactions, such as allergic reactions, hepatotoxicity, and genotoxicity. Several strategies have been reported for screening reactive metabolites, such as a covalent binding assay with radioisotope-labeled drugs and a trapping method followed by LC-MS/MS analyses. Of these, a trapping method using glutathione is the most common, especially at the early stage of drug development. However, the cysteine of glutathione is not the only nucleophilic site in vivo; lysine, histidine, arginine, and DNA bases are also nucleophilic. Indeed, the glutathione trapping method tends to overlook several types of reactive metabolites, such as aldehydes, acylglucuronides, and nitroso compounds. Here, we introduce an alternate way for screening reactive metabolites as follows: A mixture of the light and heavy isotopes of simplified amino acid motifs and a DNA motif is used as a biomimetic trapping cocktail. This mixture consists of [2H0]/[2H3]-1-methylguanidine (arginine motif, Δ 3 Da), [2H0]/[2H4]-2-mercaptoethanol (cysteine motif, Δ 4 Da), [2H0]/[2H5]-4-methylimidazole (histidine motif, Δ 5 Da), [2H0]/[2H9]-n-butylamine (lysine motif, Δ 9 Da), and [13C0,15N0]/[13C1,15N2]-2'-deoxyguanosine (DNA motif, Δ 3 Da). Mass tag triggered data-dependent acquisition is used to find the characteristic doublet peaks, followed by specific identification of the light isotope peak using MS/MS. Forty-two model drugs were examined using an in vitro microsome experiment to validate the strategy. Graphical abstract Biomimetic trapping cocktail to screen reactive metabolites.

Acute Kidney Injury Following Cardiopulmonary Bypass in Children　- Risk Factors and Outcomes.

BACKGROUND: Acute kidney injury (AKI) is the most common and most serious complication following heart surgery. We aimed to determine the prevalence of, and risk factors for, AKI following pediatric cardiac surgery.Methods and Results:We retrospectively analyzed 135 patients aged ≤18 years who underwent cardiac surgery for congenital heart defects; by RACHS-1 category, 58 patients (43%) had an operative risk score ≥3. AKI was defined and classified using the pediatric pRIFLE criteria (Pediatric Risk, Injury, Failure, Loss, and End-stage Kidney Disease); 19 patients (14.1%) developed AKI: 17 had AKI with a severity classified as risk (R) and 2 had AKI classified as injury (I). Body weight, height, body surface area, and preoperative mechanical ventilation were all independently associated with AKI development (P=0.038, 0.040, 0.033 and 0.008, respectively). Preoperative ventilation strongly correlated with AKI severity. Higher pRIFLE classification positively correlated with increased incidence of peritoneal dialysis, increased postoperative mechanical ventilation duration, and longer hospital stay (P=0.009, 0.039 and 0.042, respectively). CONCLUSIONS: In this study, we found a low prevalence of postoperative AKI in pediatric patients undergoing severe cardiac surgery. AKI was associated with worse early postoperative outcomes. Early prediction and appropriate treatment of AKI during the postoperative period are emphasized.

High-yield production of pure tagatose from fructose by a three-step enzymatic cascade reaction.

OBJECTIVE: To produce tagatose from fructose with a high conversion rate and to establish a high-yield purification method of tagatose from the reaction mixture. RESULTS: Fructose at 1 M (180 g l-1) was converted to 0.8 M (144 g l-1) tagatose by a three-step enzymatic cascade reaction, involving hexokinase, plus ATP, fructose-1,6-biphosphate aldolase, phytase, over 16 h with a productivity of 9 g l-1 h-1. No byproducts were detected. Tagatose was recrystallized from ethanol to a purity of 99.9% and a yield of 96.3%. Overall, tagatose at 99.9% purity was obtained from fructose with a yield of 77%. CONCLUSION: This is the first biotechnological production of tagatose from fructose and the first application of solvent recrystallization for the purification of rare sugars.

Consumer Awareness and Preferences Related to Taurine-Containing Drinks in Korean Female High School Students.

The purpose of this cross-sectional study was to investigate awareness, consumption patterns, and preferences related to intake experience of taurine-containing drinks (TCD) in Korean female high school students. Study subjects were 335 female high school students residing in Incheon, Korea. Data were collected using self-administered questionnaires. A total of 249 students (74.3%) consumed TCD while 86 students (25.7%) did not. In the TCD consumption group, 66.7% of consumers drank TCD once every 2 or 3 months while most consumers consumed it during the examination period (57.4%). Regarding the effects of TCD intake, 45.8% of students cited 'relieve sleepiness' while 41.8% showed 'no effect'. According to self-reported school records, there were significant differences in intake time of TCD, effects of TCD intake, and degree of interest in TCD (p < 0.05). About 82.7% of all the subjects perceived TCD as an energy drink for fatigue recovery. Degree of interest in TCD (p < 0.001), degree of harmfulness to the body (p < 0.01), and improvement for learning-ability (p < 0.001) had significant effects on intake frequency of TCD. Regarding preferences, 'Vita 500' was preferred by 52.2% of subjects, 'Bacchas' by 20.1%, and 'Hot Six' by 17.3%. Although subjects preferred 'Vita 500' as a caffeine-free TCD, caffeine was perceived as the most abundant ingredients in TCD by 77.1% of subjects, taurine by 16.1%, and vitamin by 4.8%. These results show most Korean female high school students consumed TCD in order to stay awake during the examination periods. Therefore, nutritional education is needed to correct Korean high school students' consumption of TCD.

An LC/ESI-SRM/MS method to screen chemically modified hemoglobin: simultaneous analysis for oxidized, nitrated, lipidated, and glycated sites.

Proteins are continuously exposed to various reactive chemical species (reactive oxygen/nitrogen species, endogenous/exogenous aldehydes/epoxides, etc.) due to physiological and chemical stresses, resulting in various chemical modifications such as oxidation, nitration, glycation/glycoxidation, lipidation/lipoxidation, and adduct formation with drugs/chemicals. Abundant proteins with a long half-life, such as hemoglobin (Hb, t 1/2 63 days, ∼150 mg/mL), are believed to be major targets of reactive chemical species that reflect biological events. Chemical modifications on Hb have been investigated mainly by mechanistic in vitro experiments or in vivo/clinical experiments focused on single target modifications. Here, we describe an optimized LC/ESI-SRM/MS method to screen oxidized, nitrated, lipidated, and glycated sites on Hb. In vivo preliminary results suggest that this method can detect simultaneously the presence of oxidation (+16 Da) of α-Met(32), α-Met(76), ß-Met(55), and ß-Trp(15) and adducts of malondialdehyde (+54 Da) and glycation (+162 Da) of ß-Val(1) in a blood sample from a healthy volunteer. Graphical Abstract Screening chemical modifications on hemoglobin.

Hydroxyl Radical-Mediated Novel Modification of Peptides: N-Terminal Cyclization through the Formation of α-Ketoamide.

The hydroxyl radical-mediated oxidation of peptides and proteins constitutes a large group of post-translational modifications that can result in structural and functional changes. These oxidations can lead to hydroxylation, sulfoxidation, or carbonylation of certain amino acid residues and cleavage of peptide bonds. In addition, hydroxyl radicals can convert the N-terminus of peptides to an α-ketoamide via abstraction of the N-terminal α-hydrogen and hydrolysis of the ketimine intermediate. In the present study, we identified N-terminal cyclization as a novel modification mediated by a hydroxyl radical. The reaction of angiotensin (Ang) II (DRVYIHPF) and the hydroxyl radical generated by the Cu(II)/ascorbic acid (AA) system or UV/hydrogen peroxide system produced N-terminal cyclized-Ang II (Ang C) and pyruvamide-Ang II (Ang P, CH3COCONH-RVYIHPF). The structure of Ang C was confirmed by mass spectrometry and comparison to an authentic standard. The subsequent incubation of isolated Ang P in the presence of Cu(II)/AA revealed that Ang P was the direct precursor of Ang C. The proposed mechanism involves the formation of a nitrogen-centered (aminyl) radical, which cyclizes to form a five-membered ring containing the alkoxy radical. The subsequent ß-scission reaction of the alkoxyl radical results in the cleavage of the terminal CH3CO group. The initial aminyl radical can be stabilized by chelation to the Cu(II) ions. The affinity of Ang C toward the Ang II type 1 receptor was significantly lower than that of Ang II or Ang P. Ang C was not further metabolized by aminopeptidase A, which converts Ang II to Ang III. Hydroxyl radical-mediated N-terminal cyclization was also observed in other Ang peptides containing N-terminal alanine, arginine, valine, and amyloid ß 1-11 (DAEFRHDSGYE).

Predicted multiple selected reaction monitoring to screen activated drug-mediated modifications on human serum albumin.

Metabolic activation of drugs frequently generates electrophilic products that may undergo covalent binding to biological macromolecules, such as proteins and DNA. The resulting covalent adducts are of considerable concern in drug discovery and development. Several strategies for assessing the potential risks of candidate drugs have been reported. Of these, glutathione trapping is the most commonly used method together with mass spectrometry. Furthermore, drug-mediated protein modifications have been studied using serum albumin and CYP enzymes to clarify target amino acids and mechanism-based inhibition, respectively. In this article, we introduce a practical way to screen drug-mediated protein modifications. The method, referred to as "predicted multiple selected reaction monitoring," is based on the selected reaction monitoring (SRM) strategy, but targets all possible chemically modified tryptic peptides. The creation of SRM lists may require patience; however, this strategy could facilitate more sensitive screening compared with the common strategy of data-dependent product ion scanning. Ketoprofen-N-hydroxysuccinimidyl ester (equivalent to glucuronide) and N-acetyl-p-benzoquinone imine (NAPQI) were allowed to react with human serum albumin as a model experiment. Using this strategy, 11 ketoprofen-adduction sites (at Lys(137, 195, 199, 212, 351, 402, 432, 436, 525, 536, and 541)) and 1 NAPQI-adduction site (at Cys(34)) were easily identified.

N-terminal α-ketoamide peptides: formation and transamination.

We have previously reported that N-terminal α-ketoamide peptides can be formed through 4-oxo-2(E)-nonenal (ONE)-derived oxidative decarboxylation of aspartic acid (Asp), which converts angiotensin (Ang) II (DRVYIHPF) to pyruvamide-Ang II (Ang P, CH3COCONH-RVYIHPF). The pyruvamide group significantly inhibits Ang P binding to the Ang II type 1 receptor, which mediates the major biological effects of Ang II. In the present study, we found that ONE can also introduce an α-ketoamide moiety at the N-terminus of peptides containing N-terminal residues other than Asp. Subsequent investigation of alternative biosynthetic pathways for N-terminal α-ketoamide peptides revealed that hydroxyl radical-mediated formation is a much more efficient route. The proposed mechanism involves initial abstraction of the N-terminal α-hydrogen and hydrolysis of the ketimine intermediate. The resulting N-terminal α-ketoamide is then converted to the D- and L-amino acids by nonenzymatic transamination in the presence of pyridoxamine (PM). The formation of the epimeric N-terminus depended on the incubation time and the concentration of PM, and increased further upon the addition of Cu(II) ions. A conversion of approximately 60% after three days of incubation was observed for Ang P. We propose that the reaction intermediate contains a prochiral α-carbon and is stabilized by the chelate effect of Cu(II) ions. The ONE- and hydroxyl radical-derived formation of N-terminal α-ketoamide and its transamination in the presence of PM were also observed in amyloid ß 1-11 (DAEFRHDSGYE), where the N-terminal Asp was converted to epimeric alanine. This suggests that these N-terminal modifications could occur in vivo and modulate the biological functions of peptides and proteins.

Personalized prediction of survival rate with combination of penalized Cox models in patients with colorectal cancer.

The investigation into individual survival rates within the patient population was typically conducted using the Cox proportional hazards model. This study was aimed to evaluate the performance of machine learning algorithm in predicting survival rates more than 5 years for individual patients with colorectal cancer. A total of 475 patients with colorectal cancer (CRC) and complete data who had underwent surgery for CRC were analyze to measure individual's survival rate more than 5 years using a machine learning based on penalized Cox regression. We conducted thorough calculations to measure the individual's survival rate more than 5 years for performance evaluation. The receiver operating characteristic curves for the LASSO penalized model, the SCAD penalized model, the unpenalized model, and the RSF model were analyzed. The least absolute shrinkage and selection operator penalized model displayed a mean AUC of 0.67 ±â€…0.06, the smoothly clipped absolute deviation penalized model exhibited a mean AUC of 0.65 ±â€…0.07, the unpenalized model showed a mean AUC of 0.64 ±â€…0.09. Notably, the random survival forests model outperformed the others, demonstrating the most favorable performance evaluation with a mean AUC of 0.71 ±â€…0.05. Compared to the conventional unpenalized Cox model, recent machine learning techniques (LASSO, SCAD, RSF) showed advantages for data interpretation.

Prognostic impact of suspicious extraabdominal lymph nodes on patient survival in advanced ovarian cancer.

OBJECTIVE: To evaluate the clinical impact of suspicious extra-abdominal lymph nodes (EALNs) identified preoperatively on CT and/or PET/CT images in advanced ovarian cancer. METHODS: A retrospective study was conducted with 122 patients diagnosed with stage III or IV ovarian cancer with preoperative CT and/or PET/CT images from 2006 to 2022. Imaging studies were evaluated for the presence, size and location of suspicious EALNs. Suspicious lymph node enlargement was defined by a cut-off ≥5mm short-axis dimension on CT and/or lesions with maximum standardized uptake values of ≥2.5 on PET/CT. This study only included patients who did not have their EALNs surgically removed. RESULTS: A total 109 patients met the inclusion criteria; 36 (33%) had suspicious EALNs and were categorized as "node-positive". The median overall survival (OS) was 45.73 months for the "node-positive" and 46.50 months for the "node-negative" patients (HR 1.17, 95% CI 0.68-2.00, p = 0.579). In multivariate analysis, after adjusting for other variables selected by process of backward elimination using a significance level of p<0.20, suspicious EALNs still showed no clinical significance on OS (aHR 1.20, 95% CI 0.67-2.13, p = 0.537) as well as progression-free survival (aHR 1.43, 95% CI 0.85-2.41, p = 0.174). Old age (aHR 2.23, 95% CI 1.28-3.89, p = 0.005) and platinum resistance (aHR 1.92, 95% CI 1.10-3.36, p = 0.023) affects adversely on OS. CONCLUSION: Suspicious EALNs did not worsen the prognosis of patients with advanced ovarian cancer. However, its impact on survival is not yet clarified. Further investigation is required to assess the clinical significance of suspicious EALNs on preoperative imaging studies.