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BACKGROUND: We aimed to investigate the distinct immunological characteristics of the tumor immune microenvironment in epithelial ovarian cancer (EOC) according to BRCA1/2 mutations status and differential PD-1 expression levels. METHODS: Tumor-infiltrating lymphocytes (TILs) were collected from patients with newly diagnosed advanced-stage EOC (YUHS cohort, n=117). This YUHS cohort was compared with The Cancer Genome Atlas (TCGA) data for ovarian serous cystadenocarcinoma (n=482), in terms of survival outcomes and immune-related gene profiles according to BRCA1/2 status. We used multicolor flow cytometry to characterize the immune phenotypes and heterogeneity of TILs with or without BRCA1/2 mutations. In vitro functional assays were conducted to evaluate the reinvigorating ability of CD8+ TILs on anti-PD-1 treatment. RESULTS: We found that EOC patients with BRCA1/2 mutations (BRCA1/2mt) exhibited better survival outcomes and significantly higher tumor mutation burden (TMB), compared with BRCA1/2 non-mutated (BRCA1/2wt) patients. Furthermore, CD8+ TILs within BRCA1/2mt tumors displayed characteristics indicating more severe T-cell exhaustion than their BRCA1/2wt counterparts. Notably, the capacity for anti-PD-1-mediated reinvigoration of CD8+ TILs was significantly greater in BRCA1/2wt tumors compared with BRCA1/2mt tumors. Additionally, within the BRCA1/2wt group, the frequency of PD-1highCD8+ TILs was positively correlated with the reinvigoration capacity of CD8+ TILs after anti-PD-1 treatment. CONCLUSION: Our results highlight unique immune features of CD8+ TILs in EOC and a differential response to anti-PD-1 treatment, contingent on BRCA1/2 mutation status. These findings suggest that immune checkpoint blockade may be a promising frontline therapeutic option for selected BRCA1/2wt EOC patients.
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Proteína BRCA1 , Linfocitos T CD8-positivos , Carcinoma Epitelial de Ovario , Linfocitos Infiltrantes de Tumor , Mutación , Humanos , Femenino , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/inmunología , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Proteína BRCA1/genética , Persona de Mediana Edad , Proteína BRCA2/genética , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Neoplasias Ováricas/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/mortalidad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Adulto , Microambiente Tumoral/inmunología , AncianoRESUMEN
BACKGROUND: The oxidative balance score (OBS) is a comprehensive pro- and anti-oxidative marker for assessing the risk of various metabolic diseases and cancers. However, it is not well established whether OBS is related to type 2 diabetes mellitus (T2DM), particularly in elderly populations. Therefore, our objective was to investigate the longitudinal effect of OBS on T2DM in a large cohort of Korean adults aged 60 years and older. METHODS: We assessed the data for 3516 participants aged 60 years and older without diabetes mellitus from the Health Examinees cohort of the Korean Genome and Epidemiology Study. We classified the participants into three groups according to OBS tertiles. We prospectively assessed hazard ratios (HRs) with 95 % confidence intervals (CIs) for new-onset T2DM using multivariable Cox proportional-hazard regression models during the mean 3.5 years following the baseline survey. RESULTS: A total of 109 participants (3.1 %) developed T2DM during a mean follow-up of 3.5 years. The incidence rates per 1000 person-years were 11.73 for the lowest OBS tertile (T1), 8.19 for the second tertile (T2), and 6.23 for the highest tertile (T3). Adjusting for all confounding factors, compared with the referent T1, the HR (95 % CI) of new-onset T2DM was not significant in T2 (0.71 [0.47-1.07]) but was significant in T3 at (0.47 [0.30-0.75]) (p for trend = 0.002). CONCLUSIONS: The study suggests that a OBS could serve as a valuable predictive marker for new-onset T2DM in older adults. Our study suggests that maintaining an appropriate body weight through healthy lifestyle modification has the potential to lower T2DM incidence in elderly. This implies that the OBS may be a useful tool for assessing the incidence of T2DM even in older individuals.
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Biomarcadores , Diabetes Mellitus Tipo 2 , Modelos de Riesgos Proporcionales , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Masculino , República de Corea/epidemiología , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Incidencia , Factores de Riesgo , Estrés Oxidativo , Estudios LongitudinalesRESUMEN
OBJECTIVE: To identify the effects of subcutaneous drain insertion on wound dehiscence and infection in patients who underwent gynecological midline laparotomy. METHODS: This analysis identified the secondary endpoints of the KGOG 4001 study, a prospective, multicenter, non-blind, randomized controlled trial. Patients scheduled to undergo midline laparotomy for gynecological diseases and, with body mass index<35 kg/m2, were randomized (1:1) to treatment (with subcutaneous drain) and control (without subcutaneous drain) groups from February 2021 to December 2021. We compared the incidence rate of wound dehiscence 4 weeks post-surgery and the cumulative incidence rate of wound dehiscence and infection up to 4 weeks post-surgery between the two groups. RESULTS: Of 174 patients randomized to the treatment (n = 84) and control (n = 90) groups, 12 were excluded owing to loss to follow-up; finally, 162 patients (treatment, n = 79; control, n = 83) were included in intention-to-treat analysis. The frequency of cancer surgery (79.7 % vs. 77.1 %, p = 0.683), mean surgery time (227.7 vs. 226.7 min, p = 0.960), and mean wound length (24.2 vs. 24.3 cm, p = 0.933) were comparable between two groups. No significant differences were observed in the incidence rate of wound dehiscence 4 weeks post-surgery (1.3 % vs. 2.4 %, p > 0.999), cumulative incidence rate of wound dehiscence (8.9 % vs. 6.0 %, p = 0.491), and cumulative incidence rate of wound infection (1.3 % vs. 0.0 %, p = 0.488) up to 4 weeks post-surgery between the two groups. CONCLUSION: Subcutaneous drain insertion is not associated with a significant improvement in the incidence of wound dehiscence and infection in patients who undergo gynecological midline laparotomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04643197.
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AIM: The C-reactive protein to albumin (CRP/Alb) ratio has emerged as a novel biomarker for various inflammatory diseases. This study aimed to evaluate the association between the CRP/Alb ratio and incident metabolic syndrome (MetS) with a large-sample, community-based Korean cohort over a 12-year follow-up period. MATERIALS AND METHODS: Among 10,030 participants, a total of 6205 participants aged 40-69 years without MetS were selected from the Korean Genome and Epidemiology Study (KoGES). The baseline CRP/Alb ratio was divided into quartiles. The definition of newly developed MetS was the one proposed by the 2009 Joint Interim Statement of Circulation. Hazard ratios (HRs) with 95% confidence intervals (CIs) for incident MetS were calculated using multivariable Cox proportional hazards regression models after adjusting for potentially confounding variables. RESULTS: During the 12-year follow-up period, MetS developed in 2535 subjects (40.9%, 2535/6205) with an incidence rate of 5.6-11.9 (over 2 years). Compared to the reference first quartiles, the HRs (95% CIs) of incident MetS in the second, third, and fourth quartiles increased in a dose-response manner. Compared to the reference quartile, the HRs (95% CIs) of the incidence of MetS for the second, third, and fourth quartiles of CRP/Alb ratio were 1.12 (0.99-1.27), 1.24 (1.11-1.40), and 1.51 (1.34-1.69) after adjusting for age, sex, smoking status, alcohol intake, physical activity, total cholesterol, mean arterial pressure, HOMA-IR, and total energy intake. CONCLUSIONS: High CRP/Alb ratio at baseline may be a useful surrogate indicator of future incident MetS.
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Background: The metabolic score for insulin resistance index (METS-IR) is a novel non insulin-based marker that indicates the risk for metabolic syndrome and type 2 diabetes mellitus (T2DM). However, METS-IR has not been investigated in relation to all-cause mortality. We investigated the longitudinal effect of METS-IR on all-cause mortality in a significantly large cohort of Korean adults over 60 years old. Methods: Data were assessed from 30,164 Korean participants over 60 years of age from the Korean Genome and Epidemiology Study-Health Examinees (KoGES-HEXA) cohort data, linked with the death certificate database of the National Statistical Office. The participants were grouped into three according to METS-IR tertiles. We used multivariate Cox proportional-hazard regression models to prospectively assess hazard ratios (HRs) for all-cause mortality with 95% confidence intervals (CIs) over an 11-year postbaseline period. Results: During the mean 11.7 years of follow-up, 2,821 individuals expired. The HRs of mortality for METS-IR tertiles were 1.16 (95% CI, 1.01-1.34) in T3 after adjustment for metabolic parameters, but the T2 did not show statistical significance towards increases for incident mortality respectively. In subgroup analysis depending on the cause of mortality, higher METS-IR was associated with cancer mortality (HR, 1.23, 95% CI, 1.01-1.51) but not with cardiovascular mortality (HR, 1.14, 95% CI, 0.83-1.57) after adjustment for the same confounding variables. Conclusion: The METS-IR may be a useful predictive marker for all-cause mortality and cancer mortality, but not for cardiovascular mortality in subjects over 60 years of age. This implies that early detection and intervention strategies for metabolic syndrome could potentially benefit this identified group.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Síndrome Metabólico , Neoplasias , Adulto , Humanos , Persona de Mediana Edad , Anciano , Síndrome Metabólico/epidemiología , Síndrome Metabólico/genética , Síndrome Metabólico/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Insulina , Enfermedades Cardiovasculares/complicaciones , República de Corea/epidemiología , Neoplasias/epidemiología , Neoplasias/complicacionesRESUMEN
OBJECTIVE: To investigate the efficacy of cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in predicting survival outcomes based on breast cancer gene (BRCA) mutational status in epithelial ovarian cancer. METHODS: Medical records of 448 patients diagnosed with epithelial ovarian cancer at a single tertiary institution in Korea were retrospectively analyzed. Area under the curve, sensitivity, specificity, and accuracy were assessed using the CA125 and HE4 values after surgery and 3 cycles of chemotherapy to predict 1-year survival based on the BRCA mutational status. Kaplan-Meier analysis was used to obtain progression-free and overall survival to evaluate CA125 and HE4 effectiveness in predicting survival outcomes. RESULTS: A total of 423 patients were analyzed, including 180 (42.6%) who underwent interval debulking surgery (IDS) and 243 (57.4%) who underwent primary debulking surgery (PDS). BRCA mutations were observed in 37 (15.2%) and 44 (22.4%) patients in the PDS and IDS groups, respectively. CA125 and HE4 normalization demonstrated the highest specificity in patients with or without BRCA mutations, with specificities of 97.1% and 99.1% in the PDS group and 78.6% and 86.2% in the IDS group, respectively. Normalizing HE4 alone may be an effective prognostic marker, with an area under the curve of 0.774 and specificity of 75.0%, in patients with BRCA mutations. CONCLUSION: Normalizing both biomarkers emerged as the most effective predictive marker for the 1-year recurrence rate, regardless of BRCA mutational status. A negative HE4 value can be a useful predictor for 1-year recurrence-free survival in patients with BRCA mutations.
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BACKGROUND: Research on identifiable risks for metabolic syndrome (MetS) is ongoing, and growing evidence suggests that bilirubin is a potent antioxidant and cytoprotective agent against MetS. However, there have been conflicting results on the association between bilirubin and MetS. Our study aimed to validate the association by separately stratifying data for men and women in a longitudinal prospective study. METHODS: Data were derived from the Korean Genome Epidemiology Study provided by the Korea Centers for Disease Control and Prevention. Data from 5,185 adults aged 40-69 years (3,089 men and 2,096 women) without MetS were analyzed. The participants were divided according to sex-specific quartiles of serum total bilirubin levels and followed up biennially for 16 years (until 2018). The log-rank test was used for obtaining the Kaplan-Meier curves of cumulative incidence of MetS according to sex-specific serum total bilirubin quartiles, and the hazard ratios (HRs) with 95% confidence intervals (CIs) for incident metabolic syndrome were analyzed with a multiple Cox proportional hazard regression analysis model, after propensity score matching for removing differences at baseline. RESULTS: With increasing serum total bilirubin quartiles, the incidence rate per 1000 person-years proportionally decreased in both men and women. After propensity score matching and adjusting for confounding variables, the HRs (95% CIs) for MetS of the highest quartile in reference to the lowest quartile were 1.00 (0.80-1.24) for men and 0.80 (0.65-0.99) for women. Higher quartiles of serum total bilirubin showed significantly lower cumulative incidence of MetS in women (log-rank test p = 0.009), but not in men (log-rank test p = 0.285). CONCLUSION: Serum total bilirubin levels were significantly inversely associated with MetS in women, but there was no significant association observed in men. Sex differences in the effects of serum total bilirubin should be noted when predicting incident MetS by sex in clinical settings.
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Síndrome Metabólico , Adulto , Humanos , Femenino , Masculino , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Factores de Riesgo , Estudios Prospectivos , Caracteres Sexuales , Vida Independiente , Puntaje de Propensión , Bilirrubina , Incidencia , República de Corea/epidemiologíaRESUMEN
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.
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Neoplasias Endometriales , Neoplasias de los Genitales Femeninos , Neoplasias Ováricas , Neoplasias del Cuello Uterino , Femenino , Humanos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Endometriales/tratamiento farmacológicoRESUMEN
The oxidative balance score (OBS) is a novel composite of pro- and anti-oxidative markers for assessing the risk of cardiometabolic diseases and non-alcoholic fatty liver disease (NAFLD). However, it has not yet been established whether the OBS is related to type 2 diabetes mellitus (T2DM), especially in a population without NALFD. Therefore, we aimed to investigate the longitudinal effect of the OBS on T2DM in a large cohort of Korean adults without NALFD. Data were assessed from 9798 participants without NALFD from the Korean Genome and Epidemiology Study-Health Examinees (KoGES-HEXA) cohort. The participants were divided into three groups according to OBS tertiles, identified as T1-T3. We prospectively assessed the hazard ratios (HRs) with 95% confidence intervals (CIs) for new-onset T2DM using multivariable Cox proportional hazard regression models over 6 years following the baseline survey. During the mean 3.5 years of follow-up, 145 individuals (1.48%; 56 men and 89 women) developed T2DM. The HRs of T2DM for the OBS tertiles were 0.79 (95% CI, 0.53-1.18) and 0.60 (95% CI, 0.39-0.93) in the T2 and T3 groups after adjusting for metabolic parameters in subjects without NALFD, respectively; however, the T2 group did not show statistical significance toward a decrease in incident T2DM. A low OBS may be a useful predictive marker in new-onset T2DM for middle-aged and older subjects without NALFD. This implies that the OBS could be an additional valuable tool for assessing the incidence of T2DM among individuals without NAFLD.
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OBJECTIVES: To assess the prognostic value of human epididymis protein 4 (HE4) kinetics during and after neoadjuvant chemotherapy (NACT) cycles compared with cancer antigen 125 (CA-125), in predicting the surgical outcomes of interval debulking surgery (IDS) in patients with advanced-stage, high-grade serous ovarian cancer. METHODS: This retrospective cohort study was conducted at Severance Hospital in Seoul, South Korea and involved 123 women with high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who were diagnosed between April 2015 and July 2020. Three outcomes were considered: the chemotherapy response score (CRS) by omentum, residual disease after IDS, and recurrence. Other clinical, imaging, and biological parameters at baseline, during NACT cycles, and pre- and postoperative time were collected and analyzed. RESULTS: We observed a substantial and gradual decrease in both CA-125 level (median from 1612 to 85.55 U/mL; p < 0.001) and HE4 level (514.7 to 87.7 pmol/L; p < 0.001) during NACT cycles, while pre-to-postoperative reduction was only significant for HE4 (median from 77.3 to 62.0 pmol/L (p < 0.001)). Of the total patients, 4.1% showed no response to NACT (chemoresistance) and 65.9% had a partial response. Residual disease was observed in 55 (44.7%) patients. Recurrence occurred in 90 patients (73.2%), with a median progression-free survival of 15.28 months. The percent reduction in CA-125 level- but not HE4 - during NACT was significantly associated with CRS (by omentum); the reduction in CA-125 during NACT cycles was higher when the CRS was found to be 3 and 2 (median = 96.4 [IQR = 8.3] and 93.7 [12.2] respectively) compared to score 1 (68.3 [34.1]), and the difference was statistically significant (p = 0.004). However, no significant association was observed between the percent reduction in CA-125 or HE4 levels during NACT and residual disease or recurrence. The normalization of HE4 - but not CA-125 - before surgery was predictive for surgery outcome; that is, an abnormal preop HE4 level was associated with a residual disease risk ratio of 2.72 (95% CI = 1.27-5.79). CONCLUSION: Monitoring HE4 or CA-125 levels has low prognostic value in patients with advanced-stage, high-grade serous ovarian cancer who are treated with NACT followed by IDS. However, the preoperative level of the HE4 biomarker may be useful in identifying patients at higher risk for suboptimal cytoreductive surgery or who may require more extensive surgery. Further prospective studies are warranted to explore the prognostic utility of eventual combinations of clinical, radiological, and biological parameters, notably by using artificial intelligence-based models.
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Cistadenocarcinoma Seroso , Neoplasias Ováricas , Femenino , Humanos , Inteligencia Artificial , Antígeno Ca-125 , Carcinoma Epitelial de Ovario/cirugía , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Quimioterapia Adyuvante , Cistadenocarcinoma Seroso/tratamiento farmacológico , Procedimientos Quirúrgicos de Citorreducción , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The Korean Society of Gynecologic Oncology (KSGO) had been making an effort to standardize and enhance the quality of domestic uterine corpus cancer treatment by developing updated clinical practice guidelines in 2021. The KSGO revised the guidelines based on a literature search using 4 key elements: Population, Intervention, Comparison, and Outcome framework. These elements include the evaluation of the efficacy and safety of immune checkpoint inhibitor treatment in recurrent/advanced endometrial cancer patients who have failed platinum-based chemotherapy, as well as the effect of combined treatment with trastuzumab in patients with HER2/neu-positive endometrial cancer. Additionally, the guideline assessed the efficacy and safety of omitting lymph node dissection in low-risk endometrial cancer patients, investigated the effect of sentinel lymph node mapping in early-stage endometrial cancer surgery, addressed the outcome of chemoradiation therapy as a postoperative treatment in patients with advanced (stage III-IVA) endometrial cancer, and explored the impact of initial treatment with immune checkpoint inhibitors on survival in patients with advanced or recurrent endometrial cancer patients.
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Neoplasias Endometriales , Ganglio Linfático Centinela , Neoplasias Uterinas , Femenino , Humanos , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/patología , Neoplasias Uterinas/patología , Neoplasias Endometriales/patología , Escisión del Ganglio Linfático , República de Corea , Biopsia del Ganglio Linfático Centinela , Ganglio Linfático Centinela/patología , Ganglios Linfáticos/patologíaRESUMEN
Circulating tumor DNA (ctDNA) may aid in personalizing ovarian cancer therapeutic options. Here, we aimed to assess the clinical utility of serial ctDNA testing using tumor-naïve, small-sized next-generation sequencing (NGS) panels. A total of 296 patients, including 201 with ovarian cancer and 95 with benign or borderline disease, were enrolled. Samples were collected at baseline (initial diagnosis or surgery) and every 3 months after that, resulting in a total of 811 blood samples. Patients received adjuvant therapy based on the current standard of care. Cell-free DNA was extracted and sequenced using an NGS panel of 9 genes: TP53, BRCA1, BRCA2, ARID1A, CCNE1, KRAS, MYC, PIK3CA, and PTEN. Pathogenic somatic mutations were identified in 69.2% (139/201) of patients with ovarian cancer at baseline but not in those with benign or borderline disease. Detection of ctDNA at baseline and/or at 6 months follow-up was predictive of progression-free survival (PFS). PFS was significantly poorer in patients with detectable pathogenic mutations at baseline that persisted at follow-up than in patients that converted from having detectable ctDNA at baseline to being undetectable at follow-up; survival did not differ between patients without pathogenic ctDNA mutations in baseline or follow-up samples and those that converted from ctDNA positive to negative. Disease recurrence was also detected earlier with ctDNA than with conventional radiologic assessment or CA125 monitoring. These findings demonstrate that serial ctDNA testing could effectively monitor patients and detect minimal residual disease, facilitating early detection of disease progression and tailoring of adjuvant therapies for ovarian cancer treatment. SIGNIFICANCE: In ovarian cancer, serial circulating tumor DNA testing is a highly predictive marker of patient survival, with a significantly improved recurrence detection lead time compared with conventional monitoring tools.
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ADN Tumoral Circulante , Neoplasias Ováricas , Humanos , Femenino , ADN Tumoral Circulante/genética , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Biomarcadores de Tumor/genética , MutaciónRESUMEN
PURPOSE: Although the correlation between insulin resistance (IR) and cardiovascular disease (CVD) risk is well-established, the impact of changes in IR status over time has received little attention. This study aimed to investigate the effect of IR on CVD risk in a large prospective cohort of middle-aged Korean adults. METHODS: We assessed 3597 participants from the Korean Genome and Epidemiology Study (KoGES). Participants were categorized as having IR if their HOMA-IR was ≥2.5 at least once during the exposure period. Multivariate Cox proportional hazards regression analysis was performed to assess hazard ratios (HRs) with 95% CIs for incident CVD after adjusting for confounders. RESULTS: Among a total of 3597 participants, 2259 did not have IR and 1138 had IR. The cumulative incidence rate of CVD in the IR group was significantly higher than that in the non-IR group (log-rank test, p = 0.015). Compared to the non-IR group, the HR and 95% CI for incident CVD in the IR group was 1.40 (1.07-1.83) in the unadjusted model. The presence of IR during the exposure period was significantly associated with a higher risk of incident CVD after adjusting for age, sex, body mass index, diabetes, hypertension, dyslipidemia, C-reactive protein, physical activity, alcohol intake, and smoking status (HR = 1.37; 95% CI: 1.01-1.84). CONCLUSION: Individuals who have experienced IR have a consistently higher likelihood of developing CVD than those who have never had IR. More intensive efforts should be made to prevent IR in middle-aged and older adults.
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This study presents a novel nondestructive analysis method for precise characterization of corroded copper oxidation using optical coherence microscopy (OCM). By exploiting the partial light transmission through metallic oxide layers, we employed a specialized OCM system with a wavelength of 1700nm and enhanced the analysis accuracy compared to conventional optical coherence tomography (OCT). The developed OCM system featured a numerical aperture (NA) of 0.15, providing improved surface profiling and higher lateral resolution than OCT. we developed a peak-finding algorithm to accurately determine the thickness of the copper oxide layer from the acquired interference data with zero padding. Our method was validated by comparing the measured thickness profiles with those obtained from scanning electron microscope (SEM) images of corroded metals. The copper oxidation specimens were prepared after heat treatment for 1, 2, 4, and 8â h in an alumina tube furnace at a temperature of 900 °C to find the correlation between the OCM thickness measurement. Additionally, the acquired enface 3D images enabled the identification of local corrosion distribution within a 4 mm × 4 mm area. The en-face mapping images are utilized to analyze the uniformity of the metal oxidation process across the imaging area of the copper oxidation specimens. With an increase in heat treatment time, the median value of the thickness histogram for the copper oxide within the area consistently remained around 10â µm. However, the thickness variation ranged from -2â µm to 5â µm. This indicates that as the heat treatment time progresses, the thickness of the copper oxide becomes more non-uniform. Our technique holds great potential for nondestructive and noncontact detection of metal corrosion and assessment of corrosion rates in various industrial applications. Future research efforts could focus on expanding the application of OCM to different metals and exploring its commercialization prospects for practical implementation in diverse industries.
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Background: There are few reports on the preventative value of intensive blood pressure (BP) management for stroke, especially hemorrhagic stroke (HS), after new criteria for hypertension (HTN) were announced by the American College of Cardiology/American Heart Association in 2017. Aims: This study aimed to identify the optimal BP for the primary prevention of HS in a healthy population aged between 20 and 65 years. Methods: We conducted a 10-year observational study on the risk of HS, subclassified as intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) according to BP categories (e.g., low normal BP, high normal BP, elevated BP, stage 1 HTN, and stage 2 HTN) using the National Health Insurance Service Database. Results: Out of 8,327,751 participants who underwent a health checkup in 2008, 949,550 were included in this study and observed from 2009 to 2018. The risk of ICH was significantly increased in men with stage 2 HTN {adjusted hazard ratio [aHR] 2.002 [95% confidence interval (CI) 1.203-3.332]} and in women with stage 1 HTN [aHR 2.021 (95% CI, 1.251-3.263)]. The risk of SAH was significantly increased in both men [aHR 1.637 (95% CI, 1.066-2.514)] and women [aHR 4.217 (95% CI, 2.648-6.715)] with stage 1 HTN. Additionally, the risk of HS was significantly increased in men with stage 2 HTN [aHR 3.034 (95% CI, 2.161-4.260)] and in women with stage 1 HTN [aHR 2.976 (95% CI, 2.222-3.986)]. Conclusion: To prevent primary HS, including ICH and SAH, BP management is recommended for adults under the age of 65 years with stage 1 HTN.
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To compare the perioperative outcomes of surgical staging performed using conventional laparotomy (LT) or the da Vinci SP robotic system (SP) in patients with endometrial cancer. We retrospectively analyzed 180 patients with stage I-III endometrial cancer who underwent surgical staging using LT (n = 126) or SP (n = 54) at the Yonsei Cancer Center between November 2018 and December 2022. Propensity score matching (PSM) was performed to mitigate potential confounding biases. Fifty-one pairs of patients were matched by PSM. SP required longer total operation time than LT (221 vs. 142 min in SP vs. LT, respectively, p < 0.001). However, estimated blood loss and postoperative hemoglobin change were lower in SP than in LT (30 vs. 100 mL, p < 0.001; 0.6 vs. 1.6 g/dL, p < 0.001 for SP vs. LT respectively). Furthermore, postoperative minor complications (13.7% in SP vs. 33.3% in LT, p = 0.02), perioperative transfusion rate (0% in SP vs. 11.8% in LT, p = 0.03), and postoperative hospital stay (2 days for SP vs. 8 days for LT, p < 0.001) were lower in SP than in LT. Although the patient-controlled analgesia administration rate was lower in SP (13.8% in SP vs. 100% in LT, p < 0.001), the median postoperative pain score at 6, 12, and 24 h after surgery was lower in SP than in LT (2 vs. 3, p = 0.002; 2 vs. 3, p = 0.005; 2 vs. 3, p = 0.001 for SP vs. LT, respectively). Although SP required longer total operation time, it demonstrated several advantages over LT in endometrial cancer staging.
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Neoplasias Endometriales , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Robótica , Femenino , Humanos , Estudios Retrospectivos , Estadificación de Neoplasias , Laparotomía , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/patología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugíaRESUMEN
BACKGROUND: Poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis) are becoming the standard of care for epithelial ovarian cancer (EOC). Recently, clinical trials of triple maintenance therapy (PARPi+anti-angiogenic agent+anti-PD-1/L1) are actively ongoing. Here, we investigated the immunological effects of PARPi or triple maintenance therapy on T cells and their impact on clinical responses. METHODS: We collected serial blood from EOC patients receiving PARPi therapy (cohort 1: PARPi, n = 49; cohort 2: olaparib+bevacizumab+pembrolizumab, n = 31). Peripheral T cells were analyzed using flow cytometry and compared according to the PARPi response. Progression-free survival (PFS) was assessed according to prognostic biomarkers identified in a comparative analysis. RESULTS: Regulatory T cells (Tregs) were suppressed by PARPi therapy, whereas PD-1 was not significantly changed. Short PFS group exhibited a higher percentage of baseline PD-1+Tregs than long PFS group, and the patients with high percentage of PD-1+Tregs before treatment showed poor PFS in cohort 1. However, the expression of PD-1 on Tregs significantly decreased after receiving triple maintenance therapy, and the reduction in PD-1+Tregs was associated with superior PFS in cohort 2 (P = 0.0078). CONCLUSION: PARPi suppresses Tregs, but does not affect PD-1 expression. Adding anti-PD-1 to PARPi decreases PD-1+Tregs, which have negative prognostic value for PARPi monotherapy.
Asunto(s)
Antineoplásicos , Neoplasias Ováricas , Humanos , Femenino , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/uso terapéutico , Linfocitos T Reguladores , Antineoplásicos/uso terapéutico , Poli(ADP-Ribosa) PolimerasasRESUMEN
Background: Carcinoembryonic antigen (CEA) is a commonly used tumor marker in cancer screening. However, it has also been associated with metabolic alterations. Hepatic steatosis, the accumulation of fat in liver cells, is associated with various cardiovascular risk factors. This study investigated the risk of ischemic heart disease (IHD) in individuals with elevated CEA levels, hepatic steatosis, and their co-occurrence. Methods: The study cohort comprised 5,580 Korean adults who underwent health examinations between November 2006 and June 2010. Data regarding baseline CEA levels, hepatic steatosis status, and development of IHD were collected. Hepatic steatosis was defined as more than two findings: deep attenuation, vascular blurring, and increased liver echogenicity on abdominal ultrasound. Participants were divided into four groups based on their CEA and hepatic steatosis status: no hepatic steatosis and low CEA (group 1), no hepatic steatosis and elevated CEA (group 2), low CEA and hepatic steatosis (group 3), and elevated CEA and hepatic steatosis (group 4). Results: A total of 226 (4.1%) participants developed IHD during the follow-up period. Participants with elevated CEA levels and hepatic steatosis (group 4) had the highest cumulative incidence of IHD in comparison to other groups (p < 0.001). The combined effect of elevated CEA levels and hepatic steatosis showed significantly greater area under the receiver operating characteristic curve than hepatic steatosis alone (p < 0.001). Furthermore, participants with elevated CEA and hepatic steatosis (group 4) had higher risk of developing IHD compared to those with low CEA and no hepatic steatosis (group 1) (hazard ratio: 1.63, 95% confidence interval: 1.04-2.55, p = 0.034). Conclusion: Co-occurrence of elevated CEA levels and hepatic steatosis increases the risk of IHD. Comprehensive risk assessment is crucial to guide interventions and improve cardiovascular health in individuals with both the conditions.
RESUMEN
Background: Body mass index (BMI) and waist circumference (WC) are the most widely used anthropometric indices for identifying obesity. This study aimed to compare and clarify the usefulness of BMI, WC, and the combination of these two indicators in predicting nonalcoholic fatty liver disease (NAFLD). Methods: This cross-sectional study included 15,267 Korean adults. We defined four obesity categories using BMI and WC as follows: BMI nonobese and WC nonobese (BNWN); BMI obese and WC nonobese (BOWN); BMI nonobese and WC obese (BNWO); and BMI obese and WC obese (BOWO). Analysis of variance was used to compare fatty liver severity across each category. The odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were calculated using multiple logistic regression. Results: Compared with BNWN, participants with BNWO were 3.235 (95% CI: 2.774-3.773) times more likely and participants with BOWN were 2.344 (95% CI: 2.045-2.687) times more likely to have NAFLD. Participants with BNWO had higher OR for NAFLD than those with BOWN. Moreover, BOWO participants had the highest OR of 4.788 (95% CI: 4.350-5.270) for NAFLD among all obesity categories. Conclusion: Combined obesity classification by BOWO is the most reliable indicator for NAFLD presence in Korean adults.
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Enfermedad del Hígado Graso no Alcohólico , Adulto , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Índice de Masa Corporal , Circunferencia de la Cintura , Estudios Transversales , Obesidad/complicaciones , Obesidad/diagnóstico , Factores de RiesgoRESUMEN
In the effort of isolating novel microbial species, the strain PL0132T was isolated from a fallen leaf under fresh water at a stream, which glided when grown on a tap water medium (without nutrients). The strain was determined to be Gram-negative, strictly aerobic, and rod-shaped, which grew optimally at 25 °C, pH 6-7, and the strain tolerates 1% (w/v) NaCl concentration. The complete genome of strain PL0132T comprises one contig with a sequencing depth of 76×, consisting of 8,853,064 base pairs and the genomic DNA G + C content was 46.7% (genome). 16S rRNA gene sequence analysis revealed that strain PL0132T represents a member of the phylum Bacteroidetes and is affiliated with the genus Spirosoma. Based on genomic, phenotypic, and chemotaxonomic characteristics, the strain PL0132T represents a novel species of the genus Spirosoma, for which the name Spirosoma foliorum sp. nov. is proposed (= KCTC 72228 T = InaCC B1447T).