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Context The number of women who achieve pregnancy through assisted reproductive technology (ART), including in vitro fertilisation and embryo transfer (IVF-ET), is increasing worldwide. Placenta-mediated diseases associated with ART, such as gestational hypertension, preeclampsia, disorders of placental implantation, and placental abruption, are also increasing. Aims To determine the association between placental pathologies and IVF-ET in women with preterm births. Methods This retrospective cohort study examined archived placenta specimens of women who achieved pregnancy through either spontaneous conception or IVF-ET. In total, 1677 women with singleton pregnancies who gave birth consecutively between 20 and 37 weeks of gestation at Seoul National University Bundang Hospital and underwent placental pathologic evaluation between April 2013 and October 2018 were included. Data from all pathologic reports were reviewed. Key results The IVF-ET group had a higher median maternal age and rate of nulliparity than the natural conception group. The incidence rate of obstetric complications, except preterm premature rupture of membranes and placenta previa, was similar in both groups. The IVF-ET group had a higher incidence rate of placental infarction than the natural conception group (26.4% vs 16.4%, P = 0.012). Multivariate logistic regression analysis indicated that IVF, hypertensive disorders, and fetal growth restriction were significantly associated with placental infarction. Conclusions IVF-ET was independently associated with the risk of placental infarction in women with preterm births. Implications The use of IVF-ET may cause abnormal placental formation with an increased risk of anatomical and vascular pathology, which are observed in preterm deliveries and may contribute to pregnancy complications.

Purpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.

This study aimed to examine the changes in the characteristics of community-onset fluoroquinolone-resistant (FQ-R) Escherichia coli isolates causing community-acquired acute pyelonephritis (APN) in South Korea.Blood or urine samples were prospectively collected from patients aged ≥15 years with community-acquired APN who were admitted to one of the eight Korean hospitals included in this study between September 2017 and August 2018. Phylogenetic typing, multilocus sequence typing, and molecular characterization of β-lactamase resistance and plasmid-mediated quinolone resistance (PMQR) determinants were performed. The data were compared with those from a previous study with the same design conducted in 2010-2011.A total of 300 and 346 isolates were identified in 2010-2011 and 2017-2018, respectively. Among them, 76 (22.0%) and 77 (25.7%) FQ-R isolates were identified in 2010-2011 and 2017-2018, respectively. A significantly higher antimicrobial resistance against third-to fourth-generation cephalosporins, including cefotaxime (23.9% vs. 77.9%, P 0.001), were observed among FQ-R isolates in 2017-2018 than among those in 2010-2011. A higher proportion of ST131 isolates (27.6% vs. 66.2%, P 0.001), as well as isolates that had extended-spectrum β-lactamase (ESBL)/plasmid-mediated AmpC β-lactamase (PABL) (23.7% vs. 79.2%, P 0.001), was observed in 2017-2018 than in 2010-2011. Further, more PMQR determinants (11.8% vs. 40.8%, P 0.001) were observed in 2017-2018 than in 2010-2011.Among uropathogenic FQ-R E. coli isolates in South Korea, the prevalence of ST131 and the proportion of isolates containing ESBL and/or PMQR determinants have increased.

Antimicrobial resistance is one of the most urgent global health threats. The need for the qualitative evaluation of antibiotic use at the national level is increasing. To identify areas for improvement, we aimed to assess the prevalence and appropriateness of antibiotic prescriptions during hospitalization and ambulatory care in Korea.The prevalence and appropriateness of antibiotic prescriptions on 29 August 2018 were assessed for 20 hospitals in Korea. Infectious disease specialists determined appropriateness. Except for antiviral and anti-tuberculosis agents, all antibacterial or antifungal agent prescriptions during hospitalization or ambulatory care were evaluated.The prevalence of antibiotic prescription was 14.1% (8,400/59 216 patients) on the study date. Antibiotics were prescribed for 50.8% of inpatients (6557/12 902), with two or more antibiotics prescribed for 27.4% (1798/6557) of patients. A total of 10 948 prescriptions (7999 therapeutic, 2105 surgical prophylaxes, and 844 medical prophylaxes) were included in the final analysis, and 27.7% of these were inappropriate. Surgical prophylaxis was inadequately prescribed most frequently (54.4%), followed by medical prophylaxis (29.5%) and therapeutic antibiotics (20.5%). The most common indications for therapeutic antibiotics were respiratory (29.1%, n=2332), gastrointestinal (22.4%, n=1791), and urinary tract infections (13.1%, n=1050). The most frequently prescribed antibiotics were cephalosporins (52.0%, n=5490), followed by beta lactam/beta lactamase inhibitors (13.7%, n=1373), fluoroquinolones (9.1%, n=957), and metronidazole (6.6%, n=699).This was the first nationwide qualitative antibiotic prescription adequacy evaluation in Korea. A significant proportion of antibiotic prescriptions were inappropriate. Therefore, interventions for high-frequency infections and prescription antibiotics are needed.

We sought to investigate the impact of size of residual tumors as determined by postoperative computed tomography (CT) on survival of patients with advanced, high-grade serous ovarian carcinoma (HGSC) who achieved residual disease less than 1 cm after primary debulking surgery (PDS).We collected data of patients with stage III HGSC who had residual tumor less than 1 cm after PDS between 2013 and 2018. Surgeon-assessed residual disease during surgery was defined as sR0 (no gross residual) or sR1 (gross residual1 cm), and radiologist-assessed residual disease on postoperative CT was defined as rR0 (no evidence of disease) or rRany (existing residual disease). All patients were classified into the following groups: sR0/rR0, sR1/rR0, sR0/rRany, and sR1/rRany.A total of 436 patients was placed into the sR0/rR0 (n = 187, 42.9%), sR1/rR0 (n = 59, 13.5%), sR0/rRany (n = 79, 18.1%), or sR1/rRany group (n = 111, 25.5%). Discrepancies between surgical and radiological assessments were recorded for 176 patients (40.4%) including 38 cases of sR1/rRany group with discordant residual tumor location indicated between two methods. During multivariate analysis, patients with ascites on preoperative CT, sR0/rRany group inclusion, and sR1/rRany group inclusion showed unfavorable progression-free and overall survival.The incorporation of surgical and radiological evaluations for determining the size of residual tumors was more accurate than surgical evaluation only for predicting survival among patients with advanced ovarian cancer who underwent PDS to residual disease less than 1 cm.

The aim of the study was to investigate the characteristic findings of computed tomography (CT) or magnetic resonance imaging (MRI) to discriminate metastasis from primary ovarian tumors in patients with a history of breast cancer.This retrospective study enrolled consecutive 72 patients with a history of breast cancer who underwent surgical confirmation of an ovarian mass detected on CT or MRI (primary ovarian tumors, n = 66; metastases, n = 6). Two independent readers analyzed the grade of solid portions of the ovarian mass using a 5-point scale on CT or MRI. A predominantly cystic mass was defined as a solid grade of 1 to 2. Cancer antigen 125 (CA 125) and the initial stage of breast cancer were also investigated.The proportions of predominantly cystic masses were significantly different between metastases (0% for both readers) and primary ovarian tumors (59% for reader 1 and 53% for reader 2, P0.05). For masses of solid portion grades 3 to 5, CA 125 was significantly higher for malignant epithelial tumors than for the other tumors ( P0.001), and the initial stage of breast cancer was significantly higher for metastases than for the other tumors ( P0.001), respectively.In patients with a history of breast cancer, predominantly cystic masses detected on CT or MRI seem to be primary ovarian tumors. For the other masses, knowledge of CA 125 and initial breast cancer stage may help in the differential diagnosis.

Background With the widespread use of gadolinium-based contrast agents (GBCAs), the incidence of allergic-like hypersensitivity reactions (HSRs) to GBCAs is increasing. Research on the incidence and risk factors for HSRs to GBCAs is needed for their safe use. Purpose To determine the incidence of acute and delayed reactions to GBCAs and to discuss the risk factors and strategies for the prevention of HSRs to GBCAs. Materials and Methods All cases of HSRs to contrast media that occurred at the Seoul National University Hospital from July 1, 2012, to June 30, 2020, were assessed. Information including age, sex, GBCA type, onset, and severity of HSRs was retrospectively analyzed. Results Among the 331070 cases of GBCA exposure in 154539 patients, 1304 cases of HSRs (0.4%) were reported. Acute HSRs accounted for 1178 cases (0.4%), while 126 cases (0.04%) were delayed HSRs. While both premedication (odds ratio [OR] = 0.7

Objective Premature ovarian insufficiency (POI) is a clinical disease that is diagnosed by the loss of ovarian function before the age of 40. Despite recent progress in molecular diagnosis, the genetic etiology of POI is not well established. The aim of this study is to reveal pathogenic genetic variants involved in POI. Study design and main outcome measures To reveal pathogenic genetic variants involved in POI, whole exome sequencing was performed in nonconsanguineous family members with POI. Constitutional variants were filtered against population databases and a missense mutation of natriuretic peptide C (NPPC) (c.131A>G, p.Q44R) was selected as a convincing candidate mutation among 14 heterozygous mutant alleles in 13 genes. Results The wild-type NPPC and mutant NPPC (NPPC131A>G) were expressed in HeLa cells, and cells expressing NPPC131A>G secreted unique peptides. The ProP 1.0 Server, a neural network prediction tool, predicted the presence of a cleavage site at the substituted arginine residue (p.Q44R) of NPPC. The molecular weight of predicted cleaved peptides processed from mutant NPPC precursor corresponded to that of the actual mutant peptide. The cGMP synthetic activity of NPR2-expressing cells was significantly decreased by interaction with the mutant NPPC peptide compared with wild-type NPPC. Conclusions The peptide generated by a rare mutation of NPPC might influence paracrine C-type natriuretic peptide (CNP)-mediated preantral follicle development and/or sustain meiotic arrest in oocytes. We therefore suggest that a mutation of the NPPC gene is involved in the pathogenesis of POI.

Introduction: Metastasis of primary pancreatic cancer (PC) to adjacent or distant organs is responsible for the poor survival rate of affected individuals. Chemotherapy, radiotherapy, immunotherapy is being prescribed currently to treat PC in addition to surgical resection. Surgical resection is the preferred treatment for PC that leads to 20% of 5-year survival, but only less than 20% of patients are eligible for surgical resection, because of the poor prognosis. To improve the prognosis and clinical outcome, early diagnostic markers need to be identified, and targeting them would be of immense benefit to increase the efficiency of the treatment. Cell migration inducing hyaluron binding protein (CEMIP) is identified as an important risk factor for the metastasis of various cancers including PC. Emerging studies point out the crucial role forCEMIP in the regulation of various signaling mechanismleading to enhanced migration and metastasis of PC. Methods: The published findings in the area of pancreatic cancer metastasis, phyto-constituents and CEMIP were retrieved from Pubmed, Sciencedirect, Cochrane library. Computational tools such as gene expression profiling interactive analysis (GEPIA) and Kaplan–Meier (KM) plotter were used to study the relationship between CEMIP expression and survival of PC individuals. Results: Gene expression analysis using GEPIA database identified a stupendousincrease in the CEMIP transcript in PC when compared with adjacent normal tissue. KM plotter analysis revealed a critical role for CEMIP on the overall survival (OS) and disease-free survival (DFS) among PC patients. Subsequently several risk factors associated with the development of PC were screened and analyzed its ability to regulate CEMIP gene expression using computational tools. Conclusion: The current review is focused on gathering information about the regulatory role of phytocomponents on PC migration and exploring their possible impact on the CEMIP expression.

Although improvements in acute care for traumatic brain injury (TBI) have increased the patient survival rate, many survivors often suffer from neuropsychiatric sequelae such as depression. This study investigated the influence of TBI on the risk of depression using South Korean nationwide data. Data were extracted from the National Health Insurance Service database for patients who experienced TBI from 2010 to 2017 (

An "ovarian cancer cluster region" (OCCR) has been reported in both BRCA1 and BRCA2. However, the clinical significance of the OCCR of BRCA1/2 has not yet been investigated.The medical records of 991 patients with epithelial ovarian, primary peritoneal, and fallopian tube cancer who underwent genetic testing for BRCA1 and/or BRCA2 from January 1, 2006, to August 31, 2019, were retrospectively reviewed. Sanger and next-generation sequencing analyses were used to test the BRCA1 and BRCA2 mutation status. Progression-free survival (PFS) and overall survival (OS) were compared according to the mutation location (OCCR vs. non-OCCR region). Survival outcomes were determined using Kaplan-Meier survival analysis.A total of 162 patients had BRCA1 pathogenic variants (PVs), and 76 had BRCA2 PVs. Patients with BRCA1 PV that in the OCCR region showed shorter PFS than those with BRCA1 PV outside the OCCR (22.6 months vs. 27.6 months, P = 0.038). In the platinum-sensitive subgroup of BRCA1, patients with BRCA1 PV in the OCCR region showed shorter PFS than those in the non-OCCR group (P = 0.0197). On the other hand, BRCA2 variants did not exhibit any particular trend (32.8 months vs. 27.9 months, P = 0.468). However, no significant differences were detected in OS between patients with BRCA1/2 PVs, regardless of the location of the variants.Patients with BRCA1 PV in the OCCR had shorter PFS than those outside the OCCR. This tendency was more pronounced in the platinum-sensitive subgroup. To our knowledge, this is the first study of BRCA1/2 mutations based on the OCCR.

Objectives To evaluate the effect of maternal age to the cesarean section rate of twin pregnancies in late preterm and term gestation. Methods A retrospective study was performed on twin pregnancies delivered at Seoul National University Bundang Hospital from June 2003 to December 2020. Preterm births before 34 weeks of gestation were excluded, and only live births were analyzed. The patients were classified into four groups according to maternal age ( Results The median value of maternal body mass index, the rate of assisted reproductive technology, dichorionic twin pregnancy, preeclampsia, and gestational diabetes increased significantly according to the maternal age group (all p Conclusions The rate of cesarean section in twin pregnancies significantly increased as maternal age increased, even in multiparous women.

Experimental study.In this study, the ambient temperature of a radiofrequency (RF) electrode tip was compared and analyzed in terms of products, mode, flow quantity, and flow rate.Endoscopic spine surgery is a widely used operation for degenerative lumbar stenosis and herniated lumbar disc. To perform endoscopic spine surgery, dedicated instruments like a RF generator and electrode are essential.An evaluation system capable of measuring temperature under equal conditions at a certain distance from the electrode tip was manufactured. The distance between the electrode tip and the temperature sensor was set to 1, 5, and 10 mm. The flow quantities of 0, 50, 100, and 150 mL/min and the flow rates of 0, 0.20, 0.53, and 0.80 m/s were compared and statistically analyzed.The temperatures measured in the experiments conducted on the four combinations of RF device showed similar values, and showed differences according to the characteristics of each mode of the RF. As the distance between the electrode tip and the temperature sensor increased, the temperature decreased, and as flow quantity or flow rate increased, the temperature decreased. The maximum temperatures differed significantly according to flow quantity, between flow quantities of 0 and 100 mL/min (P = 0.03) and between 0 and 150 mL/min (P ≤ 0.01). The maximum temperatures also differed significantly between the flow rate of 0 m/s, and the flow rates of 0.20, 0.53, and 0.80 m/s, with P ≤ 0.01 in all three comparisons.This is the first study in which we made a customized RF temperature evaluation system and verified the temperature changes in various environments. When irrigation was performed, we could confirm that the maximum temperature was less than 60°C. Irrigation is considered essential in endoscopic spine surgery.3.

Background This study aimed to validate the performance of the Korean Gynecologic Oncologic Group (KGOG)-1024 risk model in predicting the risk of distant failure after chemoradiation in patients with locally advanced cervical cancer (LACC). Methods In a retrospective cohort of 297 patients who received concurrent chemoradiation for advanced cervical cancer, individual risk was calculated using the KGOG-1024 risk model. The cohort was categorized into three risk groups (low-, intermediate-, and high-risk groups) according to the calculated risk. The means of the calculated and observed risks were compared within each group. Results The study population was classified into low-, intermediate-, and high-risk groups according to the KGOG-1024 risk model (27.2%, 49.3%, and 23.5% of patients, respectively). The calculated and observed 5-year cumulative incidence rates were 12.4% vs. 16.4% in the low-risk group, 23.2% vs. 25.9% in the intermediate-risk group, and 50.7% vs. 36.3% in the high-risk group. Overall, the calculated and observed risk was 26.7% vs. 25.6%. Conclusions The KGOG-1024 risk assessment model accurately predicted distant recurrence after chemoradiation in patients with LACC, especially in the low- and intermediate-risk groups. The model may be helpful for identifying patients for future trials assessing the possible benefit of adjuvant systemic treatment after chemoradiation.

Organisms develop unique systems in a given environment. In the process of adaptation, they employ materials in a clever way, which has inspired mankind extensively. Understanding the behavior and material properties of living organisms provides a way to emulate these natural systems and engineer various materials. Silk is a material that has been with human for over 5000 years, and the success of mass production of silkworm silk has realized its applications to medical, pharmaceutical, optical, and even electronic fields. Spider silk, which was characterized later, has expanded the application sectors to textile and military materials based on its tough mechanical properties. Because silk proteins are main components of these materials and there are abundant creatures producing silks that have not been studied, the introduction of new silk proteins would be a breakthrough of engineering materials to open innovative industry fields. Therefore, in this review, we present diverse silk and silk-like proteins and how they are utilized with respect to organism's survival. Here, the range of organisms are not constrained to silkworms and spiders but expanded to other insects, and even marine creatures which produce silk-like proteins that are not observed in terrestrial silks. This viewpoint broadening of silk and silk-like proteins would suggest diverse targets of engineering to design promising silk-based materials. STATEMENT OF SIGNIFICANCE: Silk has been developed as a biomedical material due to unique mechanical and chemical properties. For decades, silks from various silkworm and spider species have been intensively studied. More recently, other silk and silk-like proteins with different sequences and structures have been reported, not only limited to terrestrial organisms (honeybee, green lacewing, caddisfly, and ant), but also from marine creatures (mussel, squid, sea anemone, and pearl oyster). Nevertheless, there has hardly been well-organized literature on silks from such organisms. Regarding the relationship among sequence-structure-properties, this review addresses how silks have been utilized with respect to organism's survival. Finally, this information aims to improve the understanding of diverse silk and silk-like proteins which can offer a significant interest to engineering fields.

Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity, insulin resistance, and endoplasmic reticulum (ER) stress. Elevated circulating levels of the hepatokine leukocyte cell-derived chemotaxin-2 (LECT2) have also been noted in NAFLD; however, the mechanism underlying this association is unclear. To investigate a possible link between ER stress/unfolded protein response (UPR) signaling and LECT2 secretion, HepG2 cells were incubated with ER stress inducers with or without an ER stress-reducing chemical chaperone. Additionally, UPR pathway genes were knocked down and overexpressed, and a ChIP assay was performed. In diet-induced obese mice, hepatic expression of LECT2 and activating transcription factor 4 (ATF4) was measured. In HepG2 cells, LECT2 expression was increased by ER stressors, an effect blocked by the chemical chaperone. Among UPR pathway proteins, only knockdown of ATF4 suppressed ER stress-induced LECT2 expression, while overexpression of ATF4 enhanced LECT2 expression. The ChIP assay revealed that ATF4 binds to three putative binding sites on the LECT2 promoter and binding is promoted by an ER stress inducer. In steatotic livers of obese mice, LECT2 and ATF4 expression was concomitantly elevated. Our data indicate that activation of ER stress/UPR signaling induces LECT2 expression in steatotic liver; specifically, ATF4 appears to mediate upregulation of LECT2 transcription.

Background We aimed to investigate the prevalence and associated factors of newly developed depression in patients who underwent craniotomy for brain tumor removal, as well as its effect on long-term mortality. Methods Using a nationwide cohort database in South Korea, we included adult patients diagnosed with brain tumors who underwent craniotomy for brain tumor removal from January 1, 2011, to December 31, 2017. We excluded patients with a preoperative history of depression. Results Among 4,275 patients, 727 (17.0%) patients were newly diagnosed with depression within one year, postoperatively. Two-year all-cause mortality and mortality due to brain cancer occurred in 1,233 (28.8%) and 1,099 (25.7%) patients, respectively. In the multivariable logistic regression model, older age, living in rural areas, newly acquired brain disability, underlying other psychiatric disorders, and longer length of hospital stay were associated with a higher incidence of newly developed depression. In the multivariable Cox regression model, newly acquired depression was associated with a 1.58-fold higher 2-year all-cause mortality compared with that in other patients (hazard ratio: 1.58, 95% confidence interval: 1.38–1.80; P Limitation Lack of information regarding severity and pathologic tumor type. Conclusion Within one follow-up year, 17.0% of patients were newly diagnosed with depression after craniotomy for brain tumor removal. Some factors (old age, living in rural areas, newly acquired brain disability, longer length of hospital stay, and underlying other psychiatric illnesses) could be risk factors for newly diagnosed depression. Furthermore, newly developed depression was associated with an increased 2-year all-cause mortality.

Background The prevalence of sarcopenia increases as renal function decreases, and a considerable number of hemodialysis (HD) patients have sarcopenia. Exercise and nutritional support are established interventions to prevent and treat sarcopenia. Recently, many studies evaluating intradialytic neuromuscular electrical stimulation (NMES) showed improvement of muscular strength and mass, functional capacity, and quality of life (QOL). However, there has been no research about the effect of simultaneous nutritional support and NMES in HD patients. Methods This is a 12-week, randomized controlled, parallel-group, multicenter trial of intradialytic NMES and protein supplementation for HD patients. Seventy-two patients receiving HD will be randomly assigned in a 1:1:1:1 ratio to control, intradialytic NMES only, protein supplementation only, and intradialytic NMES combined with protein supplementation groups. NMES will be delivered to a total of four areas of the bilateral vastus medialis and vastus lateralis using a 4-channel NMES instrument. A total of 25 g of protein supplements will be provided at the beginning of every dialysis session or after the NMES. The primary endpoint is the difference of hand grip and leg muscle strength at 12 weeks among 4 treatment groups. Secondary endpoints include muscle mass, physical performances, and questionnaires about QOL and physical activity. Discussion In this study, we will evaluate the differential effectiveness of nutritional support and NMES during HD on muscle strength, muscle mass, physical function, and QOL. We expect that this study can provide guidelines for a new therapeutic option for HD patients who are unable or hesitant to exercise. Furthermore, this option can offer an opportunity to improve the physical function, QOL, and prognosis of HD patients. Trial registration Clinical Research Information Service (CRIS), Korea, KCT0005573. Retrospectively registered on 03 November 2020

Introduction This study was designed to investigate the molecular epidemiology of Clostridioides difficile in South Korea, and to evaluate the risk factors of rifaximin-nonsusceptible C. difficile infections (CDI). Methods A total of 413 patients with CDI from two sentinel hospitals in South Korea were enrolled in this study. Putative clinical risk factors for CDI were identified using the digital medical records of the patients, and pathogen profiles, including antimicrobial susceptibility, toxin generation, and ribotype, were evaluated for each of the causative C. difficile isolates. Results A total of 81 (19.6%) C. difficile isolates were shown to be rifaximin-nonsusceptible with the most common ribotypes being described as 018 (56.8%, 46/81), 017 (16.0%, n = 13), and 027 (6.2%, n = 5). Rifaximin-nonsusceptible C. difficile isolates exhibited higher nonsusceptibility rates to most of the other drugs tested in this study when compared to the rifaximin-susceptible isolates. Previous history of pulmonary tuberculosis and prior rifaximin treatment were shown to be linked with the occurrence of rifaximin-nonsusceptible CDIs than those with susceptible CDIs. Conclusions The rifaximin-nonsusceptibility rates for the C. difficile isolates identified in this study were reasonably high with most of these resistant strains belonging to either the 018 or 017 RT. The widespread dissemination of these clones may be the result of the antimicrobial selection pressure introduced by the widespread use of rifaximin. These results suggest that a sustainable surveillance program for C. difficile infections and resistance is needed in order to better control CDIs and improve therapeutic efficacy.

To evaluate the effect of continuous infusion of nicardipine on the management of uncontrolled blood pressure (BP) during postpartum period. This retrospective study included 209 women diagnosed in hospital with hypertensive disorders during pregnancy and had uncontrolled BP after delivery between January 2018 to December 2020 Uncontrolled BP was defined as persistent elevation of systolic BP ≥ 160 mm Hg or diastolic BP ≥ 110 mm Hg. Patients were divided into 2 groups: nicardipine (N = 53; continuous nicardipine infusion and additional bolus of labetalol or hydralazine) and control (N = 156; consecutive bolus of labetalol or hydralazine). BP data were analyzed using the Mann-Whitney U and χ2 tests by dividing the time interval of 4 hours by the delivery time. The highest BP trends showed that the mean values of both systolic and diastolic BP immediately before delivery were higher in the nicardipine group than in the control. After 8 to 12 hours following delivery, both systolic and diastolic BP were lower in the nicardipine group than in the control. Subsequently, 16 to 20 hours after delivery, both systolic and diastolic BP were significantly lower in the nicardipine group than in the control (137/80 vs 141/84 mm Hg). Initially, the proportions of uncontrolled BP in the nicardipine group were higher than those in the control; however, it then became lower at all time intervals 8 hours after delivery. The proportions of patients who received additional antihypertensive agents and the median cumulative dosages were lower in the nicardipine group than in the control. Continuous infusion of nicardipine can help manage uncontrolled BP during the postpartum period.

Background and Objectives: Identification and targeting of membrane proteins in tumor cells is one of the key steps in the development of cancer drugs. The receptor tyrosine kinase-like orphan receptor (ROR) type 1 is a type-I transmembrane protein expressed in various cancer tissues, which is in contrast to its limited expression in normal tissues. These characteristics make ROR1 a candidate target for cancer treatment. This study aimed to identify the prognostic value of ROR1 expression in cancers. Materials and Methods: We conducted a comprehensive systematic search of electronic databases (PubMed) from their inception to September 2021. The included studies assessed the effect of ROR1 on overall survival (OS) and progression-free survival (PFS). Hazard ratios (HR) from collected data were pooled in a meta-analysis using Revman version 5.4 with generic inverse-variance and random effects modeling. Results: A total of fourteen studies were included in the final analysis. ROR1 was associated with worse OS (HR 1.95, 95% confidence interval (CI) 1.50–2.54; p < 0.001) with heterogeneity. The association between poor OS and ROR1 expression was high in endometrial cancer, followed by ovarian cancer, and diffuse large B cell lymphoma. In addition, ROR1 was associated with poor PFS (HR 1.84, 95% CI 1.60–2.10; p < 0.001), but heterogeneity was not statistically significant. In subgroup analysis, high ROR1 expression showed a significantly higher rate of advanced stage or lymph node metastasis. Conclusions: This meta-analysis provides evidence that ROR1 expression is associated with adverse outcome in cancer survival. This result highlights ROR1 as a target for developmental therapeutics in cancers.

Background Ureteral reconstruction is required after surgical resection of the tumor invading the urinary tract in ovarian cancer with low incidence. There are no currently reported surgical outcomes of ureteral reconstruction during cytoreductive surgery. The aim of the study is to investigate the clinical features and surgical outcomes of ureteral reconstruction during primary, interval and secondary cytoreductive surgery for ovarian cancer. Methods A total of 3226 patients who underwent primary, interval or secondary cytoreductive surgery for ovarian cancer between January 2000 and May 2021 were reviewed. Fifty-six patients who underwent ureteral reconstruction during cytoreductive surgery were included in the analysis. Results Ureteral reconstruction was required in 1.7% (56/3226) of ovarian cancer patients. Of the 56 patients who underwent ureteral reconstruction during cytoreductive surgery, 35 (62.5%) had primary ovarian cancer, and 21 (37.5%) had recurrent ovarian cancer. The median tumor size invading the lower urinary tract was 2.0 cm (range, 0.4–9.5 cm). Ureteroneocystostomy with direct implantation (51.8%) and psoas hitch (8.9%), transureteroureterostomy (7.1%), and ureteroureterostomy (32.1%) were required as part of cytoreductive surgery. Complete cytoreduction with ureteral reconstruction was achieved in 83.9% (47/56) and the rest of the patient population (16.1%) achieved a gross residual tumor size of less than 1 cm. All complications, including hydronephrosis (33.9%), were managed, none resulting in long-term sequelae. In primary ovarian cancer, the 5-year disease-free survival and overall survival were 50.0% and 89.5%, respectively. In patients with recurrent ovarian cancer, the 5-year disease-free survival and overall survival were 23.6% and 64.0%, respectively. Conclusions Ureteral reconstruction as a part of cytoreductive surgery for ovarian cancer could be performed with acceptable morbidities. Complete cytoreduction by a multidisciplinary surgical team, including urologic oncologists, should be pursued for the surgical management of ovarian cancer. Trial registration Retrospectively registered.

Globally, the incidence of gastric cancer is lower in women than in men. It is thought that menstrual and reproductive factors may be related to their lower incidence of gastric cancer. This cross-sectional study examined menstrual, reproductive, and other factors in 20,784 postmenopausal women from the 2007–2020 Korea National Health and Nutrition Examination Survey (KNHANES). A univariate logistic regression analysis was performed, and then a multivariate logistic regression analysis for significant factors in the univariate analysis was conducted. In the multivariate logistic regression analysis, the age at menarche (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.00−1.06, p = 0.035) and myocardial infarction (OR 2.43, 95% CI 1.05−5.62, p = 0.026) showed a significant association with increased incidence of gastric cancer. The age at menopause (OR 0.97, 95% CI 0.95−1.00, p = 0.03), the age at the first childbirth (OR 0.93, CI 0.89−0.97, p = 0.007), and the experience of alcohol consumption (OR 0.68, 95% CI 0.5–0.91, p = 0.003) showed a significant association with a decreased incidence of gastric cancer. Late menarche, early menopause, early aged first childbirth, and myocardial infarction are estimated to be risk factors for gastric cancer in postmenopausal Korean women.

Context The upregulation of TRIB3 (Tribbles homolog 3), a stress-inducible gene encoding a pseudokinase, has been implicated in the development of insulin resistance in the skeletal muscle and liver of patients with obesity and type 2 diabetes. However, there is little information regarding TRIB3 expression in human adipose tissue. Objective To investigate whether TRIB3 expression is dysregulated in human adipose tissue in the context of obesity and type 2 diabetes and whether TRIB3 expression in adipose tissues is associated with insulin resistance. Methods We measured metabolic parameters and TRIB3 expression in abdominal subcutaneous and visceral adipose tissue in obese (with or without type 2 diabetes) and normal-weight women. Regulation of TRIB3 expression was studied in human adipocytes. Results TRIB3 expression in both fat depots was higher in patients with obesity and/or type 2 diabetes; in addition, the expression level was significantly associated with insulin resistance. Incubating adipocytes under conditions mimicking the microenvironment of obese adipose tissue, including increased endoplasmic reticulum (ER) stress, induced TRIB3 expression. In human adipocytes, the overexpression of TRIB3 impaired insulin-stimulated protein kinase B (AKT) phosphorylation and caused dysregulation of the transcription of genes encoding bioactive molecules released from adipocytes, such as proinflammatory cytokines, adiponectin, and leptin. Pioglitazone, an insulin-sensitizing agent, reduced both these effects of TRIB3 and the ER stressor–induced expression of TRB3. Conclusion Our data indicate that TRIB3 expression in adipose tissue is enhanced in patients with obesity and suggest that increased TRIB3 dysregulates adipocyte function, which may contribute to the development of insulin resistance.

This study was performed to investigate the prevalence, clinical characteristics, and treatment response according to BRCA1 and BRCA2 (BRCA) mutations in Korean patients with epithelial ovarian cancer (EOC). Two‐hundred and ninety‐eight Korean women diagnosed with high‐grade serous and/or endometrioid EOC from 2010 to 2015 were tested for germline and 86 specimens for somatic BRCA mutations, regardless of the family history. Clinical characteristics including survival outcomes were compared in patients with and without BRCA mutations (NCT02963688). A total of 43 different germline BRCA mutations were identified in 78 patients among 298 patients (26.2%). Somatic BRCA mutations were identified in 11 (12.8%) patients among patients without germline BRCA mutations. Haplotype analysis demonstrated no founder mutations in our Korean patient cohort. Insignificant differences in age at diagnosis, primary site, and residual disease after surgery were observed between patients with and without BRCA mutations. In multivariate analysis for overall survival (OS), the presence of BRCA mutation was significantly associated with OS (P = .049) in addition to platinum sensitivity (P, A total of 43 different germline BRCA mutations were identified in 78 patients among 298 patients (26.2%). Somatic BRCA mutations were identified in 11 (12.8%) patients among patients without germline BRCA mutations. BRCA mutation is an independent prognostic factor for survival regardless of platinum sensitivity to first‐line chemotherapy. A higher response rate to subsequent chemotherapy after recurrence was observed in patients with BRCA mutation, resulting in better overall survival in these patients.

Malignant ovarian germ cell tumor (MOGCT) is a rare ovarian malignancy accounting for less than 5% of all ovarian cancers. We aimed to evaluate the incidence, survival, and subsequent malignancies after the diagnosis of MOGCT.Data from the Korea Central Cancer Registry were used to identify MOGCTs between 1999 and 2017. The age-standardized rates (ASRs), 5-year relative survival rates (RSR) and standardized incidence ratio (SIR) for subsequent cancer after diagnosis of MOGCT were estimated.Of 2125 cases of newly diagnosed MOGCTs, 596 (28.0%) were diagnosed with dysgerminoma and 1529 (72.0%) with non-dysgerminoma. The ASR per 100,000 women-years was 0.539; ASR slightly increased over the study period (annual percent change [APC] = 1.01%; p = 0.02). There was an increase and decrease in the incidence of MOGCTs in the age groups 0-19 years (APC = 1.96%; p0.01) and ≥ 50 years (APC = -6.51%; p0.01), respectively. Patients with dysgerminoma showed significantly higher RSR than patients with non-dysgerminoma (98.0% vs. 94.9%, p0.01). Patients aged ≥50 years showed worst 5-year RSR (68.7%) than patients aged 0-19 years (97.8%) and 20-34 years (96.4%) (p0.01). The overall SIR for a subsequent cancer occurrence was 2.07, with the most frequent site of subsequent primary cancer being the thyroid (SIR = 2.78).Our data demonstrated an excellent prognosis of MOGCTs among Korean women. There was a slight increase in MOGCT prevalence, which was more pronounced among those aged19 years. After MOGCT diagnosis, the risk of developing a subsequent malignancy was doubled compared with the general population.

Background Hair cortisol concentration (HCC) has received attention as a useful marker of stress, but evidence on associations between psychological factors and cortisol concentration is inconsistent. The purpose of this study was to investigate the sex differences in the relationship between cortisol concentration and psychological factors in healthy young adults. Methods A total of 205 (103 females, 102 males) healthy young adults participated. HCC and various stress-related psychological measures were compared between sexes. Multiple linear regression analyses were performed to assess associations between HCC and stress-related psychological measures for all participants and for each sex. Results The difference in HCC according to sex was not significant. The reported number of stressful life events in the past year, stress perception, depressive and anxiety-related symptoms, and emotion dysregulation were not different between sexes, either. The association between HCC and emotion dysregulation was significant in females but not males. Conclusion We observed a sex-specific association between HCC and psychological factors. Our findings may imply that HCC could be a useful biomarker of stress and stress-related emotion dysregulation in healthy young women., Highlights Associations between hair cortisol level and psychological factors have been inconclusive.In healthy young adults, the hair cortisol concentration was not significantly different between sexes.The association between emotion dysregulation and hair cortisol was only found in women, but not in men.The role of sex should be considered in utilizing hair cortisol as a biomarker for psychological stress response.

Background: The prevalence of delirium and its association with long-term outcomes of extracorporeal membrane oxygenation (ECMO) therapy have not yet been identified. We aimed to investigate the prevalence of delirium and its associated factors during hospitalization among ECMO survivors. We also examined whether the occurrence of delirium was associated with 1-year all-cause mortality among ECMO survivors. Methods: As a population-based cohort study, data were obtained from the National Health Insurance Service database in South Korea. Adults older than 18 years who received ECMO therapy between 2005 and 2018 were included in this study. ECMO survivors were defined as patients who were discharged from the hospital. Results: The analysis included a total of 8153 ECMO survivors, of whom 551 (6.8%) experienced delirium during hospitalization. Older age (odds ratio [OR]: 1.01, 95% confidence interval [CI]: 1.00-1.02; P = 0.004), male sex (OR: 1.38, 95% CI: 1.13-1.68; P = 0.002), underlying depression (OR: 1.90, 95% CI: 1.49-2.41; P

BACKGROUND/AIM Niraparib is effective against epithelial ovarian cancer (EOC), but with adverse effects. In this study, we retrospectively investigated niraparib maintenance treatment feasibility in Korean patients newly diagnosed with EOC. PATIENTS AND METHODS The medical records of 35 patients were reviewed. Data on the baseline clinical characteristics were collected, and adverse effects were described. RESULTS Sixteen patients underwent treatment suspension or dose reduction. There was no significant difference in adverse effects (A/E) due to the interval between adjuvant chemotherapy conclusion and niraparib initiation. The two groups had similar International Federation of Gynaecology and Obstetrics (FIGO) stages. The number of patients with a history of bevacizumab use was higher in the dose modification group than in the standard dose group. CONCLUSION Niraparib use must be considered in those previously treated with bevacizumab. There is a need for prospective research on lower dose (

Background The prevalence of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) in the community has increased worldwide due to multifactorial reasons. ESBL-EC bloodstream infection (BSI) complicates the decision for proper antimicrobial administration. In this multicenter study, we investigated the prevalence, risk factors, and molecular background of community-onset (CO) ESBL-EC BSI. Methods We included data for all episodes of ESBL-EC BSI of community origin from May 2016 to April 2017 obtained from the Korean national antimicrobial resistance surveillance system, which comprises six sentinel hospitals. Data, including previous history of admission and use of antimicrobials and medical devices before BSI, were collected, along with microbiological analysis results. Results Among 1,189 patients with CO BSI caused by E. coli, 316 (27%) were identified as ESBL producers. History of admission, especially to a long-term care hospital (LTCH), and previous use of β-lactams/β-lactamase inhibitors, carbapenem, lincosamide, aminoglycoside, and extended-spectrum cephalosporin were independent risk factors for CO ESBL-EC BSI; admission to an LTCH showed the highest odds ratio (3.8, 95% confidence interval 2.3-6.1). The most common genotype was CTX-M-15 (N=131, 41%), followed by CTX-M-14 (N=86, 27%). ST131 was the most common sequence type among ESBL-EC groups (57%). Conclusions In Korea, 27% of CO E. coli BSI were caused by ESBL producers. From perspectives of empirical treatment and infection control, history of admission to an LTCH and antimicrobial use should be noted.

INTRODUCTION Hypertension is common and has a significant effect on cardiovascular morbidity and death. However, despite the development of several guidelines to manage SBP, there is little research or guidance on the evaluation and management of DBP or isolated diastolic hypertension (IDH). METHOD To determine the association of DBP with all-cause and cardiovascular mortality, we used NHANES data from 1999 to 2014 and included adults aged at least 18 years. The relationship between DBP, IDH and all-cause, cardiovascular mortality was evaluated. RESULTS Of the 35 109 participants, all-cause death occurred in 10.6%, and cardiovascular death occurred in 2.1% over a median follow-up of 7.2 years. Multivariate Cox regression analysis revealed that the risk of all-cause mortality was significantly higher in the lowest (≤56.9 mmHg) DBP groups than in the reference group (DBP 74-76.9 mmHg). However, the risk of cardiovascular mortality was significantly higher in the lowest and highest (≥83 mmHg) DBP group than in the reference group. The risk of all-cause mortality was higher for most groups with SBP at least 140 mmHg than for the reference group with DBP 74-76.9 mmHg and SBP 100-139.9 mmHg. Both the 2018 ESC/NICE and the 2017 AHA/ACC-defined IDH was not significantly associated with all-cause mortality. CONCLUSION DBP and all-cause mortality had an inverse relationship, whereas DBP and cardiovascular mortality had a U-shaped relationship, with the DBP reference group having the lowest risk for all-cause and cardiovascular mortality. There was no significant relationship between IDH and death.

Data on the longevity of humoral and cell-mediated immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19) are limited. We evaluated the detailed kinetics of antibody and T-cell responses at the acute, convalescent, and post-convalescent phases in COVID-19 patients with a wide range of severity. We enrolled patients with COVID-19 prospectively from four hospitals and one community treatment center between February 2020 and January 2021. symptom severity was classified as mild, moderate, or severe/critical. Patient blood samples were collected at 1 week (acute), 1 month (convalescent), and 2 months after symptom onset (post-convalescent). Human SARS-CoV-2 IgG and IgM antibodies were measured using in-house-developed ELISA. The SARS-CoV-2-specific T-cell responses against overlapping peptides of spike proteins and nucleoprotein were measured by interferon-γ enzyme-linked immunospot assays. Twenty-five COVID-19 patients were analyzed (mild, n = 5; moderate, n = 9; severe/critical, n = 11). IgM and IgG antibody responses peaked at 1 month after symptom onset and decreased at 2 months. IgG response levels were significantly greater in the severe/critical group compared with other groups. Interferon-γ-producing T-cell responses increased between 1 week and 1 month after symptom onset, and had a trend toward decreasing at 2 months, but did not show significant differences according to severity. Our data indicate that SARS-CoV-2-specific antibody responses were greater in those with severe symptoms and waned after reaching a peak around 1 month after symptom onset. However, SARS-CoV-2-specific T-cell responses were not significantly different according to symptom severity, and decreased slowly during the post-convalescent phase.

Objective This study investigated site-specific differences in clinical factors for recurrence in patients who were newly diagnosed and treated for endometrial cancer. A model for predicting recurrence sites was generated. Methods Electronic medical records’ data were retrieved from January 2006 to December 2018 for patients who were diagnosed with endometrial cancer at the National cancer center in Korea. Recurrence sites were classified as local, regional, or distant. We used multinomial logistic regression models that modeled the log-odds for the three recurrence sites relative to non-recurrence as a linear combination of possible risk factors for the recurrence of endometrial cancer. Results The data of 611 patients were selected for analysis; there were 20, 12, and 25 cases of local, regional, and distant recurrence, respectively, and 554 patients had no recurrence. High-grade disease was associated with local recurrence; non-endometrioid histology and parametrial invasion were risk factors for regional recurrence; additionally, parametrial invasion and no lymphadenectomy were associated with distant metastasis. Conclusion We identified different risk factors specific for each type of recurrence site. Using these risk factors, we suggest that individually tailored adjuvant treatments be introduced for patients.

BACKGROUND Currently, it is necessary to investigate how to combine biparametric magnetic resonance imaging (bpMRI) with various clinical parameters for the detection of clinically significant prostate cancer (csPCa). PURPOSE To develop a multivariate prebiopsy nomogram using clinical and bpMRI parameters for estimating the probability of csPCa. STUDY TYPE Retrospective, single-center study. SUBJECTS Two hundred and twenty-six patients who underwent targeted biopsy (TBx) for the MRI-suspected index lesion because of clinical suspicions of PCa. FIELD STRENGTH/SEQUENCE A 3 T MRI including turbo spin-echo T2 -weighted and diffusion-weighted single-shot echo-planar imaging sequences. ASSESSMENT Prebiopsy clinical and bpMRI parameters were patient age, biopsy history (biopsy-naive or repeated biopsy status), prostate-specific antigen density (PSAD), Prostate Imaging-Reporting and Data System version 2.1 (PI-RADSv2.1), and apparent diffusion coefficient ratio (ADCR). ADCR was defined as mean ADC of the index lesion divided by mean ADC of the contralateral prostatic region. A multivariate prebiopsy nomogram for csPCa (i.e. Gleason sum ≥7) was developed. Area under the curve (AUC) of each parameter and prebiopsy nomogram was assessed. Five-fold cross-validation was performed for robust estimation of performance of the prebiopsy nomogram. STATISTICAL TESTS Logistic regression, receiver-operating curve, and 5-fold cross-validation. P-value

Purpose This study aimed to determine the proportion of gastric cancer attributable to Helicobactor pylori in the Korean population. Infection with H. pylori has been recognized as the most significant risk factor for gastric cancer. In Korea, gastric cancer is the most common cancer that accounted for 13.3% of all cancers in 2016. In particular, men are most commonly diagnosed with gastric cancer; the age-standardized incidence rate in men is 49.6 per 100,000, which is more than twice the incidence in women.Materials and Methods The population attributable fraction (PAF) was calculated as a function of the relative risk (RR) of gastric cancer associated with H. pylori infections. To estimate PAF of gastric cancer due to H. pylori, the prevalence of H. pylori infections was extrapolated for the year of 1990 and a pooled RR was obtained by conducting a meta-analysis of studies recently published in Korea.Results The estimated prevalence of H. pylori was 76.4% in men and 71.9% in women. The RRs (95% confidence interval) pooled from case-control studies using a random effects model was 1.69 (1.29-2.22) for overall gastric cancer and 2.17 (1.04-4.55) for non-cardia gastric cancer. Using the RR for overall gastric cancer, the estimated PAFs due to H. pylori were 34.5% in men and 33.2% in women.Conclusion The occurrence of gastric cancer in Koreans may be affected by other risk factors in addition to H. pylori infection, which may contribute to increasing baseline risk for gastric cancer.

To the best of our knowledge there have been no randomized controlled trials comparing lobectomy—a standard treatment for patients with early-stage non-small cell lung cancer (NSCLC)—and particle beam therapy (PBT), the best performing existing radiotherapy. We conducted a virtual randomized trial in medically operable patients with stage IA NSCLC to compare lobectomy and PBT effectiveness. A Markov model was developed to predict life expectancy after lobectomy and PBT in a cohort of patients with stage IA NSCLC. Ten thousand virtual patients were randomly assigned to each group. Sensitivity analyses were performed as model variables and scenarios changed to determine which treatment strategy was best for improving life expectancy. All estimated model parameters were determined using variables extracted from a systematic literature review of previously published articles. The preferred strategy differed depending on patient age. In young patients, lobectomy showed better life expectancy than that of PBT. The difference in life expectancy between lobectomy and PBT was statistically insignificant in older patients. Our model predicted lobectomy as the preferred strategy when operative mortality was under 5%. However, the preferred strategy changed to PBT if operative mortality post lobectomy was over 5%. For medically operable patients with stage IA NSCLC, our Markov model revealed the preferred strategy of lobectomy or PBT regarding operative mortality changed with varying age and comorbidity. Until randomized controlled trial results become available, we hope the current results will provide a rationale background for clinicians to decide treatment modalities for patients with stage IA NSCLC.

This study aimed to analyze the diagnostic yield of modified transrectal ultrasound (TRUS)-guided 12-core combined biopsy (CB) using prebiopsy magnetic resonance imaging (MRI) for detecting clinically significant prostate cancer (csPCa). This retrospective study included 130 consecutive patients who underwent modified TRUS-guided 12-core CB using cognitive fusion for lesions of Prostate Imaging-Reporting and Data System (PI-RADS) category ≥ 3. The 12-core CB comprised 3–6-core targeted biopsy (TB) and systematic biopsy (SB). For SB, tissue sampling in TB regions was omitted, and 3-core sampling (i.e., apex, mid, and base) in the contralateral peripheral zone of TB was mandatory. csPCa was defined as International Society of Urological Pathology (ISUP) grade ≥ 2 cancer. The per-patient cancer detection rates (CDRs) according to biopsy type or PI-RADS category were investigated. The CDRs of TB, SB, and CB for csPCa were 47.7% (62/130 patients), 29.2% (38/130), and 52.3% (68/130), respectively. For csPCa, the CDRs of TB and CB according to PI-RADS categories of 3, 4, or 5 were 25.0% (8/32) and 31.3% (10/32), 41.2% (28/68) and 45.6% (31/68), or 86.7% (26/30) and 90.0% (27/30), respectively. In 6 (4.6%) patients, csPCa was detected only by SB. In 18 (13.8%) patients, SB detected PCa of a higher ISUP grade than TB. In 11 (8.5%) patients, SB detected csPCa at contralateral peripheral zone of TB. Modified TRUS-guided 12-core CB using prebiopsy MRI seems to be feasible. It may reduce total biopsy cores in patients who are suitable for CB based on prebiopsy MRI findings.

Background/aimsTo evaluate subtypes and characteristics of dry eye (DE) using conventional tests and dynamic tear interferometry, and to investigate determinants of disease severity in each DE subtype.Methods309 patients diagnosed with DE and 69 healthy controls were prospectively enrolled. All eyes were evaluated using Ocular Surface Disease Index (OSDI), Schirmer’s test I (ST1) and Meibomian gland dysfunction (MGD) grade were analysed. The tear interferometric pattern and lipid layer thickness were determined using DR-1α and LipiView II, respectively.ResultsDynamic interferometric analysis revealed 56.6% of patients with DE exhibited Jupiter patterns, indicative of aqueous-deficiency, while 43.4% exhibited crystal patterns, indicative of lipid deficiency. These findings were in accordance with classification based on ST1 scores and MGD grade. Conventional assessment indicated 286 patients exhibited evidence of evaporative DE (EDE) due to MGD, while only 11 exhibited signs of pure aqueous-deficient DE (pure ADDE, only ST1 ≤5 mm). Interestingly, of 286 patients with EDE, 144 were categorised into the mixed-ADDE/EDE group, in which ST1 was identified as a strong negative determinant of OSDI. In contrast, 72.2% of patients with mixed-ADDE/EDE exhibited Jupiter patterns (Jupiter mixed), while 27.8% exhibited crystal patterns (crystal mixed). OSDI values were significantly higher in the crystal-mixed group than in the Jupiter mixed, in which OSDI scores were independently associated with ST1 values only.ConclusionsOur findings indicate that majority of EDE patients also exhibit aqueous deficiency, which can aggravate symptoms even in patients with lipid-deficient mixed-ADDE/EDE. Conventional assessments should be combined with interferometric tear analysis to determine the most appropriate treatment for each DE patient.

Background Recently, pulsed dye laser (PDL) combined with triamcinolone intralesional injection (TAILI) has been introduced for surgical scar prevention. However, little is known about this procedure's effectiveness in preventing hypertrophic scar following surgical scar removal. Objectives This study aimed to evaluate the outcome of early intervention using PDL combined with TAILI after surgical removal of hypertrophic cesarean section (CS) scars. Methods The medical records of 35 patients who underwent early intervention using PDL and TAILI after removal of hypertrophic CS scars were retrospectively reviewed. The scars' average Vancouver Scar Scale (VSS) scores before scar removal and three months after the final treatment were compared. Results The patients received 4.23 treatments on average and were followed up for a mean period of 7.74 months. The mean final VSS was 3.11 ± 1.52 and was significantly lower than that of the previous VSS (9.29 ± 1.74, P = 0.000). VSS of the previous CS scar, and the presence or absence of keloid formation in other areas, were associated with treatment outcome (P = 0.003 and 0.008, respectively). Conclusions Early intervention using PDL combined with TAILI could prevent the recurrence or progression of hypertrophic CS scarring after surgical scar removal.

Objective Healthcare personnel vaccinations are important to prevent vaccine-preventable diseases in hospitals. We evaluated the seroprevalence, vaccination rates, and barriers to vaccination among newly employed nurses and doctors. Methods A cross-sectional study was conducted at a university hospital in the Republic of Korea from 2017 to 2020. The immune status for hepatitis B virus (HBV), varicella zoster virus (VZV), and hepatitis A virus (HAV) was tested. HBV, VZV, measles, mumps, and rubella (MMR) vaccinations were mandatory. HAV and tetanus-diphtheria-pertussis (Tdap) vaccinations were also recommended by specialists. A web-based survey on factors affecting vaccination completion was conducted. Results For the 668 participants, the mean age was 26 ± 2 (±SD) years. Seroprevalence was 86% for HBV, 93% for VZV, and 59% for HAV. Vaccine completion rates were 40% for HBV, 70% for VZV, 65% for MMR, 42% for HAV, and 70% for Tdap. Overall compliance for mandatory vaccines was 54%. A total of 402 subjects who had worked for over one year were surveyed, with a 22% response rate. More than 50% of respondents gave the following reasons for not receiving recommend vaccines: 1) they were busy (77%), 2) vaccination process was complicated (68%), and 3) they simply forgot about vaccination (55%). Healthcare personnel agreed to be frequently informed of immunization requirements and for monitoring of vaccination rates. Conclusion Vaccination compliance among newly employed doctors and nurses was 54%. Active interventions such as simplifying the vaccination process and frequent notifications are needed to achieve optimal immunization rates.

Suicide is an important public health issue during the current pandemic of emerging infectious diseases (EIDs). In EIDs, various symptoms persist even after recovery, and chronic fatigue is among those that are commonly reported. The aim of this study was to examine the effects of chronic fatigue syndrome on suicidality during the recovery phase among survivors of Middle East respiratory syndrome (MERS). MERS survivors were recruited from five centers and prospectively followed up for 2 years. In total, 63 participants were registered at 12 months (T1), of whom 53 and 50 completed the assessments at 18 months (T2) and 24 months (T3), respectively. Suicidality and chronic fatigue were evaluated using the suicidality module of the Mini-International Neuropsychiatric Interview (MINI) and the Fatigue Severity Scale (FSS), respectively. We analyzed the relationship between chronic fatigue and suicidality during the follow-up period using the generalized estimating equation (GEE). The suicidality rates were 22.2% (n = 14), 15.1% (n = 8), and 10.0% (n = 5) at T1–T3, respectively. Of the 63 participants, 29 had chronic fatigue syndrome at T1. The group that reported chronic fatigue syndrome at T1 was more likely to experience suicidality during the 2-year follow-up than the group that reported otherwise (RR: 7.5, 95% CI: 2.4–23.1). This association was present even after adjusting for potential confounders (RR: 7.6, 95% CI: 2.2–26.0). Chronic fatigue syndrome and suicide risk among emerging infectious disease (EID) survivors should be acknowledged, and effective interventions must be developed.

Background Researchers have yet to investigate the specific association between 10-μm particulate matter (PM10) levels and the risk of graft failure, kidney disease, or the functional decline of transplanted kidneys, in kidney transplant recipients (KTRs). Furthermore, we know very little about the association between PM10 levels and the development of allograft rejection in transplanted kidneys. Identification of air pollution as a potential contributor to kidney disease could help reduce future disease burden, stimulate policy discussions on the importance of reducing air pollution with respect to health and disease, and increase public awareness of the hazards of air pollution. We aimed to evaluate the relationship of PM10 with the risk of graft failure, mortality, and decline of graft function in KTRs. Methods Air pollutant data were obtained from the Korean National Institute of Environmental Research. We then investigated potential associations between these data and the clinical outcomes of 1532 KTRs who underwent kidney transplantation in a tertiary hospital between 2001 and 2015. Survival models were used to evaluate the association between PM10 concentrations and the risk of death-censored graft failure (DCGF), all-cause mortality, and biopsy-proven rejection (BPR), over a median follow-up period of 6.31 years. Results The annual mean PM10 exposure after kidney transplantation was 27.1 ± 8.0 μg/m3. Based on 1-year baseline exposure, 1 μg/m3 increase in PM10 concentration was associated with an increased risk of DCGF (hazard ratio (HR): 1.049; 95% confidence interval (CI): 1.014–1.084) and BPR (HR: 1.053; 95% CI: 1.042–1.063). Fully adjusted models showed that all-cause mortality was significantly associated with 1-year average PM10 concentrations (HR, 1.09; 95% CI, 1.043 to 1.140). Conclusions Long-term PM10 exposure is significantly associated with BPR, DCGF, and all-cause mortality in KTRs.

Radiofrequency ablation is an established treatment for atrial fibrillation (AF). However, coronary artery spasm (CAS) is a rare but a potentially lethal complication associated with this procedure. A 54-year-old man with paroxysmal AF underwent pulmonary vein isolation. The procedure was completed and AF could not be induced after burst pacing and the administration of isoproterenol. Suddenly, ST-segment elevation developed in the anterior leads and frequent premature ventricular contractions followed by non-sustained ventricular fibrillation. The diagnosis of CAS was made by urgent coronary angiography. We identified isoproterenol as a potential cause of CAS. Physicians should be aware of this potentially lethal side effect.

Purpose We aimed to investigate the risk factors and patterns of locoregional recurrence (LRR) after radical nephrectomy (RN) in patients with locally advanced renal cell carcinoma (RCC).Materials and Methods We retrospectively analyzed 245 patients who underwent RN for non-metastatic pT3-4 RCC from January 2006 to January 2016. We analyzed the risk factors associated with poor locoregional control using Cox regression. Anatomical mapping was performed on reference computed tomography scans showing intact kidneys.Results The median follow-up duration was 56 months (range, 1 to 128 months). Tumor extension to renal vessels or the inferior vena cava (IVC) and Fuhrman’s nuclear grade IV were identified as independent risk factors of LRR. The 5-year actuarial LRR rates in groups with no risk factor, one risk factor, and two risk factors were 2.3%, 19.8%, and 30.8%, respectively (p < 0.001). The locations of LRR were distributed as follows: aortocaval area (n=2), paraaortic area (n=4), retrocaval area (n=5), and tumor bed (n=11). No LRR was observed above the celiac axis (CA) or under the inferior mesenteric artery (IMA).Conclusion Tumor extension to renal vessels or the IVC and Fuhrman’s nuclear grade IV were the independent risk factors associated with LRR after RN for pT3-4 RCC. The locations of LRR after RN for RCC were distributed in the tumor bed and regional lymphatic area from the bifurcation of the CA to that of the IMA.

We compared the mean interleukin-6 (IL-6) level in the amniotic fluid after rupture of membranes during labour at term pregnancy according to the delivery methods through prospective cohort study. Cases with premature rupture of membranes, multifetal pregnancy, and major congenital anomalies were excluded. Amniotic fluid was obtained from vaginal canal immediately after spontaneous rupture of membranes. A total of 47 cases were analysed, and 72.3% (34/47) had successful vaginal delivery. The mean concentration of IL-6 in the amniotic fluid was significantly higher in the vaginal delivery group than in the caesarean section group (5,229 pg/mL vs. 1,702 pg/mL

Antibody-based therapeutics targeting the inhibitory receptors PD-1, PD-L1, or CTLA-4 have shown remarkable clinical progress on several cancers. However, most patients do not benefit from these therapies. Thus, many efforts are being made to identify new immune checkpoint receptor-ligand pathways that are alternative targets for cancer immunotherapies. Nectin and nectin-like molecules are widely expressed on several types of tumor cells and play regulatory roles in T- and NK-cell functions. TIGIT, CD226, CD96 and CD112R on lymphoid cells are a group of immunoglobulin superfamily receptors that interact with Nectin and nectin-like molecules with different affinities. These receptors transmit activating or inhibitory signals upon binding their cognate ligands to the immune cells. The integrated signals formed by their complex interactions contribute to regulating immune-cell functions. Several clinical trials are currently evaluating the efficacy of anti-TIGIT and anti-CD112R blockades for treating patients with solid tumors. However, many questions still need to be answered in order to fully understand the dynamics and functions of these receptor networks. This review addresses the rationale behind targeting TIGIT, CD226, CD96, and CD112R to regulate T- and NK-cell functions and discusses their potential application in cancer immunotherapy. [BMB Reports 2021; 54(1): 2-11].

To investigate usefulness of biphasic computed tomography (CT) in characterizing hyperattenuating adrenal lesions in lung cancer. This retrospective study included 239 patients with lung cancer who underwent adrenal CT for hyperattenuating (> 10 Hounsfield unit) adrenal lesions. Adrenal CT comprised unenhanced and 1-min and 15-min enhanced images. We dichotomized adrenal lesions depending on benign or metastatic lesions. Reference standard for benignity was histologic confirmation or ≥ 6-month stability on follow-up CT. Two independent readers analyzed absolute (APW) or relative percentage wash-out (RPW) using triphasic CT, and enhancement ratio (ER) or percentage wash-in (PWI) using biphasic CT (i.e., unenhanced and 1-min enhanced CT). Criteria for benignity were as follows: criteria 1, (a) APW ≥ 60% or (b) RPW ≥ 40%, and criteria 2, (a) ER > 3 and (b) PWI > 200%. We analyzed area under the curve (AUC) and accuracy for benignity, and inter-reader agreement. Proportion of benign adrenal lesion was 71.1% (170/239). For criteria 1 and 2, AUCs were 0.872 (95% confidence interval [CI], 0.822–0.911) and 0.886 (95% CI, 0.838–0.923), respectively, for reader 1 (p = 0.566) and 0.816 (95% CI, 0.761–0.863) and 0.814 (95% CI, 0.759–0.862), respectively, for reader 2 (p = 0.955), and accuracies were 87.9% (210/239) and 86.2% (206/239), respectively, for reader 1 (p = 0.479) and 81.2% (194/239) and 80.3% (192/239), respectively, for reader 2 (p = 0.763). Weighted kappa was 0.725 (95% CI, 0.634–0.816) for criteria 1 and 0.736 (95% CI, 0.649–0.824) for criteria 2. Biphasic CT can reliably characterize hyperattenuating adrenal lesions in patients with lung cancer. • Criteria from biphasic computed tomography (CT) for diagnosing benign adrenal lesions were enhancement ratio of > 3 and percentage wash-in of > 200%. • In the analysis by two independent readers, area under the curve between criteria 1 and 2 was not significantly different (0.872 and 0.886 for reader 1; 0.816 and 0.814, for reader 2; p > 0.05 for each comparison). • Wash-in characteristics from biphasic CT are helpful to predict benign adrenal lesions in lung cancer.