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Periodontitis and osteoarthritis are major public health concerns that result in decreased quality of life among middle-aged and older adults. We sought to examine whether the severity of periodontitis is related to osteoarthritis according to the presence of type 2 diabetes mellitus.This study included 3,527 participants age ≥50 years from the Korean National Health and Nutrition Examination Survey. Periodontitis was assessed using the Community Periodontal Index; severe periodontitis was defined as periodontal tissue forming deep periodontal pockets ≥6-mm depth. Osteoarthritis was defined as Kellgren/Lawrence grade ≥2 on radiographic images of the knee or hip area with joint pain. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for osteoarthritis according to the severity of periodontitis, stratified by type 2 diabetes mellitus, were calculated using multiple logistic regression analyses.Participants with type 2 diabetes mellitus were more likely to have osteoarthritis as the severity of periodontitis increased (nonsevere periodontitis OR 1.23 [95% CI 0.67-2.32]; severe periodontitis OR 3.01 [95% CI 1.51-5.84]) after adjusting for age, sex, body mass index, smoking status, alcohol consumption, regular exercise, education level, household income, hypertension, and frequent tooth-brushing. However, this positive association was not found in individuals without type 2 diabetes mellitus after adjusting for the same covariables.Severe periodontitis was positively and significantly associated with osteoarthritis in middle-aged and older individuals with type 2 diabetes mellitus. Our findings suggest that the oral inflammation manifesting in periodontitis may be at least partly involved in the pathogenesis of osteoarthritis, particularly in patients with type 2 diabetes mellitus.

Prenatal exposure to valproic acid (VPA) has been implicated in the manifestation of autism spectrum disorder (ASD)-like behavioral and functional changes both in human and rodents including mice and rats. The objective of this study was to determine metabolomics profiling and biomarkers related to VPA-induced symptoms resembling ASD using proton nuclear magnetic resonance (1H-NMR) spectral data. VPA was administered to pregnant rats at gestation day 12.5 and effects measured subsequently in male 4-week-old offspring pups. The sociability of VPA-treated animals was significantly diminished and exhibited ASD-like behavior as evidenced by reduction of social adaptation disorder and lack of social interactions. To find biomarkers related to ASD, the following were collected prefrontal brain cortices, urine bladder and blood samples directly from heart puncture. In all samples, principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) displayed significant clustering pattern differences between control and treated groups. Valine, taurine, myo-inositol, 3-hydroxybutyrate and 1,3-dihydroxyacetone were significantly decreased in brain cortices in treated rats. Serum metabolites of glucose, creatine phosphate, lactate, glutamine and threonine were significantly increased in VPA-administered animals. Urinary metabolites of pimelate, 3-hydroxyisovalerate and valerate were significantly reduced in VPA-treated rat, whereas galactose and galactonate levels were elevated. Various metabolites were associated with mitochondrial dysfunction metabolism and central nervous system disorders. Data demonstrated that VPA-induced alterations in endogenous metabolites of serum, urine, and brain cortex which might prove useful as biomarkers for symptoms resembling ASD as a model of this disorder.

Introduction. The Sasang type-specific pathophysiological symptom is pivotal for the Sasang type classification and pattern identification. The Sasang Urination and Defecation Inventory (SUDI) for urinary function analysis was developed; however, the clinical usefulness of urination-related subscales of SUDI in the Sasang type and Cold-Heat subgroup was not reported with acceptable validation analysis. Methods. The clinical diagnosis of the Sasang type and Cold-Heat subgroup, responses to SUDI items, and weight and height of the 350 hospital patients were acquired retrospectively. The Sasang Urination Inventory (SUI) with SUI-CHR (problematic physical characteristics of urine), SUI-HSS (hypersensitivity of urinary urgency and high frequency), and SUI-DIS (urinary discomfort of hesitancy and residual urine sense) subscales using 12 items of SUDI were improvised. The item and construct validity of the SUI were examined using item response theory and confirmatory factor analysis, and the clinical usefulness of the SUI in Sasang type and Cold-Heat subgroup differentiation was attested. Results. The SUI and its subscales showed acceptable structural validity and have clinical usefulness in the Tae-Eum type. The Tae-Eum type has a significantly higher SUI-CHR score than did the So-Yang type, and the Heat subgroup has a significantly higher SUI-HSS score than did the Cold subgroup in the Tae-Eum type. Discussion. The distinctive Sasang type- and Cold-Heat subscale-specific pathological symptoms in urinary function were revealed using the SUI. The SUI combined with objective Sasang typology measures might be useful for integrative precision medicine combining Eastern and Western practice and for evidence-based clinical education for medical professions.

Background/Aims: Needle knife fistulotomy (NKF) is a technique to facilitate pancreatic and biliary duct access during ERCP. The double-guidewire technique (DGT) is also used in cases of difficult cannulation, but it can increase the incidence of post-ERCP-pancreatitis (PEP). This study examined the success and complication rates of NKF after unsuccessful standard cannulation or DGT in patients with pancreaticobiliary disease. Methods: The data of 209 patients who received NKF as a rescue procedure between January 2009 and December 2016 were reviewed retrospectively. The cannulation success and complication rates were assessed. Results: The overall cannulation success rate was 90.4%. The success rates of patients who received NKF after standard cannulation or DGT were similar (82.6% [142/172] and 73.0% [27/37], respectively, p=0.179). Furthermore, there was no significant difference in the incidence of procedure-related adverse events between the two groups (10.5% [18/172] and 16.2% [6/37], respectively, p=0.391). Endoscopic retrograde pancreatic drainage (ERPD) insertion decreased the incidence of PEP (0% [0/16] in ERPD and 14.6% [19/130] in non-ERPD, p=0.132) among patients who received PD cannulation. Conclusions: NKF is an effective and safe method that can be considered for rescue management after the initial failure of standard cannulation or DGT. NKF following standard cannulation can be preferred over NKF following DGT because of the higher success rate and the lower rate of pancreatitis, but the difference was not significant. PD stenting in patients at high risk of PEP can be considered to decrease pancreatitis.

Aim: Lennox-Gastaut syndrome (LGS) is a severe type of childhood-onset epilepsy with multiple types of seizures, specific discharges on electroencephalography, and intellectual disability. However, LGS-related genes are largely unknown. To identify causative genes related to LGS, we collected and analyzed data from a three-generation Korean family in which one member had LGS and two had intellectual disability. Methods: Genomic DNAs were extracted from blood samples of all participants and used in whole-exome sequencing (WES). Genetic variants were detected by the Genome Analysis Toolkit and confirmed by Sanger sequencing. Variant pathogenicity was evaluated by prediction programs and the American College of Medical Genetics criteria. The LGS patient had generalized slow spike-and-wave discharges, multiple types of seizures, and developmental delay. Results: Analyses of the WES data from the family revealed a novel variant (c.1048G>A, p.Ala350Thr) in the IQ motif and Sec7 domain 2 (IQSEC2). This variant is within a highly evolutionarily conserved IQ-like motif, indicating a decrease in the calmodulin-binding capacity or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid transmission. The hemizygous variant in the male with LGS was a maternally inherited X-linked variant from the heterozygous maternal grandmother and mother, both of whom had intellectual disability. Conclusion: These findings indicate that the variant of IQSEC2 triggered both LGS and intellectual disability dependent on sex in this family. We report a novel X-linked inherited IQSEC2 variant for LGS and intellectual disability, which enhances the spectrum of variants in the IQ-like motif of IQSEC2.

Background: Early insulin resistance without diabetes can cause cardiovascular disease, which is a public health challenge. This study aimed to investigate the effects of the triglyceride to high-density lipid (HDL)-cholesterol ratio (TG/HDL-C), which could reflect insulin resistance from the beginning, on the incident risk of ischemic heart disease (IHD).Methods: We assessed 16,455 individuals (8,426 men and 8,029 women) without diabetes in a community-dwelling Korean cohort using National Health Insurance data. Participants were classified based on the TG/HDL-C quartiles. Using multivariate Cox proportional-hazards regression models, we prospectively examined the hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD over 50 months after baseline enrolment.Results: During the follow-up period, 321 (2.0%) participants developed IHD. After adjusting for potential confounding variables, the HRs of IHD for TG/HDL-C quartiles were 1.00, 1.61 (95% CI, 1.05–2.48), 1.85 (95% CI, 1.21–2.81), and 2.29 (95% CI, 1.50–3.51), respectively. Compared with men, women showed higher HRs for the risk of incident IHD in the fourth quartile [HR (95% CI) = 2.98 [1.50–5.88] and 1.80 [1.02–3.17], respectively). Compared with metabolic syndrome, TG/HDL-C had a more powerful predictive value for IHD.Conclusions: In Koreans without diabetes, an increased TG/HDL-C precedes future IHD. Additionally, sex differences may merit serious consideration when interpreting TG/HDL-C for assessing cardiovascular risks in clinical practice.

STUDY OBJECTIVE To investigate the therapeutic efficacy of catheter-directed ethanol sclerotherapy (CDS) and its effect on ovarian reserve in patients with endometrioma at risk of decreased ovarian reserve. DESIGN Retrospective study. SETTING Teaching hospital. PATIENTS We evaluated 18 patients with ovarian endometrioma measuring ≥3 cm and preprocedural serum antimullerian hormone (AMH) levels of

Alkaline phosphatase (ALP) has long been considered a marker of hepatobiliary and bone disorders, but recent studies have shown that increased ALP activity is correlated with various cardio-metabolic diseases. Thus, we investigated the association of serum ALP level with surrogate markers of insulin resistance such as triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C ratio) and triglyceride and glucose (TyG) index in the general population. The study included 12,868 men and women aged 19 years and older. Participants were categorized into four groups based on serum ALP level (U/L) as follows: Q1: 55–190 U/L, Q2: 191–224 U/L, Q3: 225–265 U/L, and Q4: 266–923 U/L for men, Q1: 48–161 U/L, Q2: 162–198 U/L, Q3: 199–245 U/L, Q4: 246–790 U/L for women. The insulin resistance cut-off levels were defined corresponding to the 75th percentile of the TyG index and TG/HDL-C ratio in the current samples. Odds ratios (ORs) with 95% confidence intervals (CIs) of insulin resistance according to quartile of serum ALP level were calculated using weighted multivariate logistic regression analysis. Compared with Q1, the adjusted OR (95% CI) for insulin resistance of the Q4 serum ALP group was 1.517 (1.234–1.866) in men and 1.881 (1.399–2.528) in women using the TG/HDL-C ratio and 1.374 (1.093–1.728) in men and 2.047 (1.468–2.855) in women using the TyG index after adjusting for confounding variables. Serum ALP levels are independently and positively associated with surrogate markers of insulin resistance in Korean adults.

The aim of the present study was to report two cases of refractory dry eye syndrome (DES) after transconjunctival excision of the palpebral lobe of the lacrimal gland. A 25-year-old female patient with a chief complaint of a palpable mass in both upper eyelids visited our medical center. Preoperative orbital computer tomography showed high-attenuation lesions in both lacrimal glands. Incisional biopsy of the lacrimal gland palpebral lobe via transconjunctival incision was performed in January 2019. At 1 month after the biopsy, a lack of tears and persistent corneal erosions were found in both eyes. Artificial tears, punctal occlusion, autologous serum eye drops, and therapeutic contact lenses were applied in an attempt to control the dry eye symptoms. The patient continues to suffer from intractable DES at 2.5 years after the procedure. The second case involved a 52-year-old female patient who visited our medical center with a chief complaint of a palpable mass in both upper eyelids. Bilateral orbital tumors were diagnosed with preoperative magnetic resonance imaging. An incisional biopsy of the lacrimal gland was performed. Immunoglobulin G4-related dacryoadenitis was confirmed through lacrimal palpebral lobe incisional biopsy. Intractable DES and corneal erosion of her left eye persisted thereafter. A transconjunctival incision is an effective approach for minimizing postoperative scars and is suitable for the biopsy of tumors that are visible through the conjunctiva. After a biopsy of the palpebral lobe of the main lacrimal glands, the secretion of reflex tears decreases due to damage to the secreting ducts of the main lacrimal glands. However, total tear secretion can be maintained by basal tear secretion from the accessory lacrimal glands. In this report, we describe two cases of refractory DES due to decreased total tear secretion, although only the palpebral lobes of the main lacrimal glands were biopsied.

The goal of our study was to demonstrate the spectrum of genomic alterations present in the residual disease of patients with advanced high-grade serous ovarian cancer (HGSOC) after neoadjuvant chemotherapy (NAC), including matched pretreatment biopsies. During the study period between 2006 and 2017, we collected pre-NAC and post-NAC tumor tissue samples from patients with advanced HGSOC. We performed combined next-generation sequencing and immunohistochemistry to identify actionable targets and pathway activation in post-NAC residual tumors. We also examined whether post-NAC profiling of residual HGSOC identified targetable molecular lesions in the chemotherapy-resistant component of tumors. Among 102 post-NAC samples, 41 (40%) of patients had mutations in homologous recombination repair (HRR) genes (HRR deficiency). Patients with HRR mutations had higher tumor mutation burdens (p < 0.001) and higher alterations in the PI3K-AKT-mTOR pathway (p = 0.004) than patients without these HRR mutations. Nevertheless, we found no significant differences in progression-free survival (p = 0.662) and overall survival (OS; p = 0.828) between the two groups. Most patients (91%) had alterations in at least one of the targetable pathways, and those patients with cell cycle (p = 0.004) and PI3K-AKT-mTOR signaling (p = 0.005) pathway alterations had poorer OS (Bonferroni-corrected threshold = 0.0083, 0.05/6). We showed the genomic landscape of tumor cells remaining in advanced HGSOC after NAC. Once validated, these data can help inform biomarker-driven adjuvant studies in targeting residual tumors to improve the outcomes of patients with advanced HGSOC after NAC.

Aims We evaluated the prognostic significance of postoperative re-elevation of cancer antigen-125 (CA-125) levels in patients with ovarian cancer and preoperative normalization of CA-125 levels after neoadjuvant chemotherapy (NAC). Methods The data of 103 patients with preoperative CA-125 normalization after NAC at the Yonsei Cancer Hospital (2006–2017) were analyzed. We compared the clinical characteristics and survival outcomes among patients with normal postoperative CA-125 levels and those with re-elevated CA-125 levels after interval debulking surgery (IDS). CA-125 elevation was defined as levels >35 U/mL. Results Among 103 patients, 52 (50.5%) and 51 (49.5%) had normal and re-elevated CA-125 levels after IDS, respectively. Patients with CA-125 re-elevation underwent more radical surgeries during IDS than those with normal CA-125 levels (p = 0.018). We found no significant differences in progression-free survival (PFS; p = 0.726) or overall survival (OS; p = 0.293) between the two groups. Moreover, patients with persistent CA-125 elevation (3 weeks after IDS) did not have inferior PFS (p = 0.171 and p = 0.208, respectively) or OS (p = 0.128 and p = 0.095, respectively) compared to patients with early normalization (within 3 weeks of IDS) or normal CA-125 levels. Multivariate regression showed that CA-125 re-elevation had no effect on recurrence (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.43–1.30) or death (HR, 0.99; 95% CI, 0.33–2.98). Conclusion Among patients with preoperative CA-125 normalization after NAC, postoperative CA-125 re-elevation had no prognostic value. Novel and reliable biomarkers reflecting the tumor response after IDS should be identified.

The aim of this study was to investigate the prognostic significance of lymphocytopenia in advanced‐stage ovarian cancer. We retrospectively reviewed 506 patients with advanced‐stage ovarian cancer at Yonsei Cancer Hospital. This study included two cohorts of patients: a neoadjuvant chemotherapy (NAC) group (N = 247) and a primary debulking surgery (PDS) group (N = 259). The absolute lymphocyte count was recorded before treatment. A receiver operating characteristic (ROC) curve analysis was used to determine the cutoff for defining lymphocytopenia in the NAC cohort and followed by multivariate analysis. Subsequently, lymphocytopenia was assessed in the PDS cohort by multivariate analysis. A further analysis was performed to evaluate the absolute lymphocyte count as a continuous variable. An absolute lymphocyte count of 1.49 × 109/L was determined as the cutoff for the ROC curve analysis in the NAC cohort, and the multivariate analysis revealed that lymphocytopenia was an independent prognostic factor for poor progression‐free survival (PFS) [hazard ratio (HR), 1.50; 95% confidence interval (CI), 1.07‐2.11] and overall survival (OS) (HR, 2.02; 95% CI, 1.21‐3.40). In the PDS cohort, the multivariate analysis showed that lymphocytopenia was an independent prognostic factor for poor PFS (HR, 1.73; 95% CI, 1.20‐2.49) and OS (HR, 1.87; 95% CI, 1.27‐2.75). The absolute lymphocyte count was a significant factor when analyzed as a continuous variable in both the NAC and PDS cohorts. Pretreatment lymphocytopenia is an independent adverse prognostic factor in patients with advanced‐stage ovarian cancer.

Background: An increased hemoglobin (Hb) level may have detrimental effects on hepatic steatosis (HS) as well as cardiovascular disease (CVD). We investigated Hb's effect on incident ischemic heart disease (IHD) risk in the context of hepatic steatosis (HS).Methods: We assessed 17,521 non-diabetic participants and retrospectively screened for IHD using the Korea National Health Insurance data. High Hb was defined as Hb levels ≥16.3 g/dL in men and 13.9 g/dL in women (>75th percentile). The participants were divided into five groups: reference (group 1), mild HS only (group 2), mild HS and high Hb (group 3), severe HS only (group 4), and severe HS and high Hb (group 5). We assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional hazards regression models over 50 months from the baseline survey.Results: During the follow-up period, 330 (1.9%) participants developed IHD (310 angina pectoris and 20 myocardial infarction). Compared with the reference group (group 1), the HRs for IHD were 1.04 (95% CI, 0.75–1.46) in group 2, 1.14 (95% CI, 0.70–1.85) in group 3, 1.58 (95% CI, 1.08–2.32) in group 4, and 1.79 (95% CI, 1.15–2.80) in group 5, after adjusting for IHD risk factors.Conclusions: We found the combined effect of HS and Hb levels on the incidence of IHD.

Malunion after distal radius fracture is common in older patients; however, whether patient-perceived outcomes are influenced by radiologic outcome is controversial. This study evaluated patient-perceived outcomes according to radiologic parameters in older patients who underwent nonoperative treatment. The records of 167 patients older than 55 years who had a distal radius fracture were reviewed. All fractures were treated nonoperatively, and average length of follow-up was 7 years. Outcomes were evaluated using numeric rating scales for pain and satisfaction, as well as Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) scores. Radiographs were evaluated for dorsal tilt, radial inclination, and ulnar variance. Fifty-one patients (30%) developed malunion. The pain numeric rating scale score was 0.8 for patients with malunion and 0.4 for patients with acceptable alignment; this difference was not statistically significant. The QuickDASH score was higher for patients with malunion (14.9 vs 11.1 for patients with acceptable alignment); however, this difference was not clinically meaningful. Satisfaction scores were lower for patients with malunion than for patients with acceptable alignment (80.8 vs 92.3). Patients with malunion stated they would choose surgery rather than a cast (13.3% vs 7.2%) if they developed another fracture; this difference was not statistically significant. The subanalysis according to radiologic parameters showed dorsal tilt and ulnar variance affected patient satisfaction but not other outcomes. This study indicated nonoperative treatment in older adults obtained acceptable patient-perceived outcomes despite residual deformity. However, patients whose radiologic parameter exceeded the tolerable range were less satisfied. [ Orthopedics . 2021;44(2):e190–e196.]

Background The optimal treatment of BRCA wild-type patients with platinum-sensitive recurrent ovarian cancer remains unknown. Recently, there is an increase in the evidence to support the role of the combination of a poly(adenosine diphosphate-ribose) polymerase inhibitor, anti-angiogenic agents, and immunotherapy as maintenance therapy in BRCA wild-type patients with platinum-sensitive recurrence. We hypothesized that adding pembrolizumab and bevacizumab to olaparib maintenance can increase progression-free survival (PFS) in BRCA wild-type patients with platinum-sensitive recurrent ovarian cancer. Methods BRCA wild-type patients who received two previous courses of platinum-containing therapy, achieved complete or partial response to last treatment, and the treatment-free interval is >6 months after the penultimate platinum-based chemotherapy offered olaparib maintenance with pembrolizumab and bevacizumab. Forty-four patients will be included from 4 sites across Singapore and Korea. The primary endpoint of the study is 6-month PFS rate. Trial registration ClinicalTrials.gov Identifier: NCT04361370, Clinical Research Information Service Identifier: KCT0005144.

This study investigated the antitumor activity and safety of pembrolizumab in patients with recurrent cervical cancer in real-world practice. We conducted a multi-center retrospective study of patients with recurrent or persistent cervical cancer treated with pembrolizumab at sixteen institutions in Korea between January 2016 and March 2020. The primary endpoints were the objective response rate (ORR) and safety. Data were available for 117 patients. The median age was 53 years (range, 28&ndash, 79). Sixty-four (54.7%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of &ge, 2. Forty-nine (41.9%) patients were stage &ge, III at diagnosis. Eighty-eight (75.2%) patients had squamous cell carcinoma. The median number of prior chemotherapy lines was two (range, 1&ndash, 6). During the median follow-up of 4.9 months (range, 0.2&ndash, 35.3), the ORR was 9.4%, with three complete responses and eight partial responses. The median time to response was 2.8 months (range 1.3&ndash, 13.1), and the median duration of response (DOR) was not reached. In the population of patients with favorable performance status (ECOG &le, 1) (n = 53), the ORR was 18.9%, and the median DOR was 8.9 months (range, 7.3&ndash, 10.4). Adverse events occurred in 55 (47.0%) patients, including eight (6.8%) patients who experienced grade &ge, 3 events, and two of them were suspicious treatment-related deaths. Pembrolizumab had modest antitumor activity in patients with recurrent cervical cancer comparable to that found in previously reported clinical trials. However, in patients with favorable performance status, pembrolizumab showed effective antitumor activity. Some safety profiles should be carefully monitored during treatment.

Oxidative stress has been associated with many diseases as well as aging. Electrolyzed-reduced water (ERW) has been suggested to reduce oxidative stress and improve antioxidant potential. This study investigated the effects of drinking ERW on biomarkers of oxidative stress and health-related indices in healthy adults. We conducted a randomized, double-blind, placebo-controlled clinical trial on 65 participants, who were allocated into two groups. Of these, 61 received intervention (32 with ERW and 29 MW [mineral water]). All participants were instructed to drink 1.5 L/day of ERW or MW for eight weeks. Biomarkers of oxidative stress and health-related indices were assessed at baseline as well as after 4 weeks and 8 weeks of intervention. Of the primary outcome variables assessed, diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential showed a significant interaction between the groups and time, with d-ROMs levels significantly decreased at 8 weeks in ERW compared to those in MW. Among the secondary outcome variables, total, visceral, and subcutaneous fat mass significantly changed over time, with a significant association observed between the group and time. Thus, daily ERW consumption may be a potential consideration for a sustainable and innovatively simple lifestyle modification at the workplace to reduce oxidative stress, increase antioxidant potential, and decrease fat mass.

Nonalcoholic fatty liver disease (NAFLD) has become one of the most common medical problems. Inhibition of lipogenesis and promotion of lipolysis are two ways to prevent NAFLD. In this study, oleic acid-induced HepG2 cells are used as a NAFLD cell model to test whether s-petasin exerts inhibition of lipogenesis and promotion of the lipolysis effect. The results showed that s-petasin significantly inhibited the lipid level in oleic acid-induced HepG2 cells. Moreover, results showed that the triacylglycerol level was reduced by s-petasin in oleic acid-induced HepG2 cells. Western blot assay revealed that s-petasin stimulated phosphorylation of AMPKα and ACCα. The results also demonstrated that s-petasin can inhibit lipogenesis and enhance triacylglycerol turnover by down-regulation of FAS and SCD-1 and up-regulation of ATGL and HSL through the AMPK signaling-dependent regulation of transcriptional factors, FKHR and SREBP-1. This in vitro study indicates that s-petasin has potential as a candidate compound for NAFLD therapy.

Objective: To compare the efficacy and toxicity of dose-dense weekly paclitaxel and 3-weekly carboplatin (ddPC) as neoadjuvant chemotherapy (NAC) with the standard 3-weekly regimen. Methods: A retrospective study of patients diagnosed with stage IIIc and IV ovarian cancer who received at least one cycle of NAC followed by interval debulking surgery between August 2015 and January 2018 was conducted. Patient characteristics, clinical and pathological response to NAC, surgical and survival outcome, and adverse event were compared. Results: A total of 23 patients in the ddPC group and 50 patients in the standard group received a median of 3 cycles of NAC. Rate of grade ≥3 neutropenia was significantly higher in the ddPC group than the standard (82.6% vs. 22.0%, p

Objective This study introduces and evaluates the feasibility, safety, and surgical outcomes of the in-bag power morcellation technique during single-port assisted (SPA) laparoscopic myomectomy in comparison with manual scalpel morcellation. Methods This is a retrospective review of a total of 58 patients who underwent SPA laparoscopic myomectomy employing in-bag power morcellation (n=27) or manual scalpel morcellation (n=31), performed between December 2014 and December 2016. Surgical outcomes, including total operation time, estimated blood loss, postoperative hemoglobin changes, postoperative hospital stay, postoperative pain (visual analog scale), perioperative and postoperative complications were evaluated. Results The demographics and patient characteristics were similar between both groups. The median patient age was 34 years and median body mass index was 20.84 kg/m2. The median specimen weight was 110 g. The median operating time was 138 minutes. The median estimated blood loss was 50 mL and the median postoperative hemoglobin change was 2.2 g/dL. The median postoperative hospital stay was 2 days and the median postoperative pain scores were 5 after 6 hours, 3 after 24 hours, and 2 after 48 hours. Occult malignancy was not identified in any patients. There were no intraoperative complications such as LapBag ruptures or gross spillage. Conclusion In-bag power morcellation for SPA laparoscopic myomectomy is feasible and safe, minimizing the risks of open power morcellation. There were also no statistically significant differences in surgical outcomes.

Objective To investigate the relationship of the time interval from the completion of neoadjuvant chemotherapy (NAC) to the initiation of postoperative adjuvant chemotherapy (POAC) with the survival outcomes in patients with ovarian cancer. Methods We retrospectively investigated 220 patients with pathologically confirmed epithelial ovarian cancer who received NAC at Yonsei Cancer Hospital between 2006 and 2016. The time interval was defined as the period from the completion of NAC, spanning interval debulking surgery (IDS), to the initiation of POAC. Results The median time interval was 42 (range 16–178) days; 103 patients (53.1%) received POAC within 42days after NAC while 91 patients (46.9%) received it after 42days. There were no significant differences in patient characteristics between these 2 groups. Kaplan-Meier analysis showed that patients with longer time intervals (>42days) had poorer progression-free survival and overall survival (P=0.039 and 0.005, respectively). In the multivariate analysis, patients with longer time intervals had significantly poorer progression-free (hazard ratio, 1.41; 95% confidence interval, 0.98–2.03; not significant) and overall survivals (hazard ratio, 2.03; 95% confidence interval, 1.16–3.54). When the patients were categorized according to time interval quartiles (≤37, 38–42, 43–50, and >50days), longer time intervals were associated with higher risks of recurrence and death (P for trend: 0.006 and Conclusion The time interval from the completion of NAC to the initiation of POAC appears to influence survival. Efforts to reduce the time interval might improve the outcomes in ovarian cancer patients undergoing NAC.

OBJECTIVE The aim of this study was to investigate factors preventing delayed hemorrhage after the loop electrosurgical excisional procedure (LEEP). METHODS Medical records of patients who underwent LEEP at one university affiliated hospital from October 2013 to January 2015 were reviewed. Patients with or without delayed hemorrhage were classified. LEEP was performed either in an operating room under general anesthesia or in a procedure room with local anesthesia in the outpatient clinic. Delayed hemorrhage was defined as excisional site bleeding occurring between 1 and 30 days after the LEEP requiring intervention such as electro-cauterization, gauze packing, or application of another hemostatic agent. RESULTS During the study period, 369 patients underwent LEEP. Twenty-three (6.2%) patients with delayed hemorrhage returned to our hospital either to the outpatient clinic or to the emergency unit. A third of the population (103, 27.9%) underwent LEEP in the operating room under general anesthesia without injection of local anesthesia. The remaining patients (266, 72.1%) underwent LEEP with local anesthesia (lidocaine HCl 2% with epinephrine 1:100,000) in the office procedure room. Patients given local anesthesia including epinephrine had significantly lower delayed hemorrhage compared to patients with general anesthesia without injection of local anesthesia (P=0.001). Hemostats, such as fibrin glue or patch, were used for the majority of patients (346, 93.8%) during the procedure. However, using hemostats was not statistically associated with delayed hemorrhage (P=0.163). CONCLUSION Local anesthesia with the powerful vasoconstrictor epinephrine is effective not only to control perioperative bleeding, but also to prevent delayed hemorrhage after LEEP.

Background To analyze the effects of BRCA1/2 mutations on chemotherapy response scores (CRS) and survival in a cohort of patients with advanced-stage ovarian cancer who were treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS). Methods We retrospectively reviewed the medical records of 169 high-grade serous ovarian cancer patients who underwent a germline BRCA1/2 test and received three cycles of NAC at the Yonsei Cancer Center from 2006 to 2018. Chemotherapy response scores were compared in patients with and without BRCA1/2 mutations. The effects of BRCA1/2 mutations and CRS on survival were evaluated. Results BRCA1/2 mutations were detected in 47 (28.1%) of the 169 patients. Overall, 16 (34.0%) patients with BRCA1/2 mutations had a CRS 3 to chemotherapy compared to scores of 43 in patients (35.2%) without a mutation. Response scores of 3 in patients with BRCA1/2 mutations were not significantly associated with either improved progression-free survival (PFS) (P = 0.949) or overall survival (OS) (P = 0.168). However, CRS 3 in patients without BRCA mutations was significantly associated with both improved PFS (P = 0.030) and OS (P = 0.039). In patients with CRS1/2, carriers of BRCA1/2 mutations had better PFS (P = 0.0344) and OS (P = 0.043) than wild-type BRCA genotype patients. Conclusion In ovarian cancer patients treated with NAC, CRS did not predict survival for BRCA 1/2 mutation carriers but did for BRCA wild-type patients.

Background Epidemiological studies investigating the link between serum estradiol levels and inflammatory markers have produced inconsistent or conflicting results. We hypothesized that serum estrogen plays differing roles in inflammation according to menopausal status. Thus, we aimed to investigate the association between serum estradiol and C-reactive protein (CRP) levels in women according to their menopausal status.Methods We examined the association between serum estradiol and high-sensitivity CRP levels based on the menopausal status of 151 premenopausal women aged 21–52 years and in 394 postmenopausal women aged 46–75 years who participated in a health examination program. A multiple linear regression analysis was conducted using CRP level as the dependent variable.Results Multiple linear regression analysis showed that serum estradiol levels were inversely associated with CRP levels in premenopausal women (β coefficient = -0.298, P = 0.001). However, this was not the case in postmenopausal women after adjusting for age, body mass index, cigarette smoking, mean arterial pressure, fasting plasma glucose, triglyceride, high-density lipoprotein-cholesterol, aspartate aminotransaminase, and alanine aminotransaminase levels. Serum estradiol levels were inversely associated with CRP in premenopausal women but not in postmenopausal women.Conclusion Our findings suggest that lower estrogenic activity may at least partly contribute to the pathogenesis of chronic inflammation, particularly in premenopausal women.

Purpose To investigate whether transconjunctival approach surgery caused meibomian gland dysfunction in patients with inferior orbital wall fractures. Methods Twenty consecutive patients who underwent reconstruction surgery for unilateral inferior orbital wall fracture via a transconjunctival approach were enrolled in this study. All patients were asked to complete the Ocular Surface Disease Index questionnaire for each separate eyelid. Both eyelids of each patient underwent slit lamp examination to determine the lid margin abnormality scores. The structure of the meibomian gland was assessed using meibography. Intraindividual comparison of outcome measurements between both eyelids was performed using the Wilcoxon signed-rank test. The contralateral eyelid of each patient was used as a normal control. Results The mean Ocular Surface Disease Index score of the operated eyelid was 46.5 ± 8.9, which was significantly higher than that of the contralateral normal eyelid (23.4 ± 7.3; P = 0.02). The lid margin abnormality score of the operated eyelid (1.2 ± 0.7) was higher than that of the normal eyelid (0.5 ± 0.7; P = 0.033). The meibography score of the eyelid on the operated side (1.8 ± 0.8) was greater than that of the contralateral eyelid (1.0 ± 1.0; P = 0.015). Conclusions Compared to paired normal eyelids, eyelids that underwent transconjunctival approach surgery exhibited significant signs of meibomian gland dysfunction. Clinicians should be aware of such ocular symptoms in patients after transconjunctival approach surgery.

Purpose Few efforts have been made to integrate a next generation sequencing (NGS) panel into standard clinical treatment of ovarian cancer. The aim of this study was to investigate the clinical utility of NGS and to identify clinically impactful information beyond targetable alterations. Materials and methods We conducted a retrospective review of 84 patients with ovarian cancer who underwent NGS between March 1, 2017, and July 31, 2018, at the Yonsei Cancer Hospital. We extracted DNA from formalin-fixed, paraffin-embedded tissue samples of ovarian cancer. The TruSight Tumor 170 gene panel was used to prepare libraries, and the MiSeq instrument was used for NGS. Results Of the 84 patients, 55 (65.1%) had high-grade serous carcinomas. Seventy-three (86.7%) patients underwent NGS at the time of diagnosis, and 11 (13.3%) underwent NGS upon relapse. The most common genetic alterations were in TP53 (64%), PIK3CA (15%), and BRCA1/2 (13%), arising as single nucleotide variants and indels. MYC amplification (27%) was the most common copy number variation and fusion. Fifty-seven (67.9%) patients had more than one actionable alteration other than TP53. Seven (8.3%) cases received matched-target therapy based on the following sequencing results: BRCA1 or 2 mutation, poly ADP ribose polymerase inhibitor (n=5); PIK3CA mutation, AKT inhibitor (n=1); and MLH1 mutation, PD-1 inhibitor (n=1). Fifty-three (63.0%) patients had a possibility of treatment change, and 8 (9.5%) patients received genetic counseling. Conclusion Implementation of NGS may help in identifying patients who might benefit from targeted treatment therapies and genetic counseling.

Objectives The purpose of this study was to report the effects of treatments to traumatic subcutaneous hematoma on the shin using herbal medication and external application without venesection, which had no change in spite of previous 3 weeks medical conservative treatment so it had a risk of sepsis.Methods The patient diagnosed as Soyangin was prescribed with Yangkyuksanhwa-tang. The subcutaneous hematoma lesion was treated by external application of Daehwangchija-san(大黃梔子散). We evaluated the size of hematoma, pain and gait disturbance.Results and Conclusions Subcutaneous hematoma and relevant symptoms disappeared within 11 days of admission. Any kind of sequela did not show up and skin color was recovered after 4 month later follow-up.

The aim of this study is to evaluate the effects on survival outcomes of the disease burden before interval debulking surgery (IDS), surgical complexity, and residual disease after IDS in advanced-stage ovarian cancer treated with neoadjuvant chemotherapy (NAC). We reviewed the data of 268 epithelial ovarian cancer patients who had received three or four cycles of NAC and undergone optimal resections through IDS. The Kaplan&ndash, Meier method and Cox regression analysis were used to assess the effects of disease burden (peritoneal cancer index (PCI)), degree of complexity of surgery (surgical complexity score/s (SCS)), and extent of residual disease. In no residual disease (R0) patients, those with intermediate/high SCS had shorter progression-free survival (PFS, p = 0.001) and overall survival (OS, p = 0.001) than patients with low SCS. An analysis of a subset of patients with R0 and low PCIs showed those with intermediate/high SCS had worse PFS and OS than patients with low SCS (p = 0.049) and OS (p = 0.037). In multivariate analysis, patients with R0 as a result of intermediate/high SCS fared worse than patients whose R0 was achieved by low SCS (PFS hazard ratio (HR) 1.80, 95% CI 1.05&ndash, 3.10, OS HR 5.59, 95% CI 1.70&ndash, 18.39). High PCIs at the time of IDS, high SCS, and residual disease signal poor prognoses for patients treated with NAC.

Background We aimed to evaluate the structural effects of the long-term use of orthoses for pediatric flexible flat foot (PFFF) using an algorithmic approach and a structured critical framework to assess the methodological quality of reported studies. Methods A comprehensive literature search using five databases, namely MEDLINE, the Cochrane Library, Scopus, the Web of Science, and EMBASE, was performed for pertinent articles published before March 30, 2018. Studies with quantitative data on the effects of the long-term use of orthoses for PFFF were included. The search strategy was adapted as appropriate for all other databases searched considering the differences in indexing terms and search syntax for each database. Results Randomized controlled trials and prospective cohort studies could not prove the estimated effects of orthoses on the medial longitudinal arch. They revealed that flexible flat feet in young children slowly improved with growth, regardless of the type of footwear used. However, three of four case series studies revealed that positive long-term effects could be achieved using orthoses. Conclusion There is no strong evidence that the long-term use of orthoses improved the structural problem of PFFF.

Objectives We conducted a protocol-based cohort study to evaluate the outcomes of interval debulking surgery (IDS) followed by paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of advanced-stage ovarian cancer. Methods From October 2015 to May 2018, 65 patients with stages IIIC-IV ovarian cancer were treated according to the study protocol. HIPEC was performed with paclitaxel (175 mg/m??) for 90 minutes, only in cases of optimal cytoreduction. Results Of 65 patients, 40 (61.5%) patients underwent neoadjuvant chemotherapy (NAC), 34 (52.3%) patients had a high tumor burden with a Fagotti score ???8 at diagnostic laparoscopy, and 6 (9.2%) had definite stage IV metastasis and/or poor performance status before NAC. Twenty-seven (41.5%) patients underwent IDS followed by HIPEC. The mean duration of IDS with HIPEC was 543.8 (range, 277.0-915.0) minutes. Grade III/IV perioperative complications occurred in 7.4% (n=2)/3.7% (n=1) of patients and no cases of mortality were reported within 30 days postoperatively. The median progression-free survival was 21.3 months, and the median overall survival was not reached for those who received HIPEC. Conclusions According to our study protocol, IDS followed by paclitaxel-based HIPEC as a first-line treatment appears to be feasible and safe for the treatment of advanced-stage ovarian cancer. Further evaluations of this procedure are required to assess its survival benefits.

OBJECTIVE The choice between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NAC) in advanced ovarian cancer remains controversial. We evaluated NAC use in our center before and after results from a randomized trial were published, with the aim to determine the impact of changes in the neoadjuvant strategy on survival in advanced-stage ovarian cancer. METHODS We retrospectively investigated the clinical course of 435 patients with ovarian, tubal, or peritoneal carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage III or IV). According to the period of treatment, we stratified patients into a control group (n=216; diagnosed between 2006 and 2010; 83.8% underwent PDS) and a study group (n=219; diagnosed between 2011 and 2014; 48.9% received NAC followed by interval debulking surgery [IDS]). RESULTS There were no between-group differences in age, body mass index, histology findings, or tumor grade. Compared to patients in the control group, those in the study group were more likely to receive NAC followed by IDS as first-line treatment (48.9% vs. 16.2%; p

Objective The current sentinel lymph node (SLN) tracer injection procedure for endometrial cancer commonly uses cervical injection, which can detect SLNs of the uterine cervix but not the uterine body. This study describes an SLN tracer injection procedure, titled two-step SLN mapping, which can identify SLNs of the uterine body and cervix using fluorescent imaging with indocyanine green (ICG) and results of SLN biopsy. Methods In 50 consecutive patients with endometrial cancer, two-step SLN mapping was performed during laparoscopic surgical staging with the PINPOINT® real-time fluorescence imaging system. The first step was to identify SLNs of the uterine body. In total, 4–6 mL of ICG was injected into the bilateral uterine cornual areas, and lymphatic channels were traced, followed by identification and removal of paraaortic SLNs. The second step was to identify SLNs of the uterine cervix by injecting 4 mL of ICG into the cervix. After harvesting the mapped pelvic SLNs, complete pelvic and paraaortic lymphadenectomy was performed to validate the two-step SLN mapping strategy. Results Our two-step SLN mapping strategy produced excellent SLN detection rates: 100% (50/50) overall for SLNs; 98.0% (49/50) for pelvic SLNs; 94.0% (47/50) for bilateral SLNs; and 86.0% (43/50) for paraaortic SLNs. We detected microscopic metastasis in harvested SLNs of 4 patients (8.0%). The sensitivity, specificity, and negative predictive value of SLN detection were all 100%. There was no false negative case. Conclusion The two-step SLN mapping strategy to identify lymph nodes from the uterine fundus and cervix was feasible. This strategy could be more accurate in identifying paraaortic lymph node metastasis than the cervical injection method.

Various kinetic parameters of serum CA-125 have been reported to have better correlation with outcomes for patients treated with neoadjuvant chemotherapy (NAC). This study aimed to compare the available kinetic parameters of serum CA-125 in an external cohort of advanced-stage ovarian cancer. Using the cancer registry databases from the Yonsei Cancer Hospital, we retrospectively reviewed 210 patients with advanced-stage ovarian cancer, treated with NAC followed by interval debulking surgery. We compared area under the receiver-operating characteristics curves (AUCs), false negative rate, and negative predictive value (NPV) using 10 different models for optimal cytoreduction and platinum resistance. In addition, we compared incremental AUC for progression-free survival (PFS) and overall survival (OS). No gross residual tumor was observed in 37.0% and residual tumors 0.6 for predicting optimal cytoreduction. After adjusting for age, BMI, disease stage, and histologic subtypes, all models had an AUC >0.70 for predicting platinum resistance. However, no model had a high enough NPV (highest value = 82.0%) to avoid chemotherapy futility. For survival outcomes, no model had an incremental AUC >0.70 for predicting either PFS or OS. None of the proposed serum CA-125 kinetic parameters showed high accuracy in predicting optimal cytoreduction, platinum resistance, or survival in patients receiving NAC. For advanced-stage ovarian cancer treated with NAC, there is a need to discover reliable biomarkers to better stratify patient response groups for optimal treatment decision-making.

Objectives The purpose of this study is to find out whether or not there are differences of effects when we count breaths on inspiration or expiration, and how differently the effects show up according to gender or Sasang Constitution Methods A group of 79 participants were enrolled and diagnosed Sasang Constitution by Sasang Constitution Diagnosis System of the Korea Institute of Oriental Medicine. Physical responses to respiratory changes were measured by Biofeedback sensors that were attached to the participants while they were seated comfortably on a sofa and breathing normally without counting for 5 minutes, counting on inspiration for 5 minutes, and counting on expiration for 5 minutes. Results and Conclusions 1. Mean heart rate and respiration rate decreased in association with breathing counting on inspiration and expiration more than breathing normally without counting. Especially respiration rate was stabilized during counting on inspiration and mean heart rate was stabilized during counting on expiration. 2. Interaction between breathing methods and gender did not appear. In comparison between gender, LF/HF ratio was higher in male during breathing normally without counting and counting on inspiration. Body temperature was higher in male during counting on inspiration and expiration. 3. Interaction between breathing methods and Sasang Constitution did not appear. In comparison between Sasang Constitution, mean heart rate was higher in Soyang-in, Soeum-in than Taeeum-in and abdominal amplitude was lower in Taeeum-in than Soeum-in.

Four of 1237 patients who underwent abdominal, laparoscopic, and vaginal hysterectomy between October 2013 and May 2015 had severe secondary hemorrhage after hysterectomy (2 conventional multiport total laparoscopic hysterectomies, 1 single-port access hysterectomy, and 1 total abdominal hysterectomy). The median time interval between hysterectomy and secondary hemorrhage was 28.4 days (range, 16-52 days). All 4 cases were treated with transcatheter arterial embolization (TAE), all of whom required blood transfusions to maintain vital functions before TAE. The mean operative time was 90 minutes. The median length of hospital stay after TAE was 12 days (range, 4-24 days), and the patients were discharged without complications or additional surgery. These cases show the value of minimally invasive TAE for patients experiencing severe secondary hemorrhage after hysterectomy.

This study to analyze differences of cancer patient`s health utilizations in medical aid program and national health insurance by analysing health insurance claims data, and identify effects of health care systems. The majors results of the research were as follows. First, cancer patients in medical aid program more used total medical expenditures than in national health insurance mostly by many outpatient visits and long term hospitalization. Second, results of multiple regression, cancer patients in medical aid program more used total expenditures and inpatient expenditures. But, outpatient expenditures weren`t different, cancer patients in medical aid program more visited medical institutions and hospitalized long term periods than in national health insurance. Therefore, it is too early to conclude that moral hazard is in health utilizations of medical aid program, because cancer patients in medical aid program many use in benefits for many nonbenefit burdens.

Subepithelial connective tissue grafting (SCTG) is a frequently used method in the field of periodontal plastic surgery. There are relatively few reports defining epithelial thickness criteria for palatal mucosal SCTG. The aim of this study was to histologically measure the epithelial thickness of the palatal mucosa in a sample of Korean patients, with the goal of minimizing epithelium-associated complications after root coverage procedures. A total of 30 Korean patients (12 males and 18 females) were enrolled in this study. To measure epithelial thicknesses, palatal mucosa adjacent to premolars and molars was obtained during procurement of SCTG. The effects of donor site, age and gender on the thickness of the epithelium were assessed and compared by histomorphometric analysis. The mean epithelial thickness of the palatal mucosa in our 30 patients was 430.63 μm, ranging from 113 to 823 μm. Epithelial thickness was not associated with donor site or age, but there were significant differences between genders, with males having much thicker palates than females.