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Objective: We evaluated the usefulness of preoperative diagnostic laparoscopy for treatment planning in patients with advanced-stage ovarian cancer. Methods: We retrospectively analyzed 614 patients diagnosed with advanced-stage ovarian cancer between January 2010 and May 2018. Primary debulking surgery (PDS) or neoadjuvant chemotherapy (NAC) followed by interval debulking surgery were selected based on preoperative laparoscopic (Group 1, n=192) and computed tomography findings (Group 2, n=422). The primary outcomes in the PDS and NAC groups were suboptimal cytoreduction (residual disease >1 cm) rate and non-high-grade serous carcinoma (non-HGSC) rate, respectively. Results: The patients who underwent PDS in group 1 and group 2 were 49 (25.5%) and 279 (66.1%), respectively. The suboptimal cytoreduction rate after PDS was lower in Group 1 than in Group 2 (2.0% vs 11.1%, p=0.023). Moreover, Group 1 showed a tendency toward a lower proportion of non-HGSC patients who underwent NAC than that in Group 2 (9.1% vs. 15.4%, p=0.069). Further, Group 1 showed lower rates of postoperative morbidity than Group 2 (5.2% vs. 10.4%, p=0.033). However, Kaplan-Meier analysis showed no significant differences in survival outcomes between the 2 groups. Conclusion: Diagnostic laparoscopy reduced the suboptimal cytoreduction rate in the PDS group and the implementation rate of NAC in non-HGSC patients. Moreover, it reduced postoperative morbidity without affecting survival in both groups. Thus, diagnostic laparoscopy is a valuable diagnostic tool for determining the primary treatment. [ABSTRACT FROM AUTHOR]

Background: Mismatch repair deficiency (MMRd) tumors are known to be highly immunogenic and of great interest for immune checkpoint inhibitor. However, there is no data about the complete response rate of programmed cell death protein 1 (PD-1) blockade and surgery in subjects with mismatch repair deficient surgically resectable endometrial cancer. In this regard, we suggest a window of opportunity study of induction PD-1 blockade (nivolumab) in patients with surgically resectable MMRd endometrial cancer. Methods: We designed a single-arm phase 2 investigatorinitiated study utilizing the nivolumab, an anti PD-1 blockade, in patients with surgically completely resectable mismatch repair deficient endometrial cancer. Additional inclusion criteria include clinical stage I-IIIC2, tumor specimen that demonstrates MMRd by immunohistochemistry or microsatellite instability as demonstrated by next-generation sequencing or polymerase chain reaction. Exclusion criteria include multiple primary cancers, residual adverse effects of prior therapy or effects of surgery. Patients are treated with nivolumab IV 480 mg every 4 weeks up to 6 months followed by standard surgery and/or adjuvant treatment. The primary endpoint of the study is the complete response rate of PD-1 blockade and surgery. Secondary endpoints include objective response rate, progression-free survival, overall survival, and adverse events. Correlative studies include genomic characterization of tumors, assessment of immune infiltration of tumor microenvironment, and serial circulating cell-free DNA and immune biomarkers. Thirty patients will be enrolled at 4 South Korea sites. The Simon's 2-stage minimax design was used. Complete response rate from the unacceptable rate of 27.5% to an acceptable rate of 50% with type I error of 0.05 and 80% power. In the first stage, we would enroll 15 patients. If there are 4 or fewer responders, the study will stop for futility; if there are 13 or more complete responders the study will stop for efficacy. In the second stage, we will enroll an additional 15 patients for a total of 30 patients on study. [ABSTRACT FROM AUTHOR]

Objective: To analyze the effect of ovarian cancer related biomarkers and chemotherapy response score (CRS) on progression-free survival (PFS) and overall survival (OS) in advanced ovarian cancer patients treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: We retrospectively analyzed the medical records of 63 advanced-stage ovarian cancer patients who received NAC and underwent IDS with HIPEC at the Yonsei Cancer Center from 2015 to 2022. PFS and OS were compared in patients with and without BRCA1/2 mutation, TP53 mutation and programmed cell death-ligand 1 (PD-L1) expression. The effect of each biomarker and CRS on survival was evaluated. Results: BRCA1/2 mutations were detected in 23 (37.7%) of the 61 patients. PFS and OS were not significantly associated with BRCA1/2 mutation (p=0.522 and p=0.052, respectively). TP53 mutation was detected in 32 (80.0%) of the 40 patients. TP53 mutation was not significantly associated with either improved PFS (p=0.868) or OS (p=0.427). PD-L1 expression was detected in 4 (10.8%) of the 37 patients (immunohistochemistry cut-off value: 22C3 combined positive score, 10; 22C3 TPS, 1%; SP263, 25%). PD-L1 expression was significantly associated with longer PFS (p=0.029) but not with OS (p=0.270). Thirty-seven patients had CRS 1/2 and 19 had CRS 3. PFS was significantly improved in CRS 3 patients than CRS 1/2 patients (p=0.032). OS was not different from each CRS group (p=0.451). Conclusion: PD-L1 expression and CRS were significantly associated with longer PFS, but not with OS among patients with advanced ovarian cancer treated with IDS-HIPEC. [ABSTRACT FROM AUTHOR]

Objective: Clinical trials provide access to novel treatment strategies, which may offer survival benefits to ovarian cancer patients. We sought to determine if participation in any clinical trial is associated with a survival benefit in patients with newly diagnosed advanced-stage ovarian cancer. Methods: We retrospectively investigated the patients who treated for newly diagnosed advanced-stage ovarian cancer at Yonsei Cancer Hospital between 2019 and 2021. This study included 202 patients with stage III-IV, 82 patients who participated in clinical trials and 120 participants receiving standard of care therapy (SOC). Results: The median follow-up duration was 31.5 months. Disease recurrence occurred in 123 (60.9%) patients and 45 (22.3%) patients died. Among the patients in both groups, there were no significant differences in age, histologic type, stage, median cancer antigen 125 level, comorbidities, and BRCA 1/2 status. There were also no differences in the incorporation of hyperthermic intraperitoneal chemotherapy, neoadjuvant chemotherapy, residual disease after cytoreductive surgery. The patients involved in clinical trials were associated with significantly improvement in progression-free survival (PFS) (31.4 vs. 19.2 months; hazard ratio=0.67; 95% confidence interval=0.46-0.97; p=0.034) compared to SOC. There was no difference in overall survival between 2 groups (p=0.164). Conclusion: Clinical trial participation was associated with improved PFS in patients with newly diagnosed advanced-stage ovarian cancer. Clinical trial participation is considered to be beneficial to patients with newly diagnosed advanced-stage ovarian cancer. [ABSTRACT FROM AUTHOR]

Objective: The tumor immune microenvironment (TIME) have not been clearly defined in clear cell ovarian cancer (CCC). We analyzed the immunologic changes from treatment-naive to recurrence to correlate them with clinical outcomes. Methods: We compared the changes in the immune infiltration of advanced-stage CCC samples before treatment and at the time of recurrence via immunohistochemistry (programmed death-ligand 1 [PD-L1], CD8, forkhead box P3 [FOXP3]), tumor infiltration lymphocytes (TIL) and next-generation sequencing (NGS) (54 paired samples). We analyzed the association between platinum-sensitivity status and TIME. Results: Immunohistochemistry showed significantly increased PD-L1 (p=0.048) and CD8 (p=0.022) expression levels after progression. There was no significant difference in the TIL density and FOXP3 expression level. The most common genomic alterations were in PIK3CA (41.7%). ARID1A (41.7%) and ERBB2 amplification (11.1%). There were no differences in immunologic changes and survival outcomes according to PIK3CA and ARID1A mutation. Of 54 patients, 42 were platinum sensitive and 12 resistant. In patients with recurrent platinum sensitive disease showed higher level of TIL expression. There was no significant difference in the PD-L1, CD8 and FOXP3 expression level between platinum-sensitive and platinum-resistant disease. Conclusion: We characterized the TIME of patients with advanced-stage CCC. PD-L1 and CD8 expression was significantly increased after progression. Whether this could select patients for immunotherapy in the recurrence setting should be investigated. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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<0.001). Patients in the ddPC group underwent dose-reduction more frequently (34.8% vs. 4.00%, p=0.001). Normalization of cancer antigen-125 post-NAC occurred more frequently in the ddPC group (73.9% vs. 46.0%, p=0.030). No residual disease rate (43.5% vs. 60.0%, p=0.188) and chemotherapy response score of 3 (34.8% vs. 26.0%, p=0.441) were not statistically different between two groups. There was no statistical difference in progression free survival (PFS) at 2 years (36.3% vs. 28.4%, p=0.454). Cox proportional hazard model showed that ddPC was not a significant determinant of PFS (p=0.816). Conclusion: There was no difference between both regimens in terms of NAC response and survival outcomes. However, ddPC group showed higher hematologic toxicity requiring dose reduction. [ABSTRACT FROM AUTHOR]

Recent epidemiological research has indicated that men have increased health risks due to biological and social factors. Research in the area of men's health has been focused on disease events and subsequent disabilities. In future aging societies, more attention should be paid to the importance of men's health because a decreased quality of life and increased social burden are impending unless proper maneuvers are taken to slow the development and progression of morbidity through the use of preventive strategies. The adoption of a healthier lifestyle and the early identification and management of risk factors are very important and can be an initiative for prevention and for slowing the progression of morbidities with related quality of life issues. Males are rather vulnerable in terms of health, and conscious and active efforts are required to promote their health in an aging society. Here, we hope to shed light on the influence of lifestyle modifications and their clinical implications on men's health. [ABSTRACT FROM AUTHOR]

An osteochondral fracture is considered to be an injury involving the cartilage and subchondral bone. Acute traumatic osteochondral fractures can be related to joint instability because abnormal joint motion causes shearing and rotatory stress. Acute osteochondral fractures are frequently missed or misdiagnosed as a pure soft tissue injury. Thus, surgeons' proactive attention is highly required as articular cartilage has limited potential for self-repair and these lesions may develop osteoarthritis. In order to minimize the progression of posttraumatic osteoarthritis, it is important to properly identify and treat osteochondral fractures. Yet, little is known about the operative management of acute osteochondral fractures of the talus. We report here on a case of a middle-aged male with acute osteochondral fractures of the bilateral lateral talar dome. We applied different operative methods on each side with regard to fragment size and stability. A favorable clinical outcome was obtained at 18 months follow-up. [ABSTRACT FROM AUTHOR]

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/m2) 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 advancedstage 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<0.001), cytoreductive surgery to no-residual disease (21.5% vs. 10.2%; p<0.001), or radical surgery (57.5% vs. 35.6%; p<0.001). However, there was no between-group difference in postoperative morbidity. Kaplan-Meier analysis showed no between-group differences in progression-free or overall survival (p=0.449 and 0.952, respectively). Conclusion: NAC incorporation resulted in increased optimal cytoreduction rates although no significant differences in survival outcomes were noted. NAC is advantageous for patients with high perioperative morbidity or unresectable disease. [ABSTRACT FROM AUTHOR]

We propose a compact and easy to use photoacoustic imaging (PAI) probe structure using a single strand of optical fiber and a beam combiner doubly reflecting acoustic waves for convenient detection of lymph nodes and cancers. Conventional PAI probes have difficulty detecting lymph nodes just beneath the skin or simultaneously investigating lymph nodes located in shallow as well as deep regions from skin without any supplementary material because the light and acoustic beams are intersecting obliquely in the probe. To overcome the limitations and improve their convenience, we propose a probe structure in which the illuminated light beam axis coincides with the axis of the ultrasound. The developed PAI probe was able to simultaneously achieve a wide range of images positioned from shallow to deep regions without the use of any supplementary material. Moreover, the proposed probe had low transmission losses for the light and acoustic beams. Therefore, the proposed PAI probe will be useful to easily detect lymph nodes and cancers in real clinical fields. [ABSTRACT FROM AUTHOR]

We present the case of a patient with acromegaly who had pancytopenia with hypopituitarism secondary to the excision of a pituitary macroadenoma and radiation therapy. A 28-year-old man presented with pancytopenia and serum electrolyte abnormalities. He was diagnosed with acromegaly and underwent surgery and gamma-knife radiotherapy for a pituitary macroadenoma at the age of 22 years. A recent brain magnetic resonance imaging showed an empty sella, and the basal hormonal profile demonstrated deficiencies of pituitary hormones except thyrotropin. As presenting pancytopenia, his bone marrow biopsy showed hypocellular marrow. The total number of hemocytes increased after hydrocortisone replacement. Hypopituitarism was a possible cause of pancytopenia, and glucocorticoids had crucial effects on converting pancytopenia to normal in this case. [ABSTRACT FROM AUTHOR]

Eukaryotic cells have evolved mechanisms for ensuring growth and survival in the face of stress caused by a fluctuating environment. Saccharomyces cerevisiae has two homologous glycerol-3-phosphate dehydrogenases, Gpd1 and Gpd2, that are required to endure various stresses, including hyperosmotic shock and hypoxia. These enzymes are only partially redundant, and their unique functions were attributed previously to differential transcriptional regulation and localization. We find that Gpd1 and Gpd2 are negatively regulated through phosphorylation by distinct kinases under reciprocal conditions. Gpd2 is phosphorylated by the AMP-activated protein kinase Snf1 to curtail glycerol production when nutrients are limiting. Gpd1, in contrast, is a target of TORC2-dependent kinases Ypk1 and Ypk2. Inactivation of Ypk1 by hyperosmotic shock results in dephosphorylation and activation of Gpd1, accelerating recovery through increased glycerol production. Gpd1 dephosphorylation acts synergistically with its transcriptional upregulation, enabling long-term growth at high osmolarity. Phosphorylation of Gpd1 and Gpd2 by distinct kinases thereby enables rapid adaptation to specific stress conditions. Introduction of phosphorylation motifs targeted by distinct kinases provides a general mechanism for functional specialization of duplicated genes during evolution. [ABSTRACT FROM AUTHOR]

The current literature suggests that linolenic acid biohydrogenation converts to stearic acid without the formation of CLA. However, a multitude of CLA were identified in the rurnen that are generally attributed to linoleic acid biohydrogenation. This study used a stable isotope tracer to investigate the biohydrogenation intermediates of 13C-linolenic acid, including CLA. A continuous culture fermenter was used to maintain a mixed microbial population obtained from the rumen of cattle at pH 6.5 for 6 d. The mixed fermenter contents were then transferred to batch cultures containing either 13C-labeled or unlabeled linolenic acid, which were run in triplicate for 0, 3, 24, and 48 h. The 13C enrichment was determined by GC-MS. After 48 h of incubation, 8 CLA isomers were significantly enriched, suggesting that these CLA isomers originated directly from linolenic acid. The cis-10, cis-12 CLA isomer exhibited the highest enrichment (21.7%), followed by cis-9, cis-11 and trans-8, trans-10 CLA. The enrichment of these 2 CLA isomers ranged from 20.1 to 21.1% and the remaining 5 CLA including cis-9, trans-11 CLA were <15.0%. A multitude of nonconjugated and partially conjugated 18:2 and 18:3 isomers was enriched during the 48 h of incubation. The results of this study confirm that mixed ruminal microbes are capable of the formation of several CLA and 18:3 isomers from linolenic acid, indicating that linolenic acid biohydrogenation pathways are more complex than previously reported. [ABSTRACT FROM AUTHOR]

Background: It has been observed that hepatic steatosis is related to an increased risk of cardiovascular disease (CVD). Alanine aminotransferase (ALT), an indicator of the severity of hepatic steatosis is also associated with CVD. This study focused on the relationship between hepatic steatosis and ALT with coronary calcification. Methods: We performed a cross-sectional study to examine the association between hepatic steatosis and serum ALT with coronary calcification in 1218 subjects (772 men, 446 women; ages 30-75 years). We evaluated hepatic steatosis and ALT as categorical variables, and constructed four groups (reference group; only with hepatic steatosis; only with ALT >30 U/L; with both hepatic steatosis and ALT >30 U/L), which did not overlap. Multi-detected row computed tomography (MDCT) was used to measure coronary calcium score. Results: The adjusted ORs (95% CIs) for coronary calcification in the four groups were 1.00 (reference), 1.24 (0.68-2.26), 1.82 (0.78-4.23), and 2.12 (1.08-4.20) after adjusting for confounding variables. In addition, an increase in serum ALT activity of 10 U/L was associated with an increased risk of coronary atherosclerosis. Conclusions: In summary, patients with both hepatic steatosis and increases in ALT are associated with coronary calcification as a marker of coronary atherosclerosis determined by MDCT. This finding suggested that subjects with both hepatic steatosis and increased ALT should be considered for further evaluation of coronary atherosclerosis. Clin Chem Lab Med 2010;48:1829-34. [ABSTRACT FROM AUTHOR]

Background: C-reactive protein (CRP) has emerged as an important predictor for cardiovascular disease (CVD). To facilitate clinical and public health interventions, CRP thresholds have been defined as follows: low-risk (<1.0 mg/L), average-risk (1.0–3.0 mg/L), and high-risk (>3.0 mg/L). However, these cut-off thresholds are based on distributions in Western populations, and do not distinguish between men and women. Methods: We examined CRP distribution, gender difference, and determinants of CRP concentrations ranging from 0.02 mg/L to 10.0 mg/L, in 4923 Korean adults (2248 men; 2675 women) who received health checkups at Gangnam Severance Hospital from March 2006 to May 2007. Results: The distribution of CRP was highly skewed toward lower concentrations. CRP was higher in men than women, and the cut-off thresholds for the high-risk tertile of CRP concentrations corresponded to 1.01 mg/L in men and 0.62 mg/L in women, based on the current study population. Age, male gender, cigarette smoking, physical activity, body mass index, total cholesterol, high density lipoprotein cholesterol, γ-glutamyltransferase, and uric acid were independently associated with CRP concentrations. Conclusions: CRP distribution and gender difference in Korean adults were found to be different from previous Western studies, although similar risk factors influence CRP concentrations. Our results suggest that ethnicity and gender specific cut-off thresholds for CRP concentrations should be taken into consideration in CVD risk assessment. Clin Chem Lab Med 2009;47:863–9. [ABSTRACT FROM AUTHOR]

One of the current limitations in using electrospun nanofibrous materials for tissue engineering is that cells have difficulty penetrating into the materials. For this, multi-layered electrospun structures composed of polyurethane (PU) and poly(ethylene oxide) (PEO) were fabricated and tested in vitro. A 20% (w/v) PU solution was electrospun for 30 min, while a 20% (w/v) PEO solution was electrospun for 5, 15 or 30 min, alternatively. Then, the PEO was extracted by immersing the structure in distilled water to make multi-layered structure. The characteristics of fabricated structures were examined by SEM, FT-IR spectroscopy, mechanical tests and cell penetration test. The bioactivities of smooth muscle cells (SMCs) on these scaffolds were assessed by quantifying DNA, collagen and glycosaminoglycan (GAG) levels. Although hybrid PEO-extracted scaffolds had a little of residual PEO, they were more penetrable than PU alone scaffolds. Also, they showed higher bioactivity than PU-alone scaffolds. The results of this study provided potential of this structure in the application not only to the development of artificial blood vessels but also to other types for tissue engineering. [ABSTRACT FROM AUTHOR]

Background: Elevated γ-glutamyltransferase (GGT) has emerged as an independent predictor of cardiovascular disease (CVD) which is increasingly viewed as an inflammatory disease. Thus, the mechanism underlying the link between elevated GGT and CVD may be inflammation. Methods: We examined the relationship between GGT and C-reactive protein (CRP) levels and white blood cell (WBC) count in 4562 Korean adults (2104 men, 2458 women). The odds ratio (OR) and 95% confidence interval (CI) for high CRP and WBC count (≥75th percentile) for both men and women were calculated across each quartile of serum GGT. Results: Results for the OR (95% CI) for high CRP levels by GGT quartiles were 1.00, 1.67 (1.21–2.29), 2.10 (1.51–2.93) and 2.51 (1.81–3.60) in men, and 1.00, 1.05 (0.65–1.68), 1.45 (0.79–2.02) and 2.16 (1.37–3.41) in women after adjustment for age, smoking status, alcohol intake, exercise, body mass index, blood pressure, fasting plasma glucose, triglyceride, high-density lipoprotein-cholesterol, and uric acid. Similarly, positive associations between serum GGT and WBC count were also observed. Conclusions: The present study demonstrates a positive correlation between GGT and two markers of inflammation, serum CRP and WBC count. Our findings suggest that serum GGT may be a surrogate inflammatory marker and a useful additional measure in assessing cardiovascular risk. Clin Chem Lab Med 2008;46:1410–5. [ABSTRACT FROM AUTHOR]

In this paper, we demonstrate efficient modeling approach for simulation, analysis, design, and optimization of multiport radio frequency microelectromechanical systems (RF MEMS) resonating structures embedded in RF circuits. An in-house finite element method (FEM) solver is utilized to develop accurate and efficient macromodels that capture all the essential characteristics of the device. Using the datasets generated from the FEM simulations, the artificial neural network models are trained for two-way mapping between the physical input and electrical output parameters. Realized model is implemented in a circuit simulator, enabling a simple yet accurate circuit simulator compatible modeling and optimization procedure instead of memory and time demanding FEM analysis. The derivation of dynamic macromodels with preserved electromechanical behavior of the multiport resonating structures is also presented. Capabilities of the proposed approach are demonstrated with several examples featuring capacitively actuated MEMS resonating structures: a clamped–clamped beam, a free–free beam, and a coupled clamped–clamped beam. © 2007 Wiley Periodicals, Inc. Int J RF and Microwave CAE, 2007. [ABSTRACT FROM AUTHOR]

We have identified TMPRSS6, a novel type 2 transmembrane serine protease. TMPRSS6 possesses all the signature motifs of the family of transmembrane serine proteases (TMPRSSs), including a transmembrane domain, an LDL receptor class A (LDLRA) domain, a scavenger receptor cysteine-rich (SRCR) domain, and a serine protease domain. The substrate specificity of TMPRSS6 is slightly different from those of other TMPRSS family members. Combined with the finding that TMPRSS6 is expressed strongly in the thyroid and weakly in the trachea, this may indicate that TMPRSS6 has a specialized role. [ABSTRACT FROM AUTHOR]

Objective: This study compared the surgical outcomes between patients who underwent single-port laparoscopy with sentinel lymph node biopsy in enhanced recovery after surgery (ERAS) program versus conventional laparoscopy with lymph node dissection for endometrial cancer. Methods: We retrospectively reviewed the data of patients with endometrial cancer who underwent either single-port laparoscopic surgery or conventional laparoscopic surgery from January 2021 to July 2023 in single institution, Yonsei Cancer Center. We evaluated intra- and postoperative outcomes, progression-free survival, overall survival (OS), and recurrence rate. Results: A total of 173 patients, including those undergoing single-port laparoscopy with sentinel lymph node biopsy in ERAS program (n=45) and conventional laparoscopy with lymph node dissection (n=128), were analyzed. There were no significant differences in survival: 3-year disease-free survival was 95.6% versus 91.4% (p=0.497) and OS was 100% versus 98.4% (p=0.4) in single-port laparoscopy with sentinel lymph node biopsy in ERAS protocol and conventional laparoscopic surgery cohorts, respectively. The single-port laparoscopy with sentinel lymph node biopsy in ERAS protocol group had the longer operative time (205.0±56.3 minutes) but the less blood loss (47.3±90.9 mL) and the shorter postoperative hospital stay (2.0±0.9 days). In contrast, the conventional laparoscopic surgery group had the shorter operative time (133.6±56.3 minutes) but the more blood loss (55.5±69.8 mL) and the longer postoperative hospital stay (4.6±2.4 days). Conclusion: Single-port laparoscopic surgery with sentinel lymph node sampling in ERAS protocol for endometrial cancer demonstrates comparable survival outcomes and quick recovery. [ABSTRACT FROM AUTHOR]

Objective: GI-101 (CD80-IL2v) is an innovative immunocytokine designed to direct IL2v to tumor and immune cells. The IL2v of GI-101 is engineered to enhance the expansion of cytotoxic T and natural killer (NK) cells but not regulatory T (Treg) cells, and CD80 further inhibits immunosuppressive function of Treg cells. Early data from phase 1/2 study was presented at European Society for Medical Oncology 2023; in 61 patients who received GI-101, monotherapy activity was confirmed with great safety and tolerability. GI-101 induced significant expansion of lymphocytes, CD8+ T and NK cell, which was correlated with prolonged progression-free survival. Here, we present results of patients with gynecological cancer enrolled in Part A of GII-101-P101 (KEYNOTE-B59, NCT04977453). Methods: This study is an ongoing phase 1/2 study of GI-101 monotherapy and its combination with various agents in patients with advanced/metastatic solid tumors. In Part A, dose escalation using a 3+3 design (0.002-0.3 mg/kg; every 3 weeks) established the recommended phase 2 dose of GI-101 at 0.3 mg/kg, followed by an expansion cohort. The primary endpoint was safety, tolerability and investigator-assessed objective response. Results: At the data cut-off of 21 January 2024, 10 patients with gynecologic cancer who had previously failed standard of care, 5 patients with metastatic cervical cancer (mCC), a patient with metastatic endometrial cancer (mEC) and 4 patients with metastatic ovarian cancer. received 0.3 mg/kg of GI-101. Patients were aged 39-72 years and were all Asian (n=10), had an Eastern Cooperative Oncology Group performance status of 0 (n=8) or 1 (n=2), and had a median of 3 prior lines of therapy (LoT, range: 1-10), including immune checkpoint blockade (ICB; n=4). Frequent (=50%) treatment-related adverse events were pyrexia (80%) and increased aspartate aminotransferase (80%) and alanine aminotransferase (70%), Among 10 patients, 1 confirmed complete response (cCR) and 1 unconfirmed partial response (uPR) were observed in mCC and mEC, respectively. The patient with mCC received 2 prior LoT, including ICB, and had tumor characteristics of proficient mismatch repair (pMMR) and programmed cell death ligand 1 (PD-L1) Combined positive score (CPS) 70. CR was observed after 2 cycles of GI-101, and the response was maintained for 12.4+ months (treatment duration 13.8+ months), indicating durable response induced by GI-101. Immune cell analysis revealed that the patient showed significant expansion of total lymphocytes, NK, CD8+ T and central memory T (Tcm) cells, 2.9, 1.9, 1.4, and 2.6-fold increase from baseline, respectively. The patient with mEC had multiple lung metastases and failed on 2 prior LoT, with tumor characteristics of pMMR, wild type p53 and PD-L1 CPS 35. After GI-101 treatment, the patient maintained stable disease (SD) for 8.2 months and the tumor turns to reduce by -36 % from 9.7 month of the treatment, evaluated as uPR (treatment duration 11.5+ months). The patient's peripheral blood showed robust expansion of total lymphocytes, NK, CD8+ T and Tcm cells (2.8, 5.7, 2.5, and 2.8-fold change from baseline, respectively). In 4 ovarian cancers with a median 5 prior LoT (range: 3-10), all patients' best target lesion reduction is assessed as SD showing 100% disease control rate. Conclusion: GI-101 was generally well-tolerated and provided evidence of tumor response and disease control in patients with gynecological cancer, regardless of previous anti-PD(L)1 therapies. The response kinetics showed both immediate and delayed tumor reduction after GI-101 treatment. Further exploration for new therapeutic option utilizing GI-101 in gynecological cancer is warranted. [ABSTRACT FROM AUTHOR]

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

The Korean Society of Gynecologic Oncology (KSGO) had been making an effort to standardize and enhance the quality of domestic uterine corpus cancer treatment by developing updated clinical practice guidelines in 2021. The KSGO revised the guidelines based on a literature search using 4 key elements: Population, Intervention, Comparison, and Outcome framework. These elements include the evaluation of the efficacy and safety of immune checkpoint inhibitor treatment in recurrent/advanced endometrial cancer patients who have failed platinum-based chemotherapy, as well as the effect of combined treatment with trastuzumab in patients with HER2/neu-positive endometrial cancer. Additionally, the guideline assessed the efficacy and safety of omitting lymph node dissection in low-risk endometrial cancer patients, investigated the effect of sentinel lymph node mapping in early-stage endometrial cancer surgery, addressed the outcome of chemoradiation therapy as a postoperative treatment in patients with advanced (stage III-IVA) endometrial cancer, and explored the impact of initial treatment with immune checkpoint inhibitors on survival in patients with advanced or recurrent endometrial cancer patients. [ABSTRACT FROM AUTHOR]

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is clinically important because of its association with an increased risk of sudden cardiac death as well as liver-related mortality. Most cases of sudden cardiac death could be mediated by an arrhythmogenic process. Thus, we aimed to determine the association between NAFLD and corrected QT (QTc) interval in apparently healthy Korean women. Methods: This cross-sectional study included 764 women aged 20 to 74 years old who underwent a health examination program between 2014 and 2015. The QTc interval was calculated using Bazett's formula (QTc = QT/vRR). Multiple linear and logistic regression analysis were performed to assess independent relationships between NAFLD and QTc interval and prolonged QTc (= 450 milliseconds) was calculated after adjusting for confounding variables. Results: The overall prevalence of NAFLD was 23.5% in general healthy women. The standardized ß coefficient (95% confidence interval) of the QTc increment in patients with NAFLD was 6.4 milliseconds (1.2-11.8) through multiple linear regression analysis after adjusting for age, body mass index, smoking status, and regular exercise as well as mean arterial pressure, fasting plasma glucose, triglycerides, high-density lipoprotein cholesterol, aspartate aminotransferase, alanine aminotransferase, calcium, potassium levels and menopause status. Similarly, the odds ratio (95% confidence interval) of NAFLD for prolonged QTc was 2.05 (1.13-3.71) according to multiple logistic regression analysis after adjusting for the same covariables in women aged 20 to 74 years old. Conclusion: We demonstrated the arrhythmogenic potential of NAFLD, implying that careful monitoring of patient electrocardiograms is necessary to evaluate the possible arrhythmic risk in general healthy women with NAFLD. [ABSTRACT FROM AUTHOR]

Objective : To analyze the outcomes of coil embolization (CE) for unruptured intracranial aneurysm (UIA) according to region and hospital size based on National Health Insurance Service data in South Korea. Methods : The incidence of complications, including intracranial hemorrhage (ICRH) and cerebral infarction (CI), occurring within 3 months and the 1-year mortality rates in UIA patients who underwent CE in 2018 were analyzed. Hospitals were classified as tertiary referral general hospitals (TRGHs), general hospitals (GHs) or semigeneral hospitals (sGHs) according to their size, and the administrative districts of South Korea were divided into 15 regions. Results : In 2018, 8425 (TRGHs, 4438; GHs, 3617; sGHs, 370) CEs were performed for UIAs. Complications occurred in 5.69% of patients seen at TRGHs, 13.48% at GHs, and 20.45% at sGHs. The complication rate in TRGHs was significantly lower than that in GHs (p=0.039) or sGHs (p=0.005), and that in GHs was significantly lower than that in sGHs (p=0.030). The mortality rates in TRGHs, GHs, and sGHs were 0.81%, 2.16%, and 3.92%, respectively, with no significant difference. Despite no significant difference in the mortality rates, the complication rate significantly increased as the number of CE procedures per hospital decreased (p=0.001; rho=-0.635). Among the hospitals where more than 30 CEs were performed for UIAs, the incidence of CIs (p=0.096, rho=-0.205) and the mortality rates (3 months, p=0.048, rho=-0.243; 1 year, p=0.009, rho=-0.315) significantly decreased as the number of CEs that were performed increased and no significant difference in the incidence of post-CE ICRH was observed. Conclusion : The complication rate in patients who underwent CE for UIA increased as the hospital size and physicians' experience in conducting CEs decreased. We recommend nationwide quality control policies CEs for UIAs. [ABSTRACT FROM AUTHOR]

Objective: Malignant ascites (MA) of epithelial ovarian cancer (EOC) represents tumor microenvironment including immune system. The objective of this study was to analyze the tumor immune microenvironment using tumor-associated lymphocyte (TAL) isolated from MA in EOC and to observe changes after EOC relapse. Methods: We collected MA, peripheral blood and tumor samples a total of 95 patients (51 treatment naïve and 44 recurrent EOC). TALs from MA, peripheral blood mononuclear cells (PBMC) from the blood, and tumor-infiltrating lymphocyte (TIL) from the tumor were obtained. The immune phenotypes of TALs were compared with TILs using flow cytometry. Results: The percentages of CD8 T cells expressing PD-1, TIM-3, Ki-67, TOX, and CD101 in TAL were higher than those in PBMCs and similar to those in TILs. When we compared frequencies of terminally exhausted CXCR5-CD101+PD-1+CD8 T cells (Ttex) among PBMCs, TALs, and TILs of naïve patients, frequencies of Ttex were significantly higher in TILs than TALs and PBMCs and positively correlated with those in TILs. The exhaustion status of CD8+ TALs was significantly correlated with that of CD8+ TILs in terms of the expression of TCF-1 (r=0.40, p=0.047). Patients expressing high frequency of Ttex in TALs showed a trend towards poorer overall survival compared to those with lower frequency of Ttex. Conclusion: CD8+ TALs demonstrated distinct immunologic properties compared to CD8+ TILs. The frequencies of CXCR5-CD101+PD-1+CD8 Ttex in TAL could serve as a prognostic biomarker in patients with EOC. Further studies are needed to investigate the role of Ttex in MA of EOC. [ABSTRACT FROM AUTHOR]

Objective: We aimed to discover the different immunological properties of tumor immune microenvironment in epithelial ovarian cancer (EOC) according to BRCA1/2 mutations (BRCA1/2muts) status and differential programmed cell death protein 1 (PD-1) expression levels. Methods: Tumor-infiltrating lymphocytes (TILs) were collected from patients with newly diagnosed advanced-stage EOC (Yonsei University Health System [YUHS] cohort, n = 117). This YUHS cohort was compared with The Cancer Genome Atlas data for ovarian serous cystadenocarcinoma (n=482), in terms of survival outcomes and immune-related gene profiles according to BRCA1/2 status. We used multicolor flow cytometry to characterize the immune phenotypes and heterogeneity of TILs with or without BRCA1/2muts. In vitro functional assays were conducted to evaluate the reinvigorating ability of CD8+ TILs upon anti-PD-1 treatment. Results: We found that EOC patients with BRCA1/2muts exhibited better survival outcomes and significantly higher tumor mutation burden, compared to BRCA1/2 wild type (BRCA1/2wt) patients. Furthermore, CD8+ TILs within BRCA1/2mut tumors displayed characteristics indicating more severe T-cell exhaustion than their BRCA1/2wt counterparts. Notably, the capacity for anti-PD-1- mediated reinvigoration of CD8+ TILs was significantly greater in BRCA1/2wt tumors compared to BRCA1/2mut tumors. Additionally, within the BRCA1/2wt group, the frequency of PD-1high CD8+ TILs was positively correlated with the reinvigoration capacity of CD8+ TILs after anti-PD-1 treatment. Conclusion: Our results highlight unique immune features of CD8+ TILs in EOC and a differential response to anti-PD-1 treatment, contingent upon BRCA1/2mut status. These findings suggest that immune checkpoint blockade may be a promising frontline therapeutic option for selected BRCA1/2wt EOC patients. [ABSTRACT FROM AUTHOR]

Objective: The trend in the initial severity of aneurysmal subarachnoid hemorrhage (SAH) is unclear. This study aimed to evaluate whether there was an improvement in the initial severity of SAH over time. Methods: From January 1, 2005, to December 31, 2020, we identified patients who visited the emergency department of our institution with SAH due to intracranial aneurysm rupture. We identified the Hunt Hess (HH) grade and modified Fisher grade of each patient from the medical records, and the Mann-Kendal method was used to estimate the trend of each grade system. Results: A total of 547 patients with SAH were identified. The mean age of the patients was 59.3 years (standard deviation (SD), 14.6). The mean aneurysm size was 6.9 mm (SD, 4.6 mm). The most frequent aneurysm location was the anterior communicating artery (28.7%). In the Mann-Kendal estimates for the analysis of the trend, there was no statistically significant grade throughout the HH and modified Fisher grades. Similarly, there was no improvement throughout all grades in the modified Fisher grade over time. Conclusions: The initial severity of SAH due to cerebral aneurysm rupture did not improve over time. [ABSTRACT FROM AUTHOR]

Purpose: Matrix metalloproteinases (MMPs) have been implicated in atherosclerosis, and therefore, are considered risk factors for metabolic dysfunction in adults. However, there is little data regarding circulating levels of MMPs and tissue inhibitors of MMPs (TIMPs) in the general adolescent population with regard to obesity-related biomarkers. In the present study, we determined the associations of MMP-8, MMP-9, and TIMP-1 levels and MMP-8/TIMP-1 and MMP-9/TIMP-1 ratios with obesityrelated biomarkers in apparently healthy adolescent boys. Methods: We measured MMP and TIMP concentrations in plasma samples using the enzyme-linked immunosorbent assay and analyzed their associations with obesity-related biomarkers, such as liver enzymes and lipid profiles, in a sample of 91 Korean boys aged 13–14 years who participated in a general health check-up. Results: The mean age of the boys was 13.8±0.3 years; 72 boys were normal weight and 19 were overweight/obese. The Pearson correlation coefficients revealed a significant correlation between MMP-8 and aspartate aminotransferase (r=0.217, P =0.039) and alanine aminotransferase (r=0.250, P =0.017) and between TIMP-1 and aspartate aminotransferase (r=0.267, P =0.011). In a multivariate linear regression analysis, serum alanine aminotransferase was positively associated with the MMP-8 level. There were no significant differences in the MMP-8, MMP-9, and TIMP-1 levels or MMP-8/ TIMP-1 and MMP-9/TIMP-1 ratios between control and overweight/obese subjects. Conclusion: We found a significant association between the MMP-8 level and alanine aminotransferase in the apparently healthy adolescent boys. These findings indicate that there may be a pathophysiological mechanism underlying the relationship between MMP-8 and liver enzymes in young adolescents. [ABSTRACT FROM AUTHOR]

Objective: This study aims to identify distinct immune characteristics of tumor-infiltrating lymphocytes (TILs) according to molecular classification for an optimal therapeutic strategy in endometrial cancer. Methods: We isolated peripheral blood mononuclear cells and TILs from 81 patients. The expression of immune checkpoint receptors (ICRs) and T-cell transcription factors of TILs were examined using flowcytometry. Fourteen fresh frozen tumor tissues were processed for bulk RNA sequencing. The formalin-fixed, paraffin-embedded biopsies of patients (n=66) were evaluated according to the ProMisE algorithm based on immunohistochemistry for mismatch repair (MMR) proteins and p53, sequencing for the presence of POLE mutations; POLE-mutated (POLE), MMR deficient (MMRd), p53-abnormal (p53abn), and non-specific molecular profile (NSMP). Results: Immune exhausted genes (PDCD1, CTLA-4, TIGIT, TOX, ENTPD-1) are upregulated in high mutational load group (POLE+MMRd). In gene set enrichment analysis, upregulated gene sets in regulatory T (Treg) cells (GSE14415) were enriched in POLE+MMRd. Sixty-six tumors were classified to POLE (n=6), MMRd (n=17), NSMP (n=23) and p53abn (n=20). CD8+TILs of POLE+MMRd showed higher expression of ICRs (PD-1, TIM-3, CD39, TOX) than those of NSMP and p53abn, also, lower expression of TCF-1. CTLA-4+, TIGIT+ Treg cells were more infiltrated in MMRd than NSMP. Immune exhausted markers (PD-1, TIGIT, CD39, TOX, CD101) are enriched in CD8+ TILs of L1CAM(+) NSMP than those of L1CAM(-) NSMP. Conclusion: CD8+TILs of POLE+MMRd highly expressed ICRs and were more exhausted compared to those of others, providing evidence for immunotherapy. TIGIT and PD-1 blockade for L1CAM(+) NSMP were considered promising. there is needed for clinical trials to optimize immunotherapy according to molecular subtypes. [ABSTRACT FROM AUTHOR]

Vitamin D is an essential component of bone and mineral metabolism; its deficiency causes growth retardation and skeletal deformities in children and osteomalacia and osteoporosis in adults. Hypovitaminosis D (vitamin D insufficiency or deficiency) is observed not only in adults but also in infants, children, and adolescents. Previous studies suggest that sufficient serum vitamin D levels should be maintained in order to enhance normal calcification of the growth plate and bone mineralization. Moreover, emerging evidence supports an association between 25-hydroxyvitamin D (25[OH]D) levels and immune function, respiratory diseases, obesity, metabolic syndrome, insulin resistance, infection, allergy, cancers, and cardiovascular diseases in pediatric and adolescent populations. The risk factors for vitamin D insufficiency or deficiency in the pediatric population are season (winter), insufficient time spent outdoors, ethnicity (non-white), older age, more advanced stage of puberty, obesity, low milk consumption, low socioeconomic status, and female gender. It is recommended that all infants, children, and adolescents have a minimum daily intake of 400 IU (10 μg) of vitamin D. Since the vitamin D status of the newborn is highly related to maternal vitamin D levels, optimal vitamin D levels in the mother during pregnancy should be maintained. In conclusion, given the important role of vitamin D in childhood health, more time spent in outdoor activity (for sunlight exposure) and vitamin D supplementation may be necessary for optimal health in infants, children, and adolescents. [ABSTRACT FROM AUTHOR]

Background: The ratio of triglycerides (TG, mg/dl) to high-density lipoprotein cholesterol (HDL-C, mg/dl) is a reliable indicator of insulin resistance and atherosclerotic diseases. The purpose of this study was to examine the association between TG/HDL-C and chronic kidney disease (CKD) in a nationally representative sample of Korean adults. Methods: This cross-sectional study included 5,503 subjects (≥19 years of age) who participated in the 2005 Korean National Health and Nutrition Examination Survey. CKD was defined as an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2 as calculated by the abbreviated formula from the Modification of Diet in Renal Disease study. Results: The overall prevalence of CKD in our sample was 9.0%. eGFR was negatively correlated with logarithm-transformed TG/HDL-C in Pearson's correlation. The prevalence of CKD in increasing TG/HDL-C quintiles was 4.4, 6.6, 9.5, 11.9, and 12.8%. In comparison with the lowest quintile of TG/HDL-C (<1.38), the odds ratio (95% confidence interval) for CKD in the highest quintile of TG/HDL-C (≥4.50) was 2.15 (1.38-3.37), after adjustment for multiple covariates (p value for trend = 0.036). Conclusions: TG/HDL-C was independently associated with increased prevalence of CKD in a sample of Korean adults. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background & Aims: The fatty liver index (FLI) is a simple and non-invasive method for the diagnosis of fatty liver disease with an increased risk of cardiovascular disease (CVD) as well as liver-related mortality. We examined the association between FLI and 10-year CVD risk as determined by the Framingham risk score. Methods: This cross-sectional study included 7,240 individuals aged 30 to 69 years who underwent a health examination between 2015 and 2017. The FLI was calculated using an algorithm based on triglyceride, β-glutamyltransferase, body mass index (BMI), and waist circumference. Multiple linear and logistic regression analyses were performed to assess independent relationships between the FLI and Framingham risk score after adjusting for confounding variables. Results: The overall prevalence of fatty liver disease among study participants as assessed by an FLI = 60 was 19.7%. Compared with non-hepatic steatosis (FLI < 30), the odds ratio (95% confidence interval) for a high Framingham 10-year CVD risk = 10% in individuals with hepatic steatosis (FLI = 60) was 2.56 (1.97-3.33) after adjusting for age, gender, fasting plasma glucose, high-density and low-density lipoprotein cholesterol, blood pressure, C-reactive protein, regular exercise, alcohol-drinking, and current smoking. Conclusions: The FLI was positively and independently associated with a Framingham 10-year CVD risk in the general Korean population. Our findings suggest that the FLI, a simple, useful, and economical index, may be an indicator of CVD events. [ABSTRACT FROM AUTHOR]

There has been a growing demand for developing naturally occurring non-meat ingredients, which could replace or reduce synthetic additives that have been used extensively in manufacturing processed meat products. Chitin, which is a major component of crustacean shells and a precursor of chitosan, is the second most abundant polysaccharide followed by cellulose. While some functional properties of chitin such as water/fat binding capacity and emulsifying ability have been reported, there are almost little to no studies determining the efficacy of chitin as a non-meat ingredient. The objective of this study was to evaluate the functional properties of chitins as a novel non-meat ingredient for manufacturing emulsified sausages. Fresh pork hind leg and pork back fat from 9 carcasses at 4 d postmortem were obtained. The trimmed pork hind legs were randomly assigned into three independent batches for emulsion and sausage production. Chitins were extracted from chitin-like material (CLM) from two different crustacean shell sources, such as crawfish (CF) and blue crab (BC). The CLM were extracted and used in the following order: dryingdeproteinization (1% calcium oxide)-demineralization (2N HCl)-deacetylation (6M NaOH). For the emulsion and sausage manufacturing, control was prepared with 70% raw meat, 18% backfat, 10% water, 1.5% sodium chloride and 0.5% sodium phosphate. The treatments were prepared with 70% raw meat, 18% backfat, 10% water, 1.5% sodium chloride, 0.2% phosphate, and 0.5% CLM. The functional properties of CLM were evaluated by measuring binding capacity, emulsion capacity, and color attributes. For the evaluation of meat batter and emulsified sausage products, instrumental color, texture profile analysis, emulsion stability, cooking loss, and pH were measured. The data analysis was conducted by mixed model, and least squares means for all traits were separated (F-test, P < 0.05) by using least significant differences. No significant difference in the color attributes of meat batter between the control and the treatments (CF and BC) was found. The chitin added products from both CF and BC had a greater emulsion stability, where the treatment showed about two time greater in emulsion stability compared with control (P < 0.05). In particular, chitin extracted from CF showed greater water and fat binding capacity than CB (P < 0.05). In the emulsified sausage, the treatments showed significantly greater redness and hardness than control (P < 0.05). In particular, the CF showed greater cohesiveness and gumminess than control or BC (P < 0.05). The results of the present study showed the beneficial impacts of chitin addition for meat emulsions. The chitin inclusion improved the quality characteristics of emulsified sausage such as textural properties and emulsion stability, while less amount of phosphate was added compared with control. Additionally, chitin from crawfish had superior functional properties to that from blue crab, indicating different chitin functionality between crustacean shell sources. [ABSTRACT FROM AUTHOR]

Purpose: Little is known regarding the extent to which dying patients with chronic obstructive pulmonary disease (COPD) receive life-sustaining procedures and palliative care in U.S. hospitals. We examine hospital cost trends and the impact of palliative care utilization on the use of life-sustaining procedures in this population. Methods: Retrospective nationwide cohort analysis was performed using National Inpatient Sample (NIS) data from 2005 and 2014. We examined the receipt of both palliative care and intensive medical procedures, defined as systemic procedures, pulmonary procedures, or surgeries using the International Classification of Diseases, 9th revision (ICD-9-CM). Results: We used compound annual growth rates (CAGR) to determine temporal trends and multilevel multivariate regressions to identify factors associated with hospital cost. Among 77,394,755 hospitalizations, 79,314 patients were examined. The CAGR of hospital cost was 5.83% (P＜0.001). The CAGRs of systemic procedures and palliative care were 5.98% and 19.89% respectively (each P＜0.001). Systemic procedures, pulmonary procedures, and surgeries were associated with increased hospital cost by 59.04%, 72.00%, 55.26%, respectively (each P＜0.001). Palliative care was associated with decreased hospital cost by 28.71% (P＜0.001). Conclusion: The volume of systemic procedures is the biggest driver of cost increase although there is a cost-saving effect from greater palliative care utilization. [ABSTRACT FROM AUTHOR]

Background: It has not been determined which obesity index might be most appropriate to predict nonalcoholic fatty liver disease in Asian populations. This study aimed to evaluate the usefulness of the waist-to-height ratio in assessing patients with nonalcoholic fatty liver disease and to identify the optimal cut-off values useful for predicting nonalcoholic fatty liver disease. Methods: Receiver operating characteristic curve analyses were conducted in order to assess the accuracy of the waist circumference, body mass index, and waist-to-height ratio for detecting nonalcoholic fatty liver disease among 616 women aged 20 years or older. To evaluate the optimal value of anthropometric indices, the Youden J-index (sensitivity+specificity-1) was used. Results: The area under the ROC curve of waist-to-height ratio was highest among anthropometric obesity indices as follows: 0.776 (0.731- 0.822) for waist circumference, 0.775 (0.728-0.822) for body mass index, and 0.792 (0.748-0.836) for waist-to-height ratio, respectively. Using a waist-to-height ration cut-off value of 0.49, the sensitivity and specificity for detecting nonalcoholic fatty liver disease were 72.3% and 74.7%, respectively. Conclusion: These results demonstrated that the waist-to-height ratio may be a better obesity index for identifying individuals at risk for nonalcoholic fatty liver disease in Korean women. [ABSTRACT FROM AUTHOR]

The incidence of acute leukemia during pregnancy is extremely rare, and often it is not easy to differentiate it from other diseases associated with pregnancy such as sepsis or hemorrhage. Pregnancy itself is not known to affect the natural course of leukemia; however, complications of leukemia like anemia, infections, and coagulopathy can adversely influence both the fetus and the mother. In this case, a pregnant patient misdiagnosed with septic shock and severe leukocytosis was correctly diagnosed with acute myeloid leukemia after surgical delivery. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is associated with visceral obesity, insulin resistance and an increased risk of cardiovascular diseases. Visceral fat tissue primarily consists of adipocytes that secrete cytokines leading to a state of systemic inflammation in obese conditions. One of the IGF-independent functions of IGFBP-3 is its role as an anti-inflammatory molecule. Our study in obese adolescents show a decrease in total IGFBP-3 levels and increase in proteolyzed IGFBP-3 in circulation when compared to their normal counterparts and establishes a positive correlation between IGFBP-3 proteolysis and adiposity parameters as well as insulin resistance. In human adipocytes, we show that IGFBP-3 inhibits TNF-α-induced NF-κB activity in an IGF-independent manner, thereby restoring the deregulated insulin signaling and negating TNF-α-induced inhibition of glucose uptake. IGFBP-3 further inhibits TNF-α, CRP and high glucose-induced NF-κB activity in human aortic endothelial cells (HAECs) and subsequently suppresses monocyte adhesion to HAEC through the IGFBP-3 receptor. In conclusion, these findings suggest that reduced levels of IGFBP-3 in circulation and reduced expression of IGFBP-3 in macrophages in obesity may result in suppression of its anti-inflammatory functions and therefore IGFBP-3 may present itself as a therapeutic for obesity-induced insulin resistance and for events occurring in the early stages of atherosclerosis. [ABSTRACT FROM AUTHOR]

Bilateral adrenal neoplasms are associated with metastatic cancer, pheochromocytoma and lymphoma. The coexistence of a unilateral functioning adrenocortical adenoma with contralateral pheochromocytoma is extremely rare. A 52-year-old woman complained of fatigue, headache, palpitation, and progressive weight gain. Hormonal assessment demonstrated high 24 hours urine epinephrine, norepinephrine, and free cortisol. A dexamethasone suppression test (overnight 1 mg, low dose 2 mg) showed insuppressible cortisol. Computerized tomographic scanning revealed a bilateral adrenal tumor. To preserve adrenal function, right adrenalectomy along with left adrenal tumorectomy was performed. Histological finding of the right adrenal tumor was pheochromocytoma and the left adrenal tumor was adrenocortical adenoma. This patient was the first case of a functional adrenocortical adenoma with contralateral cystic pheochromocytoma in Korea. We report the case with a review of the literature. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) has emerged as an independent predictor for cardiovascular disease (CVD), which is now regarded as an inflammatory disease. This study aimed to determine the association of CKD with white blood cell (WBC) count as a marker of systemic inflammation. Methods: We examined the association of WBC count with CKD in 2825 Korean adults (1155 men, 1670 women) in the 2007 Korean National Health and Nutrition Examination Survey (KNHANES). CKD was defined as either proteinuria or a glomerular filtration rate (GFR) <60 mL/min/1.73 m2. The odds ratios (ORs) for CKD were calculated using multivariate logistic regression analysis after adjusting for confounding variables across gender-specific WBC count quartiles. Results: The proportion of CKD increased with increasing WBC quartiles, from 9.7% in the lowest quartile to 20.7% in the highest quartile for women. In multivariate logistic regression analysis, the corresponding odds ratios (95% confidence intervals [CIs]) for a CKD across WBC count quartiles among women were 1.00, 1.45 (0.91-2.31), 1.65 (1.03-2.63), and 2.11 (1.33-3.35), after adjusting for age, body mass index (BMI), systolic blood pressure, fasting plasma glucose, smoking status, current drinking high-density lipoprotein cholesterol (HDL-C), and triglyceride. In contrast, compared with women, men appeared to have no significant results of a relationship between WBC quartiles and CKD. Conclusions: Our study shows a significant association between WBC count and the risk for CKD in women. Accordingly, potential health benefits of early detection of a higher level of WBC count may be useful for CKD risk assessment in women. [ABSTRACT FROM AUTHOR]

Background: The nuclear inclusion a (NIa) protease of turnip mosaic virus (TuMV) is responsible for the processing of the viral polyprotein into functional proteins. NIa was previously shown to possess a relatively strict substrate specificity with a preference for Val-Xaa-His-Gln↓, with the scissile bond located after Gln. The presence of the same consensus sequence, Val12-His-His-Gln15, near the presumptive α -secretase cleavage site of the amyloid-β (Aβ) peptide led us to hypothesize that NIa could possess activity against Aβ. Methodology/Principal Findings: Western blotting results showed that oligomeric as well as monomeric forms of Aβ can be degraded by NIa in vitro. The specific cleavage of Aβ was further confirmed by mass spectrometry analysis. NIa was shown to exist predominantly in the cytoplasm as observed by immunofluorescence microscopy. The overexpression of NIa in B103 neuroblastoma cells resulted in a significant reduction in cell death caused by both intracellularly generated and exogenously added Aβ. Moreover, lentiviral-mediated expression of NIa in APPsw/PS1 transgenic mice significantly reduced the levels of Aβ and plaques in the brain. Conclusions/Significance: These results indicate that the degradation of Aβ in the cytoplasm could be a novel strategy to control the levels of Aβ, plaque formation, and the associated cell death. [ABSTRACT FROM AUTHOR]

We investigated the potential of a nanofiber-based poly(DL-lactide-co-glycolide) (PLGA) scaffold to be used for cartilage reconstruction. The mechanical properties of the nanofiber scaffold, degradation of the scaffold and cellular responses to the scaffold under mechanical stimulation were studied. Three different types of scaffold (lactic acid/glycolic acid content ratio = 75 : 25, 50 : 50, or a blend of 75 : 25 and 50 : 50) were tested. The tensile modulus, ultimate tensile stress and corresponding strain of the scaffolds were similar to those of skin and were slightly lower than those of human cartilage. This suggested that the nanofiber scaffold was sufficiently mechanically stable to withstand implantation and to support regenerated cartilage. The 50 : 50 PLGA scaffold was degraded faster than 75 : 25 PLGA, probably due to the higher hydrophilic glycolic acid content in the former. The nanofiber scaffold was degraded faster than a block-type scaffold that had a similar molecular weight. Therefore, degradation of the scaffold depended on the lactic acid/glycolic acid content ratio and might be controlled by mixing ratio of blend PLGA. Cellular responses were evaluated by examining toxicity, cell proliferation and extracellular matrix (ECM) formation using freshly isolated chondrocytes from porcine articular cartilage. The scaffolds were non-toxic, and cell proliferation and ECM formation in nanofiber scaffolds were superior to those in membrane-type scaffolds. Intermittent hydrostatic pressure applied to cell-seeded nanofiber scaffolds increased chondrocyte proliferation and ECM formation. In conclusion, our nanofiber-based PLGA scaffold has the potential to be used for cartilage reconstruction. [ABSTRACT FROM AUTHOR]

The light extraction characteristics of low-index spin-on-glass (SOG)-assisted, planarized photonic crystal organic light-emitting diodes (PC OLEDs) are reported. The light extraction efficiencies of planarized two-dimensional (2D) SiNx/SOG PC OLEDs (type II) and 2D SiNx/SOG PC OLEDs with an additional high-index SiNx layer (type III) are significantly better under typical operating conditions than those of the first generation of 2D SiO2/SiNx PC OLEDs (type I). The enhancements in the extraction efficiencies of type-II and type-III PC OLEDs are about 63% and 85%, respectively, with respect to those of conventional OLEDs with indium tin oxide layers of identical thicknesses. These improvements in extraction efficiencies are attributed not only to the liberation of the photons trapped in the high-index guiding layer but also to a reduction in the surface plasmon contribution. [ABSTRACT FROM AUTHOR]