Publications by authors named "Sung-Hoon Kim"

1,165 Publications

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Single-Incision versus Multiport Robotic Myomectomy: A Propensity Score Matched Analysis of Surgical Outcomes and Surgical Tips.

J Clin Med 2021 Aug 31;10(17). Epub 2021 Aug 31.

Department of Obstetrics and Gynecology, Seoul Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.

We aimed to compare the perioperative outcomes of single-incision robotic myomectomy (SIRM) and multiport robotic myomectomy (MPRM) and provide surgical tips. We retrospectively analyzed the medical records of 462 patients with symptomatic leiomyoma who underwent MPRM or SIRM between March 2019 and April 2021. Demographic characteristics and surgical outcomes, including the total operative time (OT), estimated blood loss (EBL), and surgical complication rate, were compared between the two groups. Patients in the SIRM group had lower a body mass index and rate of previous pelvic surgery and were younger than those in the MPRM group. The myoma type was not different between groups; however, the MPRM group had larger, and more myomas than the SIRM group. After propensity score matching, these variables were not significantly different between the groups. The total OT, EBL, difference in hemoglobin levels, transfusion rate, and postoperative fever were not different between the groups. No postoperative complications occurred in the SIRM group. In the MPRM group, one patient needed conversion to laparotomy, and two patients had postoperative complications (umbilical incisional hernia and acute kidney injury). In conclusion, both MPRM and SIRM are feasible and effective surgical options for symptomatic myomas with cosmetic benefits and minimal risk of laparotomy conversion.
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http://dx.doi.org/10.3390/jcm10173957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432212PMC
August 2021

Dual-mechanism estrogen receptor inhibitors.

Proc Natl Acad Sci U S A 2021 Aug;118(35)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL 33458;

Efforts to improve estrogen receptor-α (ER)-targeted therapies in breast cancer have relied upon a single mechanism, with ligands having a single side chain on the ligand core that extends outward to determine antagonism of breast cancer growth. Here, we describe inhibitors with two ER-targeting moieties, one of which uses an alternate structural mechanism to generate full antagonism, freeing the side chain to independently determine other critical properties of the ligands. By combining two molecular targeting approaches into a single ER ligand, we have generated antiestrogens that function through new mechanisms and structural paradigms to achieve antagonism. These dual-mechanism ER inhibitors (DMERIs) cause alternate, noncanonical structural perturbations of the receptor ligand-binding domain (LBD) to antagonize proliferation in ER-positive breast cancer cells and in allele-specific resistance models. Our structural analyses with DMERIs highlight marked differences from current standard-of-care, single-mechanism antiestrogens. These findings uncover an enhanced flexibility of the ER LBD through which it can access nonconsensus conformational modes in response to DMERI binding, broadly and effectively suppressing ER activity.
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http://dx.doi.org/10.1073/pnas.2101657118DOI Listing
August 2021

Simulated and Experimental Investigation of the Mechanical Properties and Solubility of 3D-Printed Capsules for Self-Healing Cement Composites.

Materials (Basel) 2021 Aug 15;14(16). Epub 2021 Aug 15.

School of Mechanical Engineering, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea.

In the concrete industry, various R&D efforts have been devoted to self-healing technology, which can maintain the long-term performance of concrete structures, which is important in terms of sustainable development. Cracks in cement composites occur and propagate because of various internal and external factors, reducing the composite's stability. Interest in "self-healing" materials that can repair cracks has led researchers to embed self-healing capsules in cement composites. Overcoming the limitations of polymer capsules produced by chemical manufacturing methods, three-dimensional (3D) printing can produce capsules quickly and accurately and offers advantages such as high material strength, low cost, and the ability to fabricate capsules with complex geometries. We performed structural analysis simulations, experimentally evaluated the mechanical properties and solubility of poly(lactic acid) (PLA) capsules, and examined the effect of the capsule wall thickness and printing direction on cement composites embedded with these capsules. Thicker capsules withstood larger bursting loads, and the capsule rupture characteristics varied with the printing angle. Thus, the capsule design parameters must be optimized for different environments. Although the embedded capsules slightly reduced the compressive strength of the cement composites, the benefit of the encapsulated self-healing agent is expected to overcome this disadvantage.
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http://dx.doi.org/10.3390/ma14164578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401703PMC
August 2021

Low Preoperative Antithrombin III Level Is Associated with Postoperative Acute Kidney Injury after Liver Transplantation.

J Pers Med 2021 Jul 26;11(8). Epub 2021 Jul 26.

Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

We aimed to determine the association between the preoperative antithrombin III (ATIII) level and postoperative acute kidney injury (AKI) after LT (post-LT AKI). We retrospectively evaluated 2395 LT recipients between 2010 and 2018 whose data of perioperative ATIII levels were available. Patients were divided into two groups based on the preoperative level of ATIII (ATIII < 50% vs. ATIII ≥ 50%). Multivariable regression analysis was performed to assess the risk factors for post-LT AKI. The mean preoperative ATIII levels were 30.2 ± 11.8% in the ATIII < 50% group and 67.2 ± 13.2% in the ATIII ≥ 50% group. The incidence of post-LT AKI was significantly lower in the ATIII ≥ 50% group compared to that in the ATIII < 50% group (54.7% vs. 75.5%, < 0.001); odds ratio (OR, per 10% increase in ATIII level) 0.86, 95% confidence interval (CI) 0.81-0.92; < 0.001. After a backward stepwise regression model, female sex, high body mass index, low albumin, deceased donor LT, longer duration of surgery, and high red blood cell transfusion remained significantly associated with post-LT AKI. A low preoperative ATIII level is associated with post-LT AKI, suggesting that preoperative ATIII might be a prognostic factor for predicting post-LT AKI.
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http://dx.doi.org/10.3390/jpm11080716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401622PMC
July 2021

Pelvic Organ Prolapse Is Associated with Osteoporosis in Korean Women: Analysis of the Health Insurance Review and Assessment Service National Patient Sample.

J Clin Med 2021 Aug 23;10(16). Epub 2021 Aug 23.

Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.

Background And Objectives: Pelvic organ prolapse (POP) and osteoporosis are major disease entities in older women that have the same epidemiology and might also have the same molecular physiology. However, few data have been reported on the relationship between POP and osteoporosis. We designed this study to examine the association between POP and osteoporosis in Korean women.

Materials And Methods: We used the Health Insurance Review and Assessment Service 2015 to 2017 National Patient Sample (HIRA-NPS). A total of 4,368,141 individuals were included in this study, and a total of 842,228 individuals aged 50 years and above were included in the final analysis. POP patients were defined by the Korean Informative Classification of Diseases (KOICD) codes (KCD-7, N81, or N99.3) and patients who underwent a pelvic reconstructive procedure. The osteoporosis patients were defined by KOICD (KCD-7, R4113, R3620, R0402,) who were prescribed osteoporosis medication. A 1:10 age-stratified matching and chi-squared test were used for statistical analysis, and < 0.05 was considered as significant.

Results: A total of 7359 women were included in this analysis. Advanced POP was correlated with osteoporosis in Korean women aged 50 years and above in 2015-2017 ( < 0.0001). After adjusting for age, advanced POP was correlated with osteoporosis in the 2015, 2016, and 2017 dataset ( = 0.013, 0.0009, 0.0119, respectively).

Conclusions: Advanced POP is correlated with osteoporosis in Korean women aged 50 years and above. Evaluation for osteoporosis and education about bone health can be especially important, even in relatively young women, aged 50-59 years, and POP patients.
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http://dx.doi.org/10.3390/jcm10163751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396992PMC
August 2021

Inhibition of STAT3/PD-L1 and Activation of miR193a-5p Are Critically Involved in Apoptotic Effect of Compound K in Prostate Cancer Cells.

Cells 2021 Aug 20;10(8). Epub 2021 Aug 20.

Department of Korean Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.

Since the signal transducer and activator of transcription 3 (STAT3)/programmed death-ligand 1 (PD-L1) signaling plays an important role in tumor-immune microenvironments, in the present study, the role of STAT3/PD-L1 signaling in the apoptotic mechanism of an active ginseng saponin metabolite compound K (CK) was investigated in human prostate cancer cells. Here, CK exerted significant cytotoxicity without hurting RWPE1 normal prostate epithelial cells, increased sub-G1 and cleavage of Poly ADP-ribose polymerase (PARP) and attenuated the expression of pro-PARP and Pro-cysteine aspartyl-specific protease3 (pro-caspase-3) in LANCap, PC-3 and DU145 cells. Further, CK attenuated the expression of p-STAT3 and PD-L1 in DU145 cells along with disrupted the binding of STAT3 to PD-L1. Furthermore, CK effectively abrogated the expression of p-STAT3 and PD-L1 in interferon-gamma (INF-γ)-stimulated DU145cells. Additionally, CK suppressed the expression of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), interleukin 6 (IL-6) and interleukin 10 (IL-10) as immune escape-related genes in DU145 cells. Likewise, as STAT3 targets genes, the expression of CyclinD1, c-Myc and B-cell lymphoma-extra-large (Bcl-xL) was attenuated in CK-treated DU145 cells. Notably, CK upregulated the expression of microRNA193a-5p (miR193a-5p) in DU145 cells. Consistently, miR193a-5p mimic suppressed p-STAT3, PD-L1 and pro-PARP, while miR193a-5p inhibitor reversed the ability of CK to attenuate the expression of p-STAT3, PD-L1 and pro-PARP in DU145 cells. Taken together, these findings support evidence that CK induces apoptosis via the activation of miR193a-5p and inhibition of PD-L1 and STAT3 signaling in prostate cancer cells.
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http://dx.doi.org/10.3390/cells10082151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394796PMC
August 2021

miR193a-5p Mediated ZNF746 and c-Myc Signaling Axis Is Critically Involved in Morusin Induced Apoptosis in Colorectal Cancer Cells.

Cells 2021 Aug 12;10(8). Epub 2021 Aug 12.

Department of Korean Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.

Novel target therapy is on the spotlight for effective cancer therapy. Hence, in the present study, the underlying apoptotic mechanism of Morusin was explored in association with miR193a-5p mediated ZNF746/c-Myc signaling axis in colorectal cancer cells (CRCs). Herein, Morusin reduced the viability and the number of colonies in HCT116 and SW480 CRCs. Additionally, Morusin increased sub-G1 population, cleavages of poly (ADP-ribose) polymerase (PARP) and caspase-3 and inhibited the expression of zinc finger protein 746 (ZNF746) and c-Myc in HCT116 and SW480 cells. Conversely, overexpression of ZNF746 suppressed the ability of Morusin to abrogate the expression of c-Myc in HCT116 cells, as ZNF746 enhanced the stability of c-Myc via their direct binding through nuclear colocalization in HCT116 cells by immunofluorescence and immunoprecipitation. Notably, Morusin upregulated miR193a-5p as a tumor suppressor, while miR193a-5p inhibitor masked the ability of Morusin to reduce the expression of ZNF746, c-Myc, and pro-PARP in HCT116 cells. To our knowledge, these findings provide the novel insight on miR193a-5p mediated inhibition of ZNF746/c-Myc signaling in Morusin induced apoptosis in CRCs.
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http://dx.doi.org/10.3390/cells10082065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395021PMC
August 2021

Genetic Parameters for Different Measures of Feed Efficiency and Their Relationship to Production Traits in Three Purebred Pigs.

Life (Basel) 2021 Aug 13;11(8). Epub 2021 Aug 13.

Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Korea.

Residual feed intake (RFI) gained attention as a potential alternative to the feed conversion ratio (FCR). Thus, this study aimed to estimate genetic parameters for different feed efficiency (FE) traits (FCR, RFI1 to RFI5) and their genetic correlation to on-test daily weight gain (ADG), backfat (BFT), loin muscle area (LMA), lean percentage (LP), and total feed intake (FI) for 603 Male Duroc (DD), 295 Landrace (LL), and 341 Yorkshire (YY). The common spatial pen effect was also estimated in these traits. Five RFI measures were estimated by regressing daily feed intake on initial testing age (ITA), initial testing weight (IBW), and ADG for RFI1; other models were the same as RFI1 except for additional BFT for RFI2; LMA for RFI3; BFT and LMA for RFI4; BFT, LMA, and average metabolic body weight (AMBW) instead of IBW for RFI5. Genetic parameters estimated using two animal models and the REML method showed moderate heritability for FCR in all breeds (0.22 and 0.28 for DD, 0.31 and 0.39 for LL, 0.17 and 0.22 for YY), low heritability for the majority of RFI measures in DD (0.15 to 0.23) and YY (0.14 to 0.20) and moderate heritability for all RFI measures in LL (0.31 to 0.34). Pen variance explained 7% to 22% for FE and 0% to 9% for production traits' phenotypic variance. The genetic correlation revealed that selection against less complex RFI1 in DD and LL and RFI2 in YY would bring the most advantageous reduction to FI (0.71 for DD, 0.49 for LL, 0.43 YY) without affecting ADG in all breeds (0.06 for DD, -0.11 for LL, 0.05 for YY), decrease in BFT, and increase in LP in DD (0.51 in BFT, -0.77 in LP) and LL (0.45 in BFT, -0.83 in LP). Therefore, inclusion of these breed-specific RFI measures in the future selection criteria would help improve feed efficiency in the swine industry.
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http://dx.doi.org/10.3390/life11080830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401224PMC
August 2021

Association between Neutrophil-Lymphocyte Ratio and Herpes Zoster Infection in 1688 Living Donor Liver Transplantation Recipients at a Large Single Center.

Biomedicines 2021 Aug 5;9(8). Epub 2021 Aug 5.

Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Liver transplantation (LT) is closely associated with decreased immune function, a contributor to herpes zoster (HZ). However, risk factors for HZ in living donor LT (LDLT) remain unknown. Neutrophil-lymphocyte ratio (NLR) and immune system function are reportedly correlated. This study investigated the association between NLR and HZ in 1688 patients who underwent LDLT between January 2010 and July 2020 and evaluated risk factors for HZ and postherpetic neuralgia (PHN). The predictive power of NLR was assessed through the concordance index and an integrated discrimination improvement (IDI) analysis. Of the total cohort, 138 (8.2%) had HZ. The incidence of HZ after LT was 11.2 per 1000 person-years and 0.1%, 1.3%, 2.9%, and 13.5% at 1, 3, 5, and 10 years, respectively. In the Cox regression analysis, preoperative NLR was significantly associated with HZ (adjusted hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.02-1.09; = 0.005) and PHN (HR, 1.08; 95% CI, 1.03-1.13; = 0.001). Age, sex, mycophenolate mofetil use, and hepatitis B virus infection were risk factors for HZ versus age and sex for PHN. In the IDI analysis, NLR was discriminative for HZ and PHN ( = 0.020 and = 0.047, respectively). Preoperative NLR might predict HZ and PHN in LDLT recipients.
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http://dx.doi.org/10.3390/biomedicines9080963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391531PMC
August 2021

Immune functions as a ligand or a receptor, cancer prognosis potential, clinical implication of VISTA in cancer immunotherapy.

Semin Cancer Biol 2021 Aug 21. Epub 2021 Aug 21.

Cancer Molecular Target Herbal Research Lab, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address:

Since cancer immunotherapy with immune checkpoint inhibitors of PD/PDL-1 and CTLA-4 limited efficacy to the patients due to resistance during the current decade, novel target is required for customized treatment due to tumor heterogeneity. V-domain Ig-containing suppressor of T cell activation (VISTA), a programmed death protein-1(PD-1) homolog expressed on T cells and on antigen presenting cells(APC), has emerged as a new target in several cancers. Though VISTA inhibitors including CA-170 are considered attractive in cancer immunotherapy to date, the information on VISTA as a potent biomarker of cancer prognosis and its combination therapy is still lacking to date. Thus, in this review, we discussed extracellular domain, ligands, expression, immune functions and clinical implications of VISTA and finally suggested conclusion and perspectives.
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http://dx.doi.org/10.1016/j.semcancer.2021.08.008DOI Listing
August 2021

Oral health status of inpatients with varying physical activity limitations in rehabilitation wards: A cross-sectional study.

Medicine (Baltimore) 2021 Aug;100(32):e26880

Department of Dental Hygiene, College of Software and Digital Healthcare Convergence, Yonsei University, Wonju, Republic of Korea.

Abstract: Poor oral hygiene can be potentially life-threatening in inpatients. However, no basic protocol on oral hygiene customized for inpatients exists, and lack of oral care related knowledge, attitude, and skills among caregivers could be detrimental to the general health of patients. This study sought to identify the oral care practices and oral health status of inpatients with varying physical activity limitations in a rehabilitation ward.Sixty-one inpatients in a rehabilitation ward were evaluated for their medical and physical conditions and oral health status. These were assessed using the bedside oral exam, decayed, missing, filled teeth index, plaque index, gingival index, and caries activity test.In total, 40 men and 21 women (mean age, 56.6 years) were included in this study. Among them, 50.8% of the patients could brush their teeth unassisted, whereas 49.2% required assistance from an assistant for oral care. The proportion of patients receiving nasogastric tube feeding was higher in the group that could not provide oral self-care; 36.7% and 33.3% of these patients showed moderate and severe dysfunction, respectively, based on bedside oral exam. Scores for the swallowing, tongue, and total domains of bedside oral exam were poorer for patients who could not provide oral self-care (P < .01). The caries activity test indicated a moderate risk for both groups.Our findings suggest that an oral care protocol that considers the physical activity limitations in inpatients in rehabilitation wards is necessary to minimize negative influences on the systemic health of these patients.
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http://dx.doi.org/10.1097/MD.0000000000026880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360428PMC
August 2021

Comparison of intraoperative and short-term postoperative outcomes between robot-assisted laparoscopic multi-port pyeloplasty using the da Vinci Si system and single-port pyeloplasty using the da Vinci SP system in children.

Investig Clin Urol 2021 Sep 20;62(5):592-599. Epub 2021 Jul 20.

Department of Urology, Yonsei University College of Medicine, Seoul, Korea.

Purpose: We compared the intraoperative and postoperative outcomes of single-port robot-assisted laparoscopic pyeloplasty (S-RALP) using the da Vinci SP® system and conventional multi-port robot-assisted laparoscopic pyeloplasty (M-RALP) in pediatric patients.

Materials And Methods: Multi-port and single-port pyeloplasty have been performed in pediatric patients in our institution since October 2015 and February 2019, respectively. We conducted an entire cohort comparison. Considering the learning curve of M-RALP, we defined the last 15 cases of M-RALP as a subgroup of M-RALP and compared this subgroup with the entire cohort of S-RALP patients.

Results: Thirty-one patients who underwent multi-port pyeloplasty and 15 patients who underwent single-port pyeloplasty were enrolled in this study. Age, height, body weight, laterality, surgical indication, and ipsilateral differential renal function were statistically similar in the M-RALP and S-RALP groups. The median operative time (3.0 h vs. 2.4 h; p=0.01) and the median console time (2.2 h vs. 1.5 h; p<0.001) were longer in the M-RALP group than in the S-RALP group. There was no significant difference in operative time or console time between the M-RALP subgroup and the S-RALP group. There were no significant differences in the length of hospitalization, pain score, morphine-equivalent use of analgesics, or postoperative differential renal function in all comparisons.

Conclusions: This study confirmed that pyeloplasty using the da Vinci® SP system can be started by robotic surgeons who can overcome the learning curve. Robot-assisted laparoscopic single-port pyeloplasty is feasible in noninfant pediatric patients.
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http://dx.doi.org/10.4111/icu.20200569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421989PMC
September 2021

Estimation of Stroke Volume Variance from Arterial Blood Pressure: Using a 1-D Convolutional Neural Network.

Sensors (Basel) 2021 Jul 29;21(15). Epub 2021 Jul 29.

Asan Medical Center, Department of Anesthesiology and Pain Medicine, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Seoul 05505, Korea.

Background: We aimed to create a novel model using a deep learning method to estimate stroke volume variation (SVV), a widely used predictor of fluid responsiveness, from arterial blood pressure waveform (ABPW).

Methods: In total, 557 patients and 8,512,564 SVV datasets were collected and were divided into three groups: training, validation, and test. Data was composed of 10 s of ABPW and corresponding SVV data recorded every 2 s. We built a convolutional neural network (CNN) model to estimate SVV from the ABPW with pre-existing commercialized model (EV1000) as a reference. We applied pre-processing, multichannel, and dimension reduction to improve the CNN model with diversified inputs.

Results: Our CNN model showed an acceptable performance with sample data (r = 0.91, MSE = 6.92). Diversification of inputs, such as normalization, frequency, and slope of ABPW significantly improved the model correlation (r = 0.95), lowered mean squared error (MSE = 2.13), and resulted in a high concordance rate (96.26%) with the SVV from the commercialized model.

Conclusions: We developed a new CNN deep-learning model to estimate SVV. Our CNN model seems to be a viable alternative when the necessary medical device is not available, thereby allowing a wider range of application and resulting in optimal patient management.
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http://dx.doi.org/10.3390/s21155130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347322PMC
July 2021

Estimation of Stroke Volume Variance from Arterial Blood Pressure: Using a 1-D Convolutional Neural Network.

Sensors (Basel) 2021 Jul 29;21(15). Epub 2021 Jul 29.

Asan Medical Center, Department of Anesthesiology and Pain Medicine, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Seoul 05505, Korea.

Background: We aimed to create a novel model using a deep learning method to estimate stroke volume variation (SVV), a widely used predictor of fluid responsiveness, from arterial blood pressure waveform (ABPW).

Methods: In total, 557 patients and 8,512,564 SVV datasets were collected and were divided into three groups: training, validation, and test. Data was composed of 10 s of ABPW and corresponding SVV data recorded every 2 s. We built a convolutional neural network (CNN) model to estimate SVV from the ABPW with pre-existing commercialized model (EV1000) as a reference. We applied pre-processing, multichannel, and dimension reduction to improve the CNN model with diversified inputs.

Results: Our CNN model showed an acceptable performance with sample data (r = 0.91, MSE = 6.92). Diversification of inputs, such as normalization, frequency, and slope of ABPW significantly improved the model correlation (r = 0.95), lowered mean squared error (MSE = 2.13), and resulted in a high concordance rate (96.26%) with the SVV from the commercialized model.

Conclusions: We developed a new CNN deep-learning model to estimate SVV. Our CNN model seems to be a viable alternative when the necessary medical device is not available, thereby allowing a wider range of application and resulting in optimal patient management.
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http://dx.doi.org/10.3390/s21155130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347322PMC
July 2021

Clinical features and long-term outcomes of pediatric-onset inflammatory bowel disease in a population-based cohort in the Songpa-Kangdong district of Seoul, Korea.

J Crohns Colitis 2021 Jul 26. Epub 2021 Jul 26.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background And Aims: The long-term outcomes of pediatric-onset inflammatory bowel disease (pIBD) in non-Caucasian populations are unknown. We, therefore, evaluated and compared the clinical features and long-term outcomes of pIBD with those of adult-onset IBD (aIBD) using a population-based cohort in the Songpa-Kangdong district of Seoul, Korea.

Methods: Clinical characteristics and prognoses were compared between the two groups: pIBD (defined as <18 years of age at diagnosis) and aIBD (18-59 years of age at diagnosis).

Results: We identified 131 patients with pIBD (48 ulcerative colitis [UC], 83 Crohn's disease [CD]) and 1192 patients with aIBD (866 UC, 326 CD) during 1986-2015. An extensive colitis at diagnosis was more prevalent in pUC than in aUC (45.8% vs. 22.3%, P<0.001), and the overall exposure to corticosteroids, thiopurines, and anti-tumor necrosis factor agents was higher in pUC than in aUC (P<0.001). The cumulative risk of colectomy was higher in pUC than in aUC during a median follow-up of 125.0 and 112.1 months, respectively (8.9% vs. 1.8% at 10 years after diagnosis, P=0.030). Ileocolonic location and inflammatory behavior at diagnosis were more common in pCD than in aCD; however, patients with pCD and aCD did not differ regarding treatment or disease course during a median follow-up of 137.2 and 120.9 months, respectively.

Conclusion: Our study showed clear differences between pIBD and aIBD, especially in UC. pUC presents with more extensive diseases and may have a more severe disease course, as suggested by an earlier time to administering medications and performing colectomy.
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http://dx.doi.org/10.1093/ecco-jcc/jjab132DOI Listing
July 2021

Combined association of skeletal muscle mass and grip strength with cardiovascular diseases in patients with type 2 diabetes.

J Diabetes 2021 Jul 20. Epub 2021 Jul 20.

Department of Internal Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea.

Background: Appendicular skeletal muscle mass (ASM) and grip strength (GS) have been suggested to be related to cardiovascular diseases (CVDs), but their association with type 2 diabetes (T2D) remains unclear. Therefore, we examined the combined association of ASM and GS with the prevalence of CVD in patients with T2D.

Methods: A total of 1230 patients with T2D were recruited and divided into four groups based on the sex-specific median values of ASM adjusted for body mass index (ASM/BMI; short: SM) and GS: high SM/high GS (HSM/HGS), high SM/low GS (HSM/LGS), low SM/high GS (LSM/HGS), and low SM/low GS (LSM/LGS).

Results: The LSM/LGS group was older and had higher values of systolic blood pressure, homeostasis model assessment of insulin resistance, waist circumference, and C-reactive protein but lower high-density lipoprotein cholesterol concentrations than the HSM/HGS group. After adjusting for potential confounders, the odds ratios (ORs) and 95% CIs for CVD, coronary heart disease (CHD), ischemic stroke, and peripheral arterial disease (PAD) in the LSM/LGS group were 2.90 (1.89-4.47), 2.39 (1.46-3.92), 1.77 (0.84-3.71), and 5.83 (1.58-21.48), respectively. After adjusting for variable confounders among patients with higher glycosylated hemoglobin (HbA1c) (≥7.1%), the ORs and 95% CIs for CVD and CHD in the LSM/LGS group were 7.27 (3.37-15.67) and 6.17 (2.65-14.37), respectively.

Conclusions: The combination of low SM and GS was strongly associated with CVD, CHD, and PAD in patients with T2D, especially in those with higher HbA1c levels.
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http://dx.doi.org/10.1111/1753-0407.13216DOI Listing
July 2021

The Number of Myomas Is the Most Important Risk Factor for Blood Loss and Total Operation Time in Robotic Myomectomy: Analysis of 242 Cases.

J Clin Med 2021 Jun 30;10(13). Epub 2021 Jun 30.

Asan Medical Center, Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Seoul 05505, Korea.

To identify factors affecting blood loss and operation time (OT) during robotic myomectomy (RM), we reviewed a total of 448 patients who underwent RM at Seoul Asan Hospital between 1 January 2019, and 28 February 2021, at Seoul Asan Hospital. To avoid variations in surgical proficiency, only 242 patients managed by two surgeons who each performed >80 RM procedures during the study period were included in this study. All cases of RM were performed with a reduced port technique. We obtained the following data from each patient's medical chart: age, gravidity, parity, body mass index, and history of previous abdominal surgery including cesarean section. We also collected information on the maximal diameter and type of myomas, number and weight of removed myomas, concomitant surgery, total OT from skin incision to closure, estimated blood loss (EBL), and blood transfusion. Data on preoperative use of gonadotropin-releasing hormone agonists (GnRHas) and perioperative use of hemostatic agents (tranexamic acid or vasopressin) were also collected. Data on the length of hospital stay, postoperative fever within 48 h, and any complications related to RM were also obtained. The primary endpoint in this study was the identification of factors affecting EBL and the secondary endpoint was the identification of factors affecting the total OT during multiport RM. Univariate and multivariate analyses were used to identify the factors affecting EBL and OT during multiport RM. The medians of the maximal diameter and weight of the removed myomas were 9.00 (interquartile range [IQR], 7.00 to 10.00) cm and 249.75 (IQR, 142.88 to 401.00) g, respectively. The median number of myomas was two (IQR, one to four), ranging from 1 to 34. Of the cases, 155 had low EBL and 87 had high EBL. Most myomas were of the intramural type (n = 179). The odds of EBL > 320 mL increased by 251% (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.16-5.42) for five to nine myomas and by 647% (OR, 6.47; 95% CI, 1.87-22.33) for ≥10 myomas. The odds of subserosal-type myomas decreased by 67% compared with intramural-type myomas (OR, 0.33; 95% CI, 0.14-0.80). History of abdominal surgery other than cesarean section was positively correlated with EBL. The weight of the removed myomas and a history of previous cesarean section were not correlated with the EBL. : The number of myomas (5-9 and ≥10), maximal myoma diameter, and history of abdominal surgery other than cesarean section affect the EBL in RM.
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http://dx.doi.org/10.3390/jcm10132930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268424PMC
June 2021

Impact of Sarcopenia on Acute Kidney Injury after Infrarenal Abdominal Aortic Aneurysm Surgery: A Propensity Matching Analysis.

Nutrients 2021 Jun 27;13(7). Epub 2021 Jun 27.

Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.

Background: Sarcopenia contributes to increased morbidity and mortality in patients undergoing surgery for abdominal aortic aneurysms (AAA). However, few reports have demonstrated whether sarcopenia would affect the development of postoperative acute kidney injury (AKI) in these patients. This study aimed to examine whether sarcopenia is associated with AKI and morbidity and mortality after infrarenal AAA operation.

Methods: We retrospectively analysed 379 patients who underwent infrarenal AAA surgery. The diagnosis of sarcopenia was performed using the skeletal muscle index, which was calculated from axial computed tomography at the level of L3. The patients were separated into those with sarcopenia ( = 104) and those without sarcopenia ( = 275). We applied multivariable and Cox regression analyses to evaluate the risk factors for AKI and overall mortality. A propensity score matching (PSM) evaluation was done to assess the postoperative results.

Results: The incidence of AKI was greater in sarcopenia than non-sarcopenia group before (34.6% vs. 15.3%; < 0.001) and after the PSM analysis (34.6% vs. 15.4%; = 0.002). Multivariable analysis revealed sarcopenia to be associated with AKI before ( = 0.010) and after PSM ( = 0.016). Sarcopenia was also associated with overall mortality before ( = 0.048) and after PSM ( = 0.032). A Kaplan-Meier analysis revealed that overall mortality was elevated patients with sarcopenia before and after PSM than in those without (log-rank test, < 0.001, = 0.022).

Conclusions: Sarcopenia was associated with increased postoperative AKI incidence and overall mortality among individuals who underwent infrarenal AAA operation.
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http://dx.doi.org/10.3390/nu13072212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308481PMC
June 2021

A randomised controlled trial to clinically validate follitropin delta in its individualised dosing regimen for ovarian stimulation in Asian IVF/ICSI patients.

Hum Reprod 2021 Aug;36(9):2452-2462

Reproductive Medicine & Maternal Health, Ferring Pharmaceuticals, Copenhagen, Denmark.

Study Question: Is ovarian stimulation with follitropin delta in its individualised fixed-dose regimen at least as efficacious as follitropin alfa in a conventional dosing regimen in Asian population?

Summary Answer: Ovarian stimulation with individualised follitropin delta dosing resulted in a non-inferior ongoing pregnancy rate, a significantly higher live birth rate and a significantly lower incidence of early ovarian hyperstimulation syndrome (OHSS) and/or preventive interventions compared to conventional follitropin alfa dosing.

What Is Known Already: Previous randomised controlled trials conducted in Japan as well as in Europe, North- and South America have demonstrated that ovarian stimulation with the individualised follitropin delta dosing regimen based on serum anti-Müllerian hormone (AMH) level and body weight modulated the ovarian response and reduced the risk of OHSS without compromising pregnancy and live birth rates.

Study Design, Size, Duration: Randomised, controlled, multi-centre, assessor-blind trial conducted in 1009 Asian patients from mainland China, South Korea, Vietnam and Taiwan, undergoing their first IVF/ICSI cycle. Randomisation was stratified by age (<35, 35-37, 38-40 years). The primary endpoint was ongoing pregnancy rate assessed 10-11 weeks after embryo transfer in the fresh cycle (non-inferiority limit -10.0%; analysis adjusted for age stratum).

Participants/materials, Setting, Methods: The follitropin delta treatment consisted of a fixed daily dose individualised according to each patient's initial AMH level and body weight (AMH <15 pmol/l: 12 μg; AMH ≥15 pmol/l: 0.19 to 0.10 μg/kg; min-max 6-12 μg). The follitropin alfa dose was 150 IU/day for the first 5 days with subsequent potential dose adjustments according to individual response. A GnRH antagonist protocol was applied. OHSS was classified based on Golan's system. Women with an ongoing pregnancy were followed until live birth and 4 weeks after.

Main Results And The Role Of Chance: The number of oocytes retrieved was significantly (P < 0.001) lower with individualised follitropin delta versus conventional follitropin alfa (10.0 ± 6.1 versus 12.4 ± 7.3). Nevertheless, compared to the conventional dosing approach, the individualised follitropin delta dosing regimen resulted in on average 2 more oocytes (9.6 ± 5.3 versus 7.6 ± 3.5) in potential low responders as indicated by AMH <15 pmol/l, and on average 3 fewer oocytes (10.1 ± 6.3 versus 13.8 ± 7.5) in potential high responders as indicated by AMH ≥15 pmol/l. Among women with AMH ≥15 pmol/l, excessive response occurred less frequently with individualised follitropin delta than with follitropin alfa (≥15 oocytes: 20.2% versus 39.1%; ≥20 oocytes: 6.7% versus 18.5%; both P < 0.001). The incidence of early OHSS and/or preventive interventions for early OHSS was significantly (P = 0.004) reduced from 9.6% with follitropin alfa to 5.0% with individualised follitropin delta. The total gonadotropin use was significantly (P < 0.001) reduced from an average of 109.9 ± 32.9 μg (1498 ± 448 IU) follitropin alfa to 77.5 ± 24.4 μg follitropin delta. Non-inferiority of follitropin delta in its individualised dosing regimen to conventional follitropin alfa was established with respect to the primary endpoint of ongoing pregnancy rate which was 31.3% with follitropin delta compared to 25.7% with follitropin alfa (estimated mean difference 5.4% [95% CI: -0.2%; 11.0%]). The live birth rate was significantly higher at 31.3% with individualised follitropin delta compared to 24.7% with follitropin alfa (estimated mean difference 6.4% [95% CI: 0.9%; 11.9%]; P = 0.023). The live birth rate for each stratum were as follows for follitropin delta and follitropin alfa, respectively; <35 years: 31.0% versus 25.0%, 35-37 years: 35.3% versus 26.7%, 38-40 years: 20.0% versus 14.3%.

Limitations, Reasons For Caution: The trial only covered the clinical outcome of one treatment cycle with fresh cleavage-stage embryo transfers.

Wider Implications Of The Findings: The present trial shows that in addition to reducing the early OHSS risk, follitropin delta in its individualised fixed-dose regimen has the potential to improve the success rate in fresh cycles across all ages and with a lower gonadotropin consumption compared to conventional follitropin alfa dosing.

Study Funding/competing Interest(s): This study was funded by Ferring Pharmaceuticals. J.Q., Y.Z., X.L., T.H., H.-Y.H. and S.-H.K. have received institutional (not personal) clinical trial fees from Ferring Pharmaceuticals. M.G., B.M. and J.-C.A. are employees of Ferring Pharmaceuticals. J.-C.A. has pending and issued patent applications in the WO 2013/020996 and WO 2019/043143 patent families that comprise allowed and granted patent rights related to follitropin delta.

Trial Registration Number: NCT03296527 (clinicaltrials.gov).

Trial Registration Date: 28 September 2017.

Date Of First Patient’s Enrolment: 1 December 2017.
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http://dx.doi.org/10.1093/humrep/deab155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373472PMC
August 2021

Changes in the Long-term Prognosis of Crohn's Disease between 1986 and 2015: The Population-Based Songpa-Kangdong Inflammatory Bowel Disease Cohort Study.

Gut Liver 2021 Jun 22. Epub 2021 Jun 22.

Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background/aims: The long-term course of Crohn's disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis of Korean CD patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort.

Methods: Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015.

Results: During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio [aHR], 2.70; 95% confidence interval [CI], 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68).

Conclusions: The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades.
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http://dx.doi.org/10.5009/gnl210044DOI Listing
June 2021

Suppression of phosphoinositide 3-kinase/phosphoinositide-dependent kinase-1/serum and glucocorticoid-induced protein kinase pathway.

Phytother Res 2021 Aug 16;35(8):4547-4554. Epub 2021 Jun 16.

College of Korean Medicine, Kyung Hee University, Seoul, South Korea.

In the current study, the pivotal roles of serum and glucocorticoid-induced protein kinase (SGK1) and NF-kB related signalings known as prognostic biomarkers in cervical cancers were explored in the antitumor effect of a ginseng saponin metabolite compound K (CK) in HeLa and SiHa cervical cancer cells. CK exerted significant cytotoxicity, induced sub-G1 accumulation, and attenuated the expression of proPoly (ADP-ribose) polymerase (pro-PARP) and Pro-cysteine aspartyl-specific protease (pro-caspase3) in HeLa cells more than in SiHa cells. CK inhibited phosphorylation of SGK1 and its upstream genes, phosphoinositide 3-kinases (PI3K), and phosphoinositide-dependent kinase-1 (PDK1) in HeLa cells. In addition, CK suppressed the phosphorylation of SGK1, NF-κB, and inhibitor of kappa B (IκB) and also NF-κB target genes such as X-linked inhibitor of apoptosis protein and B-cell lymphoma 2 (Bcl-2) in HeLa cells. Notably, Immunoprecipitation revealed that SGK1 binds to PI3K or PDK1 and also CK disturbed the binding between SGK1 and PI3K or PDK1 in HeLa cells. Furthermore, PI3K inhibitor LY294002 decreased expression of PI3K, p-PDK1, p-SGK1, and pro-caspase3 and SGK1 inhibitor GSK650394 also reduced expression of NF-κB and pro-caspase3 just like CK in HeLa cells. Overall, these findings suggest that CK induces apoptosis via suppression of PI3K/PDK1/SGK1 and NF-κB signaling axis.
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http://dx.doi.org/10.1002/ptr.7157DOI Listing
August 2021

Inhibition of TMPRSS4 mediated epithelial-mesenchymal transition is critically involved in antimetastatic effect of melatonin in colorectal cancers.

Phytother Res 2021 Aug 11;35(8):4538-4546. Epub 2021 Jun 11.

College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

In the current study, the underlying anti-metastatic mechanism of melatonin contained in some edible plants was explored in association with transmembrane protease serine 4 (TMPRSS4) mediated metastasis and epithelial-mesenchymal transition (EMT) signaling in human HCT15 and SW620 colorectal cancer cells. Here, TMPRSS4 was highly expressed in HCT15, but was weakly expressed in SW620 cells. Melatonin exerted weak cytotoxicity, decreased invasion, adhesion, and migration, and attenuated the expression of TMPRSS4, cyclin E, pro-urokinase-type plasminogen activator (pro-uPA), p-signal transducer and activator of transcription 3 (p-STAT3), p-focal adhesion kinase (p-FAK), Snail and increased the expression of E-cadherin, p27, pp38 and p-Jun N-terminal kinases (p-JNK) in HCT15 cells. Conversely, overexpression of TMPRSS4 reduced the ability of melatonin to activate E-cadherin and reduce Snail. Furthermore, even in SW620 cells transfected with TMPRSS4-overexpression plasmid, melatonin effectively suppressed invasion and migration along with decreased expression of Snail, cyclin A, cyclin E, pro-uPA and p-FAK and increased expression of E-cadherin and p27. Overall, these findings provide evidence that melatonin suppresses metastasis in colon cancer cells via inhibition of TMPRSS4 mediated EMT.
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http://dx.doi.org/10.1002/ptr.7156DOI Listing
August 2021

Congenital Obstructive Müllerian Anomaly: The Pitfalls of a Magnetic Resonance Imaging-Based Diagnosis and the Importance of Intraoperative Biopsy.

J Clin Med 2021 May 29;10(11). Epub 2021 May 29.

Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.

A retrospective cohort study of the concordance between the magnetic resonance imaging (MRI) diagnosis and final diagnosis in patients with Müllerian duct anomalies (MDAs) was conducted, and diagnostic clues were suggested. A total of 463 cases of young women who underwent pelvic MRIs from January 1995 to February 2019 at Seoul Asan Medical Center were reviewed. Interventions consisted of clinical examinations, abdominal or transvaginal/rectal ultrasound, MRI, and operative procedures, including hysteroscopy and laparoscopy. The concordance of the diagnosis between the results obtained with MRI and those obtained with surgeries was evaluated. It was found that a total of 225 cases (48.6%) showed genital tract anomalies on MRI. Among them, 105 cases (46.7%) underwent reconstructive surgery. Nineteen cases (8.4%) revealed discrepancies between the final diagnosis after surgery and the initial MRI findings and eleven cases (57.9%) had cervical anomalies. Incorrect findings associated with the MRIs were particularly evident in biopsied cases of cervical dysgenesis. A combination of physical examination, ultrasound, and MRI is suitable for preoperative work-up in the diagnoses of congenital obstructive anomalies. However, it is recommended that a pathologic confirmation of tissue at the caudal leading edge be made in obstructive genital anomalies, in cases of presumptive vaginal or cervical dysgenesis.
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http://dx.doi.org/10.3390/jcm10112414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198439PMC
May 2021

Increased Expression of Retinol-Binding Protein 4 in Ovarian Endometrioma and Its Possible Role in the Pathogenesis of Endometriosis.

Int J Mol Sci 2021 May 29;22(11). Epub 2021 May 29.

Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea.

Although endometriosis is a benign disease characterized by the presence of endometrial tissues outside the uterus, ectopic endometrial cells can exhibit malignant biological behaviors. Retinol-binding protein4 (RBP4) is a novel adipocyte-derived cytokine, which has important roles in regulating insulin sensitivity and energy metabolism. RBP4 is a potent modulator of gene transcription, and acts by directly controlling cell growth, invasiveness, proliferation and differentiation. Here, we evaluated the possible role of RBP4 in the pathogenesis of endometriosis. We compared the levels of RBP4 in the tissues and peritoneal fluid (PF) of women with and without endometriosis and evaluated the in vitro effects of RBP4 on the viability, invasiveness, and proliferation of endometrial stromal cells (ESCs). RBP4 levels were significantly higher in the PF of the women in the endometriosis group than in the controls. RBP4 immunoreactivity was significantly higher in the ovarian endometriomas of women with advanced stage endometriosis than those of controls. In vitro treatment with human recombinant-RBP4 significantly increased the viability, bromodeoxyuridine expression, and invasiveness of ESCs. Transfection with RBP4 siRNA significantly reduced ESC viability and invasiveness. These findings suggest that RBP4 partakes in the pathogenesis of endometriosis by increasing the viability, proliferation and invasion of endometrial cells.
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http://dx.doi.org/10.3390/ijms22115827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199072PMC
May 2021

Association of Preoperative Prognostic Nutritional Index and Postoperative Acute Kidney Injury in Patients Who Underwent Hepatectomy for Hepatocellular Carcinoma.

J Pers Med 2021 May 18;11(5). Epub 2021 May 18.

Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Various biological indicators are reportedly associated with postoperative acute kidney injury (AKI) in the surgical treatment of hepatocellular carcinoma (HCC). However, only a few studies have evaluated the association between the preoperative prognostic nutritional index (PNI) and postoperative AKI. This study evaluated the association of the preoperative PNI and postoperative AKI in HCC patients. We retrospectively analyzed 817 patients who underwent open hepatectomy between December 2007 and December 2015. Multivariate regression analysis was performed to evaluate the association between the PNI and postoperative AKI. Additionally, we evaluated the association between the PNI and outcomes such as postoperative renal replacement therapy (RRT) and mortality. Cox regression analysis was performed to assess the risk factors for one-year and five-year mortality. In the multivariate analysis, high preoperative PNI was significantly associated with a lower incidence of postoperative AKI (odds ratio (OR): 0.92, 95% confidence interval (CI): 0.85 to 0.99, = 0.021). Additionally, diabetes mellitus and the use of synthetic colloids were significantly associated with postoperative AKI. PNI was associated with postoperative RRT (OR: 0.76, 95% CI: 0.60 to 0.98, = 0.032) even after adjusting for other potential confounding variables. In the Cox regression analysis, high PNI was significantly associated with low one-year mortality (Hazard ratio (HR): 0.87, 95% CI: 0.81 to 0.94, < 0.001), and five-year mortality (HR: 0.93, 95% CI: 0.90-0.97, < 0.001). High preoperative PNI was significantly associated with a lower incidence of postoperative AKI and low mortality. These results suggest that the preoperative PNI might be a predictor of postoperative AKI and surgical prognosis in HCC patients undergoing open hepatectomy.
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http://dx.doi.org/10.3390/jpm11050428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157861PMC
May 2021

Association of Preoperative Prognostic Nutritional Index and Postoperative Acute Kidney Injury in Patients with Colorectal Cancer Surgery.

Nutrients 2021 May 11;13(5). Epub 2021 May 11.

Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

The prognostic nutritional index (PNI) has been reported to be associated with postoperative complications and prognosis in cancer surgery. However, few studies have evaluated the association between preoperative PNI and postoperative acute kidney injury (AKI) in colorectal cancer patients. This study evaluated association of preoperative PNI and postoperative AKI in patients who underwent colorectal cancer surgery. This study retrospectively analyzed 3543 patients who underwent colorectal cancer surgery between June 2008 and February 2012. The patients were classified into four groups by the quartile of PNI: Q1 (≤43.79), Q2 (43.79-47.79), Q3 (47.79-51.62), and Q4 (≥51.62). Multivariate regression analysis was performed to assess the risk factors for AKI and 1-year mortality. AKI was defined according to Kidney Disease Improving Global Outcomes classification (KDIGO) criteria. Additionally, we assessed surgical outcomes such as hospital stay, ICU admission, and postoperative complications. The incidence of postoperative AKI tended to increase in the Q1 group (13.4%, 9.2%, 9.4%, 8.8%). In the multivariate analysis, high preoperative PNI was significantly associated with low risk of postoperative AKI (adjusted odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.93-0.99, = 0.003) and low 1-year mortality (OR: 0.92, 95% CI: 0.86-0.98, = 0.011). Male sex, body mass index, diabetes mellitus, and hypertension were risk factors for AKI. The Q1 (≤43.79) group had poor surgical outcomes, such as postoperative AKI (OR: 1.52, 95% CI: 1.18-1.95, = 0.001), higher rates of ICU admission (OR: 3.13, 95% CI: 1.82-5.39, < 0.001) and higher overall mortality (OR: 3.81, 95% CI: 1.86-7.79, < 0.001). In conclusion, low preoperative PNI levels, especially in the Q1 (≤43.79), were significantly associated with postoperative AKI and surgical outcomes, such as hospital stay, postoperative ICU admission, and mortality.
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http://dx.doi.org/10.3390/nu13051604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170895PMC
May 2021

The Association between Prognostic Nutritional Index (PNI) and Intraoperative Transfusion in Patients Undergoing Hepatectomy for Hepatocellular Carcinoma: A Retrospective Cohort Study.

Cancers (Basel) 2021 May 21;13(11). Epub 2021 May 21.

Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Background: PNI is significantly associated with surgical outcomes; however, the association between PNI and intraoperative transfusions is unknown.

Methods: This study retrospectively analyzed 1065 patients who underwent hepatectomy. We divided patients into two groups according to the PNI (<44 and >44) and compared their transfusion rates and surgical outcomes. We performed multivariate logistic and Cox regression analysis to determine risk factors for transfusion and the 5-year survival. Additionally, we found the net reclassification index (NRI) to validate the discriminatory power of PNI.

Results: The PNI <44 group had higher transfusion rates (adjusted odds ratio [OR]: 2.20, 95%CI: 1.06-4.60, = 0.035) and poor surgical outcomes, such as post hepatectomy liver failure (adjusted [OR]: 3.02, 95%CI: 1.87-4.87, < 0.001), and low 5-year survival (adjusted OR: 1.68, 95%CI: 1.17-2.24, < 0.001). On multivariate analysis, PNI <44, age, hemoglobin, operation time, synthetic colloid use, and laparoscopic surgery were risk factors for intraoperative transfusion. On Cox regression analysis, PNI <44, MELD score, TNM staging, synthetic colloid use, and transfusion were associated with poorer 5-year survival. NRI analysis showed significant improvement in the predictive power of PNI for transfusion ( = 0.002) and 5-year survival ( = 0.004).

Conclusions: Preoperative PNI <44 was significantly associated with higher transfusion rates and surgical outcomes.
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http://dx.doi.org/10.3390/cancers13112508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196581PMC
May 2021

Influence of pretreatment of insulin on the phosphorylation of extracellular receptor kinase by gonadotropin-releasing hormone and gonadotropins in cultured human granulosa cells.

Eur J Obstet Gynecol Reprod Biol 2021 Jul 11;262:113-117. Epub 2021 May 11.

Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address:

Objective: To investigate the influence of pretreatment of insulin on the phosphorylation of ERK1/2 by gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in cultured human granulosa cells.

Study Design: Human granulosa cells were collected from 20 women (age: 20-35 years) who underwent controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer at Asan Medical Center (Seoul, South Korea). The presence of the receptors for insulin, GnRH, FSH, and LH in human granulosa cells was identified by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The granulosa cells were treated with 10 nM insulin or 10 nM GnRH for 5 min or 30 min and with 10 nM FSH or 10 nM LH for 24 h or 48 h. The cells were also pretreated with insulin for 30 min prior to treatment with GnRH, FSH, or LH. Western blot analysis was used to analyze ERK1/2 phosphorylation.

Results: RT-PCR showed that the receptors for insulin, GnRH, FSH, and LH were expressed in human granulosa cells. Insulin, GnRH, FSH, and LH could activate ERK1/2 phosphorylation. Pretreatment with insulin inhibited ERK1/2 phosphorylation induced by GnRH and FSH while augmenting ERK1/2 phosphorylation induced by LH.

Conclusions: Insulin might have a negative effect on GnRH and FSH regulation by attenuating the action of GnRH and FSH in the phosphorylation of ERK1/2 in human granulosa cells. In contrast, insulin might have a positive effect on LH regulation by potentiating the action of LH in the phosphorylation of ERK1/2. Our results showed that insulin is clearly an important regulator of human reproductive function at the ovarian level.
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http://dx.doi.org/10.1016/j.ejogrb.2021.05.016DOI Listing
July 2021

Developmental features and predicting airway failure risk in critically ill children with mandibular hypoplasia using 3D computational tomographic analysis.

Sci Rep 2021 May 10;11(1):9881. Epub 2021 May 10.

Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

In children with mandibular hypoplasia, airway management is challenging. However, detailed cephalometric assessment data for this population are sparse. The aim of this study was to find risk factors for predicting difficult airways in children with mandibular hypoplasia, and compare upper airway anatomical differences using three-dimensional computed tomography (3D CT) between children with mandibular hypoplasia and demographically matched healthy controls. There were significant discrepancies in relative tongue position (P < 0.01) and anterior distance of the hyoid bone (P < 0.01) between patients with mandibular hypoplasia and healthy controls. All mandibular measures were significantly different between the two groups, except for the height of the ramus of the mandible. After adjusting for age and sex, the anterior distance of hyoid bone and inferior pogonial angle were significantly associated with a difficult airway (P = 0.01 and P = 0.02). Quantitative analysis of upper airway structures revealed significant discrepancies, including relative tongue position, hyoid distance, and mandible measures between patients with mandibular hypoplasia and healthy controls. The anterior distance of the hyoid bone and inferior pogonial angle may be risk factors for a difficult airway in patients with mandibular hypoplasia.
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http://dx.doi.org/10.1038/s41598-021-89302-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110979PMC
May 2021

Arrhythmia incidence and associated factors during volatile induction of general anesthesia with sevoflurane: a retrospective analysis of 950 adult patients.

Anaesth Crit Care Pain Med 2021 06 5;40(3):100878. Epub 2021 May 5.

Department of Anaesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Sevoflurane has been used to induce anaesthesia in adults due to its suitability for airway management and haemodynamic stability. Few studies have reported arrhythmia during volatile induction with sevoflurane in adults. Here, we investigated the incidence of arrhythmia and risk factors associated with its occurrence during sevoflurane induction of anaesthesia in adults.

Patients And Methods: We retrospectively analysed 950 adult patients who underwent elective ear nose and throat surgery with volatile induction using sevoflurane between May and December 2015. The incidence of arrhythmia and the factors associated with its development were analysed.

Results: Arrhythmia was observed in 164 (17.3%) of 950 adult patients. The most frequently observed arrhythmia was sinus tachycardia (heart rate > 120 bpm) (77 patients, 47.0%). The multivariable logistic analysis showed four independent risk factors: age (odds ratio [OR] = 0.984, 95% confidence interval [CI] = 0.973-0.996, p = 0.006), coronary artery disease (OR = 3.749, 95% CI = 1.574-8.927, p = 0.003), maximal concentration (8 vol%) of sevoflurane from the start of induction (OR = 2.696, 95% CI = 1.139-6.382, p = 0.024), and maintenance of 8 vol% sevoflurane concentration after eyelash reflex loss (OR = 1.577, 95% CI = 1.083-2.296, p = 0.018). The risk of hypotension was greater in patients in whom arrhythmia occurred, although blood pressure recovered to baseline after the concentration of sevoflurane was adjusted.

Conclusions: We recommend that the sevoflurane concentration be gradually increased with continuous and vigilant electrocardiogram and blood pressure monitoring. The sevoflurane concentration should be adjusted after sufficient unconsciousness is reached.
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http://dx.doi.org/10.1016/j.accpm.2021.100878DOI Listing
June 2021
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