Publications by authors named "Tae-Hwan Kim"

621 Publications

Self-Assembly of 2D Gold Nanoparticle Superlattice in a Polymer Vesicle Layer Driven by Hydrophobic Interaction.

J Phys Chem Lett 2021 Jul 15;12(28):6736-6743. Epub 2021 Jul 15.

Department of Quantum System Engineering, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju 54896, Republic of Korea.

Self-assembly of gold nanoparticles (AuNPs) into highly ordered superstructures provides a promising route toward fabricating materials with new functionalities or enhanced physical properties. Although self-assembly of AuNPs has garnered significant research attention recently, a highly ordered superlattice of AuNPs under a low concentration in a confined geometry formed by nonfunctionalized materials has not been reported. Herein, we investigate the self-assembly of a 2D AuNPs superlattice in a polymer vesicle layer using hydrophobic interactions, which exhibits centered rectangular lattice symmetry. To create the highly ordered AuNPs superlattice, the P(EG--iPGE) block copolymers that form the thickness of the hydrophobic vesicle layer comparable to the size of the AuNP are used as a template to control the AuNP degree of freedom. To the best of our knowledge, this study provides the first demonstration of a centered rectangular structure formation of AuNPs at the vesicle layer in 2D confined geometry.
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http://dx.doi.org/10.1021/acs.jpclett.1c01684DOI Listing
July 2021

Clinical characteristics of non-radiographic axial spondyloarthritis: Results of the Korean Nonradiographic Axial SPondyloArthritis (KONASPA) data.

Int J Rheum Dis 2021 Jul 11. Epub 2021 Jul 11.

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Aim: To evaluate clinical characteristics and natural history of non-radiographic axial spondyloarthritis (nr-axSpA) using KOrean Nonradiographic Axial SPondyloArthritis (KONASPA) data.

Methods: Data were collected from 11 centers in South Korea. A total of 278 patients with nr-axSpA from January 2018 to July 2020 were included. Demographic data, clinical features, comorbidities, disease activity, medications, and laboratory results were collected.

Results: Mean age at symptom onset was 28.2 ± 14.2 years. Of 278 patients, 152 (54.7%) were male. Mean Bath Ankylosing Spondylitis Disease Activity Index at diagnosis was 3.5 ± 2.1. Dyslipidemia was the most common comorbidity (8.4%), followed by hypertension (6.1%). Mean age at diagnosis of nr-axSpA was older in female patients than in male patients (31.8 ± 15.8 years vs 24.9 ± 12.0 years, P < 0.001). Enthesitis and uveitis were more frequently found in female patients than in male patients. Thirty-one (11.1%) participants with nr-axSpA progressed to ankylosing spondylitis. The median follow-up duration was 48 months. In multivariable Cox regression analysis, age at symptom onset (hazard ratio [HR] 0.93, 95% confidence interval (CI) 0.88-0.97, P = 0.006), body mass index (BMI) (HR 1.24, 95% CI 1.06-1.44, P = 0.005) and sacroiliitis grade (HR 1.86, 95% CI 1.19-2.92, P = 0.006) were associated with progression to ankylosing spondylitis.

Conclusions: Results of nationwide data revealed that women with nr-axSpA showed a late disease onset and more extra-articular manifestations than men. Young age at symptom onset, high BMI, and presence of radiographic sacroiliitis at diagnosis were risk factors for progression to AS.
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http://dx.doi.org/10.1111/1756-185X.14175DOI Listing
July 2021

Upadacitinib in Active Ankylosing Spondylitis: 1-Year Results From the Double-Blind, Placebo-Controlled SELECT-AXIS 1 Study and Open-Label Extension.

Arthritis Rheumatol 2021 Jul 1. Epub 2021 Jul 1.

AbbVie Inc, North Chicago, IL, United States.

Objective: To report efficacy and safety of upadacitinib through 1 year in patients with ankylosing spondylitis (AS).

Methods: In the SELECT-AXIS 1 study, adults with active AS and inadequate response to non-steroidal anti-inflammatory drugs were randomized to upadacitinib 15 mg once daily (QD) or placebo. At week 14, patients continued in the open-label extension and received upadacitinib up to week 104; reported here are interim data up to week 64.

Results: Of 187 patients, 178 completed week 14 on study drug and entered the open-label extension. Similar proportions of patients in either group (continuous upadacitinib or placebo-to-upadacitinib) achieved Assessment of SpondyloArthritis international Society (ASAS) 40 or Ankylosing Spondylitis Disease Activity Score (ASDAS) low-disease activity at week 64: ≥70% of patients achieved these endpoints based on non-responder imputation (NRI) and ≥81% based on as-observed (AO) analyses. Furthermore, ≥34% (NRI) and ≥39% (AO) of patients achieved ASDAS inactive disease or ASAS partial remission at week 64. Mean changes from baseline (week 0) to week 64 in pain, function, and inflammation showed consistent improvement or sustained maintenance through the study. Among 182 patients receiving upadacitinib (237.6 PY), 618 adverse events (260.1/100 PY) were reported. No serious infections, major adverse cardiovascular events, venous thromboembolic events, gastrointestinal perforation, or deaths were reported.

Conclusion: Upadacitinib 15 mg QD showed sustained and consistent efficacy over 1 year. Patients who switched from placebo to upadacitinib at week 14 showed similar efficacy versus those who received continuous upadacitinib.
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http://dx.doi.org/10.1002/art.41911DOI Listing
July 2021

Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis.

Ann Rheum Dis 2021 Apr 20. Epub 2021 Apr 20.

Rheumatology Department, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Objective: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain.

Methods: PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), and sacroiliac MRI.

Results: In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for testing alone (AUC=0.869), MRI (AUC=0.885) or C-reactive protein (AUC=0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC=0.948). Assuming a prior probability of AS of 10% such as in patients with chronic back pain under 45 years of age, compared with testing alone, PRS provides higher positive values for 35% of patients and negative predictive values for 67.5% of patients. For PRS, in people of European descent, the maximum positive predictive value was 78.2% and negative predictive value was 100%, whereas for these values were 51.9% and 97.9%, respectively.

Conclusions: PRS have higher discriminatory capacity for AS than CRP, sacroiliac MRI or status alone. For optimal performance, PRS should be developed for use in the specific ethnic groups to which they are to be applied.
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http://dx.doi.org/10.1136/annrheumdis-2020-219446DOI Listing
April 2021

The Prognosis and Oncological Predictor of Urachal Carcinoma of the Bladder: A Large Scale Multicenter Cohort Study Analyzed 203 Patients With Long Term Follow-Up.

Front Oncol 2021 31;11:683190. Epub 2021 May 31.

Department of Urology, Seoul National University Bundang Hospital, Seongnam, Korea.

Aim: This study evaluated the prognosis and survival predictors for bladder urachal carcinoma (UC), based on large scale multicenter cohort with long term follow-up database.

Methods: A total 203 patients with bladder UC treated at 19 hospitals were enrolled. Clinical parameters on carcinoma presentation, diagnosis, and therapeutic methods were reviewed for the primary cancer and for all subsequent recurrences. The stage of UC was stratified by Mayo and Sheldon pathological staging system. Oncological outcomes and the possible clinicopathological parameters associated with survival outcomes were investigated.

Results: The mean age of the patients was 54.2 years. Among the total of 203 patients, stages I, II, III, and IV (Mayo stage) were 48 (23.8%), 108 (53.5%), 23 (11.4%), and 23 (11.4%), respectively. Gross hematuria and bladder irritation symptoms were the two most common initial symptoms. The mean follow-up period was 65 months, and 5-year overall survival rates (OS), cancer-specific survival rates (CSS), and recurrence-free survival rates (RFS) were 88.3, 83.1, and 63.9%, respectively. For the patients with Mayo stage ≥III, OS, CSS, and RFS were significantly decreased to 38.0, 35.2, and 28.4%, respectively. The higher pathological stage (Mayo stage ≥III, Sheldon stage ≥IIIc), positive surgical margin (PSM), and positive lymphovascular invasion (PLM) were independent predictors of shorter OS, CSS, and RFS.

Conclusion: The pathological stage, PSM, and PLM were significantly associated with the survival of UC patients, emphasizing an importance of the complete surgical resection of tumor lesion.
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http://dx.doi.org/10.3389/fonc.2021.683190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202399PMC
May 2021

Treatment Guideline for Patients with Native Culture-negative Pyogenic Vertebral Osteomyelitis.

Clin Orthop Relat Res 2021 Jun 15. Epub 2021 Jun 15.

Spine Center, Department of Orthopedics, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.

Background: With the development of evidence-based guidelines for the diagnosis and antibiotic treatment of patients with pyogenic vertebral osteomyelitis, various nonsurgical and surgical treatment strategies have achieved favorable results. However, sufficient administration of appropriate antibiotics is a prerequisite for treatment success, which cannot be guaranteed in patients with culture-negative pyogenic vertebral osteomyelitis. Unfortunately, previous studies on culture-negative pyogenic vertebral osteomyelitis were limited by small patient groups, short follow-up periods, varied treatment protocols, and inconsistently defined clinical endpoints.

Questions/purposes: Among patients treated according to our center's treatment protocol for culture-negative pyogenic vertebral osteomyelitis, which included patients treated without surgery, with surgery but without spinal instrumentation, as well as patients treated with instrumented surgery, (1) what proportion of patients in each treatment group experienced recurrence (or persistence) of infection, complications of treatment, and death; and (2) what factors were independently associated with recurrent or persistent infection after treatment under this algorithm?

Methods: This was a retrospective evaluation of a treatment protocol in use at one center from 2008 to 2020. During that time, we treated 183 patients for culture-negative pyogenic vertebral osteomyelitis. The diagnosis was based on clinical, laboratory, and radiological features excluding disease that presents similar features to pyogenic vertebral osteomyelitis. For those patients, our protocol included three possible approaches: nonsurgical treatment, including the use of empirical antibiotics (nonoperative group, n = 82); spinal decompression without instrumentation (noninstrumented group, n = 41); and spinal decompression with instrumentation (instrumented group, n = 60). The indications for each treatment during the period remained relatively consistent. Nonsurgical treatment including empirical antibiotics was applied to all patients according to the specified antibiotic protocol. Spinal decompression without instrumentation was employed when a patient presented substantial or aggravating neurologic deficits or intractable pain from an abscess. Instrumentation was added in patients with mechanical instability before or after spinal decompression. Minimum follow-up to be included in this study was 1 year, and 91% (252 of 277) of patients were accounted for at that time, with no differential loss to follow-up among the study groups (12, five, and four patients missing from the three groups, respectively, at 1 year). Chart review was performed to ascertain the proportion of patients in each group who experienced recurrence, complications, and death. Factors associated with recurrence were assessed across the entire cohort using a multivariable logistic model. We analyzed 1-year recurrence and mortality rates using the Kaplan-Meier method, and their 95% confidence intervals were calculated using the method by Hosmer and Lemeshow.

Results: At 1 year, the recurrence-free survival rate was 87% (95% confidence interval 78% to 93%) in the nonoperative group, 87% (95% CI 72% to 94%) in the noninstrumented group, and 91% (95% CI 80% to 96%) in the instrumented group. The proportion of patients who experienced a major medical complication in each group was 12% (10 of 82), 10% (4 of 41), and 8% (5 of 60), respectively. At 1 year, the survival rate with patient death as the endpoint was 95% (95% CI 88% to 98%) in the nonoperative group, 95% (95% CI 82% to 99%) in the noninstrumented group, and 97% (95% CI 87% to 99%) in the instrumented group. After controlling for potentially confounding variables including age, medical comorbidities, and anatomical involvement of infection, the following factors were independently associated with increased odds of infection recurrence or persistence: higher Charlson Comorbidity Index (CCI) score (odds ratio 1.6 per point on the CCI [95% CI 1.2 to 2.1]; p = 0.004) and the presence of a psoas abscess (OR 4.7 [95% CI 1.6 to 13.9]; p = 0.005).

Conclusion: Among patients with negative initial nonoperative culture results, spinal decompression and abscess drainage can be used in those with substantial or aggravating neurological deficits or intractable pain caused by an abscess, while additional early spinal instrumentation can be applied upon consideration of their medical comorbidities and the presence of a psoas abscess when mechanical instability is present before or after the spinal decompression. Reasonable clinical results can be expected, regardless of the results from subsequent operative cultures. However, our study results should be replicated by other centers, and further studies that consider individual differences such as bone mineral density and include patients with previous spinal instrumentation or recurrent infection should be performed to establish a more comprehensive treatment protocol.

Level Of Evidence: Level IV, therapeutic study.
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http://dx.doi.org/10.1097/CORR.0000000000001866DOI Listing
June 2021

Vitamin C Deficiency Inhibits Nonalcoholic Fatty Liver Disease Progression through Impaired de Novo Lipogenesis.

Am J Pathol 2021 Jun 11. Epub 2021 Jun 11.

Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, Republic of Korea. Electronic address:

Despite the increasing clinical importance of nonalcoholic fatty liver disease (NAFLD), little is known about its underlying pathogenesis or specific treatment. The senescence marker protein 30 (SMP30), which regulates the biosynthesis of vitamin C (VC) in many mammals, except primates and humans, was recently recognized as a gluconolactonase. However, the precise relation between VC and lipid metabolism in NAFLD is not completely understood. Therefore, we aimed to clearly reveal the role of VC in NAFLD progression. SMP30 knockout (KO) mice were used as a VC-deficient mouse model. To investigate the precise role of VC on lipid metabolism, 13- to 15-week-old SMP30 KO mice and wild-type mice fed a 60% high-fat diet were exposed to tap water or VC-containing water (1.5 g/L) ad libitum for 11 weeks. Primary mouse hepatocytes isolated from the SMP30 KO and wild-type mice were used to demonstrate the relation between VC and lipid metabolism in hepatocytes. We found that long-term VC deficiency significantly suppressed the progression of simple steatosis. The high-fat diet-fed VC-deficient SMP30 KO mice exhibited impaired sterol regulatory element-binding protein-1c activation because of excessive cholesterol accumulation in hepatocytes. Long-term VC deficiency inhibits de novo lipogenesis through impaired sterol regulatory element-binding protein-1c activation.
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http://dx.doi.org/10.1016/j.ajpath.2021.05.020DOI Listing
June 2021

Blocking TNFα attenuates progressive cartilage matrix degradation in inflammatory arthritis.

Exp Ther Med 2021 Aug 27;22(2):808. Epub 2021 May 27.

Hanyang University Institute for Rheumatology Research, Seoul 04763, Republic of Korea.

Because damage to hyaline cartilage is irreversible, relieving progressive cartilage destruction is an important therapeutic approach for inflammatory arthritis. In the present study, human hyaline chondrocytes were isolated from total knee replacements of 15 patients with osteoarthritis (OA) and three with rheumatoid arthritis (RA). Synovial fluid of OA (n=25) and RA (n=34) were collected to measure tumor necrosis factor α (TNFα) using ELISA. Consistent with previous studies, the synovial fluid exhibited high TNFα levels and hyaline cartilage was severely destroyed in patients with RA. TNFα-treated chondrocytes were used as model for inflammatory arthritis. TNFα did not influence proliferation or extracellular matrix expression in chondrocytes, but induced matrix metalloproteinase (MMP)1, 3 and 13 expression levels in chondrocytes, which was accompanied by activation of nuclear factor-κB signaling. During chondrogenic differentiation, TNFα attenuated mRNA expression levels of anabolic factors (collagen type 2 and aggrecan) and enhanced mRNA expression of catabolic factors (, and ) in chondrocytes. Moreover, anti-TNFα agents (Golimumab) inhibited the TNFα-induced metabolic shift in chondrocytes and chondrogenic differentiation. The present study revealed a mechanism by which TNFα may induce metabolic shift in chondrocytes, leading to progressive chondrocyte destruction.
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http://dx.doi.org/10.3892/etm.2021.10240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170641PMC
August 2021

Superconductivity emerging from a stripe charge order in IrTe nanoflakes.

Nat Commun 2021 May 26;12(1):3157. Epub 2021 May 26.

Center for Artificial Low Dimensional Electronic Systems, Institute for Basic Science, Pohang, Korea.

Superconductivity in the vicinity of a competing electronic order often manifests itself with a superconducting dome, centered at a presumed quantum critical point in the phase diagram. This common feature, found in many unconventional superconductors, has supported a prevalent scenario in which fluctuations or partial melting of a parent order are essential for inducing or enhancing superconductivity. Here we present a contrary example, found in IrTe nanoflakes of which the superconducting dome is identified well inside the parent stripe charge ordering phase in the thickness-dependent phase diagram. The coexisting stripe charge order in IrTe nanoflakes significantly increases the out-of-plane coherence length and the coupling strength of superconductivity, in contrast to the doped bulk IrTe. These findings clarify that the inherent instabilities of the parent stripe phase are sufficient to induce superconductivity in IrTe without its complete or partial melting. Our study highlights the thickness control as an effective means to unveil intrinsic phase diagrams of correlated van der Waals materials.
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http://dx.doi.org/10.1038/s41467-021-23310-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154908PMC
May 2021

Pharmacodynamics of ceftazidime plus tobramycin combination dosage regimens against hypermutable Pseudomonas aeruginosa isolates at simulated epithelial lining fluid concentrations in a dynamic in vitro infection model.

J Glob Antimicrob Resist 2021 May 21;26:55-63. Epub 2021 May 21.

Centre for Medicine Use and Safety, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia. Electronic address:

Objectives: Hypermutable Pseudomonas aeruginosa strains are a major challenge in cystic fibrosis. We investigated bacterial killing and resistance emergence for approved ceftazidime and tobramycin regimens, alone and in combination.

Methods: Pseudomonas aeruginosa PAOΔmutS and six hypermutable clinical isolates were examined using 48-h static concentration time-kill (SCTK) studies (inoculum ~10 CFU/mL); four strains were also studied in a dynamic in vitro model (IVM) (inoculum ~10 CFU/mL). The IVM simulated concentration-time profiles in epithelial lining fluid following intravenous administration of ceftazidime (3 g/day and 9 g/day continuous infusion), tobramycin (5 mg/kg and 10 mg/kg via 30-min infusion 24-hourly; half-life 3.5 h), and their combinations. Time courses of total and less-susceptible populations were determined.

Results: Ceftazidime plus tobramycin demonstrated synergistic killing in SCTK studies for all strains, although to a lesser extent for ceftazidime-resistant strains. In the IVM, ceftazidime and tobramycin monotherapies provided ≤5.4 and ≤3.4 log initial killing, respectively; however, re-growth with resistance occurred by 72 h. Against strains susceptible to one or both antibiotics, high-dose combination regimens provided >6 log initial killing, which was generally synergistic from 8-24 h, and marked suppression of re-growth and resistance at 72 h. The time course of bacterial density in the IVM was well described by mechanism-based models, enabling Monte Carlo simulations (MCSs) to predict likely effectiveness of the combination in patients.

Conclusion: Results of the IVM and MCS suggested antibacterial effect depends both on the strain's susceptibility and hypermutability. Further investigation of the combination against hypermutable P. aeruginosa strains is warranted.
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http://dx.doi.org/10.1016/j.jgar.2021.04.021DOI Listing
May 2021

Effect of intraoperative fluid volume on postoperative ileus after robot-assisted radical cystectomy.

Sci Rep 2021 May 18;11(1):10522. Epub 2021 May 18.

Department of Urology, Korea University College of Medicine, 73 Inchon-ro, Seongbuk-gu, Seoul, 02841, Korea.

This study aimed to investigate the effect of intraoperative fluid volume on the postoperative ileus (POI) recovery period. A retrospective review of the Korean robot-assisted radical cystectomy database identified 718 patients who underwent robot-assisted radical cystectomy (RARC). Regression analyses were performed to identify the associations between the amount of intraoperative fluid administration (crystalloid/colloid/total), POI period (time to flatus/bowel movements), and length of hospital stay (LOS) after adjusting for covariates. In addition, we analyzed the risk factors for gastrointestinal complications and prolonged POI using a logistic regression model. An increasing volume of the administered crystalloid/total fluid was associated with prolonged POI (crystalloid R = 0.0725 and P < 0.0001; total amount R = 0.0812 and P < 0.0001), and the total fluid volume was positively associated with the LOS (R = 0.099 and P < 0.0001). The crystalloid amount was a risk factor for prolonged POI (P < 0.001; odds ratio, 1.361; 95% confidence interval, 1.133-1.641; P < 0.001). In the context of RARC, increased intravenous fluids are associated with prolonged POI and longer LOS.
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http://dx.doi.org/10.1038/s41598-021-89806-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131600PMC
May 2021

Administration in fed state but not controlled release in the colon increases oral bioavailability of DF030263, a promising drug candidate for chronic lymphocytic leukemia.

Eur J Pharm Biopharm 2021 Aug 12;165:106-112. Epub 2021 May 12.

School of Pharmacy & Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK. Electronic address:

For treatment of chronic cancers, the oral administration route is preferred as it provides numerous advantages over other delivery routes. However, these benefits of oral chemotherapy can be limited due to unfavorable pharmacokinetics. Accordingly, pharmacokinetic development of chemotherapeutic agents is crucial to the improvement of cancer treatment. In this study, assessment and optimization of biopharmaceutical properties of a promising drug candidate for cyclin-dependent kinase 9 (CDK9) inhibitor (DF030263) was performed to promote oral delivery. Oral bioavailability of DF030263 in fasted rats was 23.8%, and a distinct double-peak phenomenon was observed. A two-site absorption windows mechanism was proposed as a possible explanation to the phenomenon. The two-site absorption window hypothesis was supported by in vitro solubility assays in biorelevant fluids with different pH levels, as well as by in silico simulation by GastroPlus™. Controlled release to the colon was conducted in rats in order to exploit the colonic absorption window but did not improve the oral bioavailability. On the other hand, oral administration at postprandial conditions in rats (performed based on the high in vitro solubility in fed state simulated fluid and reduced pH-dependency) resulted in an almost 3-fold increase in bioavailability to 63.6%. In conclusion, this study demonstrates an efficient in vitro-in vivo-in silico drug development approach for improving the oral bioavailability of DF030263, a promising candidate for the treatment of chronic lymphocytic leukemia.
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http://dx.doi.org/10.1016/j.ejpb.2021.05.006DOI Listing
August 2021

Effects of losartan and l-serine in a mouse liver fibrosis model.

Life Sci 2021 Aug 6;278:119578. Epub 2021 May 6.

Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, 41566 Daegu, Republic of Korea; Stem Cell Therapeutic Research Institute, Kyungpook National University, 41566 Daegu, Republic of Korea. Electronic address:

Hepatic fibrosis is a common liver disease caused by excessive collagen deposition in the liver. Since liver transplantation is the only current treatment for cirrhosis with worsened fibrosis, a new strategy to develop anti-fibrosis drugs with no adverse effects is necessary. In recent studies, amino acids have been applied as a type of therapy in various fields. l-serine plays a major role in antioxidant production via the maintenance of nicotinamide adenine dinucleotide phosphate hydride production in the mitochondria. l-serine may reduce fibrotic lesions in a mouse model of chronic liver injury. This study used 27 six-week-old C57BL/6 mice and injected them three times a week for eight weeks with carbon tetrachloride (CCl) (1.5 mg/kg, 10% v/v CCl in olive oil) to create a hepatic fibrosis mouse model. The mice, which weighed approximately 20-30 g, were randomly classified into four groups: 1) the olive oil group, which received intraperitoneal injection of olive oil (1.5 mg/kg, 3 times per week for 8 weeks); 2) the CCl4-only group; 3) the CCl4 + losartan (10 mg/kg, PO, 5 days on, weekend off for 8 weeks) group; and 4) the CCl4 + l-serine (100 g/L, free access for 8 weeks) group. Hematoxylin and eosin staining and Masson's trichrome staining showed reduced inflammatory cell deposition and collagen deposition in the liver tissue in the l-serine supplemented group. l-serine was found to reduce the spread of hepatic fibrosis and has potential use in clinical settings. Based on these histopathological observations, l-serine is a potential anti-fibrosis drug.
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http://dx.doi.org/10.1016/j.lfs.2021.119578DOI Listing
August 2021

Nuclear VEGFR-2 Expression of Hepatocytes Is Involved in Hepatocyte Proliferation and Liver Regeneration During Chronic Liver Injury.

In Vivo 2021 May-Jun;35(3):1473-1483

Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea;

Background/aim: The pathological role of vascular endothelial growth factor receptor 2 (VEGFR-2) in chronic liver injury and liver regeneration is not fully understood. This study analysed the role of VEGFR-2 in liver fibrosis and its regeneration process.

Materials And Methods: We administered intraperitoneally 50 mg/kg to 300 mg/kg thioacetamide (TAA) to 9-week-old male mice for 17 weeks. We measured levels of VEGFR-2 protein and identified the location of cells that specifically express VEGFR-2.

Results: VEGFR-2 is rarely expressed in normal hepatocytes. However, high VEGFR-2 expression in liver sinusoidal endothelial cells was noted in the TAA group. Conversely, the group that experienced regeneration from liver fibrosis showed significantly higher VEGFR-2 expression in the nucleus of hepatocytes compared to the other groups.

Conclusion: VEGFR-2 plays a pivotal role in the nucleus of hepatocytes during liver regeneration and VEGFR-2 may be closely related to cell division. Therefore, VEGFR-2 may be a new therapeutic target for liver regeneration.
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http://dx.doi.org/10.21873/invivo.12400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193308PMC
June 2021

Urease and nitrification inhibitors with pig slurry effects on ammonia and nitrous oxide emissions, nitrate leaching, and nitrogen use efficiency in perennial ryegrass sward.

Anim Biosci 2021 Apr 23. Epub 2021 Apr 23.

Department of Animal Science, College of Agriculture & Life Science, Chonnam National University, Gwangju 61186, Korea.

Objective: The present study was conducted to assess the effect of urease inhibitor (hydroquinone, HQ) and nitrification inhibitor (dicyandiamide, DCD) on nitrogen (N) use efficiency of pig slurry for perennial ryegrass regrowth yield and its environmental impacts.

Methods: A micro-plot experiment was conducted using pig slurry-urea 15N treated with HQ and/or DCD and applied at a rate of 200 kg N ha-1. The flows of N derived from the pig slurry urea to herbage regrowth and soils as well as soil N mineralization were estimated by tracing pig slurry-urea 15N, and the N losses via ammonia (NH3), nitrous oxide (N2O) emission, and nitrate (NO3-) leaching were quantified for a 56 d regrowth of perennial ryegrass (Lolium perenne) sward.

Results: Herbage dry matter at the final regrowth at 56 d was significantly higher in the HQ and/or DCD applied plots, with a 24.5-42.2% increase in 15N recovery by herbage compared with the control. Significant increases in soil 15N recovery were also observed in the plots applied with the inhibitors, accompanied by the increased N content converted to soil inorganic N (NH4+ + NO3-) (17.3-28.8% higher than that of the control). The estimated loss, which was not accounted for in the herbage-soil system, was lower in the plots applied with the inhibitors (25.6% on average) than that of control (38.0%). Positive effects of urease and/or nitrification inhibitors on reducing N losses to the environment were observed at the final regrowth (56 d), at which cumulative NH3 emission was reduced by 26.8% (on average 3 inhibitor treatments), N2O emission by 50.2% and NO3- leaching by 10.6% compared to those of the control.

Conclusion: The proper application of urease and nitrification inhibitors would be an efficient strategy to improve the N use efficiency of pig slurry while mitigating hazardous environmental impacts.
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http://dx.doi.org/10.5713/ab.21.0046DOI Listing
April 2021

Identification of a novel non-invasive biological marker to overcome the shortcomings of PSA in diagnosis and risk stratification for prostate cancer: Initial prospective study of developmental endothelial locus-1 protein.

PLoS One 2021 26;16(4):e0250254. Epub 2021 Apr 26.

Department of Urology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Objective: This prospective study sought to clarify the developmental endothelial locus-1 (Del-1) protein as values of diagnosis and risk stratification of prostate cancer (PCa).

Design: From February 2017 to December 2019, a total 458 patients who underwent transrectal ultrasound guided prostate biopsy or surgery of benign prostatic hyperplasia agreed to research of Del-1 protein. We prospectively compared and analyzed the Del-1 protein and prostate specific antigen (PSA) in relation to the patients' demographic and clinicopathological characteristics.

Results: Mean age was 68.86±8.55 years. Mean PSA and Del-1 protein was 21.72±89.37, 0.099±0.145, respectively. Two hundred seventy-six (60.3%) patients were diagnosed as PCa. Among them, 181 patients underwent radical prostatectomy (RP). There were significant differences in Del-1 protein between benign and PCa group (0.066±0.131 vs 0.121±0.149, respectively, p<0.001). When we set the cut-off value of del-1 protein as 0.120, in patients with 3≤PSA≤8, positive predictive value and specificity of Del-1 protein (≥0.120) for predicting PCa were 88.9% (56/63) and 93.5% (101/108), respectively. Among 181 patients who underwent RP, there were significant differences in Del-1 protein according to stage (pT2 vs pT3a vs ≥pT3b) (0.113±0.078, 0.171±0.121, 0.227±0.161, respectively, p<0.001) and to Gleason score (6 (3+3) or 7 (3+4) vs 7 (4+3) or 8 (4+4) vs 9 or 10) (0.134±0.103, 0.150±0.109, 0.212±0.178, respectively, P = 0.044). Multivariate analysis showed that PSA, Del-1 protein and high Gleason score (≥9) were the independent prognostic factors for predicting higher pT stage (≥3b). Furthermore, age, PSA and Del-1 protein were independent prognostic factors for predicting significant PCa.

Conclusion: Patients with PCa showed higher expression of Del-1 protein than benign patients. Del-1 protein increased with the stage and Gleason score of PCa. Collaboration with PSA, Del-1 protein can be a non-invasive useful marker for diagnosis and risk stratification of PCa.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250254PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075267PMC
April 2021

Significance of albumin to globulin ratio as a predictor of febrile urinary tract infection after ureteroscopic lithotripsy.

Yeungnam Univ J Med 2021 Jul 20;38(3):225-230. Epub 2021 Apr 20.

Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea.

Backgruound: We aimed to analyze the effectiveness of albumin to globulin ratio (AGR) in predicting postoperative febrile urinary tract infection (fUTI) after ureteroscopic lithotripsy (URS) and retrograde intrarenal surgery (RIRS).

Methods: From January 2013 to May 2018, 332 patients underwent URS and RIRS. The rate of postoperative fUTI and risk factors for postoperative fUTI were analyzed using logistic regression. Patients were divided into postoperative fUTI and non-postoperative fUTI (non-fUTI) groups. AGR with other demographic and perioperative data were compared between the two groups to predict the development of fUTI after URS.

Results: Of the 332 patients, postoperative fUTI occurred in 41 (12.3%). Preoperative pyuria, microscopic hematuria, diabetes mellitus, hypoalbuminemia, and hyperglobulinemia were more prevalent in the fUTI group. Patients in the fUTI group had larger stone size, lower preoperative AGR, longer operation time, and longer preoperative antibiotic coverage period. In a multivariable logistic analysis, preoperative pyuria, AGR, and stone size were independently correlated with postoperative fUTI (p<0.001, p=0.008, and p=0.041, respectively). Receiver operating curve analysis showed that the cutoff value of AGR that could predict a high risk of fUTI after URS was 1.437 (sensitivity, 77.3%; specificity, 76.9%), while the cutoff value of stone size was 8.5 mm (sensitivity, 55.3%; specificity, 44.7%).

Conclusion: This study demonstrated that preoperative pyuria, AGR, and stone size can serve as prognostic factors for predicting fUTI after URS.
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http://dx.doi.org/10.12701/yujm.2021.00955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225490PMC
July 2021

Efficacy and safety of brodalumab, an anti-IL17RA monoclonal antibody, in patients with axial spondyloarthritis: 16-week results from a randomised, placebo-controlled, phase 3 trial.

Ann Rheum Dis 2021 Apr 7. Epub 2021 Apr 7.

Department of Internal Medicine and Rheumatology, Juntendo University Koshigaya Hospital, Saitama, Japan

Objective: To investigate the efficacy and safety of brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with axial spondyloarthritis (axSpA).

Methods: In a multicentre, placebo-controlled phase 3 study (NCT02985983) conducted at 48 sites across Japan, Korea and Taiwan, patients with axSpA were randomised 1:1 to receive subcutaneous brodalumab 210 mg (n=80) or placebo (n=79) at baseline, weeks 1 and 2 and every 2 weeks thereafter, during the 16-week double-blind period. The primary endpoint was the proportion of patients with Assessment of SpondyloArthritis International Society (ASAS) 40 response at week 16. Secondary endpoints included the proportion of patients with ASAS 20 response and change in Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) at week 16 and safety.

Results: ASAS 40 response rate (n/N; 95% CI) was 43.8% (35/80; 32.7, 55.3) with brodalumab vs 24.1% (19/79; 15.1, 35.0) with placebo (rate difference, 19.7% (5.3, 34.1); p=0.018 by stratified Cochran-Mantel-Haenszel test). ASAS 20 response rate (n/N; 95% CI) was 67.5% (54/80; 56.1, 77.6) vs 41.8% (33/79; 30.8, 53.4) and least squares mean change (95% CI) from baseline (brodalumab, 2.660; placebo, 2.716) in ASDAS-CRP was -1.127 (-1.322, -0.931) with brodalumab vs -0.672 (-0.872, -0.473) with placebo at week 16. Treatment-emergent adverse events were reported in 44 (55%) and 45 (57%) patients in the brodalumab and placebo groups, respectively.

Conclusion: Brodalumab demonstrated a significant improvement at week 16 in patients with active axSpA. Safety of brodalumab was consistent with that reported in previous global/Japanese psoriasis studies.
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http://dx.doi.org/10.1136/annrheumdis-2020-219406DOI Listing
April 2021

Drought Intensity-Responsive Salicylic Acid and Abscisic Acid Crosstalk with the Sugar Signaling and Metabolic Pathway in .

Plants (Basel) 2021 Mar 23;10(3). Epub 2021 Mar 23.

Department of Animal Science, Institute of Agricultural Science and Technology, College of Agriculture & Life Science, Chonnam National University, Gwangju 61186, Korea.

The aim of this study was to characterize hormonal crosstalk with the sugar signaling and metabolic pathway based on a time course analysis of drought intensity. Drought intensity-responsive changes in the assimilation of newly fixed carbon (C) into soluble sugar, the content of sugar and starch, and expression of genes involved in carbohydrate metabolism were interpreted as being linked to endogenous abscisic acid (ABA) and salicylic acid (SA) levels and their signaling genes. The ABA and SA levels in the drought-stressed leaves increased together during the early drought period (days 0-6), and additional ABA accumulation occurred with depressed SA during the late period (days 6-14). Although drought treatment decreased the assimilation of newly fixed C into soluble sugar, representing a 59.9%, 33.1%, and 62.9% reduction in C-glucose, C-fructose, and C-sucrose on day 14, respectively, the drought-responsive accumulation of soluble sugars was significant. During the early period, the drought-responsive accumulation of hexose and sucrose was concurrent with the upregulated expression of (, which, in turn, occurred parallel to the upregulation of ABA synthesis gene () and SA-related genes ( () and ()). During the late period, hexose accumulation, sucrose phloem loading, and starch degradation were dominant, with a highly enhanced expression of the starch degradation-related genes () and (), which were concomitant with the parallel enhancement of () and () expression in an ABA-dependent manner. These results indicate that the drought-responsive accumulation of sugars (especially SA-mediated sucrose accumulation) is part of the acclamatory process during the early period. Conversely, ABA-responsive hexose accumulation and sucrose phloem loading represent severe drought symptoms during the late drought period.
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http://dx.doi.org/10.3390/plants10030610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004980PMC
March 2021

Effect of Muscle Cell Preservation on Viability and Differentiation of Hamstring Tendon Graft In Vitro.

Cells 2021 Mar 27;10(4). Epub 2021 Mar 27.

Institute for Rheumatology Research, Hanyang University, Seoul 04763, Korea.

Muscle tissue is often removed during hamstring tendon graft preparation for anterior cruciate ligament (ACL) reconstruction. The purpose of the study was to test whether preservation of muscle remnants on a tendon graft is beneficial to the graft healing process following ACL reconstruction. Co-culturing of tendon-derived cells (TDCs) and muscle-derived cells (MDCs) was performed at various ratios, and their potential for cell viability and multilineage differentiation was compared to a single TDC cell group. Ligamentous and chondrogenic differentiation was most enhanced when a small population of MDCs was co-cultured with TDCs (6:2 co-culture group). Cell viability and osteogenic differentiation were proportionally enhanced with increasing MDC population size. MDCs co-cultured with TDCs possess both the ability to enhance cell viability and differentiate into other cell lineages.
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http://dx.doi.org/10.3390/cells10040740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065441PMC
March 2021

COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases: Clinical Guidance of the Korean College of Rheumatology.

J Korean Med Sci 2021 Mar 29;36(12):e95. Epub 2021 Mar 29.

Division of Rheumatology, Department of Internal Medicine, Gachon University College of Medicine, Gil Medical Center, Incheon, Korea.

The coronavirus disease 2019 (COVID-19) pandemic has caused more than 100 million infections and 2 million deaths worldwide. In up to 20% of cases, COVID-19 infection can take a severe, life-threatening course. Therefore, preventive measures such as mask-wearing, hand hygiene, and social distancing are important. COVID-19 vaccines that use novel vaccine technology can prevent up to 95% of infections. However, the uncertainty regarding the efficacy and safety of vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), who are immunocompromised due to underlying immune dysfunction and concomitant immunosuppressive treatment, warrants clear guidance. A task force of the Korean College of Rheumatology formulated a set of vaccination guidance based on the currently available data and expert consensus. The currently available COVID-19 vaccines are considered to be safe and effective. Every patient with AIIRD should receive one of the available COVID-19 vaccines unless contraindicated for medical reasons such as prior allergy/anaphylaxis to the COVID-19 vaccine or its components. Patients should continue immunosuppressive treatment for their underlying AIIRD, including biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). Corticosteroids should be reduced to the lowest dose possible without aggravating the AIIRD. To improve the vaccine response, methotrexate can be withheld for 1-2 weeks after each vaccination, and the timing of rituximab and abatacept infusion should be adjusted if clinically acceptable. Rheumatologists should play a leading role in educating and vaccinating patients with AIIRD.
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http://dx.doi.org/10.3346/jkms.2021.36.e95DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007420PMC
March 2021

Trastuzumab-based palliative chemotherapy for HER2-positive gastric cancer: a single-center real-world data.

BMC Cancer 2021 Mar 26;21(1):325. Epub 2021 Mar 26.

Department of Pulmonology and Critical Care Medicine, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, Suwon, 443-380, South Korea.

Background: Since the results of the ToGA trial were published, trastuzumab-based chemotherapy has been used as the standard first-line treatment for HER2-positive recurrent or primary metastatic gastric cancer (RPMGC). However, the real-world data has been rarely reported. Therefore, we investigated the outcomes of trastuzumab-based chemotherapy in a single center.

Methods: This study analyzed the real-world data of 47 patients with HER2-positive RPMGC treated with trastuzumab-based chemotherapy in a single institution.

Results: With the median follow-up duration of 18.8 months in survivors, the median overall survival (OS) and progression-free survival were 12.8 and 6.9 months, respectively, and the overall response rate was 64%. Eastern Cooperative Oncology Group performance status 2 and massive amount of ascites were independent poor prognostic factors for OS, while surgical resection before or after chemotherapy was associated with favorable OS, in multivariate analysis. In addition, 5 patients who underwent conversion surgery after chemotherapy demonstrated an encouraging median OS of 30.8 months, all with R0 resection.

Conclusions: Trastuzumab-based chemotherapy in patients with HER2-positive RPMGC in the real world demonstrated outcomes almost comparable to those of the ToGA trial. Moreover, conversion surgery can be actively considered in fit patients with a favorable response after trastuzumab-based chemotherapy.
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http://dx.doi.org/10.1186/s12885-021-08058-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995795PMC
March 2021

-Derived Protein Attenuates Inflammation and New Bone Formation in Ankylosing Spondylitis.

Front Immunol 2021 25;12:615369. Epub 2021 Feb 25.

Department of Parasitology and Tropical Medicine, Chonnam National University Medical School, Gwangju, South Korea.

Helminth infections and their components have been shown to have the potential to modulate and attenuate immune responses. The objective of this study was to evaluate the potential protective effects of -derived protein (CSp) on ankylosing spondylitis (AS). Cytotoxicity of CSp at different doses was assessed by MTS and flow cytometry before performing experiments. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analyzed using flow cytometry. The levels of INF- , IL-17A, TNF-α, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). SKG mice were treated with CSp or vehicles. Inflammation and new bone formation were evaluated using immunohistochemistry, positron emission tomography (PET), and micro-computed tomography (CT). Treatment with CSp resulted in no reduced cell viability of PBMCs or SFMCs until 24 h. In experiments culturing PBMCs and SFMCs, the frequencies of IFN- and IL-17A producing cells were significantly reduced after CSp treatment. In the SKG mouse model, CSp treatment significantly suppressed arthritis, enthesitis, and enteritis. Micro-CT analysis of hind paw revealed reduced new bone formation in CSp-treated mice than in vehicle-treated mice. We provide the first evidence demonstrating that CSp can ameliorate clinical signs and cytokine derangements in AS. In addition, such CSp treatment could reduce the new bone formation of AS.
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http://dx.doi.org/10.3389/fimmu.2021.615369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947613PMC
June 2021

Gender differences in factors associated with low quality of life and depression in Korean patients with ankylosing spondylitis.

Qual Life Res 2021 Aug 10;30(8):2299-2310. Epub 2021 Mar 10.

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222-1 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.

Purpose: To identify predictors of low health-related quality of life (HRQoL) and depression in ankylosing spondylitis (AS) patients with a focus on gender differences.

Methods: We conducted a cross-sectional cohort study. Both AS-related clinical data and contextual factors were obtained. HRQoL and depressive mood were assessed by EuroQol-5 dimension (EQ-5D) and the Center for Epidemiological Studies Depression Scale (CES-D), respectively. Gender-stratified multivariable logistic regression analyses were performed.

Results: Among 211 patients, 161 were males. Males had similar disease activity and higher radiographic damage compared with females. There was no significant difference in EQ-5D index score between genders. CES-D score was higher in females. Higher ASDAS-C-reactive protein (CRP) was associated with low HRQoL in both males (Odds ratio [OR] 4.25, 95% confidence interval [CI] 2.42-7.46) and females (OR 2.94, 95% CI 1.02-8.48). Being employed was associated with decreased possibility of having low HRQoL in males (OR 0.39, 95% CI 0.16-0.95). Regarding depression, higher ASDAS-CRP (OR 1.87, 95% CI 1.03-3.40), current smoking (OR 2.98, 95% CI 1.09-8.15), and being employed (OR 0.17, 95% CI 0.06-0.46) were associated with depression in males. For females, living with a partner was related to depression (OR 0.08, 95% CI 0.01-0.93).

Conclusion: AS patients with high disease activity are likely to be suffering from low HRQoL. Both disease-related factors and contextual factors were associated with depression, and predictors showed some differences between genders. Awareness of gender differences in comprehensive assessment can lead us to better personalized management in AS patients.
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http://dx.doi.org/10.1007/s11136-021-02800-wDOI Listing
August 2021

Oncologic Outcomes of Intracorporeal Extracorporeal Urinary Diversion After Robot-Assisted Radical Cystectomy: A Multi-Institutional Korean Study.

J Endourol 2021 May 20. Epub 2021 May 20.

Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea.

We aimed to compare the oncologic outcomes of intracorporeal urinary diversion (ICUD) and extracorporeal urinary diversion (ECUD) following robot-assisted radical cystectomy (RARC) in patients diagnosed with bladder cancer. Medical records of 730 patients who underwent RARC between April 2007 and May 2019 in 11 tertiary referral centers were retrospectively reviewed. We assessed recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) in the two groups using the Kaplan-Meier method. Cox regression models were used to identify factors associated with RFS, CSS, and OS. Among 591 patients, neobladder diversion was performed more frequently in the ICUD group (70.8% 52.5%,  = 0.001). The median follow-up duration was shorter in the ICUD group than in the ECUD group (16 26 months,  < 0.001). The rates of overall recurrence (36.5% 25.5%,  = 0.013) and pelvic recurrence (12.1% 5.9%,  = 0.031) were higher in the ECUD group. However, no differences in 5-year RFS (43.2% 58.4%,  = 0.516), CSS (79.3% 89.7%,  = 0.392), and OS (74.3% 81.4%,  = 0.411) were noted between the two groups. Multivariable analysis revealed that when compared to ICUD, ECUD was not associated with RFS (hazard ratio [HR], 0.982;  = 0.920), CSS (HR, 0.568;  = 0.126), and OS (HR, 0.642;  = 0.124). Although there was a difference in recurrence rate between the two groups, multivariable analysis indicated that the diversion technique after RARC did not affect the oncologic outcomes. Large prospective studies with long-term follow-up are warranted to verify the oncologic outcomes of ICUD and ECUD following RARC.
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http://dx.doi.org/10.1089/end.2021.0067DOI Listing
May 2021

Senescence Marker Protein 30 (SMP30): A Novel Pan-Species Diagnostic Marker for the Histopathological Diagnosis of Breast Cancer in Humans and Animals.

Int J Mol Sci 2021 Feb 26;22(5). Epub 2021 Feb 26.

Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea.

Senescence marker protein 30 (SMP30) is a cell survival factor playing an important role in vitamin C synthesis and antiapoptosis. Moreover, its cytoprotective role suggests a possibility to be related to cancer cell survival. Mammary carcinoma is a common cancer in both humans and animals. Because of its histopathological diversity, especially in the early stage, histopathological diagnosis may be complicated; therefore, a diagnostic marker is helpful for confirmation. The present study analyzed the expression pattern of SMP30 in mammary carcinoma in humans, dogs, and cats. Immunohistochemistry, immunofluorescence, and western blot analysis were used to investigate SMP30 expression patterns. The expression was specifically observed in neoplastic glandular epithelial cells. The expression increased with the malignancy of glandular epithelial cells with a highly proliferative status. However, SMP30 expression was low in normal mammary gland tissues or well-differentiated adenoma tissues. The patterns were consistently reproduced in canine primary mammary carcinoma cells and MCF-7 and MDA-MB-231 human carcinoma cell lines. This study provides useful information to understand SMP30 expression in various stages of mammary carcinoma and to suggest its utility as a pan-species diagnostic marker, thereby helping to establish strategies for diagnosing mammary carcinoma in several species.
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http://dx.doi.org/10.3390/ijms22052340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956281PMC
February 2021

Combating Multidrug-Resistant Bacteria by Integrating a Novel Target Site Penetration and Receptor Binding Assay Platform Into Translational Modeling.

Clin Pharmacol Ther 2021 Apr 24;109(4):1000-1020. Epub 2021 Mar 24.

Laboratory for Antimicrobial Pharmacodynamics, University at Buffalo, Buffalo, New York, USA.

Multidrug-resistant bacteria are causing a serious global health crisis. A dramatic decline in antibiotic discovery and development investment by pharmaceutical industry over the last decades has slowed the adoption of new technologies. It is imperative that we create new mechanistic insights based on latest technologies, and use translational strategies to optimize patient therapy. Although drug development has relied on minimal inhibitory concentration testing and established in vitro and mouse infection models, the limited understanding of outer membrane permeability in Gram-negative bacteria presents major challenges. Our team has developed a platform using the latest technologies to characterize target site penetration and receptor binding in intact bacteria that inform translational modeling and guide new discovery. Enhanced assays can quantify the outer membrane permeability of β-lactam antibiotics and β-lactamase inhibitors using multiplex liquid chromatography tandem mass spectrometry. While β-lactam antibiotics are known to bind to multiple different penicillin-binding proteins (PBPs), their binding profiles are almost always studied in lysed bacteria. Novel assays for PBP binding in the periplasm of intact bacteria were developed and proteins identified via proteomics. To characterize bacterial morphology changes in response to PBP binding, high-throughput flow cytometry and time-lapse confocal microscopy with fluorescent probes provide unprecedented mechanistic insights. Moreover, novel assays to quantify cytosolic receptor binding and intracellular drug concentrations inform target site occupancy. These mechanistic data are integrated by quantitative and systems pharmacology modeling to maximize bacterial killing and minimize resistance in in vitro and mouse infection models. This translational approach holds promise to identify antibiotic combination dosing strategies for patients with serious infections.
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http://dx.doi.org/10.1002/cpt.2205DOI Listing
April 2021

Low BASDAI score alone is not a good predictor of anti-tumor necrosis factor treatment efficacy in ankylosing spondylitis: a retrospective cohort study.

BMC Musculoskelet Disord 2021 Feb 4;22(1):140. Epub 2021 Feb 4.

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222-1 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.

Background: The purpose of this study was to determine the prevalence of high disease activity as measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS) in ankylosing spondylitis (AS) patients who nonetheless have low Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores after anti-tumor necrosis factor (TNF) treatment. Its clinical impact on anti-TNF survival was also investigated.

Methods: We conducted a single-centre retrospective cohort study of AS patients having low BASDAI scores (< 4) and available ASDAS-C-reactive protein (CRP) data after 3 months of first-line anti-TNF treatment. Patients were grouped into high-ASDAS (≥ 2.1) and low-ASDAS (< 2.1) groups according to the ASDAS-CRP after 3 months of anti-TNF treatment. Their characteristics were compared. And survival analyses were carried out using Kaplan-Meier curves and log-rank test with the event being discontinuation of anti-TNF treatment due to lack/loss of efficacy.

Results: Among 116 AS patients with low BASDAI scores after 3 months of anti-TNF treatment, 38.8% were grouped into the high-ASDAS group. The high-ASDAS group tended to have greater disease activity after 9 months of treatment (BASDAI 2.9 ± 1.1 vs. 2.3 ± 1.4, p=0.007; ASDAS-CRP 1.8 ± 0.6 vs. 1.5 ± 0.7, p=0.079; proportion of high ASDAS-CRP 27.8% vs. 13.8%, p=0.094) and greater risk of discontinuing anti-TNF treatment due to lack/loss of efficacy than the low-ASDAS group (p=0.011).

Conclusions: A relatively high proportion of AS patients with low BASDAI scores had high ASDAS-CRP. These low-BASDAI/high-ASDAS-CRP patients also had a greater risk for discontinuation of anti-TNF treatment due to low/lack of efficacy than the low-ASDAS group. The use of the ASDAS-CRP alone or in addition to the BASDAI may improve the assessment of AS patients treated with anti-TNF agents.
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http://dx.doi.org/10.1186/s12891-020-03941-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860220PMC
February 2021

Decrease of Preoperative Serum Albumin-to-Globulin Ratio as a Prognostic Indicator after Radical Cystectomy in Patients with Urothelial Bladder Cancer.

Urol J 2021 Jan 30;18(1):66-73. Epub 2021 Jan 30.

Department of Urology, Kyungpook National University Hospital, Daegu, Korea.

Purpose: This study aims to evaluate whether preoperative serum albumin-to-globulin ratio (AGR) could predict the prognosis of patients with urothelial bladder cancer (UBC) after radical cystectomy (RC).

Materials And Methods: A total of 176 patients with UBC who underwent RC in a tertiary hospital between 2008 and 2019 were retrospectively analyzed. The AGR was calculated as albumin/(total protein - albumin). In addition, the AGR was divided into two groups for the time-dependent receiver operating characteristic curve (ROC) analysis. Survival was estimated using the Kaplan-Meier analysis and compared using the log-rank test. Cox proportional- hazards models were used for multivariate survival analysis.

Results: The best cutoff AGR value for metastasis prediction was 1.32 based on the ROC curve analysis. Patients who had lower pretreatment AGR (<1.32) values composed the low-AGR group (n = 57; 32.4%). On the other hand, the remaining patients (n = 119; 67.6%) composed the high-AGR group. The patients in the low-AGR group had more advanced stage tumors compared with the patients in the high-AGR group. The Kaplan-Meier curves revealed that the patients in the low-AGR group had significantly lower rates of metastasis-free survival (MFS) and cancer-specific survival (CSS). The multivariate Cox regression analysis showed that preoperative AGR was an independent prognostic factor for MFS and CSS.

Conclusion: In this single-institution retrospective study, lower preoperative AGR values demonstrated a poor prognostic effect on MFS and CSS in patients with UBC who underwent RC.
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http://dx.doi.org/10.22037/uj.v16i7.6350DOI Listing
January 2021
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