Publications by authors named "Min Young Lee"

355 Publications

A Case of Misdiagnosed Sacroiliac Joint Tuberculosis as Axial Spondyloarthritis.

Pain Pract 2021 May 4. Epub 2021 May 4.

Department of Rehabilitation Medicine, College of Medicine, Yeungnam University, Daegu, Republic of Korea.

A 27-year-old woman presented at a university hospital for right buttock pain (NRS:3) that has progressively increased in severity over 6 months. Patrick and sacral thrust tests elicited pain at the right sacroiliac joint (SIJ). The pelvis AP radiograph was unremarkable and computed tomography (CT) showed subtle focal erosion on the iliac side of the right SIJ (Figure 1). Magnetic resonance imaging (MRI) revealed bone marrow edema around the right SIJ. Mild periarticular edema was noted anterior to the joint.
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http://dx.doi.org/10.1111/papr.13028DOI Listing
May 2021

Effects of Dipsacus asperoides Extract on Monosodium Iodoacetate-Induced Osteoarthritis in Rats Based on Gene Expression Profiling.

Front Pharmacol 2021 13;12:615157. Epub 2021 Apr 13.

Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Naju-si, Korea.

The root of C. Y. Cheng et T. M. Ai is traditionally used as an analgesic and anti-inflammatory agent to treat pain, rheumatoid arthritis, and bone fractures. However, neither its effects on osteoarthritis (OA) nor its effects on the arthritic cartilage tissue transcriptome have not been fully investigated. In this study, we used a rat model of monosodium iodoacetate- (MIA-) induced OA to investigate the therapeutic effects of a ethanolic extract (DAE, 200 mg/kg for 21 days). The study first assessed joint diameter, micro-CT scans, and histopathological analysis and then conducted gene expression profiling using RNA sequencing in articular cartilage tissue. We found that DAE treatment ameliorates OA disease phenotypes; it reduced the knee joint diameter and prevented changes in the structural and histological features of the joint, thereby showing that DAE has a protective effect against OA. Based on the results of gene expression profiling and subsequent pathway analysis, we found that several canonical pathways were linked to DAE treatment, including WNT/β-catenin signaling. Taken together, the present results suggest molecular mechanism, involving gene expression changes, by which DAE has a protective effect in a rat model of MIA-induced OA.
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http://dx.doi.org/10.3389/fphar.2021.615157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076797PMC
April 2021

The Findings of SPECT/CT Concerning Bypass Lymph Circulation in Lymphedema Following Breast Cancer Surgery.

Healthcare (Basel) 2021 Apr 15;9(4). Epub 2021 Apr 15.

Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University, Daegu 42415, Korea.

This study aimed to determine whether bypass circulation was present in lymphedema and its effect. This was a retrospective, cross-sectional study. Patients who underwent unilateral breast cancer surgery with axillary lymph node dissection were recruited and underwent single-photon emission tomography/computed tomography (SPECT/CT). SPECT/CT was performed to detect the three-dimensional locations of radio-activated lymph nodes. Patients with radioactivity in anatomical locations other than axillary lymph nodes were classified into a positive group. All patients received complete decongestive therapy (CDT). Exclusion criteria were as follows: History of bilateral breast cancer surgery, cervical lymph node dissection history, and upper extremity amputation. The difference in the upper extremity circumference (cm) was measured at four points: Mid-point of the upper arm, elbow, and 10 and 15 cm below the elbow. Twenty-nine patients were included in this study. Fifteen patients (51.7%) had bypass lymphatic systems on the affected side, six (20.7%) had a bypass lymphatic system with axillary lymph nodes on the unaffected side, and 11 (37.9%) showed new lymphatic drainage. The positive group showed significantly less swelling than the negative group at the mid-arm, elbow, and 15 cm below the elbow. Bypass lymphatic circulation had two patterns: Infraclavicular lymph nodes and supraclavicular and/or cervical lymph nodes. Changes in lymph drainage caused by surgery triggered the activation of the superficial lymphatic drainage system to relieve lymphedema. Superficial lymphatic drainage has a connection through the deltopectoral groove.
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http://dx.doi.org/10.3390/healthcare9040471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071444PMC
April 2021

Multiplexed targeting of miRNA-210 in stem cell-derived extracellular vesicles promotes selective regeneration in ischemic hearts.

Exp Mol Med 2021 Apr 20;53(4):695-708. Epub 2021 Apr 20.

Department of Biology Education, College of Education, Pusan National University, Busan, Republic of Korea.

Extracellular vesicles (EVs) are cell derivatives containing diverse cellular molecules, have various physiological properties and are also present in stem cells used for regenerative therapy. We selected a "multiplexed target" that demonstrates multiple effects on various cardiovascular cells, while functioning as a cargo of EVs. We screened various microRNAs (miRs) and identified miR-210 as a candidate target for survival and angiogenic function. We confirmed the cellular and biological functions of EV-210 (EVs derived from ASC) secreted from adipose-derived stem cells (ASCs) transfected with miR-210 (ASC). Under hypoxic conditions, we observed that ASC inhibits apoptosis by modulating protein tyrosine phosphatase 1B (PTP1B) and death-associated protein kinase 1 (DAPK1). In hypoxic endothelial cells, EV-210 exerted its angiogenic capacity by inhibiting Ephrin A (EFNA3). Furthermore, EV-210 enhanced cell survival under the control of PTP1B and induced antiapoptotic effects in hypoxic H9c2 cells. In cardiac fibroblasts, the fibrotic ratio was reduced after exposure to EV-210, but EVs derived from ASC did not communicate with fibroblasts. Finally, we observed the functional restoration of the ischemia/reperfusion-injured heart by maintaining the intercommunication of EVs and cardiovascular cells derived from ASC. These results suggest that the multiplexed target with ASC is a useful tool for cardiovascular regeneration.
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http://dx.doi.org/10.1038/s12276-021-00584-0DOI Listing
April 2021

Investigating the Presence of Interattack Astrocyte Damage in Neuromyelitis Optica Spectrum Disorder: Longitudinal Analysis of Serum Glial Fibrillary Acidic Protein.

Neurol Neuroimmunol Neuroinflamm 2021 05 9;8(3). Epub 2021 Apr 9.

From the Department of Neurology (J.-W.H., S.-H.K., H.J.K.), Division of Clinical Research; and Research Institute and Hospital of National Cancer Center (Y.K., S.Y.K., M.Y.L., H.J.K.), Goyang, Korea.

Objectives: Information on subclinical astrocyte damage can provide further insight into neuromyelitis optica spectrum disorder (NMOSD) pathophysiology and disease-monitoring strategies. To investigate whether astrocyte and neuroaxonal damage occurs during interattack periods in individuals with NMOSD through longitudinal measurement of serum glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL) at multiple time points.

Methods: sGFAP and sNfL levels were measured in 187 serum samples from 20 participants with NMOSD treated with rituximab (median follow-up: 24 months) and 19 age-/sex-matched healthy controls using a highly sensitive single-molecule array assay. From the NMOSD cohort of National Cancer Center, Korea, 14 clinically stable participants were randomly selected for focused investigation of interattack periods, and 6 participants with clinical attacks despite treatment were enrolled for attack-related measurements.

Results: Significant elevations of sGFAP levels were observed in all clinical attacks, and 95% (19/20) of patients showed reduction of sGFAP levels below the cutoff value (3 SDs above mean levels in age-/sex-matched healthy controls) within 3 months of their clinical attacks. The sGFAP levels were consistently low during interattack periods in 90% (17/19) of patients whose sGFAP levels returned to below the cutoff value. Changes in sNfL levels were similar to but slower than those in sGFAP levels.

Conclusions: Subclinical astrocyte damage represented by increasing sGFAP levels rarely occurred during interattack periods in individuals with NMOSD; however, a certain degree of astrocyte damage did occur at the time of clinical attacks without exception, but it was not evident within 3 months of the attack.
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http://dx.doi.org/10.1212/NXI.0000000000000965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054958PMC
May 2021

Real-World Incidence of Suboptimal Response to Anti-Tumor Necrosis Factor Therapy for Ulcerative Colitis: A Nationwide Population-Based Study.

Gut Liver 2021 Apr 2. Epub 2021 Apr 2.

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

Background/aims: Although anti-tumor necrosis factor (TNF) agents have been widely used to treat ulcerative colitis (UC), the real-world incidence of suboptimal response to anti-TNF agents has not been thoroughly investigated, especially among Asians.

Methods: Using the Korean National Health Insurance database, we collected data on UC patients who initiated anti-TNF agents between July 1, 2014, and June 30, 2017. We assessed suboptimal responses, including anti-TNF discontinuation or dose escalation, switching to other biologics, augmentation with a non-biologic therapy, and the requirement for colectomy.

Results: A total of 1,268 patients were included as new anti-TNF users (infliximab 713, adalimumab 433, golimumab 122). The proportion of patients who experienced at least one suboptimal response within 1 year among all patients was 63.5%, including 59.1%, 69.5%, and 68.0% of patients treated with infliximab, adalimumab, and golimumab, respectively. The cumulative incidences of at least one suboptimal response over time were 41.5%, 63.7%, 80.5%, and 87.1% at 6, 12, 24, and 36 months, respectively. Cox proportional hazards modeling revealed that adalimumab was associated with a higher risk of at least one suboptimal response (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.13 to 1.48), dose escalation (HR, 4.35; 95% CI, 2.97 to 6.38) and discontinuation (HR, 1.25; 95% CI, 1.03 to 1.52) than infliximab. Golimumab was associated with a higher risk of switching to other biologics than infliximab (HR, 1.78; 95% CI, 1.21 to 2.60).

Conclusions: More than half of Korean UC patients had suboptimal responses to anti-TNF agents within 1 year. UC patients treated with infliximab might be less prone to suboptimal responses than those treated with adalimumab or golimumab.
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http://dx.doi.org/10.5009/gnl20353DOI Listing
April 2021

Rapid and sensitive multiplex molecular diagnosis of respiratory pathogens using plasmonic isothermal RPA array chip.

Biosens Bioelectron 2021 Jun 19;182:113167. Epub 2021 Mar 19.

Department of Medical Device Management and Research, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, 115, Irwon-ro, Gangnam-gu, Seoul, 06355, Republic of Korea; Biomedical Engineering Research Center, Samsung Medical Center, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea. Electronic address:

The current clinically available multiplex molecular diagnostic technologies are difficult to apply to onsite diagnostic platforms due to their large and sophisticated instrumentation, long amplification times and limited number of simultaneous detections. We developed a plasmonic isothermal recombinase polymerase amplification (RPA) array chip for rapid and sensitive multiplex molecular detection. The 3D plasmonic substrate composed of Au nanoparticles (NPs) on dense Au nanopillars (NPOP) showed highly enhanced plasmon-enhanced fluorescence (PEF) of RPA products with long DNA amplicons (~200 bp). The plasmonic 4-plex RPA array chip successfully detected bacterial DNA within 30 min and viral RNA within 40 min; the sensitivity of the plasmonic RPA array chip was comparable to or 10-fold higher than that of the 4-pelx liquid-phase RPA and 4-plex liquid-phase PCR techniques. Additionally, no cross-reactivity was observed. The 4-plex plasmonic RPA array chip was preliminary evaluated using clinical respiratory viral-positive nasopharyngeal swab samples. This approach enables rapid, sensitive and high-multiplex molecular detection and can be used in the realization of a simplified and miniaturized platform for onsite multiplex molecular diagnostics.
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http://dx.doi.org/10.1016/j.bios.2021.113167DOI Listing
June 2021

Modulation of SETDB1 activity by APQ ameliorates heterochromatin condensation, motor function, and neuropathology in a Huntington's disease mouse model.

J Enzyme Inhib Med Chem 2021 Dec;36(1):856-868

Department of Chemical & Molecular Engineering/Applied Chemistry, Center for Bionano Intelligence Education and Research, Hanyang University, Ansan, Republic of Korea.

The present study describes evaluation of epigenetic regulation by a small molecule as the therapeutic potential for treatment of Huntington's disease (HD). We identified 5-allyloxy-2-(pyrrolidin-1-yl)quinoline (APQ) as a novel SETDB1/ESET inhibitor using a combined and cell based screening system. APQ reduced SETDB1 activity and H3K9me3 levels in a HD cell line model. In particular, not only APQ reduced H3K9me3 levels in the striatum but it also improved motor function and neuropathological symptoms such as neuronal size and activity in HD transgenic (YAC128) mice with minimal toxicity. Using H3K9me3-ChIP and genome-wide sequencing, we also confirmed that APQ modulates H3K9me3-landscaped epigenomes in YAC128 mice. These data provide that APQ, a novel small molecule SETDB1 inhibitor, coordinates H3K9me-dependent heterochromatin remodelling and can be an epigenetic drug for treating HD, leading with hope in clinical trials of HD.
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http://dx.doi.org/10.1080/14756366.2021.1900160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008885PMC
December 2021

A case of porokeratotic adnexal ostial nevus misdiagnosed as wart.

Clin Case Rep 2021 Mar 22;9(3):1092-1094. Epub 2021 Jan 22.

Department of Dermatology Ewha Womans University Seoul Hospital Seoul Korea.

Porokeratotic adnexal ostial nevus may be misdiagnosed as wart based on clinical appearance and morphology. An accurate diagnosis through skin biopsy is crucial, as is the inclusion of rare disorders such as porokeratotic adnexal ostial nevus in the differential diagnosis.
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http://dx.doi.org/10.1002/ccr3.3648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981734PMC
March 2021

High Blood Glucose Levels Affect Auditory Brainstem Responses after Acoustic Overexposure in Rats.

Audiol Neurootol 2021 Mar 18:1-8. Epub 2021 Mar 18.

Department of Otolaryngology-Head and Neck Surgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University, College of Medicine, Cheonan, Republic of Korea.

Introduction: Diabetes mellitus (DM) is a systemic disease characterized by hyperglycemia and several pathological changes. DM-related hearing dysfunctions are associated with histological changes. Here, we explore hearing function and synaptic changes in the inner hair cells (IHCs) of rats with streptozotocin (STZ)-induced diabetes.

Methods: STZ was injected to trigger diabetes. Rats with DM were exposed to narrow-band noise (105 dB SPL) for 2 h, and hearing function was analyzed 1, 3, 7, and 14 days later. Both the hearing threshold and the peak 1 amplitude of the tone auditory brainstem response were assessed. After the last functional test, animals were sacrificed for histological evaluation.

Results: We found no changes in the baseline hearing threshold; however, the peak 1 amplitude at the low frequency (4 kHz) was significantly higher in both DM groups than in the control groups. The hearing threshold had not fully recovered at 14 days after diabetic rats were exposed to noise. The peak 1 amplitude at the higher frequencies (16 and 32 kHz) was significantly larger in both DM groups than in the control groups. The histological analysis revealed that the long-term DM group had significantly more synapses in the 16 kHz region than the other groups.

Conclusions: We found that high blood glucose levels increased peak 1 amplitudes without changing the hearing threshold. Diabetic rats were less resilient in threshold changes and were less vulnerable to peak 1 amplitude and synaptic damage than control animals.
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http://dx.doi.org/10.1159/000511448DOI Listing
March 2021

Need for Confirmatory Neutralization Tests for Hepatitis B Surface Antigen Tests in Populations with Intermediate Prevalence.

Lab Med 2021 Feb 25. Epub 2021 Feb 25.

Department of Laboratory Medicine, Kyung Hee University School of Medicine and Kyung Hee University Hospital at Gangdong, Seoul, Korea.

Objective: Hepatitis B surface antigen (HBsAg) is known as the hallmark of hepatitis B virus (HBV) infection. This study aimed to determine whether an HBsAg neutralization test is necessary to accurately interpret HBsAg test results.

Methods: Initially reactive HBsAg specimens from a 5-year period, with cutoff index values between 1.0 and 2.0, were subjected to neutralization confirmatory testing using an Elecsys HBsAg Confirmatory test kit (Roche Diagnostics GmbH. Mannheim, Germany).

Results: The neutralization test showed 46.1% positive (confirmed positive group) and 53.9% negative (confirmed negative group) results from the total specimens. Among the confirmed negative group, 79.5% of patients were confirmed to be negative for the current infection, whereas 4 patients in the chronic hepatitis B subgroup showed a neutralization percentage close to 40%. More than half of patients in the confirmed positive group were considered to be in the hepatitis B e antigen-negative inactive HBsAg carrier phase.

Conclusion: In populations with intermediate HBV prevalence, a neutralization test is necessary to confirm an HBsAg result and reduce the false positive and false negative rates of initial HBsAg tests.
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http://dx.doi.org/10.1093/labmed/lmab006DOI Listing
February 2021

Discontinuation of Immunosuppressive Therapy in Patients With Neuromyelitis Optica Spectrum Disorder With Aquaporin-4 Antibodies.

Neurol Neuroimmunol Neuroinflamm 2021 03 23;8(2). Epub 2021 Feb 23.

From the Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, South Korea.

Objective: To evaluate the outcomes of immunosuppressive therapy (IST) discontinuation in patients with neuromyelitis optica spectrum disorder (NMOSD) after a sustained remission period.

Methods: We retrospectively reviewed the medical records of 17 patients with antiaquaporin-4 antibody-positive NMOSD who discontinued IST after a relapse-free period of ≥3 years.

Results: IST was discontinued at a median age of 40 years (interquartile range [IQR], 32-51) after a median relapse-free period of 62 months (IQR, 52-73). Among the 17 enrolled patients, 14 (82%) relapsed at a median interval of 6 months (IQR, 4-34) after IST discontinuation, 3 (18%) of whom experienced severe attacks; notably, all 3 of these patients had a history of severe attack before IST. These 3 patients received steroids, followed by plasma exchange for acute treatment, but 2 exhibited poor recovery and significant disability worsening at 6 months after relapse.

Conclusions: IST discontinuation may increase the risk of relapse in seropositive patients with NMOSD even after 5 years of remission. Given the potentially devastating consequence of a single attack of NMOSD, caution is advised with IST discontinuation, particularly in patients with severe attack before IST.
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http://dx.doi.org/10.1212/NXI.0000000000000947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903808PMC
March 2021

Chemical meningitis after cervical transforaminal epidural steroid injection: a case report.

J Int Med Res 2021 Feb;49(2):300060521993974

Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University, Namku, Taegu, Republic of Korea.

We herein report a case of chemical meningitis that developed after cervical transforaminal steroid injection. A 49-year-old man presented with symptoms of meningitis (severe headache and neck stiffness) after cervical transforaminal steroid injection at the right C5-6 level. The injection solution was a mixture of lidocaine (0.3 mL), hyaluronidase (1 mL), placenta hydrolysate (2 mL), and normal saline (1 mL). The patient developed symptoms of meningitis 2.5 hours after the cervical epidural injection. Cerebrospinal fluid (CSF) analysis was performed 1 day after the injection, and the results showed an elevated white blood cell count at 7106 cells/µL. The patient's CSF analysis findings and symptoms did not differ from those of bacterial meningitis. However, considering that his symptoms developed 2.5 hours after the epidural injection, we believe that the patient developed chemical meningitis; therefore, he was symptomatically treated with an analgesic. Three days after the cervical transforaminal epidural injection, the patient experienced complete relief from the headache and neck stiffness. A Gram stain of the CSF revealed no organisms. Hence, the diagnosis of chemical meningitis was confirmed. Clinicians should be knowledgeable about the risk of this complication.
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http://dx.doi.org/10.1177/0300060521993974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903832PMC
February 2021

Photobiomodulation with a wavelength > 800 nm induces morphological changes in stem cells within otic organoids and scala media of the cochlea.

Lasers Med Sci 2021 Feb 18. Epub 2021 Feb 18.

Beckman Laser Institute Korea, Dankook University, 119 Dandae-ro, Cheonan, 31116, Republic of Korea.

Photobiomodulation (PBM) is a therapeutic approach to certain diseases based on light energy. Currently, stem cells (SCs) are being considered as putative treatments for previously untreatable diseases. One medical condition that could be treated using SCs is sensorineural hearing loss. Theoretically, if properly delivered and differentiated, SCs could replace lost hair cells in the cochlea. However, this is not currently possible due to the structural complexity and limited survival of SCs within the cochlea. PBM facilitates SC differentiation into other target cells in multiple lineages. Using light with a wavelength > 800 nm, which can penetrate the inner ear through the tympanic membrane, we assessed morphological changes of mouse embryonic stem cells (mESCs) during "otic organoid" generation, and within the scala media (SM) of the cochlea, after light energy stimulation. We observed enhanced differentiation, which was confirmed by an increased number of otic vesicles and increased cell attachment inside the SM. These results suggest that > 800-nm light affected the morphology of mESCs within otic organoids and SM of the cochlea. Based on our results, light energy could be used to enhance otic sensory differentiation, despite the structural complexity of the inner ear and limited survival time of SCs within the cochleae. Additional studies to refine the light energy delivery technology and maximize the effect on otic differentiation are required.
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http://dx.doi.org/10.1007/s10103-021-03268-3DOI Listing
February 2021

Label-Free SERS Analysis of Urine Using a 3D-Stacked AgNW-Glass Fiber Filter Sensor for the Diagnosis of Pancreatic Cancer and Prostate Cancer.

Anal Chem 2021 03 12;93(8):3778-3785. Epub 2021 Feb 12.

Department of Medical Device Management and Research, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, 81, Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea.

Metabolomics shows tremendous potential for the early diagnosis and screening of cancer. For clinical application as an effective diagnostic tool, however, improved analytical methods for complex biological fluids are required. Here, we developed a reliable rapid urine analysis system based on surface-enhanced Raman spectroscopy (SERS) using 3D-stacked silver nanowires (AgNWs) on a glass fiber filter (GFF) sensor and applied it to the diagnosis of pancreatic cancer and prostate cancer. Urine samples were pretreated with centrifugation to remove large debris and with calcium ion addition to improve the binding of metabolites to AgNWs. The label-free urine-SERS detection using the AgNW-GFF SERS sensor showed different spectral patterns and distinguishable specific peaks in three groups: normal control ( = 30), pancreatic cancer ( = 22), and prostate cancer ( = 22). Multivariate analyses of SERS spectra using unsupervised principal component analysis and supervised orthogonal partial least-squares discriminant analysis showed excellent discrimination between the pancreatic cancer group and the prostate cancer group as well as between the normal control group and the combined cancer groups. The results demonstrate the great potential of the urine-SERS analysis system using the AgNW-GFF SERS sensor for the noninvasive diagnosis and screening of cancers.
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http://dx.doi.org/10.1021/acs.analchem.0c04200DOI Listing
March 2021

2020 Korean guidelines for the management of metastatic prostate cancer.

Korean J Intern Med 2021 Feb 10. Epub 2021 Feb 10.

Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea.

In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.
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http://dx.doi.org/10.3904/kjim.2020.213DOI Listing
February 2021

Auditory Brainstem Response to Paired Click Stimulation as an Indicator of Peripheral Synaptic Health in Noise-Induced Cochlear Synaptopathy.

Front Neurosci 2020 11;14:596670. Epub 2021 Jan 11.

Department of Otolaryngology Head and Neck Surgery College of Medicine, Dankook University, Cheonan, South Korea.

Introduction: A defect in the cochlear afferent synapse between the inner hair cells and spiral ganglion neurons, after noise exposure, without changes in the hearing threshold has been reported. Animal studies on auditory evoked potentials demonstrated changes in the auditory brainstem response (ABR) measurements of peak I amplitude and the loss of synapses, which affect the temporal resolution of complex sounds. Human studies of auditory evoked potential have reported ambiguous results regarding the relationship between peak I amplitude and noise exposure. Paired click stimuli have been used to investigate the temporal processing abilities of humans and animals. In this study, we investigated the utility of measuring auditory evoked potentials in response to paired click stimuli to assess the temporal processing function of ribbon synapses in noise-induced cochlear synaptopathy.

Materials And Methods: Twenty-two Sprague Dawley rats were used in this study, and synaptopathy was induced by narrow-band noise exposure (16 kHz with 1 kHz bandwidth, 105 dB sound pressure level for 2 h). ABRs to tone and paired click stimuli were measured before and 1, 3, 7, and 14 days after noise exposure. For histological analyses, hair cells and ribbon synapses were immunostained and the synapses quantified. The relationships among ABR peak I amplitude, number of synapses, and ABR to paired click stimuli were examined.

Results: Our results showed that ABR thresholds increase 1 day after noise exposure but fully recover to baseline levels after 14 days. Further, we demonstrated test frequency-dependent decreases in peak I amplitude and the number of synapses after noise exposure. These decreases were statistically significant at frequencies of 16 and 32 kHz. However, the ABR recovery threshold to paired click stimuli increased, which represent deterioration in the ability of temporal auditory processing. Our results indicate that the ABR recovery threshold is highly correlated with ABR peak I amplitude after noise exposure. We also established a direct correlation between the ABR recovery threshold and histological findings.

Conclusion: The result from this study suggests that in animal studies, the ABR to paired click stimuli along with peak I amplitude has potential as an assessment tool for hidden hearing loss.
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http://dx.doi.org/10.3389/fnins.2020.596670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830024PMC
January 2021

Comparative Cost-Effectiveness of Tofacitinib With Continuing Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs for Active Rheumatoid Arthritis in South Korea.

Rheumatol Ther 2021 Mar 26;8(1):395-409. Epub 2021 Jan 26.

School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea.

Introduction: The objective of this study was to evaluate the cost-effectiveness of initiating treatment with tofacitinib and subsequently incorporating it into a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) treatment sequence and to compare the cost-effectiveness of this sequence with that of continuing csDMARDs alone in patients with active rheumatoid arthritis (RA).

Methods: A cohort-based Markov model was used to evaluate the cost-effectiveness of two tofacitinib treatment sequences compared with that of continuing the csDMARD treatment sequence over a lifetime. Of the two tofacitinib sequences, the first consisted of initial tofacitinib treatment followed by biologic DMARDs (bDMARDs) and the second consisted of csDMARD treatments followed by tofacitinib. A third treatment sequence, continuing the csDMARD treatment sequence before starting bDMARDs, was used as a comparator. Efficacy was assessed using the American College of Rheumatology (ACR) response rates (ACR 20, ACR 50, and ACR 70) after 6 months, which were converted to changes in the health assessment questionnaire-disability index (HAQ-DI) score. Utility was estimated by mapping from the HAQ-DI score, costs were analyzed from a Korean societal perspective, and outcomes were considered in terms of quality-adjusted life-years (QALYs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model.

Results: The incremental cost-effectiveness ratios over a lifetime for starting with tofacitinib and incorporating tofacitinib into the csDMARD treatment sequence versus continuing csDMARDs only were US$14,537 per QALY and US$7,086 per QALY, respectively. One-way sensitivity analysis and probabilistic sensitivity analysis confirmed the robustness of these results.

Conclusion: Starting with tofacitinib and incorporating it into a csDMARDs treatment sequence is cost-effective compared to continuing csDMARDs alone in patients with RA.
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http://dx.doi.org/10.1007/s40744-021-00278-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991041PMC
March 2021

The risk factors and incidence of major infectious diseases in patients with ankylosing spondylitis receiving tumor necrosis factor inhibitors.

Mod Rheumatol 2021 Feb 15:1-14. Epub 2021 Feb 15.

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.

Objectives: This study aimed to evaluate the risk factor and incidence of infections in patients receiving tumor necrosis factor inhibitor (TNFi) therapy for ankylosing spondylitis using data from the national health insurance service.

Methods: This was a retrospective cohort study. Data regarding patients with ankylosing spondylitis prescribed TNFis were obtained from an insurance claims database of the Health Insurance Review & Assessment Service in Korea. Outcomes used were incidence rates of serious infection, pneumonia, tuberculosis, and herpes zoster during the follow-up period as well as the relationship between each TNFi and sex, hazard ratio (HR) of infection-related risk factors, and incidence of infections.

Results: A total of 2515 patients were included. There were no significant differences among the hazard ratios of TNFis for serious infection, pneumonia, and herpes zoster. However, the hazard ratio of tuberculosis was significantly higher for infliximab than for etanercept (adjusted HR 8.40 [95% confidence interval: 1.06-66.91]). In the subgroup analysis by sex, women treated with golimumab had a significantly higher hazard of herpes zoster than those treated with etanercept (adjusted HR 12.40 [95% confidence interval: 1.40-109.58]).

Conclusion: We recommend that risk factors for these infectious diseases be identified prior to prescribing TNFis in these patients.
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http://dx.doi.org/10.1080/14397595.2021.1878985DOI Listing
February 2021

Bacteremia Caused by Moraxella Osloensis: a Fatal Case of an Immunocompromised Patient and Literature Review.

Clin Lab 2021 Jan;67(1)

Background: Moraxella osloensis rarely causes infection in humans, and most of the reported cases are not fatal. It is often difficult to identify M. osloensis using conventional biochemical methods.

Methods: Here, we report a bacteremia case caused by M. osloensis in a patient with advanced lung cancer who initially presented symptoms of fever.

Results: Blood culture revealed growth of a gram-negative bacterium, which was identified as M. osloensis through 16S rRNA gene sequencing and MALDI-TOF analyses. The patient could not recover from sepsis with empirical treatment.

Conclusions: As M. osloensis can cause serious infections in immunocompromised patients, its prompt identification is important.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200459DOI Listing
January 2021

Erratum: Song, K.; et al. Molecular Network-Guided Alkaloid Profiling of Aerial Parts of L. Using LC-HRMS. 2020, , 2636.

Molecules 2021 Jan 11;26(2). Epub 2021 Jan 11.

Korean Medicine Clinical Trial Center (K-CTC), Kyung Hee University Korean Medicine Hospital, Seoul 02454, Korea.

The authors wish to make the following change to their paper [...].
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http://dx.doi.org/10.3390/molecules26020339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826909PMC
January 2021

Dose Reduction of Tumor Necrosis Factor Inhibitor and its Effect on Medical Costs for Patients with Ankylosing Spondylitis.

Rheumatol Ther 2021 Mar 9;8(1):347-359. Epub 2021 Jan 9.

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.

Introduction: Tumor necrosis factor inhibitors (TNFis) may be administered at a reduced dose to patients with ankylosing spondylitis (AS) for various reasons. However, in practice, there is insufficient evidence of how the dose reduction of TNFi is implemented and the amount of medical costs it reduces. In this study, we investigated treatment patterns among patients with AS who were administered various TNFis. The effect on medical costs related to AS was also investigated using Korea's insurance claims database.

Methods: From the insurance claims database of the Health Insurance Review & Assessment Service in South Korea, patients with AS newly treated with TNFis (etanercept, adalimumab, golimumab, and infliximab) between July 1, 2013, and June 30, 2016, were enrolled. Patients treated with the TNFis were followed up for 2 years. Treatment patterns (continuation and discontinuation of TNFi) and dose reduction (< 50% of recommended dose) in patients who continued treatment were analyzed and compared among the TNFi groups using the Chi-square test. Healthcare costs between the dose reduction and maintenance groups were compared using general linear modeling.

Results: Of 1352 patients, 764 (56.51%) continued using TNFis for 2 years, and 17.8% of these were administered reduced doses. TNFi dose reduction was the most frequent in 36 (24.83%) patients using etanercept, followed by those using adalimumab (21.97%), golimumab (11.70%), and infliximab (11.98%) (p = 0.0028). For each TNFi group, the total healthcare cost significantly decreased, that is, by 24.85% for adalimumab, 31.80% for etanercept, 26.34% for golimumab, and 35.52% for infliximab (p < 0.0001).

Conclusions: TNFi dose reduction was identified in 17.8% of the patients with AS, and the patterns were different for each TNFi. Additionally, the dose reductions significantly reduced the medical costs associated with AS, that is, from 24.85 to 35.52% of the total medical expenditure.
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http://dx.doi.org/10.1007/s40744-020-00274-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991020PMC
March 2021

Pulmonary toxicities of molecular targeted antineoplastic agents: a single-center 10-year experience.

Korean J Intern Med 2021 Jan 8. Epub 2021 Jan 8.

Division of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea.

Background/aims: A better understanding of cancer cell biology has led to the discovery and development of several new targeted agents for cancer. These drugs are widely used in cancer treatment and have good toxicity profiles. However, some patients are extremely sensitive to these drugs and can develop severe toxicities. Among the toxicities, pulmonary complications are infrequent with most targeted therapies. This study aimed to identify the radiologic pulmonary complications in various targeted therapies and to analyze the characteristics of patients with pulmonary toxicity.

Methods: We retrospectively reviewed the medical records and chest image findings of 644 patients who were treated with targeted antineoplastic agents at Soonchunhyang University Hospital between May 2005 and September 2014.

Results: Of these 644 patients, 90 (14.0%) developed pulmonary complications as noted on chest computed tomography. Among these patients, 15 (2.3%) developed drug-related pulmonary toxicities. Treatment with targeted agents was discontinued in all patients, while 11 patients were simultaneously treated with glucocorticoids. Three patients died of drug-related pulmonary toxicity.

Conclusions: During targeted therapy, clinicians should assess for pulmonary toxicities and symptoms that occur with dyspnea. If drug-induced pulmonary toxicities are suspected, imaging studies should be performed immediately, and the possibility of variable radiological patterns should be considered. Discontinuing the use of implicated causative agents and treatment with glucocorticoids resulted in an improvement in both symptoms and imaging findings, but some patients still experienced fatal pulmonary toxicities.
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http://dx.doi.org/10.3904/kjim.2020.295DOI Listing
January 2021

Life Experiences with Using Community Care among People with Severe Physical Disabilities: A Comparative Analysis between South Korea and Japan.

Int J Environ Res Public Health 2020 12 9;17(24). Epub 2020 Dec 9.

Department of Healthcare and Public Health Research, National Rehabilitation Research Institute, Seoul 01022, Korea.

This study identified the pathways chosen by people with severe physical disabilities (PWSPD) in South Korea and Japan in using community care throughout their life and compared their experiences while navigating these pathways from their perspective. A concurrent nested mixed-method design was adopted. Quantitative data analysis included pathway mapping of facilities and services used throughout their lives. For qualitative data, interpretative phenomenological analysis (IPA) was applied. Eleven South Korean (congenital 7, acquired 4) and nine Japanese (congenital 6, acquired 3) participants were surveyed and interviewed. Pathway mapping was conducted by classifying the participants into focus groups. South Korean participants took nine years more than the Japanese participants to reach independence and showed different pathway characteristics. Superordinate themes from the IPA provided insight into the differences in experiences between PWSPD of the two countries: (1) accessibility and continuity of medical services; (2) experience of vocational training; (3) way and degree of social support for independent living; (4) care planning for receiving comprehensive services. In developing a community care model for the PWSPD to accelerate their time to independence, the government should strive for accessibility and connectivity of medical services, strengthen vocational training, social support for independent living, and information provision for the PWSPD.
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http://dx.doi.org/10.3390/ijerph17249195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764412PMC
December 2020

Protective effects of Phlomis umbrosa extract on a monosodium iodoacetate-induced osteoarthritis model and prediction of molecular mechanisms using transcriptomics.

Phytomedicine 2021 Jan 1;81:153429. Epub 2020 Dec 1.

Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Naju, Republic of Korea. Electronic address:

Background: Phlomis umbrosa Turczaninow root has been traditionally used to treat fractures, rheumatoid arthritis, and arthralgia. However, the effects and mechanisms of P. umbrosa on osteoarthritis (OA) remain poorly understood and a functional genomic approach has not been investigated.

Aim: The purpose of this study was to investigate the effects and mechanisms of P. umbrosa extract (PUE) on OA using transcriptomic analysis.

Methods: We performed joint diameter measurements, micro computed tomography, and histopathological analysis of monosodium iodoacetate (MIA)-induced OA rats treated with PUE (200 mg/kg) for 3 weeks. Gene expression profiling in articular cartilage tissue was then performed using RNA sequencing (RNA-seq) followed by signaling pathway analysis of regulatory genes.

Results: PUE treatment improved OA based on decreased joint diameter, increased joint morphological parameters, and histopathological features. Many genes involved in multiple signal transduction pathway and collagen activation in OA were differentially regulated by PUE. These included genes related to Wnt/β-catenin, OA pathway, and sonic hedgehog signaling activity. Furthermore, PUE treatment downregulated cartilage damage factors (MMP-9, MMP-13, ADAMTs4, and ADMATs5) and upregulated chondrogenesis (COL2A1 and SOX-9) by regulating the transcription factors SOX-9, Ctnnb1, and Epas1.

Conclusion: Based on the results of gene expression profiling, this study highlighted the molecular mechanisms underlying the effects of PUE in MIA-induced OA rats. The findings provide novel insight into the mechanisms by which PUE treatment-induced gene expression changes may influence OA disease progression. Taken together, the results suggest that PUE may be used as a source of therapeutic agents for OA.
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http://dx.doi.org/10.1016/j.phymed.2020.153429DOI Listing
January 2021

Immune Checkpoint Programmed Cell Death Protein-1 (PD-1) Expression on Bone Marrow T Cell Subsets in Patients With Plasma Cell Myeloma.

Ann Lab Med 2021 May;41(3):259-267

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

Background: Plasma cell myeloma (PCM) is caused by immune dysregulation. We evaluated the expression of immune checkpoint programmed cell death protein-1 (PD-1) on T cell subsets in PCM patients according to disease course and cytogenetic abnormalities. This study aimed to find a target group suitable for therapeutic use of PD-1 blockade in PCM.

Methods: A total of 188 bone marrow (BM) samples from 166 PCM patients and 32 controls were prospectively collected between May 2016 and May 2017. PD-1 expression on BM T cell subsets was measured using flow cytometry.

Results: At diagnosis, the median PD-1 expression on CD4 T cells was 24.6%, which did not significantly differ from that in controls. After stem cell transplantation, PD-1 expression on CD4 T cells was higher than that at diagnosis (<0.001), regardless of residual disease. PD-1 expression on CD4 T cells in patients with residual disease after chemotherapy was significantly higher than that at diagnosis (=0.001) and after complete remission following chemotherapy (=0.044). PD-1 expression on CD8 T cells was higher in PCM patients with cytogenetic abnormalities, including monosomy 13, 1q gain, complex karyotype, and hypodiploidy.

Conclusions: PD-1 blockade might have therapeutic potential in refractory PCM patients after chemotherapy, especially in those with high- or intermediate-risk cytogenetic abnormalities.
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http://dx.doi.org/10.3343/alm.2021.41.3.259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748102PMC
May 2021

Deletion of Promotes Kidney Fibrosis in a Murine Model of Unilateral Ureteral Obstruction.

Biomed Res Int 2020 24;2020:6143542. Epub 2020 Nov 24.

Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.

We investigated the role of Akt1, one of the three isoforms of Akt, in renal fibrosis using the murine model of unilateral ureteral obstruction (UUO). We subjected wild type and mice to UUO. The Akt1 gene was silenced in vitro using short hairpin RNA delivered via a lentiviral vector in human proximal tubular cells (HK2 cells) and kidney fibroblasts (NRK-49F cells). The obstructive kidneys of mice showed more severe tubulointerstitial fibrosis than those of wild type mice. The expression of fibronectin and type I collagen was significantly increased in obstructed kidneys of mice compared to those of wild type mice. The important finding was that the expression of transforming growth factor 1 (TGF1) was significantly increased in the mice compared to the wild type mice. The knockdown of enhanced the expression of TGF1 in HK2 cells. Interestingly, the upregulation of TGF1 due to genetic knockdown of was associated with activation of signal transducer and activator of transcript 3 (STAT3) independently of the Smad pathway in NRK-49F and HK2 cells. Immunohistochemical staining also showed that expression of phosphorylated STAT3 was more increased in mice than in wild type mice after UUO. Additionally, the deletion of led to apoptosis of the renal tubular cells in both in vivo and in vitro studies. Conclusively, these results suggest that the deletion of may contribute to renal fibrosis via induction of the TGF1/STAT3 pathway in a murine model of UUO.
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http://dx.doi.org/10.1155/2020/6143542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707954PMC
May 2021

Scar Formation and Debris Elimination during Hair Cell Degeneration in the Adult DTR Mouse.

Neuroscience 2021 01 5;453:57-68. Epub 2020 Dec 5.

Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA. Electronic address:

The auditory sensory epithelium of the mammalian inner ear is a highly organized structure that contains sensory hair cells (HCs) and non-sensory supporting cells (SCs). Following the partial loss of HCs after cochlear insults such as overstimulation or ototoxic drugs, SCs seal the luminal epithelial surface (reticular lamina) and reorganize its cellular pattern. Here we investigated the changes in the sensory epithelium following a rapid and severe cochlear insult in the diphtheria toxin receptor (DTR) mouse, where diphtheria toxin (DT) injection leads to a HC-specific lesion resulting in a complete HC loss. We found that DT-induced selective HC ablation could lead to a pattern of scar formation and apical cell-cell adherens and tight junction reorganization similar to that occurring after other types of cochlear insult. Prestin, an outer HC-specific protein, was present in amorphous clumps at the sites where SCs had expanded to fill the spaces vacated by the dead HCs for up to 2 months after the DT induced lesion. Many of the prestin clumps appeared to occupy spaces within SCs, suggesting that SCs participate in the removal process of HC corpses in the DTR deafness model. Prestin clumps could be seen in different areas all along the length of the SCs, and appeared to be inside the SCs as well as in the inter-cellular spaces between SCs. The findings suggest that HC elimination in the DTR deafness model follows a mechanism similar to that in overstimulation or ototoxicity models, making the DTR mouse useful for understanding the process underlying HC elimination and the role of SCs in this process.
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http://dx.doi.org/10.1016/j.neuroscience.2020.11.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796978PMC
January 2021

Clinical Features and Hearing Outcomes of Sudden Sensorineural Hearing Loss in Diabetic Patients.

J Audiol Otol 2021 Jan 16;25(1):27-35. Epub 2020 Nov 16.

Department of Otorhinolaryngology-Head and Neck Surgery, Dankook University Hospital, Cheonan, Korea.

Background And Objectives: This study aimed to evaluate the clinical features and the clinical factors associated with prognosis of sudden sensorineural hearing loss (SSNHL) in diabetic patients.

Subjects And Methods: Forty-nine diabetic with unilateral SSNHL were retrospectively included. All patients received systemic high dose steroid therapy within one month after onset and had more than one month of follow-up audiogram. The basic characteristics of the patients, initial and follow-up audiograms, laboratory data, and methods of steroid treatment were collected.

Results: Compared to reference values in healthy subjects, 79%, 55%, and 45% of the patients had higher values of mean neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), respectively. Older patients had significantly less degree of hearing loss, but they also had significantly worse hearing thresholds in the unaffected ear. After steroid treatment, less than half patients (47%) showed hearing recovery. Simultaneous intratympanic dexamethasone (ITD) injections with systemic steroid did not confer an additional hearing gain or an earlier recovery rate in diabetic patients with SSNHL. In the multivariate analysis, initial hearing thresholds of affected ear and timing of steroid treatment were significantly associated with hearing prognosis in diabetic patients with SSNHL.

Conclusions: Diabetic patients with SSNHL tended to have increased NLR, LMR, and PLR, which are reported to be associated with microvascular angiopathy. Simultaneous ITD injections to improve hearing recovery in diabetic patients with SSNHL seems unnecessary.
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http://dx.doi.org/10.7874/jao.2020.00262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835439PMC
January 2021

Injectable hydrogel derived from chitosan with tunable mechanical properties via hybrid-crosslinking system.

Carbohydr Polym 2021 Jan 6;251:117036. Epub 2020 Sep 6.

Department of Stem Cell and Regenerative Biotechnology, KU Convergence Science and Technology Institute, Konkuk University, Seoul, 05029, Republic of Korea. Electronic address:

Thermo-sensitive injectable hydrogels that spontaneously react to physiological temperature have been widely studied to be used in biomedical fields. However, several challenges on their unstable structures with large-sized pores and low mechanical strength under physiological conditions must be addressed to enable their practical applications. We synthesized the hydroxybutyl methacrylated chitosan (HBC-MA) hydrogel that possesses both thermo-sensitive and photo-crosslinkable properties. The HBC-MA showed effective sol-gel transition under physiological temperature as well as a sensitive photo-crosslinkable property with visible light capable of skin penetration. The co-nonsolvency property and thermo-sensitivity of HBC-MA prevented unintended loss of the hydrogel graft after being subcutaneously injected in mice. Subsequently applied visible light on the skin beneath which the hydrogel was injected significantly improved the mechanical strength and stability of the graft. The injectable HBC-MA hydrogel developed in this study can be applicable to a wide range of biomedical fields such as drug delivery system and tissue engineering.
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http://dx.doi.org/10.1016/j.carbpol.2020.117036DOI Listing
January 2021