Publications by authors named "Seong Ho Jeong"

76 Publications

Premorbid Educational Attainment and Long-Term Motor Prognosis in Parkinson's Disease.

J Parkinsons Dis 2021 Sep 16. Epub 2021 Sep 16.

Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.

Background: Premorbid educational attainment is a well-known proxy of reserve, not only with regard to cognition, but also to motor symptoms.

Objective: In the present study, we investigated the relationship between educational attainment and long-term motor prognosis in patients with Parkinson's disease (PD).

Methods: We analyzed 466 patients with de novo PD without dementia who underwent dopamine transporter (DAT) scans and were followed up more than 2 years. Patients were divided into three groups: low education (years-of-education ≤6, n = 125), intermediate education (6 
Results: Multiple regression analysis showed that higher education was associated with milder parkinsonian symptoms after adjusting for DAT availability in the posterior putamen. Survival analysis showed that the rate of LID was significantly lower in the high education group than in the low education group (HR = 0.565, p = 0.010). A linear mixed model showed that the high education group had lower LED than the low education group until a period of 30 months; however, this difference in LED was not observed thereafter.

Conclusion: The present study demonstrated that premorbid educational attainment has protective effects on the development of LID in patients with PD and has sparing effects on LED during the early treatment period. These results suggest that high educational attainment has a beneficial effect on motor outcomes in patients with PD.
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http://dx.doi.org/10.3233/JPD-212791DOI Listing
September 2021

Association of Dipeptidyl Peptidase-4 Inhibitor Use and Amyloid Burden in Patients With Diabetes and AD-Related Cognitive Impairment.

Neurology 2021 Sep 11;97(11):e1110-e1122. Epub 2021 Aug 11.

From the Department of Neurology (S.H.J., K.B., B.S.Y., Y.H.S., P.H.L.), Department of Neurology, Gangnam Severance Hospital (H.K., H.C., C.H.L.), Department of Internal Medicine, Severance Hospital, Endocrine Research Institute (N.H.), and Severance Biomedical Science Institute (P.H.L.), Yonsei University College of Medicine; Sanggye Paik Hospital (S.H.J.), Inje University College of Medicine; Global Health Technology Research Center, College of Health Science (H.R.K.), School of Biomedical Engineering (J.-K.S.), and Department of Artificial Intelligence (J.-K.S.), Korea University; Medical & Health Device Division (J.K.), Korea Testing Laboratory, Seoul; and Department of Neurology (J.H.J.), Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea.

Background And Objective: To investigate whether dipeptidyl peptidase-4 inhibitors (DPP-4i) have beneficial effects on amyloid aggregation and longitudinal cognitive outcome in diabetic Alzheimer disease-related cognitive impairment (ADCI).

Methods: We retrospectively reviewed 282 patients with ADCI with positive F-florbetaben amyloid PET images. Patients were classified into 3 groups according to prior diagnosis of diabetes and DPP-4i use: diabetic patients being treated with (ADCI-DPP-4i, n = 70) or without DPP-4i (ADCI-DPP-4i, n = 71) and nondiabetic patients (n = 141). Multiple linear regression analyses were performed to determine intergroup differences in global and regional amyloid retention using standardized uptake value ratios calculated from cortical areas. We assessed longitudinal changes in Mini-Mental State Examination (MMSE) score using a linear mixed model.

Results: The ADCI-DPP-4i group had lower global amyloid burden than the ADCI-DPP-4i group (β = 0.075, SE = 0.024, = 0.002) and the nondiabetic ADCI group (β = 0.054, SE = 0.021, = 0.010) after adjusting for age, sex, education, cognitive status, and ε4 carrier status. The ADCI-DPP-4i group had lower regional amyloid burden in temporo-parietal areas than either the ADCI-DPP-4i group or the nondiabetic ADCI group. The ADCI-DPP-4i group showed a slower longitudinal decrease in MMSE score (β = 0.772, SE = 0.272, = 0.005) and memory recall subscore (β = 0.291, SE = 0.116, = 0.012) than the ADCI-DPP-4i group.

Discussion: These findings suggest that DPP-4i use is associated with low amyloid burden and favorable long-term cognitive outcome in diabetic patients with ADCI.
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http://dx.doi.org/10.1212/WNL.0000000000012534DOI Listing
September 2021

Implication of Small Vessel Disease MRI Markers in Alzheimer's Disease and Lewy Body Disease.

J Alzheimers Dis 2021 ;83(2):545-556

Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: Small vessel disease (SVD) magnetic resonance imaging (MRI) markers including deep and periventricular white matter hyperintensities (PWMH), lacunes, and microbleeds are frequently observed in Alzheimer's disease (AD) and Lewy body disease (LBD), but their implication has not been clearly elucidated.

Objective: To investigate the implication of SVD MRI markers in cognitively impaired patients with AD and/or LBD.

Methods: We consecutively recruited 57 patients with pure AD-related cognitive impairment (ADCI), 49 with pure LBD-related cognitive impairment (LBCI), 45 with mixed ADCI/LBCI, and 34 controls. All participants underwent neuropsychological tests, brain MRI, and amyloid positron emission tomography. SVD MRI markers including the severity of deep and PWMH and the number of lacunes and microbleeds were visually rated. The relationships among vascular risk factors, SVD MRI markers, ADCI, LBCI, and cognitive scores were investigated after controlling for appropriate covariates.

Results: LBCI was associated with more severe PWMH, which was conversely associated with an increased risk of LBCI independently of vascular risk factors and ADCI. PWMH was associated with attention and visuospatial dysfunction independently of vascular risk factors, ADCI, and LBCI. Both ADCI and LBCI were associated with more lobar microbleeds, but not with deep microbleeds.

Conclusion: Our findings suggest that PWMH could reflect degenerative process related with LBD, and both AD and LBD independently increase lobar microbleeds.
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http://dx.doi.org/10.3233/JAD-210669DOI Listing
January 2021

Effects of statins on dopamine loss and prognosis in Parkinson's disease.

Brain 2021 Aug 4. Epub 2021 Aug 4.

Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.

Statins are more widely used not only for the primary and secondary prevention of cardiovascular disease by blocking cholesterol biosynthesis but also for the potential neuroprotective agents during neurological disorders due to their pleiotropic effects. In this study, we investigate whether the prior use of statins affect baseline nigrostriatal dopamine loss at the time of diagnosis and longitudinal motor and cognitive outcomes in patients with Parkinson's disease. Five hundred drug-naïve patients with Parkinson's disease who underwent dopamine transporter imaging were classified into two groups according to the prior use of statins: patients with and without statin use. Multivariate linear regression was used to determine inter-group differences in dopamine transporter availability. We evaluated the longitudinal changes in levodopa-equivalent dose and dementia conversion between the groups using a linear mixed model and survival analysis, respectively. In addition, mediation analysis was applied to examine the effect of total cholesterol. Patients with Parkinson's disease treated with statin had a lower baseline dopamine transporter availability in the anterior (2.13 ± 0.55 vs. 2.37 ± 0.67; p = 0.002), posterior (1.31 ± 0.43 vs. 1.49 ± 0.54; p = 0.003), and ventral putamina (1.40 ± 0.39 vs. 1.56 ± 0.47; p = 0.002) than that in matched patients with Parkinson's disease without statin. After adjusting for age at symptom onset, sex, disease duration and vascular risk factors, linear regression models showed that a prior treatment of statin remained significantly and independently associated with more severely decreased dopamine transporter availability in the anterior putamen (Beta = -0.140, p = 0.004), posterior putamen (Beta = -0.162, p = 0.001), and ventral putamen (Beta = -0.140, p = 0.004). A linear mixed model revealed that patients with Parkinson's disease being treated with statin had a faster longitudinal increase in levodopa-equivalent dose than those without statin. A survival analysis showed that the rate of dementia conversion was significantly higher in patients with Parkinson's disease with statin (hazard ratio, 2.019; 95% CI, 1.108 - 3.678; P = 0.022) than those without statin. Mediation analyses revealed that the effect of statin treatment on baseline dopamine transporter availability and longitudinal outcome was not mediated by total cholesterol levels. This study suggests that statin use may have a detrimental effect on baseline nigrostriatal dopamine degeneration and long-term outcomes in patients with Parkinson's disease.
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http://dx.doi.org/10.1093/brain/awab292DOI Listing
August 2021

Erratum.

Alzheimers Dement (Amst) 2021 28;13(1):e12215. Epub 2021 Jul 28.

Department of Neurology Yonsei University College of Medicine Seoul Republic of Korea.

[This corrects the article DOI: 10.1002/dad2.12177.].
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http://dx.doi.org/10.1002/dad2.12215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319653PMC
July 2021

Effects of baseline serum uric acid and apolipoprotein E4 on longitudinal cognition and cerebral metabolism.

Neurobiol Aging 2021 10 24;106:223-231. Epub 2021 May 24.

Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Serum uric acid, a natural antioxidant, may have a protective effect on the progression of Alzheimer's disease (AD). To investigate the effect of serum uric acid on longitudinal cognitive and brain metabolic changes, we utilized data on baseline serum uric acid levels, APOE genotyping, and longitudinal cognitive scores from the Alzheimer's Disease Neuroimaging Initiative for 1,343 participants with normal cognition (NC), mild cognitive impairment (MCI), or dementia. In 979 participants, brain metabolism was measured using F-fluorodeoxyglucose positron emission tomography (FDG-PET) images. Higher serum uric acid levels exhibited a detrimental effect on NC, whereas a protective trend was observed in individuals with cognitive impairment. Interestingly, higher uric acid levels were associated with a slower decline in cognitive scores and brain metabolism in females with MCI, and this effect was found in APOE4 carriers, but not in non-carriers. Longitudinal AD-like patterns of brain metabolism on FDG-PET images also appeared to mediate the effects of baseline uric acid levels on longitudinal cognitive decline. In summary, higher serum uric acid may interact with APOE4 to alleviate longitudinal metabolic changes and cognitive decline in female MCI patients.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.05.003DOI Listing
October 2021

Clinical and Dopamine Depletion Patterns in Hyposmia- and Dysautonomia-Dominant Parkinson's Disease.

J Parkinsons Dis 2021 Jul 10. Epub 2021 Jul 10.

Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.

Background: Olfactory or autonomic dysfunction is one of the earliest prodromal symptoms of Parkinson's disease (PD). It has not been investigated whether PD patients have different phenotypes depending on the presence of these prodromal symptoms.

Objective: To investigate whether hyposmia-dominant and dysautonomia-dominant patients with early PD have different clinical manifestations and nigrostriatal degeneration.

Methods: This cross-sectional study recruited 168 drug-naive PD patients and 34 control subjects. PD patients were classified as patients without hyposmia and dysautonomia (PD-H-D-, n = 51), hyposmia-dominant patients (PD-H+D-, n = 36), dysautonomia-dominant patients (PD-H-D+, n = 33), and patients with hyposmia and dysautonomia (PD-H+D+, n = 48). We then compared the baseline clinical characteristics, striatal specific to non-specific binding ratio (SNBR), neuropsychological performance, and neuropsychiatric symptoms among the groups.

Results: The PD-H+D-group had a lower SNBR in the ventral striatum (p = 0.013), a greater asymmetric index of striatal SNBRs, and higher prevalence of apathy (p = 0.021) than the PD-H-D+ group. The PD-H-D+ group had older age at onset (p = 0.043) and a higher prevalence of REM sleep behavior disorder (p = 0.041) than the PD-H+D-group. The PD-H+D+ group had higher motor deficits, lower cognitive function, and lower SNBRs in all striatal subregions than the PD-H-D-group. Decreased SNBRs in the anterior caudate, posterior caudate, and ventral striatum were associated with the presence of apathy.

Conclusion: The present study suggests that hyposmia-dominant and dysautonomia-dominant PD have different clinical characteristics and patterns of striatal dopamine depletion.
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http://dx.doi.org/10.3233/JPD-212747DOI Listing
July 2021

Implication of metabolic and dopamine transporter PET in dementia with Lewy bodies.

Sci Rep 2021 Jul 13;11(1):14394. Epub 2021 Jul 13.

Department of Neurology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.

To evaluate the implication of F-fluorodeoxyglucose (FDG)- and dopamine transporter (DAT)-positron emission tomography (PET) in the diagnosis and clinical symptoms of dementia with Lewy bodies (DLB), 55 DLB patients and 49 controls underwent neuropsychological evaluation and FDG-, DAT-, and F-Florbetaben (FBB) PET. DAT- and FDG-uptake and FDG/DAT ratio were measured in the anterior and posterior striatum. The first principal component (PC1) of FDG subject residual profiles was identified for each subject. Receiver operating characteristic curve analyses for the diagnosis of DLB were performed using FDG- and DAT-PET biomarkers as predictors, and general linear models for motor severity and cognitive scores were performed adding FBB standardized uptake value ratio as a predictor. Increased metabolism in the bilateral putamen, vermis, and somato-motor cortices, which characterized PC1, was observed in the DLB group, compared to the control group. A combination of posterior putamen FDG/DAT ratio and PC1 showed the highest diagnostic accuracy (91.8% sensitivity and 96.4% specificity), which was significantly greater than that obtained by DAT uptake alone. Striatal DAT uptake and PC1 independently contributed to motor severity and language, memory, frontal/executive, and general cognitive dysfunction in DLB patients, while only PC1 contributed to attention and visuospatial dysfunction.
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http://dx.doi.org/10.1038/s41598-021-93442-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277897PMC
July 2021

Apolipoprotein E4, amyloid, and cognition in Alzheimer's and Lewy body disease.

Neurobiol Aging 2021 10 12;106:45-54. Epub 2021 Jun 12.

Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea. Electronic address:

The role of apolipoprotein E4 (APOE4) in the risk of Alzheimer's disease (AD) and Lewy body disease (LBD), and their relationship with β-amyloid deposition and cognitive dysfunction, remain unclear. Using amyloid and dopamine transporter imaging, we enrolled 126 controls and 208 patients with typical AD (pure AD and Lewy body variant of AD), AD with dementia with Lewy bodies, or typical LBD (dementia with Lewy bodies with amyloid deposition and pure LBD). APOE4 was associated with an increased risk of all disease subtypes except pure LBD. APOE4 was associated with increased frontal β-amyloid burden, and typical LBD was associated with increased occipital β-amyloid levels through its interaction with APOE4. APOE4 was associated with deteriorated general cognition and memory dysfunction via its interaction with typical LBD and AD, respectively. In conclusion, the impact of APOE4 on disease risk depends on its effects on β-amyloid deposition, and APOE4 is associated with β-amyloid deposition regardless of the clinical diagnosis. However, it interacts with typical LBD to cause occipital β-amyloid deposition.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.06.004DOI Listing
October 2021

Neuropsychiatric Burden Is a Predictor of Early Freezing and Motor Progression in Drug-Naïve Parkinson's Disease.

J Parkinsons Dis 2021 Jun 14. Epub 2021 Jun 14.

Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.

Background: Neuropsychiatric symptoms (NPS) are the most common non-motor symptom in Parkinson's disease (PD).

Objective: To investigate the association between the burden of NPS and motor prognosis in patients with PD.

Methods: We enrolled 329 drug-naïve patients with PD, who was non-demented and followed-up≥2 years after their first visit to the clinic with baseline dopamine transporter (DAT) imaging and neuropsychiatric inventory (NPI) scores. We performed a survival analysis and a linear mixed model analysis to assess longitudinal motor outcomes according to the NPI total score.

Results: The Kaplan-Meier analysis showed no difference in the development of levodopa-induced dyskinesia and wearing-off according to the NPI total score. However, higher burden of NPI total score was associated with earlier freezing of gait (FOG) development in the time-dependent Cox regression models after adjusting for age at symptom onset, sex, disease duration, Unified PD Rating Scale motor score, baseline Mini-Mental State Examination score, DAT activity in the posterior putamen and levodopa-equivalent daily dose (LEDD) (Hazard ratio 1.047, p = 0.002). A linear mixed model analysis revealed that patients with a higher NPI total score had a more rapid LEDD increment (NPI×time, p = 0.003). Among 52 patients with PD who eventually developed FOG during the follow-up period, there was a significant correlation between the NPI total score and time with FOG development (γ= -0.472; p = 0.001) after adjusting for confounding factors.

Conclusion: The present study demonstrated that the severity of NPS is a predictor of early freezing and motor progression in patients with PD.
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http://dx.doi.org/10.3233/JPD-212660DOI Listing
June 2021

Mechanical Properties of Biocomposites Using Polypropylene and Sesame Oil Cake.

Polymers (Basel) 2021 May 15;13(10). Epub 2021 May 15.

Department of Mechanical Engineering, Yonsei University, 50, Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.

Sesame oil cakes (SOC) produced during sesame oil production can be classified as plant residues. This study aims to use SOC as a composite material for injection molding. A biocomposite containing polypropylene (PP) and SOC, namely PP/SOC, was developed and its mechanical properties were evaluated. PP/SOC is largely divided into Homo-PP/SOC (HPS) based on Homo-PP and Block-PP/SOC (BPS) based on block-PP. The specimens containing 0-50 wt% SOC were prepared through extrusion and injection molding. As a result of the evaluation, SOC acted as a reinforcement in the matrix, and HPS and BPS showed improved flexural modulus by 36.4% and 37.3% compared to the neat PP, respectively. Tensile strength, on the other hand, decreased by 58% and 55.1%, respectively. To analyze the cause of this, cross-section observation was conducted through scanning electron microscope (SEM), and phase separation and voids were confirmed to be the cause of this. Impact strength of PP/SOC tended to vary depending on the type of matrix. HPS increased by 30.9% compared to neat PP, and BPS decreased by 25%. This tendency difference appears to be the result of SOC inhibiting crystallization of PP, and it has been confirmed through x ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis. Moreover, PP/SOC can be manufactured at a low cost and is environmentally friendly because it utilizes SOC, a plant residue. It can also be applied to commercial products, such as food packaging, owing to its good moldability and improved mechanical properties.
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http://dx.doi.org/10.3390/polym13101602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156255PMC
May 2021

Interaction of CSF α-synuclein and amyloid beta in cognition and cortical atrophy.

Alzheimers Dement (Amst) 2021 21;13(1):e12177. Epub 2021 May 21.

Department of Neurology Inje University Busan Paik Hospital Busan Korea.

Introduction: Lewy body-related pathology is commonly observed at autopsy in individuals with dementia, but in vivo biomarkers for α-synucleinopathy are lacking.

Methods: Baseline cerebrospinal fluid (CSF) biomarkers, polygenic risk score (PRS) for Parkinson's disease (PRS-PD) and Alzheimer's disease (PRS-AD), longitudinal cognitive scores, and magnetic resonance imaging were measured in 217 participants from the Alzheimer's Disease Neuroimaging Initiative. Linear mixed models were used to find the relationship of CSF biomarkers and the PRS with cognition and cortical atrophy.

Results: Higher PRS-PD and PRS-AD were associated with lower CSF α-synuclein and amyloid beta (Aβ), respectively. Lower CSF α-synuclein and the interaction of CSF α-synuclein and Aβ were associated with lower cognitive scores and global cortical atrophy most prominently in the occipital cortex.

Discussion: Lower CSF α-synuclein could be a biomarker for α-synucleinopathy, and the simultaneous evaluation of CSF biomarkers for AD and CSF α-synuclein could reveal the independent and interactive effects on cognition and cortical atrophy.
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http://dx.doi.org/10.1002/dad2.12177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140203PMC
May 2021

A comparison of orthopaedic surgery and internal medicine perceptions of USMLE Step 1 pass/fail scoring.

BMC Med Educ 2021 May 3;21(1):255. Epub 2021 May 3.

Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA.

Background: United States Medical Licensing Examination Step 1 will transition from numeric grading to pass/fail, sometime after January 2022. The aim of this study was to compare how program directors in orthopaedics and internal medicine perceive a pass/fail Step 1 will impact the residency application process.

Methods: A 27-item survey was distributed through REDCap to 161 U.S. orthopaedic residency program directors and 548 U.S. internal medicine residency program directors. Program director emails were obtained from the American Medical Association's Fellowship and Residency Electronic Interactive Database.

Results: We received 58 (36.0%) orthopaedic and 125 (22.8%) internal medicine program director responses. The majority of both groups disagree with the change to pass/fail, and felt that the decision was not transparent. Both groups believe that the Step 2 Clinical Knowledge exam and clerkship grades will take on more importance. Compared to internal medicine PDs, orthopaedic PDs were significantly more likely to emphasize research, letters of recommendation from known faculty, Alpha Omega Alpha membership, leadership/extracurricular activities, audition elective rotations, and personal knowledge of the applicant. Both groups believe that allopathic students from less prestigious medical schools, osteopathic students, and international medical graduates will be disadvantaged. Orthopaedic and internal medicine program directors agree that medical schools should adopt a graded pre-clinical curriculum, and that there should be a cap on the number of residency applications a student can submit.

Conclusion: Orthopaedic and internal medicine program directors disagree with the change of Step 1 to pass/fail. They also believe that this transition will make the match process more difficult, and disadvantage students from less highly-regarded medical schools. Both groups will rely more heavily on the Step 2 clinical knowledge exam score, but orthopaedics will place more importance on research, letters of recommendation, Alpha Omega Alpha membership, leadership/extracurricular activities, personal knowledge of the applicant, and audition electives.
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http://dx.doi.org/10.1186/s12909-021-02699-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091716PMC
May 2021

Beneficial effects of dipeptidyl peptidase-4 inhibitors in diabetic Parkinson's disease.

Brain 2021 05;144(4):1127-1137

Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.

Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used hypoglycaemic agents and improve glucose metabolism by enhancing the bioavailability of active glucagon-like peptide-1. In this study, we hypothesized that treatment with DPP4 inhibitors may have beneficial effects on nigrostriatal dopamine and longitudinal motor performance in diabetic patients with Parkinson's disease. We classified 697 drug naive patients with de novo Parkinson's disease who had undergone dopamine transporter imaging into three groups according to a prior diagnosis of diabetes and use of DPP4 inhibitors: diabetic patients with Parkinson's disease being treated with (n = 54) or without DPP4 inhibitors (n = 85), and non-diabetic patients with Parkinson's disease (n = 558). Diabetic patients with Parkinson's disease being treated with DPP4 inhibitors had a higher baseline dopamine transporter availability in the anterior (2.56 ± 0.74 versus 2.10 ± 0.50; P = 0.016), posterior (1.83 ± 0.69 versus 1.40 ± 0.50; P < 0.001), and ventral putamina (1.72 ± 0.58 versus 1.35 ± 0.37; P = 0.001) than that in diabetic patients with Parkinson's disease without DPP4 inhibitors. Additionally, diabetic patients with Parkinson's disease being treated with DPP4 inhibitors had higher dopamine transporter availability in the posterior putamen than that in non-diabetic patients with Parkinson's disease (1.83 ± 0.69 versus 1.43 ± 0.59; P < 0.001). After adjusting for age, sex, disease duration, and vascular risk factors, linear regression models showed that a prior treatment of DPP4 inhibitors remained independently and significantly associated with dopamine transporter availability in the anterior (β = -0.186, P = 0.012; β = -0.207, P = 0.003), posterior (β = -0.336, P < 0.001; β = -0.286, P < 0.001), and ventral putamina (β = -0.204, P = 0.005; β = -0.250, P < 0.001). A linear mixed model revealed that the diabetic group with Parkinson's disease being treated with DPP4 inhibitors had a slower longitudinal increase in levodopa-equivalent dose than the other groups (P = 0.003). Survival analyses showed that the rate of levodopa-induced dyskinesia was significantly lower in the diabetic group with a prior treatment with DPP4 inhibitors than the diabetic group without DPP4 inhibitors (hazard ratio = 0.194, P = 0.037). These findings suggest that DPP4 inhibitors may confer beneficial effects on the baseline nigrostriatal dopamine degeneration and long-term motor outcomes in diabetic patients with Parkinson's disease and may extend its role into non-diabetic patients with Parkinson's disease.
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http://dx.doi.org/10.1093/brain/awab015DOI Listing
May 2021

Mechanism of Lipid Accumulation through PAR2 Signaling in Diabetic Male Mice.

Endocrinol Metab (Seoul) 2021 Feb 24;36(1):171-184. Epub 2021 Feb 24.

Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, Korea.

Background: Protease-activated protein-2 (PAR2) has been reported to regulate hepatic insulin resistance condition in type 2 diabetes mice. However, the mechanism of lipid metabolism through PAR2 in obesity mice have not yet been examined. In liver, Forkhead box O1 (FoxO1) activity induces peroxisome proliferator-activated receptor γ (PPARγ), leading to accumulation of lipids and hyperlipidemia. Hyperlipidemia significantly influence hepatic steatoses, but the mechanisms underlying PAR2 signaling are complex and have not yet been elucidated.

Methods: To examine the modulatory action of FoxO1 and its altered interaction with PPARγ, we utilized db/db mice and PAR2-knockout (KO) mice administered with high-fat diet (HFD).

Results: Here, we demonstrated that PAR2 was overexpressed and regulated downstream gene expressions in db/db but not in db+ mice. The interaction between PAR2/β-arrestin and Akt was also greater in db/db mice. The Akt inhibition increased FoxO1 activity and subsequently PPARγ gene in the livers that led to hepatic lipid accumulation. Our data showed that FoxO1 was negatively controlled by Akt signaling and consequently, the activity of a major lipogenesis-associated transcription factors such as PPARγ increased, leading to hepatic lipid accumulation through the PAR2 pathway under hyperglycemic conditions in mice. Furthermore, the association between PPARγ and FoxO1 was increased in hepatic steatosis condition in db/db mice. However, HFD-fed PAR2-KO mice showed suppressed FoxO1-induced hepatic lipid accumulation compared with HFD-fed control groups.

Conclusion: Collectively, our results provide evidence that the interaction of FoxO1 with PPARγ promotes hepatic steatosis in mice. This might be due to defects in PAR2/β-arrestin-mediated Akt signaling in diabetic and HFD-fed mice.
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http://dx.doi.org/10.3803/EnM.2020.850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937841PMC
February 2021

Folded Cymba Concha: Is It Large and Stable Enough for Caudal Septal Extension Graft in Asian Rhinoplasty?

Aesthet Surg J 2021 06;41(7):NP737-NP747

Department of Plastic Surgery, Korea University College of Medicine, Seoul, Republic of Korea.

Background: Septal extension grafting (SEG) is used for nasal tip projection and positioning. Often, insufficient quadrangular cartilage is available for grafting in Asians, and in most secondary cases the septum is already harvested. We utilized the folded cymba concha as an alternative for caudal SEG (CSEG) by modifying a tongue-in-groove technique.

Objectives: The aim of this study was to evaluate the physical suitability of the cymba concha for CSEG and compare its outcomes with those of septal quadrangular cartilage.

Methods: The mean length and width of 311 harvested consecutive folded cymba conchae were measured from intraoperative photographs. Data from 220 patients with >12 months of follow-up were retrospectively reviewed for clinical outcomes. Clinical demography was determined based on the need for additional spreader grafts. For clinical reliability, anthropometric photographs of patients in whom folded cymba conchae were used were compared with those in whom quadrangular cartilage was used.

Results: Mean [standard deviation] lengths and widths of the folded cymba conchae in men and women were 24.2 [3.9] and 22.4 [3.7] mm, and 7.8 [1.9] and 7.2 [1.9] mm, respectively. Use of the folded cymba concha graft significantly increased nasal tip projection by 28.9% and columellar-labial angle by 9.7%, improving both aspects postoperatively. Anthropometric comparison revealed no significant differences between folded cymba conchae and septal cartilage in terms of nasal tip projection (P = 0.264) and postoperative columellar-labial angle (P = 0.182).

Conclusions: Folded cymba conchal cartilage can be a primary option for CSEG in Asian septorhinoplasty cases or for individuals with insufficient septal cartilage remnants.
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http://dx.doi.org/10.1093/asj/sjab079DOI Listing
June 2021

White Matter Hyperintensities, Dopamine Loss, and Motor Deficits in De Novo Parkinson's Disease.

Mov Disord 2021 06 29;36(6):1411-1419. Epub 2021 Jan 29.

Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.

Background: White matter hyperintensities, prevalent in patients with Parkinson's disease (PD), significantly affect parkinsonian motor symptoms. The objective of this study was to investigate the relationship between white matter hyperintensities and nigrostriatal dopamine depletion and their interaction or mediating effects on motor symptoms in patients with drug-naive early-stage PD.

Methods: This cross-sectional study enrolled 501 patients with de novo PD who initially underwent [ F] N-(3-fluoropropyl)-2β-carbonethoxy-3β-(4-iodophenyl) nortropane positron emission tomography and brain magnetic resonance imaging scans between April 2009 and September 2015 in a tertiary-care university hospital. We quantified dopamine transporter availability in each striatal subregion and assessed the severity of periventricular and lobar white matter hyperintensities using the Scheltens scale. The relationship between white matter hyperintensities, dopamine transporter availability in the posterior putamen, and Unified Parkinson's Disease Rating Scale (UPDRS) motor scores was assessed using multivariate linear regression and mediation analyses.

Results: Periventricular and frontal white matter hyperintensities were generally associated with dopamine transporter availability in striatal subregions after adjusting for age at symptom onset, sex, disease duration, and vascular risk factors. There was an interaction effect between periventricular white matter hyperintensities and dopamine transporter availability in the posterior putamen for the axial motor score. The effect of white matter hyperintensities on UPDRS total score and bradykinesia subscore was indirectly mediated by dopamine transporter availability in the posterior putamen, whereas the axial sub-score was directly affected by white matter hyperintensities.

Conclusions: This study suggests that the detrimental effect of white matter hyperintensities on parkinsonian motor symptoms is more relevant and independent for axial motor impairments in the status of mildly decreased striatal dopamine transporter availability. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28510DOI Listing
June 2021

Potential of Tissue-Engineered and Artificial Dermis Grafts for Fingertip Reconstruction.

Plast Reconstr Surg 2020 11;146(5):1082-1095

From the Department of Plastic Surgery, Korea University College of Medicine.

Background: Management of skin and soft-tissue defects of the fingertips is functionally and aesthetically important, but controversial, especially when bones are exposed. Recent advances in wound healing technology allow the use of cells or biological dermis. The authors studied the clinical efficacy of tissue-engineered dermis grafts and artificial dermis grafts versus immediate reconstructive procedures, such as the reverse digital artery island flap, in treating bone-exposed fingertip defects.

Methods: One hundred eighty-two patients with bone-exposed fingertip defects treated with tissue-engineered dermis grafts (n = 71), artificial dermis grafts (n = 23), or reverse digital artery island flaps (n = 88) were included in this retrospective cohort study. Surgical time, duration of hospitalization, total cost, success rate, healing time, sensory recovery, range of motion, scar quality, and patient satisfaction were compared.

Results: No tissue-engineered or artificial dermis graft exhibited graft rejection or failure, whereas there was one partial loss and one total loss after reverse digital artery island flap surgery. Tissue-engineered dermis grafts were superior in scar quality, and artificial dermis grafts had shorter surgical times and lower surgical costs; both groups demonstrated superior results in postoperative range of motion and sensory recovery in two-point discrimination tests and shorter hospitalization, compared with the reverse digital artery island flap group. The reverse digital artery island flap had shorter complete closure time and less postoperative tingling sensation. There were no differences in overall patient satisfaction among the groups.

Conclusions: Tissue-engineered and artificial dermis grafts may be promising alternatives for fingertip reconstruction. In particular, tissue-engineered dermis grafts may deliver superior functional results, including recovery of sensory discomfort and aesthetic results in terms of scar quality over artificial dermis grafts.

Clinical Question/level Of Evidence: Therapeutic, III.
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http://dx.doi.org/10.1097/PRS.0000000000007258DOI Listing
November 2020

Preoperative Nasal Swab Culture: Is It Beneficial in Preventing Postoperative Infection in Complicated Septorhinoplasty?

Plast Reconstr Surg 2020 07;146(1):27e-34e

From the Department of Plastic Surgery, Korea University Guro Hospital.

Background: Surgical-site infection following complicated septorhinoplasty may result in serious complications. Therefore, efforts to prevent surgical-site infections after complicated septorhinoplasty are important. The purpose of this study was to analyze the microbiological profile of preoperative nasal swab cultures and to evaluate the effect of antibiotic prophylaxis and topical antibiotic decolonization according to the antibiotic sensitivity results of surgical-site infections in complicated septorhinoplasty.

Methods: This 10-year cohort study included the data on 437 consecutive patients who underwent complicated septorhinoplasty. The patients were categorized into three cohorts based on the time of preoperative nasal swab culture collection. Patients in cohort 1 did not undergo nasal swab cultures and received empirical antibiotics. Patients in cohort 2 underwent only one preoperative nasal swab culture and received microorganism-sensitive antibiotics. Patients in cohort 3 underwent repeated nasal swab cultures. The antibiotics were changed when microorganisms resistant to the empirical antibiotics were isolated. Microbiological data and the rates of surgical-site infection and inflammation were compared among the three cohorts.

Results: Methicillin-sensitive Staphylococcus aureus was the most commonly isolated microorganism. In cohort 1, two (5 percent) and two (5 percent) patients experienced surgical-site infections and inflammation, respectively. In cohort 2, two (3 percent) and three (4 percent) patients experienced surgical-site infections and inflammation, respectively. In cohort 3, one (0.3 percent) and one (0.3 percent) patient experienced surgical-site infection and inflammation, respectively.

Conclusion: The present study demonstrated that preoperative screening using repeated nasal swab cultures, followed by appropriate antibiotic prophylaxis and topical antibiotic decolonization, may reduce surgical-site infection in complicated septorhinoplasty.

Clinical Question/level Of Evidence: Therapeutic, III.
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http://dx.doi.org/10.1097/PRS.0000000000006893DOI Listing
July 2020

Effects of Granulocyte Macrophage Colony-Stimulating Factor Inhibition on the Skin/Nerve Cell Model In Vitro.

J Craniofac Surg 2020 Jul-Aug;31(5):1483-1487

Department of Plastic Surgery, Korea University College of Medicine, Seoul, Korea.

The present study is based on the concept of neuro-aging and how it may affect surrounding skin cells. It has been shown that many factors play a significant role in skin homeostasis by interfering with various cytokines, either through activation or inhibition. Granulocyte macrophage colony-stimulating factor (GM-CSF) is generally recognized as an inflammatory cytokine, and our previous study has shown its effects on neuronal senescence after ultraviolet (UV) irradiation of skin cells. Following our previous work, this study was performed to investigate the neuroprotective effects of a GM-CSF antagonist, and how it may play an essential role in mediating anti-senescence and anti-inflammatory effects in the keratinocyte/nerve aging model. When human blastoma cells (SH-SY5Y) were treated with 10 ng/ml of GM-CSF, the levels of regulatory RNAs associated with aging, such as matrix metalloproteinase-9 (MMP9), nuclear factor NF-kappa-B p50 subunit (NFKB), inducible nitric oxide synthase (iNOS), and interleukin 1 beta (IL-1β) increased, whereas GM-CSF inhibition caused their expression to decrease. A decrease in the antioxidant, glutathione (GSH) was observed after SH-SY5Y cells were treated with GM-CSF. This study confirms that this GM-CSF antagonist may play an important role in neural senescence, where inhibition may be a new target in the skin/nerve aging model.
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http://dx.doi.org/10.1097/SCS.0000000000006411DOI Listing
November 2020

Effects of Granulocyte Macrophage Colony-Stimulating Factor Inhibition on the Skin/Nerve Cell Model In Vitro.

J Craniofac Surg 2020 Jul-Aug;31(5):1483-1487

Department of Plastic Surgery, Korea University College of Medicine, Seoul, Korea.

The present study is based on the concept of neuro-aging and how it may affect surrounding skin cells. It has been shown that many factors play a significant role in skin homeostasis by interfering with various cytokines, either through activation or inhibition. Granulocyte macrophage colony-stimulating factor (GM-CSF) is generally recognized as an inflammatory cytokine, and our previous study has shown its effects on neuronal senescence after ultraviolet (UV) irradiation of skin cells. Following our previous work, this study was performed to investigate the neuroprotective effects of a GM-CSF antagonist, and how it may play an essential role in mediating anti-senescence and anti-inflammatory effects in the keratinocyte/nerve aging model. When human blastoma cells (SH-SY5Y) were treated with 10 ng/ml of GM-CSF, the levels of regulatory RNAs associated with aging, such as matrix metalloproteinase-9 (MMP9), nuclear factor NF-kappa-B p50 subunit (NFKB), inducible nitric oxide synthase (iNOS), and interleukin 1 beta (IL-1β) increased, whereas GM-CSF inhibition caused their expression to decrease. A decrease in the antioxidant, glutathione (GSH) was observed after SH-SY5Y cells were treated with GM-CSF. This study confirms that this GM-CSF antagonist may play an important role in neural senescence, where inhibition may be a new target in the skin/nerve aging model.
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http://dx.doi.org/10.1097/SCS.0000000000006411DOI Listing
November 2020

Tissue-engineered dermis grafts using stromal vascular fraction cells on the nose: A retrospective case-control study.

J Plast Reconstr Aesthet Surg 2020 May 28;73(5):965-974. Epub 2019 Nov 28.

Department of Plastic Surgery, Korea University College of Medicine, 148 Guro-Dong, Guro-Ku, 152-703 Seoul, Republic of Korea.

Background: In a previous study, our group demonstrated that cultured autologous fibroblast-seeded artificial dermis was superior to artificial dermis for covering defects after surgical excision of basal cell carcinoma (BCC) in terms of scar quality. However, utilizing cultured cells for clinical purposes requires Food and Drug Administration-approved facilities and techniques and a lengthy culture period. The purpose of this retrospective study was to compare the effects of tissue-engineered dermis containing stromal vascular fraction (SVF) cells with artificial dermis on scar quality after surgical excision of BCC on the nose.

Methods: Between April 2010 and February 2018, patients who were treated with tissue-engineered or artificial dermis grafts and those with a follow-up period of greater than a year were included in this study. The Patient and Observer Scar Assessment Scales (POSAS) were compared between two groups according to the location of the graft, which was classified based on nasal subunits: the upper two-thirds zone; the lower one-third zone, except for the ala; and the alar zone.

Results: A tissue-engineered dermis composed of SVF cells and an artificial dermis were applied to 30 and 47 patients, respectively. In upper two-thirds and lower one-third zones, except for the ala, no statistically significant differences were found in any parameters. In the alar zone, statistically significant differences were detected in 10 of 21 POSAS parameters.

Conclusion: To cover nasal defects, the tissue-engineered dermis graft may be superior to the artificial dermis graft regarding scar quality at the ala. However, there were no significant differences in other zones.
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http://dx.doi.org/10.1016/j.bjps.2019.11.027DOI Listing
May 2020

Risk Factors for Major Amputation on Hindfoot Ulcers in Hospitalized Diabetic Patients.

Adv Wound Care (New Rochelle) 2019 May 3;8(5):177-185. Epub 2019 May 3.

Department of Plastic Surgery, Korea University Guro Hospital, Seoul, South Korea.

The purpose of this study was to investigate the risk factors for major amputation in patients hospitalized with diabetic foot ulcers involving the hindfoot. Between January 2003 and October 2017, a total of 1,657 diabetic patients were admitted to the diabetic wound center of Korea University Guro Hospital, for the management of foot ulcers. Among the admitted patients, 117 diabetic patients with hindfoot ulcers were included in this study. One hundred and four patients (89%) healed without major amputation, while 13 patients (11%) healed with major amputation. Data related to 88 potential risk factors, including demographics, ulcer condition, vascularity, bioburden, neurology, and serology, were collected from patients in these two groups for comparison. Among the 88 potential risk factors, 15 showed statistically significant differences between the two groups. In univariate analysis of 88 potential risk factors, nine showed statistically significant differences. In stepwise multiple logistic regression analysis, three of the nine risk factors remained statistically significant. Multivariate-adjusted odds ratios for pulmonary disorders, erythrocyte sedimentation rate (ESR) levels, and total iron-binding capacity (TIBC) levels were 38.525, 1.047, and 0.976, respectively. Compared with forefoot and midfoot ulcers, diabetic foot ulcers involving the hindfoot are at increased risk of major amputation because infection may spread proximal to the ankle. However, large-scale cohort studies that specifically discuss the outcomes and characteristics of diabetic hindfoot ulcers are not widely available. Risk factors for major amputation in patients hospitalized with diabetic hindfoot ulcers include pulmonary disorders, high levels of ESR, and decreased TIBC levels.
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http://dx.doi.org/10.1089/wound.2018.0814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855283PMC
May 2019

Risk factors for major amputation in hospitalized diabetic patients with forefoot ulcers.

Diabetes Res Clin Pract 2019 Dec 29;158:107905. Epub 2019 Oct 29.

Department of Plastic Surgery, Korea University Guro Hospital, Seoul, South Korea.

Aims: The purpose of this study was to investigate the risk factors for major amputation in patients hospitalized with diabetic forefoot ulcers.

Methods: Between January 2003 and December 2018, a total of 1792 diabetic patients were admitted to the diabetic wound center for the management of diabetic foot ulcers. Among the patients, 1032 diabetic patients with forefoot ulcers were included in this study. Nine hundred and eighty-three patients (95%) healed without major amputations while 49 patients (5%) healed after major amputations. Data related to 88 potential risk factors including demographics, ulcer condition, vascularity, bioburden, neurology, and serology were collected from the patients in these two groups for comparison.

Results: Among the 88 potential risk factors, 34 showed statistically significant differences between the two groups. In the univariate analysis of 88 risk factors, 33 showed statistically significant differences. In stepwise multiple logistic regression analysis, four of the 33 risk factors remained statistically significant. The multivariate-adjusted odds ratios for gender, magnesium levels, platelet levels, and glycated hemoglobin (HbA1c) levels were 8.216, 2.480, 1.009, and 0.570, respectively.

Conclusion: Risk factors for major amputation in patients hospitalized with diabetic forefoot ulcers include male gender, increased magnesium, increased platelet levels, and low levels of HbA1c.
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http://dx.doi.org/10.1016/j.diabres.2019.107905DOI Listing
December 2019

Clinical Analysis of Nasal Bone Fracture in Patients Who Have Previously Undergone Dorsal Augmentation Using Silicone Implants: A Pilot Study.

Aesthetic Plast Surg 2019 12 6;43(6):1607-1614. Epub 2019 Jun 6.

Department of Plastic Surgery, Korea University College of Medicine, Korea University Guro Hospital, 148 Gurodong-Gil, Guro-Ku, Seoul, 08308, South Korea.

Background: There are no studies about the treatment of nasal bone fractures in patients with dorsal augmentations using silicone implants. We aimed to describe the characteristics of nasal bone fracture in patients who underwent rhinoplasty and compare the difference between closed reduction and conservative treatment of nasal bone fractures in patients with a history of rhinoplasty.

Methods: Between January 2013 and June 2018, a total of 463 patients were admitted to our center for nasal bone fracture; 17 patients with nasal bone fractures who underwent rhinoplasty were included, of which, five underwent closed reduction in the nasal bone and 12 underwent conservative treatment. Three of 12 patients who were initially treated conservatively underwent a secondary rhinoplasty for esthetic improvements. All patients were classified according to fracture site and the presence of a nasal septal fracture-in accordance with the modified Murray classification-and were analyzed for the correlation between fracture type and disease course.

Results: The nasal bone fracture types per computed tomography findings were unilateral (n = 13), bilateral (n = 4), septal (n = 1), and M-type (n = 1). No significant differences in fracture site (P > 0.05) and the presence of a nasal septal fracture (P > 0.05) were found between the groups. Fracture type did not significantly differ among patients who underwent closed reduction, conservative treatment without secondary rhinoplasty, and secondary rhinoplasty (P > 0.05).

Conclusions: Despite risking traumatic capsular rupture, implant removal is seldom required and closed reduction is recommended if visible deviations are present; otherwise, only conservative treatment is recommended.

Level Of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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http://dx.doi.org/10.1007/s00266-019-01410-9DOI Listing
December 2019

Septorhinoplasty for Destructed Septal L-Strut in Patients with Previously Applied Porous High-Density Polyethylene Implants (Medpor).

Aesthetic Plast Surg 2019 10 2;43(5):1286-1294. Epub 2019 May 2.

Department of Plastic Surgery, Korea University Guro Hospital, 148 Gurodong-Gil, Guro-Ku, Seoul, 08308, South Korea.

Background: Porous high-density polyethylene implants (Medpor) have been extensively used for septal extension grafts in Asian rhinoplasty. However, studies on the long-term complications associated with Medpor have not been reported. Therefore, the purpose of this study was to evaluate the long-term complications of septal extension grafts using Medpor and present a reconstructive strategy for destructed septal L-struts.

Methods: We conducted a 12-year retrospective medical chart review of 428 patients who visited our center for septorhinoplasty. Among 428 patients, 43 patients had Medpor for septal extension grafts previously applied at other clinics. The quadrangular cartilage was devoid or destructed in the area where Medpor was previously applied. Therefore, all patients underwent secondary septorhinoplasty using autogenous cartilage grafts. Patient outcome was assessed to evaluate satisfaction, hardness of nasal tip, functional nasal obstruction symptom evaluation (NOSE) scores, and pain scores. Anthropometric analyses were carried out with patients' photographs. Postoperative complications were also evaluated.

Results: After septal L-strut reconstruction, 87% of patients were satisfied with their aesthetic results. Hardness of nasal tip, NOSE scores, and pain scores also improved after reconstruction. Anthropometric analyses demonstrated that increased nasal length and decreased columellar-labial angle were achieved in patients with short nose deformities. No postoperative complications related to the reconstruction were recorded for any patient.

Conclusions: The devastated destruction of nasal support lines was found after the use of Medpor for septorhinoplasty. Therefore, the use of Medpor should be reduced. Autogenous cartilage grafts are the last resort for reconstruction of destructed septal L-struts.

Level Of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-019-01386-6DOI Listing
October 2019

Paranasal Augmentation Using Multi-Folded Expanded Polytetrafluorethylene (ePTFE) in the East Asian Nose.

Aesthet Surg J 2019 11;39(12):1319-1328

Department of Plastic Surgery, Korea University College of Medicine, Seoul, Korea.

Background: Paranasal augmentation has commonly been performed utilizing alloplastic materials such as silicone or porous polyethylene. However, there are problems such as bone absorption, implant migration, and infection risk attributable to intraoral approaches.

Objectives: The authors attempted anterior positioning of the alar crease junction as an adjunct method of rhinoplasty. The authors aimed to determine the long-term results of the intranasal approach for placement of multi-folded expanded polytetrafluorethylene (ePTFE).

Methods: A retrospective review was conducted of patients who underwent intranasal surgical approach for paranasal augmentation employing multi-folded ePTFE implants in 19 septorhinoplasties who were followed-up for 3 to 10 years. Patient charts were reviewed for demographic information, concomitant operations, and complications. Preoperative and postoperative photographs were utilized to evaluate operative outcomes. The photographs were reformatted to 2-dimensional images employing standard photographic methods.

Results: Of the 19 patients treated, 17 were female and 2 were male; ages ranged from 18 to 58 years. All patients reported improvement in their lateral profiles and were pleased at follow-up. There were no major complications, no nerve or vascular supply compromise, and no cases of implant malposition. The average increase in soft tissue outline near the alar crease junction was more than 3.2 mm (P < 0.001), but the alar base did not became wider.

Conclusions: Paranasal augmentation with multi-folded ePTFE is a simple, safe, and effective method that can readily improve the lateral profile. In particular, the intranasal approach combined with rhinoplasty can synergistically improve outcomes and lead to greater patient satisfaction.

Level Of Evidence: 4:
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http://dx.doi.org/10.1093/asj/sjz103DOI Listing
November 2019

Assessment of Long-term Outcomes of Soft-Tissue Augmentation by Injecting Fibroblasts Suspended in Hyaluronic Acid Filler.

JAMA Facial Plast Surg 2019 Jul;21(4):312-318

Department of Plastic Surgery, Korea University Guro Hospital, Seoul, South Korea.

Importance: In previous studies, this group has reported that cultured human fibroblasts suspended in hyaluronic acid (HA) filler might have potential use as a long-lasting injectable soft-tissue filler. However, the data were insufficient to determine the long-term outcomes.

Objective: To evaluate the long-term outcomes of cultured human fibroblasts suspended in HA filler used for soft-tissue augmentation.

Design, Setting, And Participants: A long-term case series study was performed. Between January 2010 and December 2013, a total of 38 patients were treated with fibroblast-HA filler mixture to augment nasal dorsa, nasolabial folds, and cheek depressions. Of these 38 patients, patients with follow-up period of greater than 3 years were included in this study. A total of 22 patients met the inclusion criteria.

Main Outcomes And Measures: Subjective assessment was performed to evaluate degree and time of resorption, improvement, satisfaction, softness of injection sites, and willingness to recommend this treatment to others. Objective assessment was carried out with patients' photographs. Safety and tolerability were also evaluated for this treatment.

Results: Of the 22 patients included in this study, 19 were women; mean (SD) patient age was 43 (15) years. All 22 patients experienced improvement following the treatment. Twenty (91%) patients were satisfied with the treatment. Nineteen patients (86%) considered that the injection site was as soft as it was before treatment. Patients' mean (SD) grading of improvement, satisfaction, and softness were 4.50 (0.51) (95% CI, 4.27-4.73), 4.14 (0.71) (95% CI, 3.82-4.45), and 4.82 (0.50) (95% CI, 4.59-5.00) at the last visit, respectively. Objective assessment demonstrated postoperative improvement in all patients: a rating of "much improved" was given to 7 patients (32%) by investigator 1; 8 patients (36%) by investigator 2; and 12 patients (55%) the injecting physician. This treatment was well tolerated; no adverse event was recorded for any patient.

Conclusions And Relevance: Injection of cultured human fibroblasts suspended in HA filler might be successful for long-term soft-tissue augmentation. To our knowledge, this study represents the longest follow-up study of soft-tissue augmentation with a fibroblast-HA filler mixture to date.

Level Of Evidence: 4.
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http://dx.doi.org/10.1001/jamafacial.2018.2127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583875PMC
July 2019

Possibility of Injecting Adipose-Derived Stromal Vascular Fraction Cells to Accelerate Microcirculation in Ischemic Diabetic Feet: A Pilot Study.

Int J Stem Cells 2019 Mar;12(1):107-113

Department of Plastic Surgery, Korea University Guro Hospital, Seoul, Korea.

Background And Objectives: Beneficial effects of human adipose-derived stromal vascular fraction (SVF) cell injection on microcirculation have been recently reported in and studies. However, no clinical studies have reported its effect in diabetic patients who commonly experience compromised tissue perfusion, regardless of the status of intravascular blood flow. The present piloting study was designed to clinically examine the possibility of SVF cell injection to accelerate microcirculation, particularly in ischemic diabetic feet.

Methods: Ten diabetic feet were included to receive subcutaneous injection of SVF cells around wounds. Transcutaneous partial oxygen pressure (TcPO) and cutaneous microvascular blood flow were measured before and every four weeks after cell injection until the 12 week visit.

Results: TcPO values increased from 31.3±7.4 before injection to 46.4±8.2 mmHg at 12 weeks after SVF injection (1.5-fold, p<0.05). Cutaneous microvascular blood flow levels increased from 34.0±21.1 before injection to 76.1±32.5 perfusion unit at 12 weeks after SVF injection (2.2-fold, p<0.05). There were no adverse events related to SVF cell injection.

Conclusions: Results of this study demonstrate that adipose-derived SVF cell injection have the possibility to provide beneficial effects on microcirculation in ischemic diabetic feet.
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http://dx.doi.org/10.15283/ijsc18101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457712PMC
March 2019

Comparative Biological Effects of Human Amnion and Chorion Membrane Extracts on Human Adipose-Derived Stromal Cells.

J Craniofac Surg 2019 May/Jun;30(3):947-954

Department of Plastic Surgery, Korea University Guro Hospital, Seoul, South Korea.

Although therapies with human amnion/chorion are used to ameliorate acute and chronic wounds, it is unclear which component of the amnion/chorion tissue promotes wound healing. To characterize the comparative effects of amnion and chorion in wound healing, we used human adipose-derived stromal cells to assess cell viability, migration, and gel contraction after treatment with amnion membrane extract (AME) or chorion membrane extract (CME). We then correlated the possible effectors via AME and CME protein profiling, and compared them by enzyme-linked immunosorbent assay (ELISA), western blotting, and immunocytochemistry. Cell viability was significantly increased with 50 and 100 μg/mL AME treatment, but with CME treatment, a significant increase was only observed with 100 μg/mL. With CME treatment, cell migration was 2.22-fold greater than the control, and collagen gels showed 20% greater contraction. Compared to control, the expression levels of α-smooth muscle actin (SMA) and smooth muscle protein 22-alpha (SM22α) increased both with AME and CME treatments, whereas calponin expression decreased. Protein profiling revealed significantly higher tissue inhibitor of metalloproteinase-1 (TIMP-1), interleukin-8, exotoxin, and adiponectin levels in CME than in AME, and ELISA revealed 8-fold higher adiponectin levels in cells treated with CME than those treated with AME. Immunocytochemistry revealed that α-SMA, SM22α, and calponin were significantly higher in CME- than AME-treated cells; however, adiponectin treatment did not enhance α-SMA, SM22α, or calponin expression. In conclusion, amnion and chorion membrane extracts exerted differential effects on proliferation and contraction of human adipose-derived stromal cells. Amnion extract was superior at inducing cell proliferation and migration, whereas CME was superior at inducing cell contraction.
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http://dx.doi.org/10.1097/SCS.0000000000005393DOI Listing
July 2019
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