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BACKGROUND@#Tissue engineering, including 3D bioprinting, holds great promise as a therapeutic tool for repairing cartilage defects. Mesenchymal stem cells have the potential to treat various fields due to their ability to differentiate into different cell types. The biomimetic substrate, such as scaffolds and hydrogels, is a crucial factor that affects cell behavior, and the mechanical properties of the substrate have been shown to impact differentiation during incubation. In this study, we examine the effect of the mechanical properties of the 3D printed scaffolds, made using different concentrations of cross-linker, on hMSCs differentiation towards chondrogenesis. @*METHODS@#The 3D scaffold was fabricated using 3D bioprinting technology with gelatin/hyaluronic acid (HyA) biomaterial ink. Crosslinking was achieved by using different concentrations of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methlymorpholinium chloride n-hydrate (DMTMM), allowing for control of the scaffold’s mechanical properties. The printability and stability were also evaluated based on the concentration of DMTMM used. The effects of the gelatin/HyA scaffold on chondrogenic differentiation was analyzed by utilizing various concentrations of DMTMM. @*RESULTS@#The addition of HyA was found to improve the printability and stability of 3D printed gelatin/HyA scaffolds.The mechanical properties of the 3D gelatin/HyA scaffold could be regulated through the use of different concentrations of DMTMM cross-linker. In particular, the use of 0.25 mM DMTMM for crosslinking the 3D gelatin/HyA scaffold resulted in enhanced chondrocyte differentiation. @*CONCLUSION@#The mechanical properties of 3D printed gelatin/HyA scaffolds cross-linked using various concentrations of DMTMM can influence the differentiation of hMSCs into chondrocytes.
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BACKGROUND@#Cryopreservation can cause mechanical and chemical stress, ultimately leading to the formation of reactive oxygen species (ROS) and oxidative stress. ROS inhibits the expression of antioxidant enzymes in cells, resulting in increased DNA fragmentation and apoptosis. In this paper, we used a vitrification method that has the advantage of producing less ice crystal formation, cost-effectiveness, and time efficiency during cryopreservation. The objective of this paper is to evaluate the degree of protection of ovarian tissue against oxidative stress when N-acetylcysteine (NAC) and Klotho proteins are treated in the vitrification process of ovarian tissue. @*METHODS@#The control group and the cryopreservation groups were randomly assigned, and treated NAC, Klotho, or the combination (NAC ? Klotho). The cell morphological change, DNA damage, senescence, and apoptosis of each group after the freeze–thaw process were compared using transmission electron microscopy, immunohistochemistry, and western blot analysis. @*RESULTS@#Both NAC and Klotho were found to be more effective at protecting against DNA damage than the control;however, DNA damage was greater in the NAC ? Klotho group than in the group treated with NAC and Klotho, respectively. DNA damage and cellular senescence were also reduced during the vitrification process when cells were treated with NAC, Klotho, or the combination (NAC ? Klotho). NAC increased apoptosis during cryopreservation, whereas Klotho inhibited apoptosis and NAC-induced apoptosis. @*CONCLUSION@#This study highlights Klotho’s benefits in inhibiting DNA damage, cell senescence, and apoptosis, including NAC-induced apoptosis, despite its unclear role in vitrification.
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Background@#A paucity of data addressing real-world treatment of myopic choroidal neovascularization (mCNV) in the era of anti-vascular endothelial growth factor (VEGF) drugs led us to investigate real-world treatment intensity and treatment patterns in patients with mCNV. @*Methods@#This is a retrospective, observational study using the Observational Medical Outcomes Partnership-Common Data Model database of treatment-naïve patients with mCNV over the 18-year study period (2003–2020). Outcomes were treatment intensity (time trends of total/average number of prescriptions, mean number of prescriptions in the first year and the second year after initiating treatment, proportion of patients with no treatment in the second year) and treatment patterns (subsequent patterns of treatment according to the initial treatment). @*Results@#Our final cohort included 94 patients with at-least 1-year observation period. Overall, 96.8% of patients received anti-VEGF drugs as first-line treatment, with most of injections from bevacizumab. The number of anti-VEGF injections in each calendar year showed an increasing trend over time; however, there was a drop in the mean number of injections in the second year compared to the first year from 2.09 to 0.47. About 77% of patients did not receive any treatment in their second year of treatment regardless of drugs. Most of patients (86.2%) followed non-switching monotherapy only and bevacizumab was the most popular choice either in the first-line (68.1%) or in the second-line (53.8%) of treatment. Aflibercept was increasingly used as the first-line treatment for patients with mCNV. @*Conclusion@#Anti-VEGF drugs have become the treatment of choice and second-line treatment for mCNV over the past decade. Anti-VEGF drugs are effective for the treatment of mCNV as the non-switching monotherapy is the main treatment regimen in most cases and the number of treatments decreases significantly in the second year of treatment.
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Purpose@#To investigate the radiologic and clinical outcomes of direct internal fixation for unstable atlas fractures. @*Materials and Methods@#This retrospective study included 12 patients with unstable atlas fractures surgically treated using C1 lateral mass screws, rods, and transverse connector constructs. Nine lateral mass fractures with transverse atlantal ligament (TAL) avulsion injury and three 4-part fractures with TAL injury (two avulsion injuries, one TAL substance tear) were treated. Radiologic outcomes included the anterior atlantodental interval (AADI) in flexion and extension cervical spine lateral radiographs at 6 months and 1 year after treatment. CT was also performed to visualize bony healing of the atlas at 6 months and 1 year. Visual Analog Scale (VAS) scores for neck pain, Neck Disability Index (NDI) values, and cervical range of motion (flexion, extension, and rotation) were recorded at 6 months after surgery. @*Results@#The mean postoperative extension and flexion AADIs were 3.79±1.56 (mean±SD) and 3.13±1.01 mm, respectively. Then mean AADI was 3.42±1.34 and 3.33±1.24 mm at 6 months and 1 year after surgery, respectively. At 1 year after surgery, 11 patients showed bony healing of the atlas on CT images. Only one patient underwent revision surgery 8 months after primary surgery due to nonunion and instability findings. The mean VAS score for neck pain was 0.92±0.99, and the mean NDI value was 8.08±5.70. @*Conclusion@#C1 motion-preserving direct internal fixation technique results in good reduction and stabilization of unstable atlas fractures. This technique allows for the preservation of craniocervical and atlantoaxial motion.
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A case of a 30-year-old man who was admitted following a penetrating neck injury is presented. A clinical examination and operative findings identified semi-comatose mentality, neck muscle laceration, and transection of the left common carotid and vertebral arteries and the internal jugular vein. During the operation, the carotid arteries were repaired by interposition grafting, and the internal jugular vein was ligated. The vertebral artery was managed by interventional embolization. Although the patient had some neurological deficit, he was discharged on postoperative Day 52. This surgical case prompted a discussion regarding neurological outcomes, and surgical and endovascular treatment following vascular neck injury.
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Purpose@#The aim of this study was to investigate the relationship between the anatomical location of thrombi in the lower extremities and the development of pulmonary embolism (PE). @*Materials and Methods@#We collected and analyzed the data of patients diagnosed with deep vein thrombosis (DVT) of the lower extremities between 2006 and 2015, and included those whose computed tomography (CT) data were available for PE identification. We evaluated the relationship between the laterality and the proximal/distal location of the thrombi in lower extremites and the location of PE. @*Results@#CT images were available for 388/452 patients with DVT. After excluding 32 cases with bilateral involvement, 356 cases were included for analysis in this study. The ratio of DVT in the left:right leg was 232:124. PEs developed in 121 (52.2%) patients with left-sided DVT and in 78 (62.9%) with right-sided DVT (P=0.052). PEs in the main pulmonary arteries developed in 36 (15.5%) patients with left leg DVT and in 30 (24.2%) with right leg DVT (P=0.045). The most frequent site of thrombosis associated with the development of PE was the left iliac vein (59/199, 29.6%). According to the anatomical segment of the leg affected by DVT, patients with DVT in the right femoral vein (50/71, 70.4%; P=0.016) had the highest rate of occurrence of PE. @*Conclusion@#PE develops more frequently in patients with right-sided DVT than in those with left-sided DVT. Therefore, careful observation for the possible development of PE is recommended in cases with right-sided DVT of the lower extremity.
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This report provides a detailed description of the methodology for ophthalmic examinations according to the Korea National Health and Nutrition Examination Survey (KNHANES) VII and VIII (from 2017 to 2021). The KNHANES is a nationwide survey which has been performed since 1998 in representatives of whole Korean population. During the KNHANES VII and VIII, in addition to the ophthalmic questionnaire, intraocular pressure measurement, visual field test, auto refractometry, axial length and optical coherence tomography measurements were included. This new survey will provide not only provide normative and pathologic ophthalmic data including intraocular pressure, refractive error, axial length, visual field and precise measurement of anterior segment, macula and optic nerve with optical coherence tomography, but also a more accurate diagnosis for major adult blindness diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, and other ocular diseases, for the national Korean population.
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Objective@#To gather the opinions of hands-on workers for successful introduction of the Development Safety Update Report (DSUR) according to a five-year comprehensive plan for clinical trial development [Ministry of Food and Drug Safety, 2019]. @*Methods@#We conducted a survey on considerations that industry stakeholders may have related to the enforcement of the DSUR. A questionnaire was distributed among pharmacovigilance specialists from 13 pharmaceutical companies in South Korea on June 4, 2020. The questionnaire comprised two sections: 1) current status of the Drug Safety Data Management System and 2) considerations on the implementation and management of the DSUR. @*Results@#All respondents have agreed the introduction of DSUR is inevitable for regulatory harmonization and safety of trial subject. However, most respondents (85%) felt concern about additional workload with DSUR implementation. They answered that format and operation system of DSUR should be harmonized with those of international standards and authorities need to minimize double burden due to related report. @*Conclusion@#All respondents asserted that domestic DSUR should be harmonized with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E2F guidelines. Respondents from global companies also suggested regulatory authorities allow DSUR written in English to replace Korean version considering their deadline for submission.Moreover, every respondent agreed regulatory authorities need delicate effort when implementing mandatory submission of DSUR to ensure that even small pharmaceutical companies with no experience in DSUR can comply with the system.
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Purpose@#The aim of this study was to investigate the relationship between the anatomical location of thrombi in the lower extremities and the development of pulmonary embolism (PE). @*Materials and Methods@#We collected and analyzed the data of patients diagnosed with deep vein thrombosis (DVT) of the lower extremities between 2006 and 2015, and included those whose computed tomography (CT) data were available for PE identification. We evaluated the relationship between the laterality and the proximal/distal location of the thrombi in lower extremites and the location of PE. @*Results@#CT images were available for 388/452 patients with DVT. After excluding 32 cases with bilateral involvement, 356 cases were included for analysis in this study. The ratio of DVT in the left:right leg was 232:124. PEs developed in 121 (52.2%) patients with left-sided DVT and in 78 (62.9%) with right-sided DVT (P=0.052). PEs in the main pulmonary arteries developed in 36 (15.5%) patients with left leg DVT and in 30 (24.2%) with right leg DVT (P=0.045). The most frequent site of thrombosis associated with the development of PE was the left iliac vein (59/199, 29.6%). According to the anatomical segment of the leg affected by DVT, patients with DVT in the right femoral vein (50/71, 70.4%; P=0.016) had the highest rate of occurrence of PE. @*Conclusion@#PE develops more frequently in patients with right-sided DVT than in those with left-sided DVT. Therefore, careful observation for the possible development of PE is recommended in cases with right-sided DVT of the lower extremity.
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This report provides a detailed description of the methodology for ophthalmic examinations according to the Korea National Health and Nutrition Examination Survey (KNHANES) VII and VIII (from 2017 to 2021). The KNHANES is a nationwide survey which has been performed since 1998 in representatives of whole Korean population. During the KNHANES VII and VIII, in addition to the ophthalmic questionnaire, intraocular pressure measurement, visual field test, auto refractometry, axial length and optical coherence tomography measurements were included. This new survey will provide not only provide normative and pathologic ophthalmic data including intraocular pressure, refractive error, axial length, visual field and precise measurement of anterior segment, macula and optic nerve with optical coherence tomography, but also a more accurate diagnosis for major adult blindness diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, and other ocular diseases, for the national Korean population.
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Objective@#To gather the opinions of hands-on workers for successful introduction of the Development Safety Update Report (DSUR) according to a five-year comprehensive plan for clinical trial development [Ministry of Food and Drug Safety, 2019]. @*Methods@#We conducted a survey on considerations that industry stakeholders may have related to the enforcement of the DSUR. A questionnaire was distributed among pharmacovigilance specialists from 13 pharmaceutical companies in South Korea on June 4, 2020. The questionnaire comprised two sections: 1) current status of the Drug Safety Data Management System and 2) considerations on the implementation and management of the DSUR. @*Results@#All respondents have agreed the introduction of DSUR is inevitable for regulatory harmonization and safety of trial subject. However, most respondents (85%) felt concern about additional workload with DSUR implementation. They answered that format and operation system of DSUR should be harmonized with those of international standards and authorities need to minimize double burden due to related report. @*Conclusion@#All respondents asserted that domestic DSUR should be harmonized with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E2F guidelines. Respondents from global companies also suggested regulatory authorities allow DSUR written in English to replace Korean version considering their deadline for submission.Moreover, every respondent agreed regulatory authorities need delicate effort when implementing mandatory submission of DSUR to ensure that even small pharmaceutical companies with no experience in DSUR can comply with the system.
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BACKGROUND: To investigate the effects of dipeptidyl peptidase-4 inhibitor (DPP4i) as add-on medications to metformin on progression of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus, compared with sulfonylurea (SU) or thiazolidinedione (TZD). METHODS: We identified 4,447 patients with DPP4i, 6,136 with SU, and 617 with TZD in addition to metformin therapy from the database of Korean National Health Insurance Service between January 2013 and December 2015. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for DR progression. The progression of DR was defined by the procedure code of panretinal photocoagulation, intravitreal injection or vitrectomy; or the addition of diagnostic code of vitreous hemorrhage, retinal detachment, or neovascular glaucoma. RESULTS: The age and sex-adjusted HR of DR progression was 0.74 for DPP4i add-on group compared with SU add-on group (95% confidence interval [CI], 0.62 to 0.89). This lower risk of DR progression remained significant after additional adjustments for comorbidities, duration of metformin therapy, intravitreal injections and calendar index year (HR, 0.80; 95% CI, 0.66 to 0.97). CONCLUSION: This population-based cohort study showed that the use of DPP4i as add-on therapy to metformin did not increase the risk of DR progression compared to SU.
Subject(s)
Humans , Cohort Studies , Comorbidity , Diabetes Mellitus, Type 2 , Diabetic Retinopathy , Dipeptidyl-Peptidase IV Inhibitors , Glaucoma, Neovascular , Hypoglycemic Agents , Intravitreal Injections , Light Coagulation , Metformin , National Health Programs , Retinal Detachment , Vitrectomy , Vitreous HemorrhageABSTRACT
Subject(s)
Female , Humans , Male , Cataract , Diagnosis , Glaucoma, Angle-Closure , Incidence , Korea , National Health Programs , Retrospective StudiesABSTRACT
Calcium deposition disease, including calcific tendinitis, rarely affects the knee joint. Only a few cases can be found in the literatures and there is no case report of symptomatic calcific deposition arising from the posterior cruciate ligament in Korea. The authors encountered a case of symptomatic calcific deposition arising from the posterior cruciate ligament, which was excised arthroscopically and confirmed pathologically. This paper reports this case with a review of the relevant literature.
Subject(s)
Calcinosis , Calcium , Knee Joint , Knee , Korea , Posterior Cruciate Ligament , TendinopathyABSTRACT
PURPOSE: Statins, metformin, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) have been suggested for treating age-related macular degeneration (AMD) due to their pleiotropic effects. Therefore, we investigated whether these drugs prevent AMD. MATERIALS AND METHODS: We conducted a nested case-control study using the Korean National Health Insurance Service database. Using risk-set sampling of age, sex, cohort entry date, and follow-up duration, we identified incident patients with AMD and 10 matching controls in cohorts with diabetes mellitus or cardiovascular diseases. Exposure was assessed within one year before the index date using patient prescription records. We conducted conditional logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between cardiovascular medications and AMD. RESULTS: Our study included 2330 cases and 23278 controls from a cohort of 231274 patients. The ORs (95% CI) for AMD occurrence in users prescribed with statins, metformin, ACE inhibitors, and ARBs were 1.12 (0.94–1.32), 1.15 (0.91–1.45), 0.90 (0.61–1.34), and 1.21 (1.05–1.39), respectively. A duration-response was not observed. CONCLUSION: Statins, metformin, ACE inhibitors, and ARBs did not inhibit AMD in elderly patients. The absence of a duration-response supports the lack of a causal relationship.
Subject(s)
Aged , Humans , Angiotensin II , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Angiotensins , Cardiovascular Diseases , Case-Control Studies , Cohort Studies , Diabetes Mellitus , Follow-Up Studies , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Logistic Models , Macular Degeneration , Metformin , National Health Programs , Odds Ratio , Prescriptions , Receptors, AngiotensinABSTRACT
BACKGROUND: We described a novel multi-step retinal fundus image reading system for providing high-quality large data for machine learning algorithms, and assessed the grader variability in the large-scale dataset generated with this system. METHODS: A 5-step retinal fundus image reading tool was developed that rates image quality, presence of abnormality, findings with location information, diagnoses, and clinical significance. Each image was evaluated by 3 different graders. Agreements among graders for each decision were evaluated. RESULTS: The 234,242 readings of 79,458 images were collected from 55 licensed ophthalmologists during 6 months. The 34,364 images were graded as abnormal by at-least one rater. Of these, all three raters agreed in 46.6% in abnormality, while 69.9% of the images were rated as abnormal by two or more raters. Agreement rate of at-least two raters on a certain finding was 26.7%–65.2%, and complete agreement rate of all-three raters was 5.7%–43.3%. As for diagnoses, agreement of at-least two raters was 35.6%–65.6%, and complete agreement rate was 11.0%–40.0%. Agreement of findings and diagnoses were higher when restricted to images with prior complete agreement on abnormality. Retinal/glaucoma specialists showed higher agreements on findings and diagnoses of their corresponding subspecialties. CONCLUSION: This novel reading tool for retinal fundus images generated a large-scale dataset with high level of information, which can be utilized in future development of machine learning-based algorithms for automated identification of abnormal conditions and clinical decision supporting system. These results emphasize the importance of addressing grader variability in algorithm developments.
Subject(s)
Dataset , Decision Support Systems, Clinical , Diagnosis , Machine Learning , Reading , Retinaldehyde , SpecializationABSTRACT
Mitochondrial targeting is a promising approach for solving current issues in clinical application of chemotherapy and diagnosis of several disorders. Here, we discuss direct conjugation of mitochondrial-targeting moieties to anticancer drugs, antioxidants and sensor molecules. Among them, the most widely applied mitochondrial targeting moiety is triphenylphosphonium (TPP), which is a delocalized cationic lipid that readily accumulates and penetrates through the mitochondrial membrane due to the highly negative mitochondrial membrane potential. Other moieties, including short peptides, dequalinium, guanidine, rhodamine, and F16, are also known to be promising mitochondrial targeting agents. Direct conjugation of mitochondrial targeting moieties to anticancer drugs, antioxidants and sensors results in increased cytotoxicity, anti-oxidizing activity and sensing activity, respectively, compared with their non-targeting counterparts, especially in drug-resistant cells. Although many mitochondria-targeted anticancer drug conjugates have been investigated and , further clinical studies are still needed. On the other hand, several mitochondria-targeting antioxidants have been analyzed in clinical phases I, II and III trials, and one conjugate has been approved for treating eye disease in Russia. There are numerous ongoing studies of mitochondria-targeted sensors.
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Morbidity and mortality rates associated with acute myocardial infarction accompanying chronic total occlusion are comparatively high. European guidelines recommend primary intervention for the causative lesion in patient with acute myocardial infarction. Therefore, it is important to identify the culprit lesion. We report two cases of myocardial infarction with concurrent chronic total occlusion in an emergency setting.
Subject(s)
Humans , Emergencies , Mortality , Myocardial Infarction , Percutaneous Coronary InterventionABSTRACT
Subdural abscess is relatively rare compared with epidural abscess, but it can rapidly progress to complete paraplegia with a poorer outcome. In particular, the occurrence of widespread subdural abscess is extremely rare. We experienced a case of widespread thoracolumbar subdural abscess with infectious spondylodiscitis in the thoracic spine. We report this rare case with a review of relevant literatures.
Subject(s)
Abscess , Discitis , Empyema , Epidural Abscess , Paraplegia , SpineABSTRACT
Mesenchymal stem cells (MSCs), which are multipotent and have self-renewal ability, support the regeneration of damaged normal tissue. A number of external stimuli promote migration of MSCs into peripheral blood and support their participation inwound healing. In an attempt to harness the potential beneficial effects of such external stimuli, we exposed human MSCs (hMSCs) to one such stimulus-low-dose ionizing radiation (LDIR)-and examined their biological properties. To this end, we evaluated differences in proliferation, cell cycle, DNA damage, expression of surface markers (CD29, CD34, CD90, and CD105), and differentiation potential ofhMSCs before and after irradiation with γ-rays generated using a ¹³⁷ CSirradiator.At doses less than 50 mGy, LDIR had no significant effect on the viability or apoptosis of hMSCs. Interestingly, 10 mGyofLDIR increased hMSC viability by 8% (p<0.001) comparedwith non-irradiatedhMSCs.At doses less than 50 mGy, LDIR did not induceDNA damage, including DNA strand breaks, or cause cellular senescence or cell-cycle arrest. Surface marker expression and in vitro differentiation potential of hMSCs were maintained after two exposures to LDIR at 10 mGy per dose. In conclusion, a two-dose exposure to LDIR at 10 mGy per dose not only facilitates proliferation of hMSCs, it alsomaintains the stem cell characteristics of hMSCswithout affecting their viability.These results provide evidence for the potential ofLDIRas an external stimulus for in vitro expansion of hMSCs and application in tissue engineering and regenerative medicine.