Adipose Mesenchymal Stem Cell-Derived Exosomes Promote the Regeneration of Corneal Endothelium Through Ameliorating Senescence.

Purpose: Human corneal endothelial cells (hCECs) have been considered unable to regenerate in vivo, resulting in corneal decompensation after significant loss of hCECs. adipose-derived mesenchymal stem cell (ASC)-derived exosomes can regenerate tissues and organs. In this study, we investigated whether ASC-derived exosomes could protect and regenerate CECs. Methods: We performed cell viability and cell-cycle analyses to evaluate the effect of ASC-derived exosomes on the regeneration capacity of cultured hCECs. Transforming growth factor-ß (TGF-ß) and hydrogen peroxide (H2O2) were used to induce biological stress in CECs. The effect of ASC-derived exosomes on CECs was investigated in vivo. ASC-derived exosomes were introduced into rat CECs using electroporation, and rat corneas were injured using cryoinjury. Next-generation sequencing analysis was performed to compare the differentially expressed microRNAs (miRNAs) between ASC-derived and hCEC-derived exosomes. Results: ASC-derived exosomes induced CEC proliferation and suppressed TGF-ß- or H2O2-induced oxidative stress and senescence. ASC-derived exosomes protect hCECs against TGF-ß- or H2O2-induced endothelial-mesenchymal transition and mitophagy. In an in vivo study, ASC-derived exosomes promoted wound healing of rat CECs and protected the corneal endothelium against cryoinjury-induced corneal endothelium damage. Next-generation sequencing analysis revealed differentially expressed miRNAs for ASC-derived and hCEC-derived exosomes. They are involved in lysine degradation, adherens junction, the TGF-ß signaling pathway, the p53 signaling pathway, the Hippo signaling pathway, the forkhead box O (FoxO) signaling pathway, regulation of actin cytoskeleton, and RNA degradation based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Conclusions: ASC-derived exosomes promoted wound healing and regeneration of endothelial cells by inducing a shift in the cell cycle and suppressing senescence and autophagy.

Comparison of a preservative-free nonsteroidal anti-inflammatory drug and preservative-free corticosteroid after uneventful cataract surgery: multicenter, randomized, evaluator-blinded clinical trial.

PURPOSE: To compare the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) and steroidal eyedrops for inflammation management after cataract surgery using slitlamp indicators. SETTING: 11 eye centers in South Korea. DESIGN: Randomized prospective multicenter study with a blinded evaluator. METHOD: In 125 (250 eyes) patients who underwent cataract surgery, bromfenac sodium hydrate 0.1% (NSAID group) was applied twice a day in 1 eye, whereas the other eye was treated with fluorometholone 0.1% (steroid group), 4 times a day for 4 weeks postoperatively. The primary efficacy outcome was the presence of anterior chamber cells and flare at 1 week postoperatively. Anterior chamber cells and flare at 4 to 8 weeks, corrected distance visual acuity, central corneal thickness, conjunctival hyperemia, dry eye parameters, foveal thickness, and ocular and visual discomfort were evaluated as secondary outcomes. RESULTS: At week 1, residual anterior chamber inflammation was not statistically significantly different between the groups (-1.03 ± 1.27 vs -0.95 ± 1.24, P = .4850). However, the NSAID group recovered from conjunctival hyperemia more rapidly than the steroid group (0.30 ± 0.52 vs 0.44 ± 0.81, P = .0144 at week 1). The increase in central corneal thickness in the NSAID group was less than that in the steroid group 1 week postoperatively (7.87 ± 22.46 vs 29.47 ± 46.60 µm, P < .0001). The change in foveal thickness in the NSAID group was significantly less than that in the steroid group (18.11 ± 68.19 vs 22.25 ± 42.37 µm, P = .0002). Lower levels of postoperative ocular and visual discomfort were reported in the NSAID group than in the steroid group under treatment. CONCLUSIONS: Preservative-free bromfenac was as effective as preservative-free fluorometholone eyedrops in anterior chamber inflammation control and showed better signs and symptoms after cataract surgery.

Development of clinical application program for radiotherapy induced cancer risk calculation using Monte Carlo engine in volumetric-modulated arc therapy.

BACKGROUND: The purpose of this study is to develop a clinical application program that automatically calculates the effect for secondary cancer risk (SCR) of individual patient. The program was designed based on accurate dose calculations using patient computed tomography (CT) data and Monte Carlo engine. Automated patient-specific evaluation program was configured to calculate SCR. METHODS: The application program is designed to re-calculate the beam sequence of treatment plan using the Monte Carlo engine and patient CT data, so it is possible to accurately calculate and evaluate scatter and leakage radiation, difficult to calculate in TPS. The Monte Carlo dose calculation system was performed through stoichiometric calibration using patient CT data. The automatic SCR evaluation program in application program created with a MATLAB was set to analyze the results to calculate SCR. The SCR for organ of patient was calculated based on Biological Effects of Ionizing Radiation (BEIR) VII models. The program is designed to sequentially calculate organ equivalent dose (OED), excess absolute risk (EAR), excess relative risk (ERR), and the lifetime attributable risk (LAR) in consideration of 3D dose distribution analysis. In order to confirm the usefulness of the developed clinical application program, the result values from clinical application program were compared with the manual calculation method used in the previous study. RESULTS: The OED values calculated in program were calculated to be at most approximately 13.3% higher than results in TPS. The SCR result calculated by the developed clinical application program showed a maximum difference of 1.24% compared to the result of the conventional manual calculation method. And it was confirmed that EAR, ERR and LAR values can be easily calculated by changing the biological parameters. CONCLUSIONS: We have developed a patient-specific SCR evaluation program that can be used conveniently in the clinic. The program consists of a Monte Carlo dose calculation system for accurate calculation of scatter and leakage radiation and a patient-specific automatic SCR evaluation program using 3D dose distribution. The clinical application program that improved the disadvantages of the existing process can be used as an index for evaluating a patient treatment plan.

Comparison of Dose Distribution in Regional Lymph Nodes in Whole-Breast Radiotherapy vs. Whole-Breast Plus Regional Lymph Node Irradiation: An In Silico Planning Study in Participating Institutions of the Phase III Randomized Trial (KROG 1701).

The purpose of the current in silico planning study is to compare radiation doses of whole-breast irradiation (WBI) and whole-breast plus regional lymph node irradiation (WBI+RNI) administered to the regional lymph nodes (RLN) in pN1 breast cancer. Twenty-four participating institutions were asked to create plans of WBI and WBI+RNI for two dummy cases. To compare target coverage between the participants, an isodose line equal to 90% of the prescribed dose was converted to an isodose contour (contour90% iso). The relative nodal dose (RND) was obtained using the ratio of RLN dose to the target dose. The Fleiss's kappa values which represent inter-observer agreement of contour90% iso were over 0.68. For RNI, 6 institutions included axillary lymph node (ALN), supraclavicular lymph node (SCN), and internal mammary lymph node (IMN), while 18 hospitals included only ALN and SCN. The median RND between the WBI and WBI+RNI were as follows: 0.64 vs. 1.05 (ALN level I), 0.27 vs. 1.08 (ALN level II), 0.02 vs. 1.12 (ALN level III), 0.01 vs. 1.12 (SCN), and 0.54 vs. 0.82 (IMN). In all nodal regions, the RND was significantly lower in WBI than in WBI+RNI (p < 0.01). In this study, we could identify the nodal dose difference between WBI and WBI+RNI.

Physical activity status in relation to quality of life and dietary habits in breast cancer survivors: subset analyses of KROG 14-09 nationwide questionnaire study.

PURPOSE: We investigated the relationship of physical activity with dietary habits and quality of life (QoL) in breast cancer survivors in accordance with the recommendations of the American Cancer Society. METHODS: Data of 928 breast cancer survivors were obtained from the KROG 14-09 study to measure QoL in early phase after adjuvant radiotherapy. According to the extent of physical activity, survivors were divided into four groups: inactivity (0-149 min/week, N = 144), regular activity (150-450 min/week, N = 309), moderate activity (451-900 min/week, N = 229), and marked activity (901-1800 min/week, N = 164) excluding hyperactivity (> 1800 min/week, N = 82) as it is a difficult condition to recommend to survivors. Global physical activity questionnaire, 5-dimensional questionnaire by EuroQoL (EQ-5D-3L), QoL Questionnaire-breast cancer (QLQ-BR23) from EORTC, and dietary habits were surveyed. A linear-to-linear association test for EQ-5D-3L and Kruskal-Wallis analysis for QLQ-BR23 and dietary habit were conducted. RESULTS: Overall, 15.5% respondents (144/928) were classified as physically inactive. The trends of frequent intake of fruits (p = 0.001) and vegetable (p = 0.005) and reluctance toward fatty food (p < 0.001) were observed in physically active groups. Mobility (p = 0.021) and anxiety (p = 0.030) of EQ-5D-3L, and systemic therapy side effect (p = 0.027) and future perspective (p = 0.008) of QLQ-BR23 were better in physically active groups besides body image (p = 0.003) for the survivors with breast-conserving surgery. However, moderate and marked activities did not further improve QoL than regular activity. CONCLUSION: Physicians and care-givers have to pay attention to inactive survivors to boost their physical activity, thereby facilitating a better QoL and dietary habit.

O-GlcNAc Signaling Augmentation Protects Human Corneal Endothelial Cells from Oxidative Stress via AKT Pathway Activation.

Purpose: To investigate the effect of inhibitor of O-glycosylation on human corneal endothelial cells (HCECs) under oxidative stress.Methods: HCECs were cultured and treated with 10 mM tert-butyl hydroperoxide (tBHP) with or without PUGNAc, a known inhibitor of OGA. Cell viability was assessed. Mitochondrial membrane potential (ΔΨm) was measured. Intracellular Ca2+ levels and mitochondrial Ca2+ levels were measured. Intracellular reactive oxygen species formation was measured. Levels of O-linked ß-N-acetylglucosamine (O-GlcNAc), AKT, and pAKT were evaluated by Western blotting.Results: O-GlcNAc augmentation by PUGNAc increased cell viability, attenuated the loss of ΔΨm, and intracellular ROS against tBHP-induced oxidative stress (p < .05). O-GlcNAc augmentation reduced tBHP-induced mitochondrial calcium overload (p < .05) while it did not have any effect on intracellular calcium overload with tBHP. Furthermore, AKT signaling was activated in the cells with O-GlcNAc augmentation.Conclusions: O-GlcNAc signaling augmentation protects HCECs from oxidative stress via activation of AKT pathways.

Factors affecting the negative predictive value of positron emission tomography/computed tomography for axillary lymph node staging in breast cancer patients.

BACKGROUND/OBJECTIVE: Axillary lymph node staging (ALNS) is an important step in the treatment of breast cancer and sentinel lymph node biopsy (SLNB) is a standard procedure for ALNS. Recently, the use of positron emission tomography/computed tomography (PET/CT) for whole body staging in patients with breast cancer has been increasing. The negative predictive value (NPV) of the specific diagnostic modality is the crucial value for excluding axillary lymph node metastasis (ALNM) and guiding the decision not to proceed with axillary lymph node dissection. The aim of this study was to identify patient groups in which PET/CT yields a high NPV for ALNS. METHODS: We reviewed data from the records of 262 patients with breast cancer who underwent PET/CT before surgery between February 2009 and March 2018. We searched for factors associated with pathological axillary lymph node metastasis in patients with negative ALNM on PET/CT. Then, we calculated the NPV of PET/CT for ALNS in the patient group without the identified factors and in all patients. RESULTS: Age ≥75 years and tumor size on ultrasonography (US) ≥ 15 mm were the associated factors; the NPV of PET/CT in patients without these factors compared to all patients was 97.2% versus 88.7%. CONCLUSION: The NPV of PET/CT for ALNS in patients younger than 75 years and with tumor size on US < 15 mm is higher than that in all patients and comparable to the NPV of SLNB reported in previous studies (90.1-97.0%).

Questionnaire study of the dietary habits of breast cancer survivors and their relationship to quality of life (KROG 14-09).

We evaluated the dietary habits of breast cancer survivors and investigated the relationship with quality of life (QoL), with 1,156 survivors recruited from 17 institutions. We used the Questionnaire Survey of Dietary Habits of Korean Adults (Q-DH-KOR) comprising 25 questions. The following indices were derived as follows: (1) quality of healthy dietary habits (Q-HD)-eight questions on number of meals, regularity, quantity, duration, skipping breakfast, dinner with companion(s), overeating and late-night snacks; (2) habits of nutritional balance (H-NB)-questions on consuming five food categories (grains, fruits, proteins, vegetables and dairy products); and (3) habits of unhealthy foods (H-UF)-questions on consuming three food categories (fatty, instant and fast foods). The times and regularity of meals, frequency of skipping breakfast, dinner with companion(s) and overeating were better in groups with high symptomatic and functional QoL. Symptomatic QoL positively affected Q-HD and H-NB (p < 0.001 and p = 0.024 respectively) and negatively affected H-UF (p = 0.02). Breast cancer survivors more frequently ate from the fruit, protein and vegetable categories than did the control group, with lower H-UF and higher Q-HD values (p < 0.001 and p < 0.001 respectively). Our findings supported the relationship between QoL and dietary habit and showed healthier dietary habits of breast cancer survivors than controls.

SOX2 Activation Using CRISPR/dCas9 Promotes Wound Healing in Corneal Endothelial Cells.

There are no effective treatments for corneal endothelial diseases, except for corneal transplantation, as human corneal endothelial cells (hCECs) do not regenerate. The regeneration of hCECs could be induced through regulation of the expression of specific genes. In this study, we investigated whether the overexpression of sex-determining region Y-box 2 (SOX2) can regenerate hCECs in vivo and in vitro. SOX2 was activated using the clustered regularly interspaced short palindromic repeats (CRISPR)/deactivated CRISPR-associated protein 9 (dCas9) activation system. Genes were transfected into the corneal endothelium of Sprague-Dawley rats. Central corneal thickness and opacity were measured, and alizarin red S staining was performed. Corneal opacity and central corneal thickness were reduced in the SOX2 group compared with the control group. The density of CECs was higher in the SOX2 group compared with the control group. Additionally, hCECs were cultured and analyzed after overexpressing SOX2. Cell viability, proliferation rate, and the number of cells in S-phase were increased after SOX2 overexpression (p < .05). Cyclin-dependent kinase 1 and cyclin D1 were found to be overexpressed (p < .05). WNT signaling was repressed, and the AKT pathway was activated by SOX2 overexpression. Mitochondrial oxidative stress and energy production were increased by SOX2 overexpression (p < .05). In conclusion, SOX2 activation promotes wound healing and regeneration in CECs. SOX2 activation using the CRISPR/dCas9 system may thus be useful for the treatment of hCEC diseases. Stem Cells 2018;36:1851-12.

Utility of the optical quality analysis system for decision-making in cataract surgery.

BACKGROUND: A cataract is a common cause of vision impairment that requires surgery in older subjects. The Optical Quality Analysis System (OQAS, Visiometrics SL, Terrassa, Spain) assesses the optical quality of the eye in cataract patients. This study shows the role of the optical quality evaluation system for decision-making in cataract surgery. We investigated the clinical utility of the OQAS for decision-making in cataract surgery. METHODS: Sixty-seven eyes from 67 patients undergoing cataract surgery and 109 eyes from 109 control subjects were compared. The best corrected visual acuity (BCVA) was measured. The objective scatter index (OSI), modulation transfer function (MTF), Strehl ratio, predicted visual acuity (PVA) 100%, PVA 20%, and PVA 10% were measured using the OQAS. The sensitivity and specificity of the different parameters were analyzed using the receiver operating characteristic (ROC) curve. The main parameters measured were sensitivity and specificity. RESULTS: The BCVA, OSI, PVA 100%, PVA 20%, and PVA 10% were higher in the cataract group compared to those in the control group, while the MTF and Strehl ratios were lower (p <  0.001 for all). ROC analysis showed that the OSI had the largest area under the curve and that the sensitivity and specificity of the OSI were 83.9 and 84.6%, respectively, at the optimal cut-off point of 2.35. CONCLUSION: The MTF, OSI, Strehl ratio, PVA 100%, PVA 20% and PVA 10% may be useful parameters for preoperative decision-making in cataract surgery. The OSI appears to be the most effective parameter for this purpose.

Anticancer and radiosensitizing effects of the cyclin-dependent kinase inhibitors, AT7519 and SNS­032, on cervical cancer.

Cyclin-dependent kinases (CDK) are considered to be potential targets of anticancer drugs that can interrupt the uncontrolled division of cancer cells. In this study, we selected two selective CDK inhibitors, AT7519 and SNS­032, from current clinical trials and examined their anticancer and radiosensitizing effects in a cervical cancer model. SNS­032 was found to be more potent than AT7519, with a lower half maximal inhibitory concentration (IC50) value. Both AT7519 and SNS­032 induced the apoptosis, premature senescence and cytostasis of cervical cancer cells, which led to the attenuation of tumor growth in vivo. Moreover, using these CDK inhibitors together with radiation synergistically inhibited tumor growth in a human xenograft tumor model. The concomitant activation of the p53 tumor suppressor and the suppression of cell cycle checkpoint responses mediated by Chk1 led to the cytostasis of cervical cancer cells. Finally, AT7519 and SNS­032 inhibited cancer cell migration, invasion and angiogenesis in vitro, and suppressed lung metastases in a spontaneous metastasis model. On the whole, the findings of this study indicate that the utilization of AT7519 and SNS­032 as part of an adjuvant treatment may help control cervical cancer progression.

Transcriptional Repression of High-Mobility Group Box 2 by p21 in Radiation-Induced Senescence.

High mobility group box 2 (HMGB2) is an abundant, chromatin-associated, non-histone protein involved in transcription, chromatin remodeling, and recombination. Recently, the HMGB2 gene was found to be significantly downregulated during senescence and shown to regulate the expression of senescent-associated secretory proteins. Here, we demonstrate that HMGB2 transcription is repressed by p21 during radiation-induced senescence through the ATM-p53-p21 DNA damage signaling cascade. The loss of p21 abolished the downregulation of HMGB2 caused by ionizing radiation, and the conditional induction of p21 was sufficient to repress the transcription of HMGB2. We also showed that the p21 protein binds to the HMGB2 promoter region, leading to sequestration of RNA polymerase and transcription factors E2F1, Sp1, and p300. In contrast, NF-Y, a CCAAT box-binding protein complex, is required for the expression of HMGB2, but NF-Y binding to the HMGB2 promoter was unaffected by either radiation or p21 induction. A proximity ligation assay results confirmed that the chromosome binding of E2F1 and Sp1 was inhibited by p21 induction. As HMGB2 have been shown to regulate premature senescence by IR, targeting the p21-mediated repression of HMGB2 could be a strategy to overcome the detrimental effects of radiation-induced senescence.

High tibial osteotomy accelerates lateral compartment osteoarthritis in discoid meniscus patients.

PURPOSE: The valgus high tibial osteotomy (HTO) in patients with medial osteoarthritis and discoid lateral meniscus can result in increased load on the lateral compartment and hence a higher chances of tear. This may accelerate the progression of osteoarthritis on lateral compartment. We, therefore, carried out the case control study with a hypothesis that an HTO would accelerate the progression of osteoarthritis (OA) on lateral compartment in patients with complete discoid meniscus. METHODS: The records of all patients with open wedge HTO from 2008 to 2012 were evaluated for complete lateral discoid meniscus. The patient who had a valgus HTO with or without partial meniscectomy for medial compartmental OA was included for this study. Cases to control were chosen to match age, body mass index (BMI), pre-operative osteoarthritis grade, and deformity angles in ratio 1:2. Patient's records were studied for demographic data, clinical examination records, and pre-operative knee functional scores and radiological scores and were compared with post-operative data. RESULTS: Thirty-six patients out of 674 patients, who underwent an HTO, consisted of discoid meniscus group. 72 patients were chosen as control group. Four patients showed progression of OA on the lateral compartment in discoid group compared to none in control group. Although control groups showed a little bit better functional outcomes, there were no statistical differences between two groups (n.s.). CONCLUSION: The high tibial osteotomy could result in accelerated lateral compartment osteoarthritis in patients with complete discoid meniscus, and the procedure should be used with caution in such patients. LEVEL OF EVIDENCE: IV.

Robotic Total Knee Arthroplasty with a Cruciate-Retaining Implant: A 10-Year Follow-up Study.

BACKGROUND: This study compared clinical and radiological results between robotic total knee arthroplasty (TKA) and conventional TKA with a cruciate-retaining implant at 10-year follow-up. The hypothesis was that robotic TKA would allow for more accurate leg alignment and component placement, and thus enhance clinical and radiological results and long-term survival rates. METHODS: A total of 113 primary TKAs performed using a cruciate-retaining implant in 102 patients from 2004 to 2007 were reviewed retrospectively. Of the 113 TKAs, 71 were robotic TKAs and 42 were conventional TKAs. Clinical outcomes (visual analogue scale pain score, Hospital for Special Surgery score, Western Ontario and McMaster University score, range of motion, and complications), radiological outcomes, and long-term survival rates were evaluated at a mean follow-up of 10 years. RESULTS: Clinical outcomes and long-term survival rates were similar between the two groups. Regarding the radiological outcomes, the robotic TKA group had significantly fewer postoperative leg alignment outliers (femoral coronal inclination, tibial coronal inclination, femoral sagittal inclination, tibial sagittal inclination, and mechanical axis) and fewer radiolucent lines than the conventional TKA group. CONCLUSIONS: Both robotic and conventional TKAs resulted in good clinical outcomes and postoperative leg alignments. Robotic TKA appeared to reduce the incidence of leg alignment outliers and radiolucent lines compared to conventional TKA.

An assessment of quality of life for early phase after adjuvant radiotherapy in breast cancer survivors: a Korean multicenter survey (KROG 14-09).

BACKGROUNDS: Quality of life (QoL) has become a major concern as the survival time of breast cancer increases. We investigated the changes in QoL through comprehensive categorical analysis, for the first three years after breast cancer treatment including radiotherapy. METHODS: A total of 1156 patients were enrolled from 17 institutions. All survivors were grouped according to a surveillance period of 9-15 months (first year), 21-27 months (second year), and 33-39 months (third year) from the end of radiotherapy. The 5-dimensional questionnaire by the EuroQol group (EQ-5D) and the EORTC Quality of Life Questionnaire; breast cancer specific module (QLQ-BR23) were checked by self-administrated method. RESULTS: First, second and third year groups comprised 51.0, 28.9, and 21.0%. In EQ-5D-3 L (3-Likert scale) analysis, pain/discomfort and anxiety/depression categories showed lower QoL. In multivariate analyses of EQ-5D-VAS (visual-analogue scale), categories of pain/discomfort and self-care were improved with time; axillary dissection was a significant clinical factor deteriorates pain/discomfort, self-care and usual activities. In QLQ-BR23 analysis, the lowest scored category was sexual activity, followed by sexual enjoyment, future perspective, and hair loss, and the best scored category was breast symptoms. In multivariate analyses, arm symptoms, breast symptoms and body image were improved with time. CONCLUSIONS: Categories of pain/discomfort and self-care in EQ-5D-VAS, arm/breast symptoms and body image in QLQ-BR23 were improved, while categories of anxiety/depression and future perspective BR23 were not, suggesting necessity of psychosocial support. This research provides comprehensive information on the categorical aspects of QoL and changes during early follow-up after breast cancer treatment.

Effects of chalazia on corneal astigmatism : Large-sized chalazia in middle upper eyelids compress the cornea and induce the corneal astigmatism.

BACKGROUND: A chalazion is a common eyelid disease that causes eye morbidity due to inflammation and cosmetic disfigurement. Corneal topographic changes are important factors in corneal refractive surgery, intraocular lens power calculations for cataract surgery, and visual acuity assessments. However, the effects of chalazia on corneal astigmatism have not been thoroughly investigated. The changes in corneal astigmatism according to chalazion size and location is necessary for better outcome of ocular surgery. The aim of this study is to evaluate changes in corneal astigmatism according to chalazion size and location. METHODS: In this cross-sectional study, a total of 44 eyes from 33 patients were included in the chalazion group and 70 eyes from 46 patients comprised the control group. Chalazia were classified according to location and size. An autokeratorefractometer (KR8100, Topcon; Japan) and a Galilei™ dual-Scheimpflug analyzer (Ziemer Group; Port, Switzerland) were utilized to evaluate corneal changes. RESULT: Oblique astigmatism was greater in the chalazion group compared with the control group (p < 0.05). Astigmatism by simulated keratometry (simK), steep K by simK, total root mean square, second order aberration, oblique astigmatism, and vertical astigmatism were significantly greater in the upper eyelid group (p < 0.05). Astigmatism by simK, second order aberration, oblique astigmatism, and vertical astigmatism were significantly greater in the large-sized chalazion group (p < 0.05). Corneal wavefront aberration was the greatest in the upper eyelid chalazion group, whole area group, and large-sized chalazion group (p < 0.05). CONCLUSIONS: Large-sized chalazia in the whole upper eyelid should be treated in the early phase because they induced the greatest change in corneal topography. Chalazion should be treated before corneal topography is performed preoperatively and before the diagnosis of corneal diseases.

Causes of Aseptic Persistent Pain after Total Knee Arthroplasty.

BACKGROUND: Persistent pain after total knee arthroplasty (TKA) is dissatisfying to the patient and frustrating to the surgeon. The purpose of this study is to evaluate the aseptic causes and clinical course of intractable pain following TKA. METHODS: Of the total 2,534 cases of primary TKA reviewed, 178 cases were classified as having aseptic persistent pain that was not resolved within 1 year after surgery. Except for the cases with periprosthetic fracture (56 knees), 122 cases of aseptic painful TKA were divided into two groups: intra-articular group (83 knees) and extra-articular group (39 knees). RESULTS: In the intra-articular group, the main reasons for pain were aseptic loosening (n = 40), polyethylene wear (n = 16), instability (n = 10), recurrent hemarthrosis (n = 5), patellar maltracking (n = 4), tendon ruptures (n = 4), and stiffness (n = 2). In the extraarticular group, 10 knees (25.6%) were found to have nerve entrapment in the spine, 6 knees (15.4%) were found to have hip osteoarthritis or femoral head avascular necrosis. The reasons for persistent knee pain in the remaining 23 knees (59.0%) still remain elusive. CONCLUSIONS: Persistent pain after TKA originated from pathology of extra-articular origin in a considerable number of cases in this study. Therefore, it is important to perform thorough preoperative evaluations to reduce pain resulting from extra-articular causes. Furthermore, meticulous surgical procedures and optimal alignment are required to reduce pain of intra-articular origin related to implant wear, instability, and patellar maltracking.

Predictors of Recurrent Ductal Carcinoma In Situ after Breast-Conserving Surgery.

PURPOSE: Local recurrence is a major concern in patients who have undergone surgery for ductal carcinoma in situ (DCIS). The present study assessed whether the expression levels of hormone receptors, human epidermal growth factor receptor 2 (HER2), and Ki-67, as well as resection margin status, tumor grade, age at diagnosis, and adjuvant hormonal therapy and radiotherapy (RT) are associated with recurrence in women with DCIS. METHODS: In total, 111 patients with DCIS were included in the present study. The invasive and noninvasive recurrence events were recorded. The clinicopathological features; resection margins; administration of hormonal therapy and RT; expression statuses of estrogen receptor (ER), progesterone receptor (PR), and HER2; Ki-67 expression; and molecular subtypes were evaluated. Logistic regression analysis was performed to examine the risk factors for recurrence. RESULTS: Recurrence was noted in 27 of 111 cases (24.3%). Involvement of resection margins, low tumor grade, high Ki-67 expression, and RT were independently associated with an increase in the recurrence rate (p<0.05, Pearson chi-square test). The recurrence rate was not significantly associated with patient age; ER, PR, and HER2 statuses; molecular subtype; and hormonal therapy. CONCLUSION: The results of the present study suggested that the involvement of resection margins, low tumor grade, high Ki-67 index, and the absence of adjuvant RT were independently associated with increased recurrence in patients with DCIS. Future studies should be conducted in a larger cohort of patients to further improve the identification of patients at high-risk for DCIS recurrence.

Oxidative Stress Levels in Aqueous Humor from High Myopic Patients.

PURPOSE: To compare oxidative stress status in the aqueous humor of highly myopic eyes and control eyes. METHODS: Aqueous humor samples were collected from 15 highly myopic eyes (high myopia group) and 23 cataractous eyes (control group) during cataract surgery. Central corneal thickness, corneal endothelial cell density, hexagonality of corneal endothelial cells, and cell area of corneal endothelial cells were measured using specular microscopy. Axial length was measured using ultrasound biometry. 8-Hydroxydeoxyguanosine (8-OHdG) and malondialdehyde levels were measured using enzyme-linked immunosorbent assay. RESULTS: 8-OHdG level was lower in the aqueous humor of myopic patients than in that of control group (p = 0.014) and was positively correlated with central corneal thickness and negatively correlated with axial length (r = 0.511, p = 0.02; r = -0.382, p < 0.001). There was no correlation between 8-OHdG level and corneal endothelial cell density, hexagonality, or cell area. Malondialdehyde level did not show any correlation with any parameters evaluated. CONCLUSIONS: 8-OHdG might be a sensitive biomarker for evaluating oxidative stress status in the eye. Oxidative stress level was lower in the aqueous humor of highly myopic eyes compared to that in control eyes, which indicates lower metabolic activity in these eyes.

Lanatoside C suppressed colorectal cancer cell growth by inducing mitochondrial dysfunction and increased radiation sensitivity by impairing DNA damage repair.

Cardiac glycosides are clinically used for cardiac arrhythmias. In this study, we investigated the mechanism responsible for anti-cancer and radiosensitizing effects of lanatoside C in colorectal cancer cells. Lanatoside C-treated cells showed classic patterns of autophagy, which may have been caused by lanatoside C-induced mitochondrial aggregation or degeneration. This mitochondrial dysfunction was due to disruption of K+ homeostasis, possibly through inhibition of Na+/K+-ATPase activity. In addition, lanatoside C sensitized HCT116 cells (but not HT-29 cells) to radiation in vitro. γ-H2AX, a representative marker of DNA damage, were sustained longer after combination of irradiation with lanatoside C, suggesting lanatoside C impaired DNA damage repair processes. Recruitment of 53BP1 to damaged DNA, a critical initiation step for DNA damage repair signaling, was significantly suppressed in lanatoside C-treated HCT116 cells. This may have been due to defects in the RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A that increases 53BP1 recruitment to DNA damage sites. Although lanatoside C alone reduced tumor growth in the mouse xenograft tumor model, combination of lanatoside C and radiation inhibited tumor growth more than single treatments. Thus, lanatoside C could be a potential molecule for anti-cancer drugs and radiosensitizing agents.