Osteonecrosis of the femoral head (ONFH) is a devastating disease frequently leading to femoral head collapse and hip arthritis. Specifically, non-traumatic ONFH primarily affects young and middle-aged adults. Although compromised local circulation of the femoral head seems to be pathognomonic for the disease, the pathogenesis is perplexing and continues to be an area of scrutiny and research. Comprehension of the pathogenesis is of crucial importance for developing and guiding treatments for the disease. Therefore, we provide an up-to-date consensus on the pathogenesis of non-traumatic ONFH.

Osteonecrosis of the femoral head (ONFH) is a devastating disease frequently leading to femoral head collapse and hip arthritis. Specifically, non-traumatic ONFH primarily affects young and middle-aged adults. Although compromised local circulation of the femoral head seems to be pathognomonic for the disease, the pathogenesis is perplexing and continues to be an area of scrutiny and research. Comprehension of the pathogenesis is of crucial importance for developing and guiding treatments for the disease. Therefore, we provide an up-to-date consensus on the pathogenesis of non-traumatic ONFH.

Purpose: Pharmacological inhibition of mutant isocitrate dehydrogenase (IDH) reduces R-2-hydroxyglutarate (2-HG) levels and restores cellular differentiation in vivo and in vitro. The IDH2 inhibitor enasidenib (AG-221) has been approved by the FDA as a first-in-class inhibitor for the treatment of relapsed or refractory (R/R) IDH2-mutant acute myeloid leukemia (AML). In this study,the effects of a combination of all-trans retinoic acid (ATRA) and AG-221 on AML cell differentiation was explored, along with the mechanisms employed by IDH2-mutant cells in AML. Materials and Methods: We treated the human AML cell line, IDH2-mutant-TF-1, and primary human AML cells carrying IDH2 mutation with 30 μM AG-221 and 100 nM ATRA, alone or in combination. Results: Combined treatment with AG-221 and ATRA inhibited 2-HG production and resulted in synergistic effects on differentiation among IDH2-mutant AML cells and primary AML cells expressing IDH2 mutation. Combined treatment with AG-221 and ATRA altered autophagic activity. AG-221 and ATRA treatment-induced differentiation of IDH2-mutant AML cells was associated with autophagy induction, without suppressing autophagy flux at maturation and degradation stages. A RAF-1/MEK/ERK pathway was founded to be associated with AG-221 and ATRA-induced differentiation in IDH2-mutant AML cells. IDH-associated changes in histone methylation markers decreased after AG-221 and ATRA combination treatment. Conclusion Our preliminary evidence indicates that the addition of ATRA to treatments with IDH2 inhibitor may lead to further improvements or increases in response rates in IDH2-mutant AML patients who do not appear to benefit from treatments with IDH2 inhibitor alone.

Clinical remounting of complete denture is performed to refine occlusal harmony in maxillo-mandibular relation. It has been reported that patients who used adjusted dentures with clinical remounting felt less complications such as pain and discomfort in mastication. The purpose of this study was to assess effects of clinical remounting with case series. Seven patients with existing complete prosthesis were included. Clinical remounting procedure was done through interocclusal relation recording. In addition, occlusal force was measured with pressure indicating sensor and occlusal contact areas were evaluated with photo occlusion analysis. Occlusal contact areas of prosthesis were enlarged, while bite pressure was not increased. Hit and slide phenomenon of prosthesis was reduced concurrently. Clinical remounting procedure improved denture stability and increased occlusal contact area. Therefore, clinical remounting should be considered.

BACKGROUND: Tumor markers are useful for detection and preoperative evaluation of ovarian tumors. We evaluated the clinical usefulness of cancer antigen (CA) 125, human epididymis 4 (HE4), and CA72-4 levels and Risk of Ovarian Malignancy Algorithm (ROMA) values for differential diagnosis of malignant and borderline tumors among suspected ovarian tumors, and the effects of endometriosis on these tumor markers. METHODS: In a total of 266 patients (213, 14, and 39 with benign, borderline and malignant tumors, respectively), CA125, HE4, and CA72-4 levels were measured, and ROMA values were calculated. Medians of each marker were compared among the three groups. The area under the ROC curve (AUC), sensitivity, and specificity were calculated to analyze the diagnostic performance of each marker. RESULTS: All markers were significantly higher in the malignant group than in the benign group. HE4 levels and ROMA values were significantly higher in the malignant group than in the borderline group. ROMA value had the highest AUC for distinguishing the malignant and borderline groups from the benign group in premenopausal (0.773) and postmenopausal (0.927) patients. CA125 level was significantly higher in patients with endometriosis than in those without (P<0.001), whereas HE4 and CA72-4 levels were not affected by endometriosis (P=0.128 and 0.271, respectively). CONCLUSIONS ROMA value is the best marker to distinguish malignant and borderline tumors from benign tumors in pre- and postmenopausal patients. HE4 and CA72-4 levels provide information on possible CA125 elevation due to endometriosis.

PURPOSE: Dexrazoxane has been used as an effective cardioprotector against anthracycline cardiotoxicity. This study intended to analyze cardioprotective efficacy and secondary malignancy development, and elucidate risk factors for secondary malignancies in dexrazoxane-treated pediatric patients. MATERIALS AND METHODS: Data was collected from 15 hospitals in Korea. Patients who received any anthracyclines, and completed treatment without stem cell transplantation were included. For efficacy evaluation, the incidence of cardiac events and cardiac event-free survival rates were compared. Data about risk factors of secondary malignancies were collected. RESULTS: Data of total 1,453 cases were analyzed; dexrazoxane with every anthracyclines group (D group, 1,035 patients) and no dexrazoxane group (non-D group, 418 patients). Incidence of the reported cardiac events was not statistically different between two groups; however, the cardiac event-free survival rate of patients with more than 400 mg/m2 of anthracyclines was significantly higher in D group (91.2% vs. 80.1%, p=0.04). The 6-year cumulative incidence of secondary malignancy was not different between both groups after considering follow-up duration difference (non-D, 0.52%±0.37%; D, 0.60%±0.28%; p=0.55). The most influential risk factor for secondary malignancy was the duration of anthracycline administration according to multivariate analysis. CONCLUSION: Dexrazoxane had an efficacy in lowering cardiac event-free survival rates in patients with higher cumulative anthracyclines. As a result of multivariate analysis for assessing risk factors of secondary malignancy, the occurrence of secondary malignancy was not related to dexrazoxane administration.
Anthracyclines ; Cardiotoxicity ; Dexrazoxane ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Incidence ; Korea ; Multivariate Analysis ; Neoplasms, Second Primary ; Risk Factors* ; Stem Cell Transplantation

BACKGROUND AND OBJECTIVES: Diffuse long coronary artery disease (DLCAD) still has unfavorable clinical outcomes after successful percutaneous coronary intervention (PCI). Therefore, we aimed to evaluate the effectiveness and safety of Resolute™ zotarolimus-eluting stent (R-ZES; Resolute™ Integrity) for patients with DLCAD. METHODS: From December 2011 to December 2014, 1,011 patients who underwent PCI using R-ZES for CAD with longer than 25 mm lesion were prospectively enrolled from 21 hospitals in Korea. We assessed the clinical outcome of major adverse cardiac events (MACE) defined as the composite of cardiac death, non-fatal myocardial infarction (MI), and clinically-driven target vessel revascularization at 12 months. RESULTS: Mean age was 63.8±10.8 years, 701 (69.3%) patients were male, 572 (87.0%) patients had hypertension, 339 (33.8%) patients had diabetes, 549 (54.3%) patients diagnosed with acute MI and 545 (53.9%) patients had multi-vessel disease (MVD). A total of 1,697 stents were implanted into a total of 1,472 lesions. The mean diameter was 3.07±0.38 mm and the length was 28.27±6.97 mm. Multiple overlapping stents were performed in 205 (13.8%) lesions. A 12-month clinical follow-up was available in 1,004 patients (99.3%). The incidences of MACE and definite stent thrombosis at 12-month were 3.0% and 0.3% respectively. On multivariate Cox-regression analysis, multiple overlapping stents implantation, previous congestive heart failure, MVD, and age ≥75 years were independent predictors of one-year MACE. CONCLUSIONS: Our study shows that R-ZES has an excellent 1-year clinical outcome in Korean patients with DLCAD.
Coronary Artery Disease ; Coronary Vessels ; Death ; Drug-Eluting Stents ; Follow-Up Studies ; Heart Failure ; Humans ; Hypertension ; Incidence ; Korea ; Male ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Prospective Studies ; Stents ; Thrombosis ; Treatment Outcome

BACKGROUND AND OBJECTIVES: Diffuse long coronary artery disease (DLCAD) still has unfavorable clinical outcomes after successful percutaneous coronary intervention (PCI). Therefore, we aimed to evaluate the effectiveness and safety of Resolute™ zotarolimus-eluting stent (R-ZES; Resolute™ Integrity) for patients with DLCAD. METHODS: From December 2011 to December 2014, 1,011 patients who underwent PCI using R-ZES for CAD with longer than 25 mm lesion were prospectively enrolled from 21 hospitals in Korea. We assessed the clinical outcome of major adverse cardiac events (MACE) defined as the composite of cardiac death, non-fatal myocardial infarction (MI), and clinically-driven target vessel revascularization at 12 months. RESULTS: Mean age was 63.8±10.8 years, 701 (69.3%) patients were male, 572 (87.0%) patients had hypertension, 339 (33.8%) patients had diabetes, 549 (54.3%) patients diagnosed with acute MI and 545 (53.9%) patients had multi-vessel disease (MVD). A total of 1,697 stents were implanted into a total of 1,472 lesions. The mean diameter was 3.07±0.38 mm and the length was 28.27±6.97 mm. Multiple overlapping stents were performed in 205 (13.8%) lesions. A 12-month clinical follow-up was available in 1,004 patients (99.3%). The incidences of MACE and definite stent thrombosis at 12-month were 3.0% and 0.3% respectively. On multivariate Cox-regression analysis, multiple overlapping stents implantation, previous congestive heart failure, MVD, and age ≥75 years were independent predictors of one-year MACE. CONCLUSIONS Our study shows that R-ZES has an excellent 1-year clinical outcome in Korean patients with DLCAD.

BACKGROUND/OBJECTIVES: Benign prostatic hypertrophy (BPH) is a major cause of abnormal overgrowth of the prostate mainly in the elderly. Corni Fructus has been reported to be effective in the prevention and treatment of various diseases because of its strong antioxidant effect, but its efficacy against BPH is not yet known. This study was designed to evaluate the therapeutic efficacy of Corni Fructus water extract (CF) in testosterone-induced BPH rats. MATERIALS/METHODS: To induce BPH, rats were intraperitoneal injected with testosterone propionate (TP). Rats in the treatment group were orally administered with CF with TP injection, and finasteride, which is a selective inhibitor of 5α-reductase type 2, was used as a positive control. RESULTS: Our results showed that the increased prostate weight and histopathological changes in BPH model rats were suppressed by CF treatment. CF, similar to the finasteride-treated group, decreased the levels of testosterone and dihydrotestosterone by TP treatment in the serum, and it also reduced 5α-reductase expression and concentration in prostate tissue and serum, respectively. In addition, CF significantly blocked the expression of the androgen receptor (AR), AR co-activators, and proliferating cell nuclear antigen in BPH rats, and this blocking was associated with a decrease in prostate-specific antigen levels in serum and prostate tissue. CONCLUSIONS: These results suggest that CF may weaken the BPH status through the inactivation of at least 5α-reductase and AR activity and may be useful for the clinical treatment of BPH.
Aged ; Animals ; Antioxidants ; Cornus* ; Dihydrotestosterone ; Finasteride ; Humans ; Proliferating Cell Nuclear Antigen ; Prostate ; Prostate-Specific Antigen ; Prostatic Hyperplasia* ; Rats* ; Receptors, Androgen* ; Testosterone ; Testosterone Propionate ; Water

BACKGROUND: Hip pain is a common musculoskeletal complaint in general practice. Although comprehensive diagnostic approach on hip pain is mandatory for adequate treatment, un- or mis-diagnosis is not rare in primary care. The aim of this study was to analyze descriptively un- or mis-diagnosed hip pain cases referred from primary care to a tertiary hospital, especially in young adults ≤ 50 years old. METHODS: We retrospectively analyzed a consecutive cohort of 150 patients (≤ 50 years old) with chronic hip pain (≥ 6 weeks), which was not diagnosed or misdiagnosed based on the information provided on the referral form. RESULTS: Overall an average 32 cases/month were referred due to hip pain without a diagnosis or with an incorrect diagnosis. Among them, 150 patients were enrolled in this study and 146 (97.3%) could be allocated to a specific disease by using data from routine clinical practice. Four common final diagnoses were femoroacetabular impingement (FAI) syndrome (55.3%), hip dysplasia (HD, 13.3%), referred pain from the lumbar spine (9.3%), and spondyloarthritis (SpA, 7.3%). In patients with FAI syndrome, 37 (44.0%) had pincer-type FAI and 33 (39.8%) had combined-type. Although the pain site or gender was not tightly clustered, the distribution of final diagnosis was significantly different according to hip pain location or gender. Especially, SpA or HD was not observed in younger women subgroup or elder men subgroup, respectively, when stratified by the mean age of participants. CONCLUSION: Most (> 80%) young patients with hip pain, a difficult issue to diagnosis for many primary physicians, had FAI syndrome, HD, spine lesions, and SpA. This study could give a chance to feedback information about cases with un- or mis-diagnosed hip pain, and it suggests that primary physicians need to be familiar with the diagnostic approach for these 4 diseases.
Cohort Studies ; Diagnosis ; Female ; Femoracetabular Impingement ; General Practice ; Hip Dislocation ; Hip* ; Humans ; Male ; Pain, Referred ; Primary Health Care ; Referral and Consultation ; Retrospective Studies* ; Spine ; Tertiary Care Centers ; Young Adult*