Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

BACKGROUND: Rapid and accurate diagnosis of acute myocardial infarction (AMI) is critical for initiating effective treatment and achieving better prognosis. We investigated the performance of copeptin for early diagnosis of AMI, in comparison with creatine kinase myocardial band (CK-MB) and troponin I (TnI). METHODS: We prospectively enrolled 271 patients presenting with chest pain (within six hours of onset), suggestive of acute coronary syndrome, at an emergency department (ED). Serum CK-MB, TnI, and copeptin levels were measured. The diagnostic performance of CK-MB, TnI, and copeptin, alone and in combination, for AMI was assessed by ROC curve analysis by comparing the area under the curve (AUC). Sensitivity, specificity, negative predictive value, and positive predictive value of each marker were obtained, and the characteristics of each marker were analyzed. RESULTS: The patients were diagnosed as having ST elevation myocardial infarction (STEMI; N=43), non-ST elevation myocardial infarction (NSTEMI; N=25), unstable angina (N=78), or other diseases (N=125). AUC comparisons showed copeptin had significantly better diagnostic performance than TnI in patients with chest pain within two hours of onset (AMI: P=0.022, ≤1 hour; STEMI: P=0.017, ≤1 hour and P=0.010, ≤2 hours). In addition, TnI and copeptin in combination exhibited significantly better diagnostic performance than CK-MB plus TnI in AMI and STEMI patients. CONCLUSIONS The combination of TnI and copeptin improves AMI diagnostic performance in patients with early-onset chest pain in an ED setting.

OBJECTIVES: The aim of this study was to compare differences in perception and knowledge of child abuse and child disciplinary practices according to the history of child abuse victimization. METHODS: A questionnaire survey on child abuse was conducted with 491 adults raising children. We compared the perception and knowledge of child abuse and child disciplinary practices between two groups of adults with and without a history of childhood abuse victimization. RESULTS: The group with a history of childhood abuse had lower levels of knowledge of child abuse (F=6.990, p<0.01) and engaged in more negative disciplinary practices (F=5.974, p<0.05) than those without. However, no differences in the perception of child abuse were observed between the two groups. CONCLUSION: The results suggest that adults with a history of childhood abuse have lower levels of knowledge of child abuse and use more negative disciplinary practices in raising their children. This highlights the need to administer not only educational but also more direct hands-on interventions to vulnerable parents in order to foster healthy parenting and disciplinary practices.
Adult ; Child ; Child Abuse ; Child ; Crime Victims ; Humans ; Parenting ; Parents

Pregnancy-related osteoporosis is a very rare condition characterized by the occurrence of fracture during pregnancy or the puerperium. Despite its relative rarity, it can be a dangerous condition that causes severe back pain, height loss and disability. Normal physiologic changes during pregnancy, genetic or racial difference, obstetrical history and obstetrical disease, such as preterm labor or pregnancy-induced hypertension, are presumed risk factors of pregnancy-related osteooporosis. However, exact etiology and pathogenesis are uncertain. The management and natural history are still poorly defined. Traditional medications for osteoporosis are calcium/vitamin D and bisphosphonate. Concerns with bisphosphonate include accumulation in bone and fetal exposure in subsequent pregnancies. The newly developed medication, teriparatide, has shown good results. We report six cases of pregnancy-related osteoporosis and spinal fracture with literature review.
Back Pain ; Female ; Hypertension, Pregnancy-Induced ; Natural History ; Obstetric Labor, Premature ; Osteoporosis* ; Postpartum Period ; Pregnancy ; Risk Factors ; Spinal Fractures* ; Teriparatide

OBJECTIVES: The relationship between renal function and bone mineral density (BMD) is controversial. We evaluated the relationship between markers of renal function and BMD in healthy Korean women. METHODS: A total of 1,093 women who visited the health promotion center at Pusan National University hospital were included in the cross-sectional study. We divided the study population into two groups by BMD: osteopenia-osteoporosis and normal in the lumbar and femur regions, respectively. We compared the relationship between renal function and BMD using a logistic regression model and used SAS 9.3 (SAS Institute, Inc., Cary, NC, USA) for all statistical analysis. RESULTS: Blood urea nitrogen (BUN), creatinine, and cystatin C (Cys-C) were correlated with BMD in both the normal and osteopenia-osteoporosis groups, and in logistic regression analysis, BUN and Cys-C were correlated with lumbar and femur BMD. However, after we adjusted for age, menopause, and body mass index, only creatinine showed a negative correlation with lumbar BMD, and estimated glomerular filtration rate (eGFR) was related positively with femur BMD. CONCLUSIONS: Serum creatinine could be a marker for lumbar BMD and eGFR for femur BMD in Korean women without overt nephropathy.
Blood Urea Nitrogen ; Body Mass Index ; Bone Density ; Bone Marrow* ; Busan ; Creatinine ; Cross-Sectional Studies ; Cystatin C ; Female ; Femur ; Glomerular Filtration Rate ; Health Promotion ; Humans ; Logistic Models ; Menopause ; Osteoporosis

PURPOSE: Interest in peptic ulcer in children has been relatively low because the disease is rarer in children than in adults and there were restrictions in the application of endoscopy to children, but the recent development of pediatric endoscopy is activating research on pediatric peptic ulcer. Thus, this study compared the H. pylori infection rate and clinical and endoscopic findings among pediatric patients diagnosed with peptic ulcer. METHODS: We analyzed retrospectively 58 pediatric patients for whom whether to be infected with H. pylori was confirmed selected out of pediatric patients diagnosed with gastric ulcer or duodenal ulcer through upper gastrointestinal endoscopy at the Department of Pediatrics of Gachon University Gil Hospital during the period from January 2002 to December 2007. A case was considered H. pylori positive if H. pylori was detected in the Giemsa stain of tissue or the results of UBT (urea breath test) and CLO (rapid urease test) were both positive. RESULTS: Of the pediatric patients, 37 were infected with H. pylori and 21 were not. The H. pylori infection rate increased with aging and the result was statistically significant (p<0.05). However, H. pylori infection was not in a statistically significant correlation with sex, chief complaint, and gastroduodenal ulcer (p>0.05). CONCLUSION: H. pylori infection increased with aging, but was not significantly correlated with gastroduodenal ulcer. Further research may need to examine prospectively the relation between H. pylori and gastroduodenal ulcer in the Incheon area.
Adult ; Aging ; Azure Stains ; Child ; Duodenal Ulcer ; Endoscopy ; Endoscopy, Gastrointestinal ; Helicobacter ; Helicobacter pylori ; Humans ; Pediatrics ; Peptic Ulcer ; Retrospective Studies ; Stomach Ulcer ; Urease

BACKGROUND: T cell immunoglobulin mucin containing molecule (TIM)-3 is expressed in differentiated Th1 cells and is involved in the suppression of the cytokine production by these cells. However, the regulation of the expression of other T cell genes by TIM-3 is unclear. Herein, we attempted to identify differentially expressed genes in cells abundantly expressing TIM-3 compared to cells with low expression of TIM-3. METHODS: TIM-3 overexpressing cell clones were established by transfection of Jurkat T cells with TIM-3 expression vector. For screening of differentially expressed genes, gene fishing technology based on reverse transcription-polymerase chain reaction (RT-PCR) using an annealing control primer system was used. The selected candidate genes were validated by semi quantitative and real-time RT-PCR. RESULTS: The transcription of TIMP-1, IFITM1, PAR3 and CCL1 was different between TIM-3 overexpressing cells and control cells. However, only CCL1 transcription was significantly different in cells transiently transfected with TIM3 expression vector compared with control cells. CCL1 transcription was increased in primary human CD4+ T cells abundantly expressing TIM-3 but not in cells with low expression of TIM-3. CONCLUSION: CCL1 was identified as a differentially transcribed gene in TIM-3-expressing CD4+ T cells.
Clone Cells ; Gene Expression ; Genes, vif ; Humans ; Immunoglobulins ; Mass Screening ; Mucins ; T-Lymphocytes ; Th1 Cells ; Tissue Inhibitor of Metalloproteinase-1 ; Transfection

Congenital Abnormalities ; Extremities ; Gigantism ; Hemangioma ; Humans ; Hyperostosis ; Hyperplasia ; Lipoma ; Lymphangioma ; Macrocephaly ; Male ; Mouth ; Nevus ; Osteotomy ; Proteus ; Proteus Syndrome