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.

Objective: Emerging evidence suggests that air pollution exposure may increase the risk of Parkinson’s disease (PD). We aimed to investigate the association between exposure to fine particulate matter (PM2.5) and the risk of incident PD nationwide. Methods: We utilized data from the Taiwan National Health Insurance Research Database, which is spatiotemporally linked with air quality data from the Taiwan Environmental Protection Administration website. The study population consisted of participants who were followed from the index date (January 1, 2005) until the occurrence of PD or the end of the study period (December 31, 2017). Participants who were diagnosed with PD before the index date were excluded. To evaluate the association between exposure to PM2.5 and incident PD risk, we employed Cox regression to estimate the hazard ratio and 95% confidence interval (CI). Results: A total of 454,583 participants were included, with a mean (standard deviation) age of 63.1 (9.9) years and a male proportion of 50%. Over a mean follow-up period of 11.1 (3.6) years, 4% of the participants (n = 18,862) developed PD. We observed a significant positive association between PM2.5 exposure and the risk of PD, with a hazard ratio of 1.22 (95% CI, 1.20–1.23) per interquartile range increase in exposure (10.17 μg/m3) when adjusting for both SO2 and NO2. Conclusion We provide further evidence of an association between PM2.5 exposure and the risk of PD. These findings underscore the urgent need for public health policies aimed at reducing ambient air pollution and its potential impact on PD.

The application of minimal invasive mastectomy has allowed surgeons to perform nipplesparing mastectomy via a shorter, inconspicuous incision under clear vision and with more precise hemostasis. However, it poses new challenges in microsurgical breast reconstruction, such as vascular anastomosis and flap insetting, which are considerably more difficult to perform through the shorter incision on the lateral breast border. We propose an innovative technique of transcutaneous medial fixation sutures to help in flap insetting and creating and maintaining the medial breast border. The sutures are placed after mastectomy and before flap transfer. Three 4-0 nylon suture loops are placed transcutaneously and into the pocket at the markings of the preferred lower medial border of the reconstructed breast. After microvascular anastomosis and temporary shaping of the flap on top of the mastectomy skin, the three corresponding points for the sutures are identified. The three nylon loops are then sutured to the dermis of the corresponding medial point of the flap. The flap is placed into the pocket by a simultaneous gentle pull on the three sutures and a combined lateral push. The stitches are then tied and buried after completion of flap inset.

Background: Direct-to-implant (DTI) breast reconstruction after nipple-sparing mastectomy (NSM) with the use of acellular dermal matrix (ADM) provides reliable outcomes; however, the use of ADM is associated with a higher risk of complications. We analyzed our experiences of post-NSM DTI without ADM and identified the predictive factors of adverse surgical outcomes. Methods: Patients who underwent NSM and immediate DTI or two-stage tissue expander (TE) breast reconstruction from 2009 to 2020 were enrolled. Predictors of adverse endpoints were analyzed. Results: There were 100 DTI and 29 TE reconstructions. The TE group had a higher rate of postmastectomy radiotherapy (31% vs. 11%; P=0.009), larger specimens (317.37±176.42 g vs. 272.08±126.33 g; P=0.047), larger implants (360.84±85.19 g vs. 298.83±81.13 g; P=0.004) and a higher implant/TE exposure ratio (10.3% vs. 1%; P=0.035). In DTI reconstruction, age over 50 years (odds ratio [OR], 5.43; 95% confidence interval [CI], 1.50–19.74; P=0.010) and a larger mastectomy weight (OR, 1.65; 95% CI, 1.08–2.51; P=0.021) were associated with a higher risk of acute complications. Intraoperative radiotherapy for the nipple-areolar complex increased the risk of acute complications (OR, 4.05; 95% CI, 1.07–15.27; P=0.039) and the likelihood of revision surgery (OR, 5.57; 95% CI, 1.25–24.93; P=0.025). Conclusions Immediate DTI breast reconstruction following NSM is feasible in Asian patients with smaller breasts.

Background: Direct-to-implant (DTI) breast reconstruction after nipple-sparing mastectomy (NSM) with the use of acellular dermal matrix (ADM) provides reliable outcomes; however, the use of ADM is associated with a higher risk of complications. We analyzed our experiences of post-NSM DTI without ADM and identified the predictive factors of adverse surgical outcomes. Methods: Patients who underwent NSM and immediate DTI or two-stage tissue expander (TE) breast reconstruction from 2009 to 2020 were enrolled. Predictors of adverse endpoints were analyzed. Results: There were 100 DTI and 29 TE reconstructions. The TE group had a higher rate of postmastectomy radiotherapy (31% vs. 11%; P=0.009), larger specimens (317.37±176.42 g vs. 272.08±126.33 g; P=0.047), larger implants (360.84±85.19 g vs. 298.83±81.13 g; P=0.004) and a higher implant/TE exposure ratio (10.3% vs. 1%; P=0.035). In DTI reconstruction, age over 50 years (odds ratio [OR], 5.43; 95% confidence interval [CI], 1.50–19.74; P=0.010) and a larger mastectomy weight (OR, 1.65; 95% CI, 1.08–2.51; P=0.021) were associated with a higher risk of acute complications. Intraoperative radiotherapy for the nipple-areolar complex increased the risk of acute complications (OR, 4.05; 95% CI, 1.07–15.27; P=0.039) and the likelihood of revision surgery (OR, 5.57; 95% CI, 1.25–24.93; P=0.025). Conclusions Immediate DTI breast reconstruction following NSM is feasible in Asian patients with smaller breasts.

Background/Aims: Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportunity for Asian doctors to discuss the latest findings of gynecologic cancer, including cervical, ovarian, and endometrial cancers, as well as the future of fertility-sparing treatments, minimally invasive/radical/debulking surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Clinical guidelines and position statement of Asian countries were presented by experts. Asian clinical trials for gynecologic cancers were reviewed and experts emphasized the point that original Asian study is beneficial for Asian patients. In Junior session, young gynecologic oncologists presented their latest research on gynecologic cancers.
Antineoplastic Agents ; Asian Continental Ancestry Group ; Drug Therapy ; Education ; Endometrial Neoplasms ; Female ; Gyeonggi-do ; Humans ; Immunotherapy ; Korea ; Ovarian Neoplasms ; Radiotherapy ; Uterine Cervical Neoplasms

OBJECTIVE: The purpose of this study was to examine the effect of commercially available fluoride-containing oral rinses on the corrosion behavior of titanium alloys, which are the main components of orthodontic miniscrews. METHODS: Four commercially available oral rinses (solution A, pH 4.46/260 ppm fluoride; solution B, pH 4.41/178 ppm fluoride; solution C, pH 6.30/117 ppm fluoride; and solution D, pH 4.17/3.92 ppm fluoride) were tested on titanium alloy (Ti-6Al-4V) circular plates, and saline was used as the control. The open-circuit potential and potentiodynamic polarization of these materials were measured. Thereafter, all samples were evaluated under a field-emission scanning electron microscope. RESULTS: Among the tested oral rinses, except solution D, the more the fluoride content was, the greater was the corrosion potential downtrend; the corrosion resistance of the titanium alloy sample was also lowered significantly (p < 0.05). Field-emission scanning electron microscopic analysis of the surface morphology of the titanium alloy samples revealed that all samples had some defects, crevices, or pitting after exposure to the oral rinses than before treatment. In particular, the samples in solution A showed the most changes. CONCLUSIONS: Commercially available oral rinses having a high fluoride concentration and a low pH may reduce the corrosion resistance of titanium alloys used in dental appliances such as orthodontic titanium miniscrews and brackets.
Alloys* ; Corrosion* ; Fluorides ; Hydrogen-Ion Concentration ; Titanium*