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: Primary cutaneous CD30+ lymphoproliferative disorders (pcCD30-LPDs) are a diseases with various clinical and prognostic characteristics. Objective: Increasing our knowledge of the clinical characteristics of pcCD30-LPDs and identifying potential prognostic variables in an Asian population. Methods: Clinicopathological features and survival data of pcCD30-LPD cases obtained from 22 hospitals in South Korea were examined. Results: A total of 413 cases of pcCD30-LPDs (lymphomatoid papulosis [LYP], n=237; primary cutaneous anaplastic large cell lymphoma [C-ALCL], n=176) were included. Ninety percent of LYP patients and roughly 50% of C-ALCL patients presented with multiple skin lesions. Both LYP and C-ALCL affected the lower limbs most frequently. Multiplicity and advanced T stage of LYP lesions were associated with a chronic course longer than 6 months. Clinical morphology with patch lesions and elevated serum lactate dehydrogenase were significantly associated with LPDs during follow-up in LYP patients. Extracutaneous involvement of C-ALCL occurred in 13.2% of patients. Lesions larger than 5 cm and increased serum lactate dehydrogenase were associated with a poor prognosis in C-ALCL. The survival of patients with C-ALCL was unaffected by the anatomical locations of skin lesions or other pathological factors. Conclusion The multiplicity or size of skin lesions was associated with a chronic course of LYP and survival among patients with C-ALCL.

Background: Warts are benign hyperkeratotic proliferative skin lesions caused by the human papillomavirus (HPV).Traditional destructive treatments, such as cryotherapy, have limited effectiveness and can lead to substantial adverse effects. Acyclovir, an antiviral agent against human herpes viruses, may be effective in the treatment of warts, as HPV is also a DNA virus. Objective: This study aimed to evaluate the efficacy of intralesional acyclovir for the treatment of warts. Methods: We conducted a retrospective study of 21 patients diagnosed with periungual or palmoplantar warts who were treated with intralesional acyclovir (25 mg/mL) injections between January 2022 and December 2022. The treatment was repeated at 3- to 4-week intervals, and the therapeutic effect was evaluated one month after the final treatment session. Results: Complete resolution of warts was observed in nine patients (42.9%), partial response in seven patients (33.3%), and no response in five patients (23.8%). Injection-related transient pain and hemorrhage were reported by all patients, with a hemorrhagic crust observed in one patient (4.76%) and transient onycholysis noted in another patient (4.76%). No permanent nail deformities have been reported. Conclusion Intralesional acyclovir is a potentially effective and safe treatment modality for periungual and palmoplantar warts.

Objective: This study compared the epidemiological changes before and after the coronavirus disease 2019 (COVID-19) outbreak in out-of-hospital cardiac arrest patients in a single center. This study analyzed the long-term impact of the COVID-19 pandemic. Methods: Eight hundred and sixty-one out-of-hospital cardiac arrest patients were included in the analysis. Out-of-hospital cardiac arrest patients from January 20, 2018, to January 19, 2020, were used as the control group, and those between January 20, 2020, and January 19, 2022, were used as the study group. The collected data were evaluated using a Student t-test, chi-square test, and logistic regression analysis. Results: During the COVID-19 pandemic, the number of cardiac arrests witnessed at the field level decreased. In the transport stage, mechanical CPR increased and the method for securing the airway had many changes. Transport distances, response times, and on-scene times have increased. Survival discharge from hospital decreased from 9.5% to 5.8% (P=0.045), and good neurological outcomes decreased from 8% to 4% (P=0.017). According to multivariate logistic regression analysis, good neurological outcomes (adjusted odds ratio, 0.299; 95% confidence interval, 0.116-0.772) were significantly lower after the onset of COVID-19. Conclusion With the outbreak of COVID-19, there have been many changes in the pre-hospital stages of out-of-hospital cardiac arrest patients, and the neurological outcomes have also deteriorated. This continued throughout the pandemic period.

Objective: This study examined whether the changes in reimbursement coverage of brain magnetic resonance image (MRI) affected practice for patients who visited the emergency department with dizziness as the chief complaint. Methods: Among the 5,423 patients who visited the emergency department for dizziness in 2017, 2019, and 2021, 4,497 patients were included in the study retrospectively and investigated by brain diffusion-weighted MRI and the presence of cerebral infarction on brain diffusion-weighted MRI. This study examined whether there was a significant difference before and after the change. Results: In 2017, 2019, and 2021, 1,489, 1,570, and 1,438 patients with dizziness visited the emergency department, respectively. The number of patients who underwent a brain MRI scan gradually increased from 237 (15.9%) in 2017 to 628 (40.0%) in 2019 and 948 (65.9%) in 2021 (P<0.001). The number of positive findings on brain MRI scan increased gradually from 30 patients (2.0%) in 2017 to 47 patients (3.0%) in 2019 and 53 patients (3.7%) in 2021 (P=0.025). The ratio of positive findings of brain MRI scans to the number of patients who underwent brain MRI scans decreased gradually to 12.7% in 2017, 7.5% in 2019, and 5.6% in 2021 (P=0.001). Conclusion The changes in the reimbursement coverage of brain MRI affect the number of brain MRI scans and the detection of cerebral infarction.

Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive muta-tions initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resis-tance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunc-tion, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.