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: Ovarian clear cell carcinoma (OCCC) is associated with chemoresistance. Limited data exists regarding the efficacy of targeted therapies such as immune checkpoint inhibitors (ICI) and bevacizumab, and the role of secondary cytoreductive surgery (SCS). Methods: We retrospectively analyzed genomic features and treatment outcomes of 172 OCCC patients treated at our institution from January 2000 to May 2022. Next-generation sequencing (NGS) was performed where sufficient archival tissue was available. Results: 64.0% of patients were diagnosed at an early stage, and 36.0% at an advanced stage.Patients with advanced/relapsed OCCC who received platinum-based chemotherapy plus bevacizumab followed by maintenance bevacizumab had a median first-line progressionfree survival (PFS) of 12.2 months, compared with 9.3 months for chemotherapy alone (hazard ratio=0.69; 95% confidence interval [CI]=0.33, 1.45). In 27 patients who received an ICI, the overall response rate was 18.5% and median duration of response was 7.4 months (95% CI=6.5, 8.3). In 17 carefully selected patients with fewer than 3 sites of relapse, median PFS was 35 months (95% CI=0, 73.5) and median overall survival was 96.8 months (95% CI=44.6, 149.0) after SCS. NGS on 58 tumors revealed common mutations in ARID1A (48.3%), PIK3CA (46.6%), and KRAS (20.7%). Pathogenic alterations in PIK3CA, FGFR2, and NBN were associated with worse survival outcomes. Median tumor mutational burden was 3.78 (range, 0–16). All 26 patients with available loss of heterozygosity (LOH) scores had LOH <16%. Conclusion Our study demonstrates encouraging outcomes with bevacizumab and ICI, and SCS in select relapsed OCCC patients. Prospective trials are warranted.

BACKGROUND Hypertension is the most common risk factor for cardiovascular disease in the Philippines. Despite the availability of antihypertensive medications that are effective, safe, and tolerated by Filipino patients, the numbers of uncontrolled hypertensives are still increasing. Several factors play in the poor control of blood pressure, particularly resistant hypertension and hyperactive sympathetic nervous system. Renal denervation therapy is a novel device that has been shown to lower blood pressure in patients with resistant and difficult-to-treat hypertension and is deemed safe in clinical trials. A Philippine Working Group composed of specialists in cardiology, hypertension, vascular surgery, and clinical epidemiology has come up with consensus statements in identifying patients who will benefit from the procedure. Locally, there is a need to have hypertension centers treating uncontrolled and resistant hypertension and offer renal denervation therapy to appropriate Filipino patients.
Blood Pressure

Introduction: Social media has become a ubiquitous part of daily life. However, little is known about the influence of food-related social media content (FRSMC) on the eating habits of Malaysian undergraduates. This study explored FRSMC usage of undergraduates enrolled in a non-health program, its influence on eating habits, and how such social media content influences dietary behaviours. Method: This qualitative semi-structured interview study involved chemical engineering (CE) undergraduates at a university in Penang, Malaysia. The study was carried out from April 2021 to March 2022 during which ten participants were purposively selected. Based on precedent qualitative research sampling rule of thumb, this sample size of ten participants provided sufficient data saturation for an initial exploratory study. The interview sessions were recorded, transcribed, and thematically analyzed. Results: According to study findings, in terms of usage, food advertising and promotions; cooking tutorials and food and nutrition information are the most appealing types of FRSMC. With regards to eating habits, FRSMC can lead to healthy and unhealthy food choices. The study identified several perceived challenges, namely unrealistic and untrustworthy content, difficult and repetitive content, and algorithm-driven deviations from healthy diets. The effectiveness of FRSMC can be enhanced by creating trustworthy and engaging content. Conclusion: The study highlights that social media engagement can have both positive and negative impact on food choices among undergraduates. Some FRSMC are perceived to encourage and motivate undergraduates to adopt healthier dietary habits. Future research could involve a larger sample, representative of diverse socio-demographic groups in Malaysia.

BACKGROUND

Coronavirus disease 2019 (COVID-19) has been associated with acute liver injury presenting as increased liver enzymes, specifically alanine aminotransferase (ALT) and aspartate aminotransferase (AST). There is limited data in the prevalence of liver injury in COVID 19. We aim to determine the prevalence of acute liver injury among COVID-19 patients admitted in a tertiary hospital in the Philippines.

The study is a single center, retrospective cohort of all COVID-19 patients with baseline AST and ALT admitted at St. Luke’s Medical Center - Quezon City from January 2020 to December 2021. The population was divided into those with normal liver enzymes, mild (AST and/or ALT 1-3 times ULN), and severe (AST and/or ALT >3x ULN) acute liver injury. Association of liver injury to clinical outcome, COVID 19 disease severity, and length of hospital stay were determined. Among those with elevated AST/ALT, comparison of the levels before and after treatment with hepatoprotective agents were evaluated.

Among the 669 patients included in the analysis, 448 (67%) developed liver injury of which 50 (7.5%) had severe liver injury and 398 (59.5%) developed mild liver injury. Chi squared analysis showed that acute liver injury (OR:2.64,CI:1.90-3.69, p < 0.01) was associated with COVID-19 severity. However, acute liver injury was not associated with clinical outcome (p = 0.347) and length of hospital stay (p = 0.317). There was no association between the use of hepatoprotective agents and changes in level of transaminases (p=0.087).

This study revealed that mild liver injury is commonly found in patients with COVID-19 infection. Severity of liver injury is significantly associated with COVID-19 severity, but not with clinical outcome and length of hospital stay. In this study, treatment with hepatoprotective agents did not lead to a decrease in liver enzymes. Further evaluation is needed to recognize those patients at higher risk of complications and identify effective therapies in providing better clinical outcomes.