Despite the relatively high incidence of ovarian cysts, particularly in premenopausal women, cyst rupture may on occasion present painfully and require surgical intervention to resolve. Particularly in the case of ruptured hemorrhagic ovarian cysts, resulting hemoperitoneum can create a risk of further adverse events including hypovolemic shock; proper identification and management of such cases are therefore critical. This case focuses on a 22-year-old female that presented to the emergency department (ED) with suprapubic pain in the lower left quadrant of the abdomen. Ultrasonography and computed tomography of the abdomen and pelvis revealed a ruptured hemorrhagic corpus luteum cyst of the left ovary and secondary hemoperitoneum. Patient treatment required laparoscopic left ovarian cyst wall removal, with the removal of hemoperitoneum.
Mouse double minute 2 homolog (MDM2) has emerged as a target of increasing interest in recent years following its initial identification as an oncogene and subsequent identification as an often-amplified marker of tumor aggressiveness across several cancer types, including breast cancer and several soft tissue and osteo-sarcomas. MDM2 is best characterized as a p53-targeting E3-ubiquitin ligase, and significant efforts have been made to develop inhibitors that function to block MDM2-p53 binding and subsequent ubiquitination, thereby stabilizing p53. One such inhibitor, milademetan (RAIN-32), for instance has progressed to the clinic and has completed phase I and II trials both alone and as a combination agent in several hematological malignancies and solid tumors, and a phase III trial (MANTRA, NCT04979442) is currently underway. Given the role of p53 in contributing to transcriptional activation of MDM2, however, such inhibitors of MDM2-p53WT interaction serve to increase cellular levels of MDM2, a result which we have confirmed across several MDM2-p53 inhibitors and cell lines. Non-p53 mediated roles of MDM2 have become of increasing interest in recent years, and we have previously reported on MDM2 mediated immune effects. Further, studies of immune checkpoint blockade driven hyperprogressive disease in clinical cases have preliminarily identified MDM2 amplification as a potential predictor. Indeed, use of small-molecule degrader SP-141 which drives MDM2 autoubiquitination and subsequent proteolysis in both p53WT and p53-/- HCT116 cell lines demonstrates a remarkably similar IC50 (523 and 505 nM, respectively, at 72h) that suggests the importance of non-p53-dependent MDM2 pathways. ONC201 is a small molecule imipridone that is currently in clinical trials for brain cancers and a variety of other tumor types. Initially identified for its role in driving the TRAIL-pathway and integrated stress response (ISR), we recently identified an additional effect of ONC201 in demonstrably reducing detectable MDM2 levels in cell lines upon treatment. Preliminary investigation into this effect suggests synergism in combination with milademetan treatment, with the MDM2-p53 inhibition driven increase in MDM2 levels being abolished upon cotreatment of ONC201 and milademetan. Further exploration of this combination is underway, and may serve as a novel translatable therapeutic approach, particularly in combination with checkpoint blockade. Citation Format: Andrew George, Ilyas Sahin, Shengliang Zhang, Maximilian Schwermann, Francesca Di Cristofano, Charlotte DeGeorge, Wafik S. El-Deiry. MDM2 inhibition in combination with imipridone ONC201 treatment as a synergistic combination in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 551.
Venous thromboembolism (VTE) is a significant cardiovascular disease with a relatively high incidence rate, presenting a significant clinical burden. Its effective diagnosis and treatment are critical to the proper management of patients with the condition. Though there are several risk factors associated with VTE, advanced age itself presents as particularly significant, with age-related risk alone leading to high incidences of VTE in elderly patients even in the absence of other risk factors or relevant medical history. We present such a case of an elderly male patient with limited risk factors beyond advanced age who nonetheless presented with symptoms of deep-vein thrombosis (DVT) following a mild traumatic injury, and upon further inspection, was found to have a pulmonary embolism (PE). Proper precautions taken in assessing potential PE upon initial discovery of DVT and post-diagnostic management were critical in this patient's outcome.
Though recent developments in the management of the coronavirus disease 2019 (COVID-19) pandemic have resulted in significant progress, its continued persistence demands continued consideration both of larger scale public health factors as well as individual patient management. We present a case that provides a broad perspective across several issues within both categories, of a morbidly obese 34-year-old unvaccinated female presenting with respiratory distress secondary to COVID-19 pneumonia, managed through remdesivir therapy. Though this case presents an example of successful management, it nonetheless emphasizes the demand for a renewed focus on vaccine hesitancy and obesity as public health issues, particularly within the context of the pandemic.
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