Due to a high risk of recurrent thromboembolism in patients with antiphospholipid syndrome (APS), longterm anticoagulation is recommended. For decades, vitamin K antagonists (VKAs) have been the gold standard for thromboprophylaxis in these patients. Due to the widespread use of direct oral anticoagulants (DOACs) in various thromboembolic conditions and their potential advantages compared to VKAs, several studies have been conducted to evaluate their safety and efficacy in APS.We performed a literature search using PubMed, Embase, and Cochrane databases for studies comparing DOACs to VKAs in patients with APS. Relative risk (RR) and the corresponding 95% confidence intervals (95% CI) were estimated for recurrent thromboembolic events, bleeding, and mortality.A total of 1437 patients pooled from 12 studies were analyzed. The risk of recurrent thrombosis, especially arterial thrombosis, doubled with DOACs compared to VKAs (RR 2.61, 95% CI 1.44-4.71; p=0.001). The risk further increased in patients with a triple-positive antiphospholipid antibody profile (RR 4.50, 95% CI 1.91-10.63; p=0.0006) and with the use of rivaroxaban (RR 1.95, p=0.02). The risk of major bleeding and mortality were not significantly different between the two arms. A trend favoring DOACs compared to VKAs was observed for all bleeding events. This meta-analysis comes in agreement with previous studies and supports the use of VKAs in APS. Our study revealed that VKAs remain the gold standard for the management of APS, especially triple-positive APS. DOACs, particularly rivaroxaban, are not as effective in preventing recurrent thromboembolism in high-risk APS patients. Further studies are needed to evaluate the role of DOACs apart from rivaroxaban with a focus on their efficacy in the management of isolated or double-positive APS.

Background: Aspagarinase is a fundamental component for the treatment of patients with acute lymphoblastic leukemia (ALL). Venous thromboembolism (VTE) is a known complication of asparaginase therapy during treatment for ALL. This is attributed to the depletion of anticoagulants, particularly acquired antithrombin deficiency following asparaginase administration. The incidence of thrombosis following asparaginase is more prevalent in adults versus children and is estimated to be around 5-35 % and 2.4-8% respectively. Multiple studies have investigated the efficacy and safety of antithrombin supplementation. The recent THROMBOTECT study showed that prophylactic use of antithrombin (AT) or low molecular weight heparin (LMWH) is associated with significant risk reduction of thromboembolism in children and adolescents during induction chemotherapy of ALL. Our study sought to review the cohort studies comparing VTE in adults with and without AT supplementation in ALL receiving asparaginase and specifically evaluate the efficacy of this strategy. Methods: We performed a systematic search using PubMed, Google Scholar, EMBASE, SCOPUS and ClinicalTrials.gov without language restriction up until July 20th 2020. A random effects model was utilized to calculate risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI). Results: Eight studies fulfilled our inclusion criteria (table 1) and were retrospective cohort studies. In adult patients, with ALL treated with asparaginase, the incidence of VTE was significantly lower in those who received AT [RR=0.46 (95 % CI= 0.31-0.70; p= 0.0002) (figure 1.1). The threshold for AT supplementation was 60-70% in most of the studies, with the exception of two studies where the threshold was 50%. Conclusion: In our meta-analysis of the current available data,Antithrombin supplementation in adults with ALL receiving asparaginase was associated with a significant decrease in the risk of venous thromboembolism compared to those who didn't receive thromboprophylaxis. Our data suggest the benefit of antithrombin supplementation in adults with ALL treated with asparaginase. We suggest that this strategy be implemented in a large prospective clinical trial to further confirm the benefit of this intervention. Disclosures No relevant conflicts of interest to declare.

Synchronous gynecological malignancies are rarely encountered, with a growing tide to recognize these primary tumors. However, the most observed synchronous gynecological malignancies remain ovarian and endometrial cancer. This case report presents a 35-year-old female who presented to her gynecologist with lower back pain and dysuria. Transvaginal ultrasound demonstrated a 3-4 cm irregular mass in the cervix and lower uterine segment. Pathology from cold knife conization and endometrial curetting showed serous adenocarcinoma with probable lymphovascular invasion. The patient underwent a positron emission tomography scan that demonstrated an abnormal-appearing cervix, a small number of ascites, peritoneal carcinomatosis, and abnormal left adnexa. Eighteen days later, the patient underwent exploratory laparotomy with total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, lymphadenectomy, and bowel resection. Surgical histopathological findings confirmed the presence of two primary malignant tumors, namely, cervical adenosquamous carcinoma and bilateral ovarian high-grade serous carcinoma, with extensive metastatic lesions. Although synchronous ovarian and cervical cancer is rarely encountered, patients might benefit from early identification and subsequent debulking surgery with curative intent, as well as adding an immune checkpoint inhibitor in case it is positive on checking as it might improve long-term outcomes.

Objective: To present a case of adrenocorticotropic hormone (ACTH) hypersecretion caused by a metastatic acinic cell carcinoma (AcCC) of the parotid. Only 6 cases have been reported prior to October 2019. We believe that this condition is under-reported and hope that improved recognition will improve its reporting. Methods: Diagnosis in this case was done using surgical pathology of the primary tumor, involving lymph nodes, and a metastatic lesion. Following an initial misdiagnosis, a final diagnosis of AcCC was made using immunohistochemical staining. ACTH hypersecretion was diagnosed by testing for random ACTH, cortisol, and 24-hour urine aldosterone and cortisol levels. Results: A 57-year-old man presented with hypokalemia, lower-extremity edema, and left-side rib pain 7 months following excision of a 4-cm left-parotid tumor. Immunostaining positive for DOG-1, CK7, pancytokeratin (including CAM5.2), and SOX10 led to the diagnosis of AcCC. ACTH hypersecretion was diagnosed based on a random ACTH level of 307 pg/mL (normal morning value, 7.2-63 pg/mL), a cortisol level of 33 mg/dL (normal morning value, 4.3-19.8 mg/dL; normal PM value, 3.1-15.0 mg/dL), a 24-hour urine aldosterone level of <0.7 U (normal, 2.0-20 U), and a 24-hour urine cortisol level of 4564 U (normal, 3.5-45 U). The patient's ACTH hypersecretion and hypokalemia were treated with potassium replacement, amiloride, and ketoconazole. His metastatic recurrence was treated with radiotherapy, chemotherapy, and immunotherapy. The patient died after being diagnosed with sepsis secondary to multifocal postobstructive pneumonia 4 months after the diagnosis of his metastatic recurrence. Conclusion: Ectopic ACTH production caused by metastatic AcCC is a rare phenomenon but has been increasingly described over the last 15 years. We believe that this condition likely has a greater prevalence than what is reported and that improved recognition will lead to improved outcomes.