Although genetic changes may be pivotal in the origin of cancer, cellular context is paramount. This is particularly relevant in a progenitor germ cell tumor and its differentiated mature teratoma counterpart when it concerns tumor heterogeneity and cancer dormancy in subsequent second malignancies (subsequent malignant neoplasms (SMNs)). From our tumor registry database, we identified 655 testicular germ cell tumor (TGCT) patients who developed SMNs between January 1990 and September 2018. Of the 113 solid organ SMNs, 42 had sufficient tumor tissue available for fluorescence in situ hybridization (FISH) analysis of isochromosome 12p [i(12p)]. We identified seven additional patients for targeted DNA and RNA sequencing of teratomas and adjacent somatic transformation. Finally, we established cell lines from freshly resected post-chemotherapy teratomas and evaluated the cells for stemness expression by flow cytometry and by the formation of teratomas in a xenograft model. In our cohort, SMNs comprising non-germ cell tumors occurred about 18 years after a diagnosis of TGCT. Of the 42 SMNs examined, 5 (12%) contained i(12p) and 16 (38%) had 12p gain. When comparing a teratoma and adjacent somatic transformation, targeted DNA and RNA sequencing demonstrated high concordance. Studies of post-chemotherapy teratoma-derived cell lines revealed cancer-initiating cells expressing multipotency as well as early differentiation markers. For the first time, we demonstrated the prevalence of i(12p) in SMNs and the presence of progenitor cells embedded within mature teratomas after chemotherapy. Our findings suggest a progenitor stem-like cell of origin in SMN and TGCT and highlight the importance of cellular context in this disease.

Purpose Coagulopathy is common in patients with COVID-19. The ideal approach to anticoagulation remains under debate. There is a significant variability in existing protocols for anticoagulation, and these are mostly based on sporadic reports, small studies, and expert opinion. Materials and methods This multicenter retrospective cohort study evaluated the association between anticoagulation dose and inpatient mortality among critically ill COVID-19 patients admitted to the intensive care units (ICUs) or step-down units (SDUs) of eight Beaumont Healthcare hospitals in Michigan, USA from March 10th to April 15th, 2020. Results Included were 578 patients with a median age of 64 years; among whom, 57.8% were males. Most patients (n = 447, 77.3%) received high dose and one in four (n = 131, 22.7%) received low dose anticoagulation. Overall mortality rate was 41.9% (n = 242). After adjusting for potential confounders (age, sex, race, BMI, ferritin level at hospital admission, intubation, comorbidities, mSOFA, and Padua score), administration of high anticoagulation doses at the time of ICU/SDU admission was associated with decreased inpatient mortality (OR 0.564, 95% CI 0.333–0.953, p = 0.032) compared to low dose. Conclusion Treatment with high dose anticoagulation at the time of ICU/SDU admission was associated with decreased adjusted mortality among critically ill adult patients with COVID-19.

No abstract

May-Thurner syndrome (MTS), also known as iliac vein compression syndrome which results in luminal narrowing and intimal hyperplasia, which predispose to venous stasis and recurrent deep vein thromboembolism (DVT) We present a 32-year-old woman with MTS who developed recurrent deep venous thromboses despite undergoing thrombectomy and being on recommended anticoagulation.