Brca1 deficiency causes bone marrow failure and spontaneous hematologic malignancies in mice.

BRCA1 is critical for maintenance of genomic stability and interacts directly with several proteins that regulate hematopoietic stem cell function and are part of the Fanconi anemia (FA) double-strand break DNA repair pathway. The effects of complete BRCA1 deficiency on bone marrow (BM) function are unknown. To test the hypothesis that Brca1 is essential in hematopoiesis, we developed a conditional mouse model with Mx1-Cre-mediated Brca1 deletion. Mice lacking Brca1 in the BM have baseline cytopenias and develop spontaneous bone marrow failure or diverse hematologic malignancies by 6 months of age. Brca1(-/-) BM cells have a reduced capacity to form hematopoietic colonies in vitro and to reconstitute hematopoiesis in irradiated recipients, consistent with a hematopoietic progenitor functional defect. Brca1(-/-) BM cells also show FA-like hypersensitivity to the DNA crosslinking agent mitomycin C, and karyotypes feature genomic instability. Taken together, our results show that loss of Brca1 in murine BM causes hematopoietic defects similar to those seen in people with FA, which provides strong evidence that Brca1 is critical for normal hematopoiesis and that Brca1 is a bona fide FA-like gene.

"We're playing on the same team": Communication (dis)connections between trauma patients and surgical residents.

BACKGROUND: Patient-physician communication is key to better clinical outcomes and patient well-being. Communication between trauma patients and their physicians remains relatively unexplored. We aimed to identify and characterize the range of strengths and challenges in patient-physician communication in the setting of trauma care. METHODS: A qualitative, grounded theory approach was used to explore communication strengths and challenges for patients and residents. Patients previously admitted to the trauma service for violent injuries were recruited and interviewed in-person during their trauma clinic appointments. Surgical residents were recruited via email and interviewed virtually via Zoom. Anonymous, semistructured interviews were conducted until thematic saturation was reached. RESULTS: Twenty-nine interviews with patients and 14 interviews with residents were conducted. Patients reported feeling ignored and misunderstood and having inadequate communication with physicians. Residents cited lack of time, patients' lack of health literacy, differences in background, and emotional responses to trauma as barriers to effective communication with patients. Patients and residents reported an understanding of each other's stressors, similar emotional experiences regarding traumatic stress, and a desire to communicate with each other in greater depth both inside and outside of the hospital. CONCLUSION: Trauma patients and residents can feel disconnected due to the lack of time for thorough communication and differences in background; however, they understand each other's stressors and share similar emotional responses regarding trauma and a desire for increased communication, connection, and solidarity. Leveraging these shared values to guide interventions, such as a resident curriculum, may help bridge disconnects and improve their communication. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Small cell carcinoma of the ovary, pulmonary type: A role for adjuvant radiotherapy after carboplatin and etoposide?

BACKGROUND: Primary small cell ovarian cancer of pulmonary type (SCCOPT) remains a rare ovarian tumor. Its aggressive nature is associated with poor survival outcomes. Current treatment algorithms rely on systemic chemotherapy, primarily involving platinum agents. However, given its low incidence, less is known about the potential benefits of other treatments. CASE PRESENTATION: We report a case of an 80-year-old woman who was found to have a complex pelvic mass with a mildly elevated CA-125. She underwent a laparotomy for staging with tumor debulking; she had bulky unresectable adenopathy and pathology was consistent with stage IIIC SCCOPT. Postoperative imaging revealed progression of disease. She received six cycles of carboplatin and etoposide followed by consolidative radiation therapy to her para-aortic lymph nodes. She remains disease-free for over four years after completion of adjuvant therapy. DISCUSSION: Histologically, SCCOPT resembles small cell carcinomas of the lung, which are treated with a combination of chemotherapy and radiation therapy. New approaches that build upon the current treatment approaches and incorporate strategies from non-gynecologic tumor types could be beneficial.