Recognition and management of left atrial dissection during mitral repair.

BACKGROUND: Left atrial dissection (LAtD) is a rare but potentially life-threatening complication of mitral valve surgery. Its management is not well stablished in the literature. However, early recognition through intraoperative TEE and attention to changes in the left atrial free wall during saline leak testing can lead to avoidance of severe complications. CASE PRESENTATION: We report a case of LAtD detected by intraoperative transesophageal echocardiogram (TEE) following mitral valve repair for primary mitral valve regurgitation secondary to degenerative mitral valve disease with MAZE IV procedure for atrial fibrillation. LAtD was noted on TEE as an expanding double density along the wall of the left atrium with a jet originating at the posterior annulus flowing into the LAtD which was repaired. Separation from bypass following LAtD repair was complicated by severe biventricular dysfunction requiring significant inotropic support and placement of an intra-aortic balloon pump (IABP). Patient's post-operative course was further complicated by right sided heart failure requiring placement of a right sided impella which was subsequently removed on POD 4. Patient was discharged home on POD 17. Transthoracic echo at 1 month, 3 months demonstrated resolution of the LAtD. A follow up echo at 4 years showed complete resolution of the LAtD with an intact mitral repair, trace mitral regurgitation, and a mean gradient across the repair of 3 mm Hg. CONCLUSIONS: Left atrial dissection is a rare but serious complication of mitral valve surgery. We provide a review of the current literature regarding LAtD, emphasizing the need to consider this complication early during mitral surgery to allow for uncomplicated repair.

CDK7 Inhibition Potentiates Genome Instability Triggering Anti-tumor Immunity in Small Cell Lung Cancer.

Cyclin-dependent kinase 7 (CDK7) is a central regulator of the cell cycle and gene transcription. However, little is known about its impact on genomic instability and cancer immunity. Using a selective CDK7 inhibitor, YKL-5-124, we demonstrated that CDK7 inhibition predominately disrupts cell-cycle progression and induces DNA replication stress and genome instability in small cell lung cancer (SCLC) while simultaneously triggering immune-response signaling. These tumor-intrinsic events provoke a robust immune surveillance program elicited by T cells, which is further enhanced by the addition of immune-checkpoint blockade. Combining YKL-5-124 with anti-PD-1 offers significant survival benefit in multiple highly aggressive murine models of SCLC, providing a rationale for new combination regimens consisting of CDK7 inhibitors and immunotherapies.