Sequencing-based functional assays for classification of BRCA2 variants in mouse ESCs.

Sequencing of genes, such as BRCA1 and BRCA2, is recommended for individuals with a personal or family history of early onset and/or bilateral breast and/or ovarian cancer or a history of male breast cancer. Such sequencing efforts have resulted in the identification of more than 17,000 BRCA2 variants. The functional significance of most variants remains unknown; consequently, they are called variants of uncertain clinical significance (VUSs). We have previously developed mouse embryonic stem cell (mESC)-based assays for functional classification of BRCA2 variants. We now developed a next-generation sequencing (NGS)-based approach for functional evaluation of BRCA2 variants using pools of mESCs expressing 10-25 BRCA2 variants from a given exon. We use this approach for functional evaluation of 223 variants listed in ClinVar. Our functional classification of BRCA2 variants is concordant with the classification reported in ClinVar or those reported by other orthogonal assays.

Early surgical stabilization of rib fractures for flail chest is associated with improved patient outcomes: An ACS-TQIP review.

BACKGROUND: Rib fractures are a common in thoracic trauma. Increasingly, patients with flail chest are being treated with surgical stabilization of rib fractures (SSRF). We performed a retrospective review of the Trauma Quality Improvement Program database to determine if there was a difference in outcomes between patients undergoing early SSRF (≤3 days) versus late SSRF (>3 days). METHODS: Patients with flail chest in Trauma Quality Improvement Program were identified by CPT code, assessing those who underwent SSRF between 2017 and 2019. We excluded those younger than 18 years and Abbreviated Injury Scale head severity scores greater than 3. Patients were grouped based on SSRF before and after hospital Day 3. These patients were case matched based on age, Injury Severity Score, Abbreviated Injury Scale head and chest, body mass index, Glasgow Coma Scale, and five modified frailty index. All data were examined using χ2, one-way analysis of variance, and Fisher's exact test within SPSS version 28.0. RESULTS: For 3 years, 20,324 patients were noted to have flail chest, and 3,345 (16.46%) of these patients underwent SSRF. After case matching, 209 patients were found in each group. There were no significant differences between reported major comorbidities. Patients with early SSRF had fewer unplanned intubations (6.2% vs. 12.0%; p = 0.04), fewer median ventilator days (6 days Q1: 3 to Q3: 10.5 vs. 9 Q1: 4.25 to Q3: 14; p = 0.01), shorter intensive care unit length of stay (6 days Q1: 4 to Q3: 11 vs. 11 Q1: 6 to Q3: 17; p < 0.01), and hospital length of stay (15 days Q1: 11.75 to Q3: 22.25 vs. 20 Q1: 15.25 - Q3: 27, p < 0.01. Early plating was associated with lower rates of deep vein thrombosis and ventilator-acquired pneumonia. CONCLUSION: In trauma-accredited centers, patients with flail chest who underwent early SSRF (<3 days) had better outcomes, including fewer unplanned intubations, decreased ventilator days, shorter intensive care unit LOS and HLOS, and fewer DVTs, and ventilator-associated pneumonia. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.