RESUMO
Open-book pelvic fractures are an uncommon orthopedic emergency that requires prompt recognition and treatment. A 37-year-old male was involved in high-energy trauma, resulting in an open-book pelvic fracture with bilateral sacroiliac joint diastasis, bilateral superior and inferior pubic rami fractures, a comminuted sacral fracture, and a traumatic hernia. On presentation, he was hemodynamically unstable, with bruising in the right hemipelvis. Acute treatment included a cervical collar, transfusion protocol, central venous access, and pelvic binder. Trauma and orthopedic services were consulted to manage the patient with an interdisciplinary approach. The patient initially underwent external fixation with concomitant exploratory laparotomy. Definitive treatment concluded with colorectal anastomosis, diverting loop ileostomy creation, abdominal closure, open-reduction internal fixation (ORIF) of the pelvis, and removal and reapplication of external fixation.
RESUMO
BACKGROUND: Tumors with mutations associated with homologous recombination deficiency (HRD) are uncommon in prostate cancer (PCa) and variably responsive to PARP inhibition. To better identify tumors with HRD, we developed a transcriptomic signature for HRD in PCa (HRD-P). METHODS: By using an established mutational signature, we created and validated HRD-P in six independent PCa cohorts (primary PCa, n = 8224; metastatic castration-resistant PCa [mCRPC], n = 328). Molecular and clinical features were compared between HRD-P+ tumors and those with single HR-gene mutations. RESULTS: HRD-P+ tumors were more common than tumors with single HR-gene mutations in primary (201/491, 41% vs 32/491 6.5%) and mCRPC (126/328, 38% vs 82/328, 25%) cases, and HRD-P+ was more predictive of genomic instability suggestive of HRD. HRD-P+ was associated with a shorter time to recurrence following surgery and shorter overall survival in men with mCRPC. In a prospective trial of mCRPC treated with olaparib (n = 10), all three men with HRD-P+ experienced prolonged (>330 days) PSA progression-free survival. CONCLUSION: These results suggest transcriptomics can identify more patients that harbor phenotypic HRD than single HR-gene mutations and support further exploration of transcriptionally defined HRD tumors perhaps in conjunction with genomic markers for therapeutic application.