Publications

OBJECTIVES

To examine the impact of preoperative coronal plane deformity on functional and radiographic outcomes on endosteal strut augmentation of proximal humerus fracture fixation.

DESIGN

Single surgeon, retrospective analysis of a prospective database. Case series.

SETTING

Academic level 1 trauma center.

PATIENTS/PARTICIPANTS

Seventy-two patients with isolated proximal humerus fractures fulfilled all inclusion/exclusion criteria with a minimum follow-up of 12 months.

INTERVENTION

Proximal humerus open reduction internal fixation with a laterally placed proximal humeral locking plate and endosteal placement of an allograft fibula treated through the anterolateral approach.

MAIN OUTCOME MEASUREMENTS

Global functional outcome as determined by the Disabilities of the Arm, Shoulder and Hand (DASH) score and Short Form 36 physical function. Shoulder-specific functional outcome as determined by the Constant-Murley and the University of California Los Angeles shoulder scores.

RESULTS

The mean age was 62 years old (range, 26-90 years). There were 32 varus fractures (neck-shaft angle, 110.8 degrees) and 40 valgus fractures (neck-shaft angle, 168.9 degrees). There was no significant difference in the initial postoperative (varus: 132.5 degrees, valgus: 135.5 degrees) and final (varus: 129.9 degrees, valgus: 132.2 degrees) neck-shaft angles or change in humeral height (varus: 0.94 mm, valgus: 1.48 mm). There were no significant differences in functional outcomes [Constant (varus: 85.2, valgus: 88.7) DASH (varus: 21.4, valgus: 13.9), University of California Los Angeles (28.6, varus 30.4), and Short Form 36 (varus: 66.8, valgus: 59.1)]. There were 2 patients in the valgus group and 3 patients in the varus group with an asymptomatic humeral head screw penetration (mean Constant 84.5, DASH 9.5). There was 1 deep infection in the varus group and 2 in the valgus group necessitating implant removal after fracture union. There was 1 case of avascular necrosis in the valgus group (DASH 19.4, Constant 73).

CONCLUSIONS

There were no significant differences in complication rates, radiographic, or clinical outcomes between fractures presenting with preoperative varus coronal displacement compared with those presenting with valgus coronal displacement. The equivalent outcomes may be attributed to the uniform operative technique and fibular strut augmentation used by the primary surgeon.

LEVEL OF EVIDENCE

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Occlusive vasculopathy with intimal hyperplasia and plexogenic arteriopathy are severe histopathological changes characteristic of pulmonary arterial hypertension (PAH). Although a phenotypic switch in pulmonary endothelial cells (ECs) has been suggested to play a critical role in the formation of occlusive lesions, the pathobiology of this process is poorly understood. The goal of this study was to identify novel molecular mechanisms associated with EC dysfunction and PAH-associated bone morphogenetic protein receptor 2 (BMPR2) deficiency during PAH pathogenesis. A bioinfomatics approach, patient samples, and in vitro experiments were used. By combining a metaanalysis of human idiopathic PAH (iPAH)-associated gene-expression microarrays and a unique gene expression-profiling technique in rat endothelium, our bioinformatics approach revealed a PAH-associated dysregulation of genes involving chromatin organization, DNA metabolism, and repair. Our hypothesis that altered DNA repair and loss of genomic stability play a role in PAH was supported by in vitro assays where pulmonary ECs from patients with iPAH and BMPR2-deficient ECs were highly susceptible to DNA damage. Furthermore, we showed that BMPR2 expression is tightly linked to DNA damage control because excessive DNA damage leads to rapid down-regulation of BMPR2 expression. Moreover, we identified breast cancer 1 (BRCA1) as a novel target for BMPR2 signaling and a novel modulator of pulmonary EC homeostasis. We show here that BMPR2 signaling plays a critical role in the regulation of genomic integrity in pulmonary ECs via genes such as BRCA1. We propose that iPAH-associated EC dysfunction and genomic instability are mediated through BMPR2 deficiency-associated loss of DNA damage control.