Conversion total hip arthroplasty for early failure following unstable intertrochanteric hip fracture: what can patients expect?

PURPOSE: To report surgical outcomes in patients treated with conversion total hip arthroplasty (CTHA) for early failure of cephalomedullary nails (CMNs). METHODS: A retrospective review was conducted of CTHA for treatment of failed CMN within 1 year of initial surgery for intertrochanteric (IT) hip fractures. The cohort was matched 1:5 to patients who underwent elective primary THA (PTHA). Patient demographics, mechanism of CMN failure, surgical outcomes, and complication rates were assessed. RESULTS: 22 patients met criteria with a mean time to failure of 145 days. Modes of failure included: lag screw cut-out with superior migration (9, 40.9%), or medialization (8, 36.4%), and aseptic nonunion with implant failure (2, 9.0%) and without implant failure (3, 13.6%). Fourteen of the patients (63.6%) had acetabular-sided damage secondary to lag screw penetration, all in the screw cut-out groups. Patient demographics were similar between cohorts. Compared to PTHA, CTHA patients had increased operative time, blood loss, LOS, and readmission rates. After IMN failure, the operative leg was shorter than the contralateral leg in all cases. CTHA restored leg lengths to < = 10 mm in 15 (68.1%) of patients, with an average leg length discrepancy after CTHA of 6.7 mm. CTHA patients had increased rates of overall surgical complications and medical complications, specifically anemia (all p < 0.01). Tranexamic acid was used less often in the CTHA group (p < 0.01). Rate of periprosthetic joint infection (PJI), dislocation, and revision were all higher in the CTHA, though did not reach statistical significance. CONCLUSION: The majority (77.3%) of CMN implant failure for nonunion within 1 year was due to screw cut-out. CTHA is a salvage option for early failed IT hip fracture repair, but expected surgical outcomes are more similar to revision THA than primary THA, with increased risk of readmission, longer surgery and LOS, increased blood loss, and higher complication rates. LEVEL OF EVIDENCE: III, Retrospective comparative study.

Bridging cancer biology with the clinic: relative expression of a GRHL2-mediated gene-set pair predicts breast cancer metastasis.

Identification and characterization of crucial gene target(s) that will allow focused therapeutics development remains a challenge. We have interrogated the putative therapeutic targets associated with the transcription factor Grainy head-like 2 (GRHL2), a critical epithelial regulatory factor. We demonstrate the possibility to define the molecular functions of critical genes in terms of their personalized expression profiles, allowing appropriate functional conclusions to be derived. A novel methodology, relative expression analysis with gene-set pairs (RXA-GSP), is designed to explore the potential clinical utility of cancer-biology discovery. Observing that Grhl2-overexpression leads to increased metastatic potential in vitro, we established a model assuming Grhl2-induced or -inhibited genes confer poor or favorable prognosis respectively for cancer metastasis. Training on public gene expression profiles of 995 breast cancer patients, this method prioritized one gene-set pair (GRHL2, CDH2, FN1, CITED2, MKI67 versus CTNNB1 and CTNNA3) from all 2717 possible gene-set pairs (GSPs). The identified GSP significantly dichotomized 295 independent patients for metastasis-free survival (log-rank tested p = 0.002; severe empirical p = 0.035). It also showed evidence of clinical prognostication in another independent 388 patients collected from three studies (log-rank tested p = 3.3e-6). This GSP is independent of most traditional prognostic indicators, and is only significantly associated with the histological grade of breast cancer (p = 0.0017), a GRHL2-associated clinical character (p = 6.8e-6, Spearman correlation), suggesting that this GSP is reflective of GRHL2-mediated events. Furthermore, a literature review indicates the therapeutic potential of the identified genes. This research demonstrates a novel strategy to integrate both biological experiments and clinical gene expression profiles for extracting and elucidating the genomic impact of a novel factor, GRHL2, and its associated gene-sets on the breast cancer prognosis. Importantly, the RXA-GSP method helps to individualize breast cancer treatment. It also has the potential to contribute considerably to basic biological investigation, clinical tools, and potential therapeutic targets.