Equivalent mortality after operation with sliding hip screw or intramedullary nail for trochanteric AO/OTA A1 and A2 fractures reported in the Norwegian Hip Fracture Register 2008 to 2020.

Aims: This study aimed to compare mortality in trochanteric AO/OTA A1 and A2 fractures treated with an intramedullary nail (IMN) or sliding hip screw (SHS). The primary endpoint was 30-day mortality, with secondary endpoints at 0 to 1, 2 to 7, 8 to 30, 90, and 365 days. Methods: We analyzed data from 26,393 patients with trochanteric AO/OTA A1 and A2 fractures treated with IMNs (n = 9,095) or SHSs (n = 17,298) in the Norwegian Hip Fracture Register (January 2008 to December 2020). Exclusions were made for patients aged < 60 years, pathological fractures, pre-2008 operations, contralateral hip fractures, fractures other than trochanteric A1/A2, and treatments other than IMNs or SHSs. Kaplan-Meier and Cox regression analyses adjusted for type of fracture, age, sex, cognitive impairment, American Society of Anesthesiologists (ASA) grade, and time period were conducted, along with calculations for number needed to harm (NNH). Results: In unadjusted analyses, there was no significant difference between IMN and SHS patient survival at 30 days (91.8% vs 91.1%; p = 0.083) or 90 days (85.4% vs 84.5%; p = 0.065), but higher one-year survival for IMNs (74.5% vs 73.3%; p = 0.031) compared with SHSs. After adjustments, no significant difference in 30-day mortality was found (hazard rate ratio (HRR) 0.94 (95% confidence interval (CI) 0.86 to 1.02(; p = 0.146). IMNs exhibited higher mortality at 0 to 1 days (HRR 1.63 (95% CI 1.13 to 2.34); p = 0.009) compared with SHSs, with a NNH of 556, but lower mortality at 8 to 30 days (HRR 0.89 (95% CI 0.80 to 1.00); p = 0.043). No differences were observed in mortality at 2 to 7 days (HRR 0.94 (95% CI 0.79 to 1.11); p = 0.434), 90 days (HRR 0.95 (95% CI 0.89 to 1.02); p = 0.177), or 365 days (HRR 0.97 (95% CI 0.92 to 1.02); p = 0.192). Conclusion: This study found no difference in 30-day mortality between IMNs and SHSs. However, IMNs were associated with a higher mortality at 0 to 1 days and a marginally lower mortality at 8 to 30 days compared with SHSs. The observed differences in mortality were small and should probably not guide choice of treatment.

Testing of the Survivin Suppressant YM155 in a Large Panel of Drug-Resistant Neuroblastoma Cell Lines.

The survivin suppressant YM155 is a drug candidate for neuroblastoma. Here, we tested YM155 in 101 neuroblastoma cell lines (19 parental cell lines, 82 drug-adapted sublines). Seventy seven (77) cell lines displayed YM155 IC50s in the range of clinical YM155 concentrations. ABCB1 was an important determinant of YM155 resistance. The activity of the ABCB1 inhibitor zosuquidar ranged from being similar to that of the structurally different ABCB1 inhibitor verapamil to being 65-fold higher. ABCB1 sequence variations may be responsible for this, suggesting that the design of variant-specific ABCB1 inhibitors may be possible. Further, we showed that ABCC1 confers YM155 resistance. Previously, p53 depletion had resulted in decreased YM155 sensitivity. However, TP53-mutant cells were not generally less sensitive to YM155 than TP53 wild-type cells in this study. Finally, YM155 cross-resistance profiles differed between cells adapted to drugs as similar as cisplatin and carboplatin. In conclusion, the large cell line panel was necessary to reveal an unanticipated complexity of the YM155 response in neuroblastoma cell lines with acquired drug resistance. Novel findings include that ABCC1 mediates YM155 resistance and that YM155 cross-resistance profiles differ between cell lines adapted to drugs as similar as cisplatin and carboplatin.