Save the subchondral bone plate: Debridement versus bone marrow stimulation in acetabular cartilage defects over 60 months of follow-up.

PURPOSE: Bone marrow stimulation is a common treatment for full-thickness cartilage defects in the hip joint. However, common procedures may result in poor fibrous repair tissue and changes to the subchondral anatomy. This study investigated the clinical outcome of a cohort of International Cartilage Repair Society (ICRS) grades 3 and 4 cartilage defects treated with bone marrow stimulation compared to those who received simple debridement/chondroplasty. METHODS: In this retrospective registry study, 236 patients with uni-focal acetabular chondral lesions of the hip up to 400 mm² (mean 177.4 ± 113.4 mm²) and of ICRS grade ≥3 with follow-up of at least 12 months (mean 33.2 ± 15.3 months) were included. Eighty-one patients underwent bone marrow stimulation (microfracture: n = 44, abrasion: n = 37) besides treatment of the underlying pathology, 155 patients underwent defect debridement/chondroplasty. The patient-reported outcome was measured using the International Hip Outcome Tool 33 (iHOT33) score and the Visual Analogue Scale (VAS) for pain. RESULTS: iHOT33 and VAS both improved highly statistically significantly (p < 0.001) in the debridement group after 6, 12, 24, 36 and 60 months compared to the preoperative scores, whereas iHOT33 and VAS after microfracture or abrasion did not show statistically significant changes over time. Twenty-four and sixty months postsurgery the debridement group revealed significant higher scores in the iHOT33 compared to the bone marrow stimulation groups. CONCLUSION: Patients with chondral lesions of the hip ≤400 mm2 sustainably benefit from arthroscopic debridement under preservation of the subchondral bone plate in terms of functional outcome and pain in contrast to patients treated with bone marrow stimulation. These findings discourage the currently recommended use of microfracture in the hip joint. LEVEL OF EVIDENCE: Level III.

Interaction of arsenic trioxide and etoposide in Ewing sarcoma cell lines.

Ewing sarcomas (ES) are highly malignant mesenchymal tumors, which most often occur in children and adolescents. The current treatment of choice comprises wide resection in combination with multimodal chemotherapy including etoposide (Eto). Due to the serious side effects associated with common chemotherapeutics and prevalent multidrug resistance in recurrent and metastatic ES, there is a growing demand for alternative strategies and add­on drugs. Previous research has demonstrated efficient cell death induction by Eto in combination with arsenic trioxide (ATO) in ES cell lines. The aim of the present study was to investigate the effect of different temporal sequences of ATO and Eto administration on apoptosis induction and to explore the effect of both drugs on inhibitory glycogen synthase kinase­3ß (GSK3­ß) phosphorylation as well as multidrug transporter gene expression. The intensity of caspase activation was mainly determined by the Eto doses in A673 and TC­71 cells, whereas in RD­ES cells ATO application actively suppressed Eto­induced apoptosis. This coincided with an increase in inhibitory GSK­3ß phosphorylation in ATO­treated RD­ES cells. Inherent mRNA expression of multidrug resistance­associated protein 1 (MRP1) was low in the ES cell lines compared to that observed in the mesenchymal stem cells (MSC), whereas multidrug resistance protein 1 (MDR1) gene expression was considerably increased in the ES cell lines. ATO treatment reduced MRP1 mRNA expression in the A673 and TC­71 cells, while expression was induced in the MSC and RD­ES cells. In contrast, MDR1 mRNA expression was specifically induced by ATO in the A673 and TC­71 cells, reinforcing the expression differences between MSC and the ES cell lines. Although a reliable cell death induction by the combination of ATO and Eto has been previously shown in ES cell lines, the present study showed marked heterogeneity of the ES cell response to ATO and Eto treatment, illustrating the difficulty of prediction of individual treatment outcome in ES.