PLOS ONE / Oncological and surgical outcome after treatment of pelvic sarcomas

Background and objectives Treatment of pelvic tumors remains challenging due to complex anatomy, poor oncological outcome and high complication rates. We sought to investigate the long-term oncological and surgical outcome of these patients. Methods Between 1980 and 2012, 147 patients underwent surgical treatment for pelvic sarcoma. Histological diagnosis was Chondrosarcoma in 54, Ewings Sarcoma/PNET in 37, Osterosarcoma in 32 and others in 24 patients. Statistical analysis for the evaluation of oncological and surgical outcome was performed by applying Cox proportional hazards regression and Fine-Gray regression models for competing risk (CR) endpoints. Results The estimated overall survival (OS) to death was 80%, 45% and 37% at 1, 5 and 10 years, respectively. Univariate analyses revealed a statistically significant unadjusted influence of age age (p = 0.038; HR = 1.01), margin (p = 0.043; HR = 0.51) and grade (p = 0.001; HR = 2.27) on OS. Considering the multivariable model, grade (p = 0.005; HR = 3.04) and tumor volume (p = 0.014; HR = 1.18) presented themselves as independent prognostic factors on OS. CR analysis showed a cumulative incidence for major complication of 31% at 5 years. Endoprosthetic reconstruction had a higher risk for experiencing a major complication (p<0.0001) and infection (p = 0.001). Conclusions Pelvic resections are still associated with a high incidence of complications. Patients with pelvic reconstruction and high volume tumors are especially at risk. Consequently, a cautious decision-making process is necessary when indicating pelvic reconstruction, although a restrictive approach to pelvic reconstruction is not necessarily reasonable when the other option is major amputation.(VLID)486947

Data from: Oncological and surgical outcome after treatment of pelvic sarcomas

Background and Objectives. Treatment of pelvic tumors remains challenging due to complex anatomy, poor oncological outcome and high complication rates. We sought to investigate the long-term oncological and surgical outcome of these patients. Methods. Between 1980 and 2012, 147 patients underwent surgical treatment for pelvic sarcoma. Histological diagnosis was Chondrosarcoma in 54, Ewing's Sarcoma/PNET in 37, Osterosarcoma in 32 and others in 24 patients. Statistical analysis for the evaluation of oncological and surgical outcome was performed by applying Cox proportional hazards regression and Fine-Gray regression models for competing risk (CR) endpoints. Results. The estimated overall survival (OS) to death was 80%, 45% and 37% at 1, 5 and 10 years, respectively. Univariate analyses revealed a statistically significant unadjusted influence of age age (p=0.038; HR=1.01), margin (p=0.043; HR=0.51) and grade (p=0.001; HR=2.27) on OS. Considering the multivariable model, grade (p=0.005; HR=3.04) and tumor volume (p=0.014; HR=1.18) presented themselves as independent prognostic factors on OS. CR analysis showed a cumulative incidence for major complication of 31% at 5 years. Endoprosthetic reconstruction had a higher risk for experiencing a major complication (p<0.0001) and infection (p=0.001). Conclusions. Pelvic resections are still associated with a high incidence of complications. Patients with pelvic reconstruction and high volume tumors are especially at risk. Consequently, a cautious decision-making process is necessary when indicating pelvic reconstruction, although a restrictive approach to pelvic reconstruction is not necessarily reasonable when the other option is major amputation

Fragment screening using biolayer interferometry reveals ligands targeting the SHP-motif binding site of the AAA+ ATPase p97

Biosensor techniques have become increasingly important for fragment-based drug discovery during the last years. The AAA+ ATPase p97 is an essential protein with key roles in protein homeostasis and a possible target for cancer chemotherapy. Currently available p97 inhibitors address its ATPase activity and globally impair p97-mediated processes. In contrast, inhibition of cofactor binding to the N-domain by a protein-protein-interaction inhibitor would enable the selective targeting of specific p97 functions. Here, we describe a biolayer interferometry-based fragment screen targeting the N-domain of p97 and demonstrate that a region known as SHP-motif binding site can be targeted with small molecules. Guided by molecular dynamics simulations, the binding sites of selected screening hits were postulated and experimentally validated using protein- and ligand-based NMR techniques, as well as X-ray crystallography, ultimately resulting in the first structure of a small molecule in complex with the N-domain of p97. The identified fragments provide insights into how this region could be targeted and present first chemical starting points for the development of a protein-protein interaction inhibitor preventing the binding of selected cofactors to p97

Do Elevated Serum C-Reactive-Protein Levels Excuse Delayed Surgery for Femoral Neck Fractures?

In elderly patients with femoral neck fractures, preoperative serum C-reactive protein (CRP) values might be elevated due to active infections. Although there are limited data on CRP as a predictor of periprosthetic joint infection (PJI), out of concern, this could lead to delayed surgery. Therefore, we aim to investigate whether elevated serum-CRP levels justify delayed surgery for femoral neck fractures. A retrospective analysis was performed of the records of patients undergoing arthroplasty who were found to have an elevated CRP level of 5 mg/dL or more between January 2011 to December 2020. The patients were stratified to three groups, according to initial serum CRP levels at a cut off of 5 mg/dL and the time between admission and surgery (<48 vs. ≥48 h after admission). This study revealed that the patients with elevated serum CRP levels and delayed surgery showed a worse survival rate and significantly more postoperative complications than the patients on whom surgery was performed immediately. There were no significant differences in terms of PJI and prolonged wound healing in the inter-group comparison. Therefore, delays to surgery on the basis of elevated CRP values offer no benefits to patients with femoral neck fractures

Scientific Reports / Surgical and Functional Outcome after Endoprosthetic Reconstruction in Patients with Osteosarcoma of the Humerus

Endoprosthetic reconstruction (EPR) is the most widely used reconstruction technique after humeral osteosarcoma (OSA). Complications are common and function is often compromised due to the premise of wide resection. In the current study we evaluated (1) the risk of complications after resection and EPR; (2) the functional outcome and how it is influenced by the preservation/resection of deltoid muscle (DM), rotator cuff (RC), axillary nerve or the type of resection (intra-/extraarticular) and (3) if the preservation/resection of DM, RC, axillary nerve or the type of resection has a negative influence on the oncological outcome. We retrospectively evaluated data of 49 patients with humeral OSA. All patients underwent resection and EPR. Complication-free survival according to the ISOLS classification was estimated by a competing risk model. Functional outcome was evaluated by range of motion (ROM) in abduction and the MSTS score. Eleven patients (22%) had at least one complication. The estimated cumulative incidence for the first complication was 18% at one year, 23% at five years, and 28% at ten years, respectively. Soft tissue failure was the most common complication. ROM and MSTS scores were significantly higher in patients where DM and RC (p=0.043/p=0.046) and axillary nerve (p=0.014/p=0.021) could be preserved. Preservation of these structures had no negative influence on the surgical margins. In conclusion, EPR is a good treatment method with an acceptable complication rate. Preservation of the abductor mechanism, when possible in the setting of obtaining negative margins, provides superior functional outcome.(VLID)472614

The influence of antibiotic-loaded cement spacers on the risk of reinfection after septic two-stage hip revision surgery

Purpose The aim of this study was the evaluation of possible outcome differences of patients undergoing two-stage hip exchange with antibiotic-loaded spacers, compared to patients without an interim spacer implantation. Methods We evaluated 46 patients undergoing two-stage hip revision surgery. Twenty-five patients received an interim ALS. Additional to a KaplanMeier survival analysis, a competing risk analysis was performed to estimate the cumulative incidence function for re-revisions due to infection accounting for death as a competing event. Results Nine patients (seven non-ALS vs. two ALS) had to undergo re-revision surgery due to reinfection of the hip joint. The non-ALS group showed a risk of re-revision of 19% (95% CI 538%) at 12 and 24 months and 30% (95% CI 1251%) at 36 months. The group with ALS implantation displayed a 0% risk of re-revision surgery in the first 36 months. The Gray test revealed a significant difference in the cumulative incidence between both observed groups (p = 0.026). Conclusion Our findings suggest that ALS implantation significantly reduces the risk of reinfection after two-stage hip revision surgery.(VLID)357000

PLOS One / Outcome after Reconstruction of the Proximal Tibia Complications and Competing Risk Analysis

Background and Objectives The proximal tibia (pT) is a common site for bone tumors. Improvements in imaging, chemotherapy and surgical technique made limb salvage surgery the treatment of choice. Yet, reconstructions of the pT have been associated with less favorable outcome compared to other parts of the extremities. The aim of this study was to evaluate the outcome of patients with a modular endoprosthetic reconstruction of the pT. Methods Eighty-one consecutive patients with an average age of 29 years underwent endoprosthetic reconstruction of the pT. Postoperative complications were categorized according to the ISOLS classification, and revision-free survival until first complication (any Type 15), soft tissue failure (Type 1), aseptic loosening (Type 2), structural failure (Type 3), infection (Type 4), and local tumor progression (Type 5) was estimated by using a Fine-Gray model for competing risk analyses for univariate and multivariable regression with Firths bias correction. Results A total of 45 patients (56%) had at least one complication. Cumulative incidence for complication Types 1 to 5 at 5 years with death and amputation as competing events revealed a risk of 41% for the first complication, 14% for Type 1, 16% for Type 2, 11% for Type 3, 17% for Type 4, and 1% for Type 5. Conclusion Despite inclusion of amputation and death as strong competing events, pT replacements are still associated with a high risk of postoperative failures. The results suggest that infection and soft tissue failures (Type 1 and 5) seem to depend from each other. Sufficient soft tissue reconstruction and closure allow better function and reduce the risk of infection as the most prominent complication. The use of a rotating hinge design has significantly reduced structural failures over time.(VLID)492415

Baseline characteristics and operative data.

<p>Baseline characteristics and operative data.</p

Cumulative incidence of first major complication, infection and neurovascular complication was assessed by CR analysis.

<p>Cumulative incidence of first major complication, infection and neurovascular complication was assessed by CR analysis.</p