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Simple Summary: This study investigated the impact of the general health status on the survival of patients with high-grade chondrosarcoma, a rare type of bone cancer. This systemic health status is often summarized using the American Society of Anesthesiologists (ASA) score. By analyzing data from 249 patients, the study found that a higher ASA score, older age, and more aggressive tumors were linked to poorer survival rates. This study highlights that a patient's general health, especially for those with severe systemic diseases, should be considered when determining treatment plans, alongside traditional factors like tumor grade and age. These findings can improve decision-making for complex surgeries in patients with high-grade chondrosarcoma. Background: Due to the relatively advanced age and high mortality rate of patients with high-grade chondrosarcoma (CS), it is important to holistically assess patient- and tumor characteristics in multidisciplinary team and shared decision-making with regard to treatment options. While current prognostic models include multiple tumor and treatment characteristics, the only patient characteristics that are commonly included are age and gender. Based on clinical experience, we believe that factors related to patient preoperative systemic health status such as the American Society of Anesthesiologists (ASA) score may be equally important prognostic factors for overall survival (OS). Methods: A retrospective nationwide cohort study was identified from four specialized bone sarcoma centers in The Netherlands. Patients with a primary CS grade II, III, and dedifferentiated CS were eligible. Prognostic factors including age at presentation, gender, ASA score, CVD, tobacco use, BMI, histological tumor grade, tumor size, pathological fracture, presentation after unplanned excision, type of surgery and surgical margin were evaluated. The outcome measure was OS at the time of surgery. The Kaplan–Meier methodology was employed to estimate OS; a log-rank test was used to assess the difference in survival. To study the impact of prognostic factors on OS, a multivariate Cox proportional hazard regression model was estimated. Results: In total, 249 patients were eligible for this study, and 89 were deceased at the end of follow-up. In multivariate analysis, histological grade (HR 2.247, 95% CI 1.334–3.783), ASA score III (HR 2.615, 95% CI 1.145–5.976, vs. ASA I), and age per year (HR: 1.025, 95% CI 1.004–1.045) were negatively associated with OS. No association was found between tobacco use, BMI, gender or cardiovascular disease and OS in this cohort. Pathological fracture and tumor size were only associated with OS in univariate analysis. Conclusions: This multicenter study is the first on sarcomas to include ASA in a prognostic model. Results show that ASA score as a proxy for patients' systemic health status should be included when providing a prognosis for patients with a high-grade primary CS, besides the conventional risk factors such as tumor grade and age. Specifically, severe systemic disease (ASA score III) is a strong negative predictor. Conversely, we found no difference in OS between ASA scores I and II. These findings aid multidisciplinary team and shared decision-making with regard to these complex sarcoma patients that often require life-changing surgeries. Level of Evidence: Prognostic level III. See the instructions for authors for the complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Purpose: The impact of MRI on early detection of local recurrence (LR) in high-grade soft-tissue sarcomas (STS) is unsubstantiated. To identify the contribution of MRI criteria including dynamic contrast-enhanced (DCE) MRI and knowledge of surgical margins that can be used in detecting recurrence prior to obvious proven presence of LR in soft-tissue sarcomas. The secondary aim was to determine causes for misdiagnosing LR.Methods: MRI of 23 patients (12 men; mean age, 59.7 years ± 16.5 years) with LR of STS and that of 22 age- and histology-matched controls with STS but without LR were retrospectively analyzed by two musculoskeletal radiologists. Preoperative MRI characteristics (conventional and DCE) were compared to those of MRIs made after treatment, but before LR was proven. Likelihood of recurrence was rated on a 5-point Likert scale for morphological and dynamic assessment separately, before and after adding knowledge of surgical margins. Descriptive statistics and receiver operating characteristic analysis were performed.Results: Differentiation of LR from post-therapeutic changes was the highest combining result of conventional MRI, DCE-MRI, and knowledge of surgical margins (area under the curve (AUC) 0.779), followed by DCE-MRI (AUC 0.706) and conventional MRI (AUC 0.648). Suboptimal MRI technique and overcalling post-therapeutic changes in microscopic positive margins were the main reasons for false negative and false positive results, respectively.Conclusion: MRI including DCE improves the detection of recurrent, clinically silent soft-tissue sarcoma when combined with knowledge of achieved surgical margins. LR may be missed on inadequate MRI protocols.Key Points: • Dynamic contrast-enhanced MRI is useful in the differentiation of recurrent soft-tissue sarcoma and post-therapeutic fibrosis. • Knowledge of surgical margins substantially increases the value of MRI in detecting recurrent soft-tissue sarcoma. • MR with all three image orientations, covering the entire part of the extremity in at least one sequence and comparison to initial tumor characteristics and location, is beneficial. [ABSTRACT FROM AUTHOR]

Background: Up to 40% of patients with idiopathic clubfoot who are treated with the Ponseti method experience recurrence of deformity. Many of these patients receive surgery (e.g., anterior tibial tendon transfer). An alternative approach for recurrent clubfoot is repeat Ponseti casting. The purpose of this study was to evaluate the outcome of repeat Ponseti casting in the treatment of recurrent clubfoot.Methods: Patients with recurrent idiopathic clubfoot who were treated at our hospital, between 2004 and 2012, with repeat serial casting and bracing (the recurrent group) were eligible for inclusion in the study. The recurrent group and a control group of randomly selected patients seen during the same period who had not had recurrence were compared with respect to demographic data, age at the time of treatment, number of casts, subsequent surgical intervention(s), and the Disease-Specific Instrument (DSI) clubfoot scale. Patients were deemed to have a successful outcome if they had a well-corrected foot (defined as dorsiflexion of ≥10°, hindfoot in valgus, and a straight lateral border) at the time of follow-up.Results: Of a total of 71 eligible patients with clubfeet, 35 patients participated. At the time of follow-up, success rates were 74% for the recurrent group and 83% for the control group. Dorsiflexion past neutral was significantly higher in the control group than the patient group (20° versus 12°, respectively; p < 0.001). Ninety-five percent of the control subjects had a straight lateral border in comparison with 78% in the recurrent group (p = 0.004). Likewise, 97% of controls had the hindfoot in valgus in comparison with 80% of the recurrent group (p = 0.02). There was a significant difference in the ability to squat (76% in the control group and 43% in the recurrent group; p = 0.03). There was no difference between groups in the total outcome of the DSI.Conclusions: Recurrence was seen in 19% (71) of 382 children who were eligible for our study who were typically discharged after the age of 5 years from our clinic, indicating the importance of continued follow-up until after that age. Treatment with casting was successful in many patients and may be a reasonable choice for recurrent idiopathic clubfeet.Level Of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background To support shared decision-making, we developed the first prediction model for patients with primary soft-tissue sarcomas of the extremities (ESTS) which takes into account treatment modalities, including applied radiotherapy (RT) and achieved surgical margins. The PERsonalised SARcoma Care (PERSARC) model, predicts overall survival (OS) and the probability of local recurrence (LR) at 3, 5 and 10 years. Aim Development and validation, by internal validation, of the PERSARC prediction model. Methods The cohort used to develop the model consists of 766 ESTS patients who underwent surgery, between 2000 and 2014, at five specialised international sarcoma centres. To assess the effect of prognostic factors on OS and on the cumulative incidence of LR (CILR), a multivariate Cox proportional hazard regression and the Fine and Gray model were estimated. Predictive performance was investigated by using internal cross validation (CV) and calibration. The discriminative ability of the model was determined with the C-index. Results Multivariate Cox regression revealed that age and tumour size had a significant effect on OS. More importantly, patients who received RT showed better outcomes, in terms of OS and CILR, than those treated with surgery alone. Internal validation of the model showed good calibration and discrimination, with a C-index of 0.677 and 0.696 for OS and CILR, respectively. Conclusions The PERSARC model is the first to incorporate known clinical risk factors with the use of different treatments and surgical outcome measures. The developed model is internally validated to provide a reliable prediction of post-operative OS and CILR for patients with primary high-grade ESTS. Level of significance level III. [ABSTRACT FROM AUTHOR]

Background Diabetes and particularly high blood glucose levels are implicated in neurodegeneration. One of the hallmarks of neurodegeneration is protein aggregation. We investigated the presence of protein aggregation in the frontal brain of Zucker diabetic fatty (ZDF) rats, an animal model for diabetes. Further, the effect of NaHS in suppressing protein aggregation in cultured brain slices from ZDF was assessed. Results The levels of protein synthesis, protein/gene expression, autophagy and anti-oxidant defense were evaluated in ZDF and control (Lean) brains. Compared to Lean, ZDF brains displayed a significant increase in protein aggregates, p-tau, fibronectin expression and protein glycosylation. Increased phosphorylation of mTOR and S6 ribosomal protein in ZDF indicated higher protein synthesis, while the increase in ubiquitinated proteins and LC3-I in ZDF brains accompanied by lower LC3-II expression and LC3-II/LC3-I levels indicated the blockage of proteolytic pathways. CBS (cystathionine beta synthase) protein and mRNA expression and thiol group levels in ZDF brains were lower compared to Lean. ZDF brains show a higher level of reactive oxygen species. In vitro NaHS treatment normalized proteostasis while counteracting oxidative stress. Conclusion Our data demonstrate increased protein synthesis and aggregation in the diabetic ZDF rat brain, which was reversible by NaHS treatment. This is the first report on the potential use of NaHS as a novel strategy against protein aggregation in diabetic brain. [ABSTRACT FROM AUTHOR]

Background. With soft-tissue sarcoma of the extremity (ESTS) representing a heterogenous group of tumors, management decisions are often made in multidisciplinary team (MDT) meetings. To optimize outcome, nomograms are more commonly used to guide individualized treatment decision making. Purpose. To evaluate the influence of Personalised Sarcoma Care (PERSARC) on treatment decisions for patients with high-grade ESTS and the ability of the MDT to accurately predict overall survival (OS) and local recurrence (LR) rates. Methods. Two consecutive meetings were organised. During the first meeting, 36 cases were presented to the MDT. OS and LR rates without the use of PERSARC were estimated by consensus and preferred treatment was recorded for each case. During the second meeting, OS/LR rates calculated with PERSARC were presented to the MDT. Differences between estimated OS/LR rates and PERSARC OS/LR rates were calculated. Variations in preferred treatment protocols were noted. Results. The MDT underestimated OS when compared to PERSARC in 48.4% of cases. LR rates were overestimated in 41.9% of cases. With the use of PERSARC, the proposed treatment changed for 24 cases. Conclusion. PERSARC aids the MDT to optimize individualized predicted OS and LR rates, hereby guiding patient-centered care and shared decision making. [ABSTRACT FROM AUTHOR]