Restoration of hip geometry after total hip arthroplasty: retrospective comparison of two short stems and one straight stem.

BACKGROUND: The preservation or restoration of hip geometry following total hip arthroplasty (THA) is of importance, considering that alterations in the centrum-collum-diaphysis (CCD)-angle, femoral offset (FO), acetabular offset (AO) and total offset (TO) change hip biomechanics. Therefore, the most suitable implant should be used. The aim of this study was to compare the ability of two short-stem-systems and one straight-stem-system to reconstruct hip geometry. METHODS: Two-hundred-fifty-one patients (mean age: 62.0 ± 10.0 years; 51.8% males) undergoing THA with three different stem types were retrospectively included, after excluding 11 patients with missing radiological follow-up. Pre- and postoperative radiographic images (group I, ANA.NOVA Alpha Schaft Proxy®, ImplanTec, 12 options: n = 99; group II, Optimys® Mathys, 24 options: n = 62; group III: Corail®-System, DePuy-Synthes, 76 options: n = 90) were analyzed. Differences in pre- and postoperative hip geometry (i.e. CCD, FO, AO, TO) were compared between groups with one-way-analysis-of-variance (ANOVA), and post-hoc t-tests. RESULTS: The CCD-angle increased by a mean of 8.4° ± 7.2° from pre-to postoperative, with no significant difference between groups (p = 0.097). Significantly larger increases in FO were observed for groups II (4.1 mm ± 7.8 mm) and III (4.9 ± 7.2 mm), in comparison to group I (1.6 ± 6.9 mm; p = 0.006). AO decreased by a mean of 2.2 ± 4.5 mm, with the largest decrease observed in group III (-3.3 ± 5.3 mm), and the smallest for group I (-1.4 ± 3.6 mm; p = 0.011). There was no significant difference in change of TO between groups (p = 0.177). CONCLUSIONS: Reconstruction of hip geometry using a single-version novel short-stem-system is achievable with comparable results to stem-systems offering multiple options.

T-regulatory cells predict clinical outcome in soft tissue sarcoma patients: a clinico-pathological study.

BACKGROUND: Soft tissue sarcomas (STS) are generally considered non-immunogenic, although specific subtypes respond to immunotherapy. Antitumour response within the tumour microenvironment relies on a balance between inhibitory and activating signals for tumour-infiltrating lymphocytes (TILs). This study analysed TILs and immune checkpoint molecules in STS, and assessed their prognostic impact regarding local recurrence (LR), distant metastasis (DM), and overall survival (OS). METHODS: One-hundred and ninety-two surgically treated STS patients (median age: 63.5 years; 103 males [53.6%]) were retrospectively included. Tissue microarrays were constructed, immunohistochemistry for PD-1, PD-L1, FOXP3, CD3, CD4, and CD8 performed, and staining assessed with multispectral imaging. TIL phenotype abundance and immune checkpoint markers were correlated with clinical and outcome parameters (LR, DM, and OS). RESULTS: Significant differences between histology and all immune checkpoint markers except for FOXP3+ and CD3-PD-L1+ cell subpopulations were found. Higher levels of PD-L1, PD-1, and any TIL phenotype were found in myxofibrosarcoma as compared to leiomyosarcoma (all p < 0.05). The presence of regulatory T cells (Tregs) was associated with increased LR risk (p = 0.006), irrespective of margins. Other TILs or immune checkpoint markers had no significant impact on outcome parameters. CONCLUSIONS: TIL and immune checkpoint marker levels are most abundant in myxofibrosarcoma. High Treg levels are independently associated with increased LR risk, irrespective of margins.

Incidence, treatment and outcome of abdominal metastases in extremity soft tissue sarcoma: Results from a multi-centre study.

BACKGROUND AND OBJECTIVES: Abdominal metastases (AM) from soft tissue sarcoma (STS) are rare and prognosis is poor. The aims of the study were to (a) identify risk factors for the development of AM and to (b) investigate the outcome of AM-patients. METHODS: Seven-hundred-sixty-nine STS-patients with localised disease at diagnosis treated at three tumour centres (2000-2016) were retrospectively included (409 males; mean age, 55.6 years [range, 8-96 years]; median follow-up, 4.1 years [interquartile-range, 2.5-6.6 years]). RESULTS: Two-hundred-two patients (26.3%) developed secondary metastases, and 24 of them AM (3.1%). Ten patients developed first AM (FAM) after a mean of 2.4 years and 14 patients late AM (LAM, after being diagnosed with metastases to other sites) after a mean of 2.0 years. Patients with liposarcoma had a significantly higher risk of developing AM (P = .007), irrespective of grading. There was no difference in post-metastasis-survival (PMS) between patients with AM at any time point and those with metastases to other sites (P = .585). Patients with LAM or FAM showed no difference in post-abdominal-metastasis-survival (P = .884). CONCLUSIONS: Survival in patients with AM is poor, irrespective of whether they develop secondarily to other metastases or not. Patients at high-risk of AM (ie, liposarcoma) may be followed-up regularly by abdominal-ultrasound/CT.

Current Insights into Long Non-Coding RNAs (LncRNAs) in Prostate Cancer.

The importance of long non-coding RNAs (lncRNAs) in the pathogenesis of various malignancies has been uncovered over the last few years. Their dysregulation often contributes to or is a result of tumour progression. In prostate cancer, the most common malignancy in men, lncRNAs can promote castration resistance, cell proliferation, invasion, and metastatic spread. Expression patterns of lncRNAs often change during tumour progression; their expression levels may constantly rise (e.g., HOX transcript antisense RNA, HOTAIR), or steadily decrease (e.g., downregulated RNA in cancer, DRAIC). In prostate cancer, lncRNAs likewise have diagnostic (e.g., prostate cancer antigen 3, PCA3), prognostic (e.g., second chromosome locus associated with prostate-1, SChLAP1), and predictive (e.g., metastasis-associated lung adenocarcinoma transcript-1, MALAT-1) functions. Considering their dynamic role in prostate cancer, lncRNAs may also serve as therapeutic targets, helping to prevent development of castration resistance, maintain stable disease, and prohibit metastatic spread.

Long Non-Coding RNAs in Endometrial Carcinoma.

Endometrial carcinoma (EC), the second most common form of gynaecological malignancy, can be divided into two distinct sub-types: Type I tumours arise from hyperplastic endometrium and typically effect women around the time of menopause, whereas type II tumours arise in postmenopausal women from atrophic endometrium. Long non-coding RNAs (lncRNAs) are a novel class of non-protein coding molecules that have recently been implicated in the pathogenesis of many types of cancer including gynaecological tumours. Although they play critical physiological roles in cellular metabolism, their expression and function are deregulated in EC compared with paired normal tissue, indicating that they may also participate in tumour initiation and progression. For instance, the lncRNA MALAT-1 is down-regulated in EC samples compared to normal or hyperplastic endometrium, whereas the lncRNA OVAL is down-regulated in type II disease but up-regulated in type I disease. Other notatble lncRNAs such as HOTAIR, H19 and SRA become up-regulated with increasing EC tumour grade and other features associated with poor prognosis. In the current review, we will examine the growing body of evidence linking deregulated lncRNAs with specific biological functions of tumour cells in EC, we will highlight associations between lncRNAs and the molecular pathways implicated in EC tumourigenesis and we will identify critical knowledge gaps that remain to be addressed.

30-day and one-year readmission rate in 11,270 patients with surgical treatment for proximal femoral fractures across Austria.

Aims: Patients with proximal femoral fractures (PFFs) are often multimorbid, thus unplanned readmissions following surgery are common. We therefore aimed to analyze 30-day and one-year readmission rates, reasons for, and factors associated with, readmission risk in a cohort of patients with surgically treated PFFs across Austria. Methods: Data from 11,270 patients with PFFs, treated surgically (osteosyntheses, n = 6,435; endoprostheses, n = 4,835) at Austrian hospitals within a one-year period (January to December 2021) was retrieved from the Leistungsorientierte Krankenanstaltenfinanzierung (Achievement-Oriented Hospital Financing). The 30-day and one-year readmission rates were reported. Readmission risk for any complication, as well as general medicine-, internal medicine-, and surgery/injury-associated complications, and factors associated with readmissions, were investigated. Results: The 30-day and one-year readmission rates due to any complication were 15% and 47%, respectively. The 30-day readmission rate (p = 0.001) was higher in endoprosthesis than osteosynthesis patients; this was not the case for the one-year readmission rate (p = 0.138). Internal medicine- (n = 2,273 (20%)) and surgery/injury-associated complications (n = 1,612 (14%)) were the most common reason for one-year readmission. Regardless of the surgical procedure, male sex was significantly associated with higher readmission risk due to any, as well as internal medicine-associated, complication. Advanced age was significantly associated with higher readmission risk after osteosynthesis. In both cohorts, treatment at mid-sized hospitals was significantly associated with lower readmission risk due to any complication, while prolonged length of stay was associated with higher one-year readmission risks due to any complication, as well as internal-medicine associated complications. Conclusion: Future health policy decisions in Austria should focus on optimization of perioperative and post-discharge management of this vulnerable patient population.

Effect of radiotherapy on local recurrence, distant metastasis and overall survival in 1200 extremity soft tissue sarcoma patients. Retrospective analysis using IPTW-adjusted models.

BACKGROUND AND PURPOSE: Neoadjuvant (NRTX) and adjuvant radiotherapy (ARTX) reduce local recurrence (LR) risk in extremity soft tissue sarcoma (eSTS), yet their impact on distant metastasis (DM) and overall survival (OS) is less well defined. This study aimed at analysing the influence of NRTX/ARTX on all three endpoints using a retrospective, multicentre eSTS cohort. MATERIALS AND METHODS: 1200 patients (mean age: 60.7 ± 16.8 years; 44.4 % females) were retrospectively included, treated with limb sparing surgery and curative intent for localised, high grade (G2/3) eSTS. 194 (16.2 %), 790 (65.8 %), and 216 (18.0 %) patients had received NRTX, ARTX and no RTX, respectively. For the resulting three groups (no RTX vs. NRTX, no RTX vs. ARTX, NRTX vs. ARTX) Fine&Gray models for LR and DM, and Cox-regression models for OS were calculated, with IPTW-modelling adjusting for imbalances between groups. RESULTS: In the IPTW-adjusted analysis, NRTX was associated with lower LR-risk in comparison to no RTX (SHR [subhazard ratio]: 0.236; p = 0.003), whilst no impact on DM-risk (p = 0.576) or OS (p = 1.000) was found. IPTW-weighted analysis for no RTX vs. ARTX revealed a significant positive association between ARTX and lower LR-risk (SHR: 0.479, p = 0.003), but again no impact on DM-risk (p = 0.363) or OS (p = 0.534). IPTW-weighted model for NRTX vs. ARTX showed significantly lower LR-risk for NRTX (SHR for ARTX: 3.433; p = 0.003) but no difference regarding DM-risk (p = 1.000) or OS (p = 0.639). CONCLUSION: NRTX and ARTX are associated with lower LR-risk, but do not seem to affect DM-risk or OS. NRTX may be favoured over ARTX as our results indicate better local control rates.

Cell2Grid: an efficient, spatial, and convolutional neural network-ready representation of cell segmentation data.

Purpose: Cell segmentation algorithms are commonly used to analyze large histologic images as they facilitate interpretation, but on the other hand they complicate hypothesis-free spatial analysis. Therefore, many applications train convolutional neural networks (CNNs) on high-resolution images that resolve individual cells instead, but their practical application is severely limited by computational resources. In this work, we propose and investigate an alternative spatial data representation based on cell segmentation data for direct training of CNNs. Approach: We introduce and analyze the properties of Cell2Grid, an algorithm that generates compact images from cell segmentation data by placing individual cells into a low-resolution grid and resolves possible cell conflicts. For evaluation, we present a case study on colorectal cancer relapse prediction using fluorescent multiplex immunohistochemistry images. Results: We could generate Cell2Grid images at 5 - µ m resolution that were 100 times smaller than the original ones. Cell features, such as phenotype counts and nearest-neighbor cell distances, remain similar to those of original cell segmentation tables ( p < 0.0001 ). These images could be directly fed to a CNN for predicting colon cancer relapse. Our experiments showed that test set error rate was reduced by 25% compared with CNNs trained on images rescaled to 5 µ m with bilinear interpolation. Compared with images at 1 - µ m resolution (bilinear rescaling), our method reduced CNN training time by 85%. Conclusions: Cell2Grid is an efficient spatial data representation algorithm that enables the use of conventional CNNs on cell segmentation data. Its cell-based representation additionally opens a door for simplified model interpretation and synthetic image generation.

Long-term outcomes of surgery using the Ligament Advanced Reinforcement System as treatment for anterior cruciate ligament tears.

AIMS: The aim of this prospective study was to assess the long-term clinical, radiological, functional, and quality of life (QoL)-related outcome of patients treated with the synthetic Ligament Advanced Reinforcement System (LARS) device for anterior cruciate ligament (ACL) rupture. METHODS: A total of 41 patients who underwent ACL reconstruction with the LARS device (mean age 39.8 years (SD 12.1 ); 32% females (n = 13)) were prospectively included between August 2001 and March 2005. MRI scans and radiographs were performed at a median follow-up of 2.0 years (interquartile range (IQR) 1.3 to 3.0; n = 40) and 12.8 years (IQR 12.1 to 13.8; n = 22). Functional and QoL-related outcome was assessed in 29 patients at a median follow-up of 12.8 years (IQR 12.0 to 14.0) and clinically reconfirmed at latest median follow-up of 16.5 years (IQR 15.5 to 17.9). International Knee Documentation Committee (IKDC) and Tegner scores were obtained pre- and postoperatively, and Lysholm score postoperatively only. At latest follow-up, range of motion, knee stability tests, 36-Item Short Form Health Survey (SF-36), and IKDC scores were ascertained. Complications and reoperations during follow-up were documented. RESULTS: Cumulative complication rate was 66% (n = 27), with 11 developing within one year from surgery and 16 after one year (including five patients with both early and late complications). Ten graft failures (24%) and eight cases of reactive synovitis were observed (20%). All 11 patients with early complications and ten with late complications underwent reoperation (including five with another surgical procedure for early complications), amounting to a cumulative reoperation rate of 51% (n = 21). Revision ACL reconstruction was performed in one patient (2.4%). Median IKDC at latest follow-up was 89.7 (IQR 78.2 to 93.1), being significantly worse in the event of previous complications. Lachman test was positive in 56% (n = 15) of reconstructed knees. All norm-based SF-36 items were at or above median at latest follow-up, and did not differ depending on development of complications. CONCLUSION: Despite good functional and QoL-related results in the long term, the cumulative complication rate of 66%, including graft failures and reactive synovitis, has to be viewed with great concern. Cite this article: Bone Joint J 2022;104-B(2):242-248.

A nomogram predicting risk for acute compartment syndrome following tibial plateau fractures. Single centre retrospective study.

Background This study aimed at analysing risk factors for development of acute compartment syndrome (ACS) in tibial plateau fractures, and to construct a nomogram predicting ACS-risk. Patients and Methods 243 patients (102 males; mean age: 50.7 [range: 18-85] years) with 253 tibial plateau fractures treated between 2010 and 2019 at a level-1 trauma centre were retrospectively included. Uni- and multivariate logistic regression analysis with odds ratios (OR) were performed to assess variables predicting ACS. Based on the multivariate model, ROC curve, Youden index, and nomogram were constructed. Results ACS developed in 23 patients (9.1%), with risk factors being male gender (OR: 10.606; p<0.001), BMI (OR: 1.084; p = 0.048), polytrauma (OR: 4.085; p = 0.003), and Schatzker type IV-VI fractures (OR: 6.325; p = 0.004). Age, ASA score, diabetes, renal insufficiency, hypertension, smoking or open fracture were not significantly associated with ACS-risk (all p>0.05). In the multivariate analysis, male gender (OR: 7.392; p = 0.002), and Schatzker type IV-VI fractures (OR: 5.533; p = 0.009) remained independent negative ACS-predictors, irrespective of polytrauma (p = 0.081), or BMI (p = 0.194). Area under the ROC curve was 0.840. Youden index revealed a cut-off value of ≥ 18%, upon which patients are at extremely high risk for ACS. Conclusions Particular attention should be paid to male patients with high-energy fractures of the tibial plateau towards any signs of ACS of the affected extremity to initiate early treatment. The compiled nomogram, consisting of four easily quantifiable clinical variables, may be used in clinical practice to individually predict ACS risk. Any risk score ≥ 18% should prompt critical monitoring towards ACS, or even prophylactic fasciotomy during primary surgery.

Osteoid osteoma of the foot : Presentation, treatment and outcome of a multicentre cohort.

BACKGROUND: Osteoid osteomas of the foot are rare, with a varying and atypical clinical as well as radiological presentation impeding early diagnosis and treatment. The aim of the present multicentre study was to 1) analyze epidemiological, clinical and radiological findings of patients with foot osteoid osteomas and to 2) deduce a diagnostic algorithm based on the findings. METHODS: A total of 37 patients (25 males, 67.6%, mean age 23.9 years, range 8-57 years) with osteoid osteomas of the foot were retrospectively included, treated between 2000 and 2014 at 6 participating tertiary tumor centres. Radiographic images were analyzed, as were patients' minor and major complaints, pain relief and recurrence. RESULTS: Most osteoid osteomas were located in the midfoot (n = 16) and hindfoot (n = 14). Painful lesions were present in all but one patient (97.3%). Symptom duration was similar for hindfoot and midfoot/forefoot (p = 0.331). Cortical lesions required fewer x­rays for diagnosis than lesions at other sites (p = 0.026). A typical nidus could be detected in only 23/37 of x­rays (62.2%), compared to 25/29 CT scans (86.2%) and 11/22 MRIs (50%). Aspirin test was positive in 18/20 patients (90%), 31 patients (83.8%) underwent open surgery. Pain relief was achieved in 34/36 patients (outcome unknown in one), whilst pain persisted in two patients with later confirmed recurrence. CONCLUSIONS: As previously reported, CT scans seem to be superior to MRIs towards detection of the typical nidus in foot osteoid osteomas. In patients with unclear pain of the foot and inconclusive x­rays, osteoid osteoma should be considered as differential diagnosis.

Patterns of Peripheral Blood B-Cell Subtypes Are Associated With Treatment Response in Patients Treated With Immune Checkpoint Inhibitors: A Prospective Longitudinal Pan-Cancer Study.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized systemic anti-tumor treatments across different types of cancer. Nevertheless, predictive biomarkers regarding treatment response are not routinely established yet. Apart from T-lymphocytes, the humoral immunity of B-lymphocytes is studied to a substantially lesser extent in the respective setting. Thus, the aim of this study was to evaluate peripheral blood B-cell subtypes as potential predictors of ICI treatment response. Methods: Thirty-nine cancer patients receiving ICI therapy were included into this prospective single-center cohort study. All had a first blood draw at the date before treatment initiation and a second at the time of first response evaluation (after 8-12 weeks). Seven different B-cell subtypes were quantified by fluorescence-activated cell sorting (FACS). Disease control- (DCR) and objective response rate (ORR) were co-primary study endpoints. Results: Overall, DCR was 48.7% and ORR was 25.6%, respectively. At baseline, there was no significant association of any B-cell subtype with neither DCR nor ORR. At the first response evaluation, an increase in the frequency of CD21- B-cells was a statistically significant negative predictor of response, both regarding DCR (OR=0.05, 95%CI=0.00-0.67, p=0.024) and ORR (OR=0.09, 95%CI=0.01-0.96, p=0.046). An increase of the frequency of switched memory B-cells was significantly associated with reduced odds for DCR (OR=0.06, 95%CI=0.01-0.70, p=0.025). Patients with an increased frequency of naïve B-cells were more likely to benefit from ICI therapy as indicated by an improved DCR (OR=12.31, 95%CI=1.13-134.22, p=0.039). Conclusion: In this study, certain B-cell subpopulations were associated with ICI treatment response in various human cancer types.

Evaluation of autoantibodies as predictors of treatment response and immune-related adverse events during the treatment with immune checkpoint inhibitors: A prospective longitudinal pan-cancer study.

BACKGROUND: The presence of autoantibodies in the serum of cancer patients has been associated with immune-checkpoint inhibitor (ICI) therapy response and immune-related adverse events (irAEs). A prospective evaluation of different autoantibodies in different cancer entities is missing. MATERIALS AND METHODS: In this prospective cohort study, we included a pan-cancer cohort of patients undergoing ICI treatment and measured a comprehensive panel of autoantibodies at treatment start and at the time point of first response evaluation. The presence and induction of autoantibodies (ANA, ENA, myositis, hepatopathy, rheumatoid arthritis) in different cancer entities were assessed and the association between autoantibodies and disease control rate (DCR), objective response rate (ORR), and progression-free survival (PFS), as well as the development of grade 3 or higher irAEs were evaluated by logistic regression models, cox proportional hazard models, and Kaplan-Meier estimators. RESULTS: Of 44 patients with various cancer entities, neither the presence of any positive autoantibody measurement nor the presence of positive antinuclear antibodies (ANA) [≥1:80] at baseline was associated with the examined clinical endpoints (DCR, ORR, PFS) in univariable and multivariable analyses. After 8-12 weeks of ICI treatment, DCR, ORR, and PFS did not significantly differ between patients with and without any positive autoantibody measurement or positive ANA titers. The frequency of irAEs did not differ depending on autoantibody status of the patients. CONCLUSION: Autoantibodies at treatment initiation or induction after 8-12 weeks of ICI treatment are not associated with treatment efficacy as indicated by DCR, ORR, and PFS or higher grade irAEs.

Benefit of Metastasectomy in Renal Cell Carcinoma: A Propensity Score Analysis.

INTRODUCTION: To quantify the magnitude of benefit of metastasectomy as compared to medical treatment alone in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: We therefore conducted a propensity score analysis of overall survival (OS) in 106 mRCC patients with metachronous metastasis, of whom 36 (34%) were treated with metastasectomy, and 70 (66%) with medical therapy alone. RESULTS: The most frequent metastasectomy procedures were lung resections (n = 13) and craniotomies (n = 6). Median time-to-progression after metastasectomy was 0.7 years (25th-75th percentile: 0.3-2.7). After a median follow-up of 6.2 years and 63 deaths, 5-year OS estimates were 41% and 22% in the metastasectomy and medical therapy group, respectively (log-rank P = .00007; Hazard ratio (HR) = 0.38, 95%CI: 0.21-0.68). Patients undergoing metastasectomy had a significantly higher prevalence of favorable prognostic factors, such as fewer bilateral lung metastases and longer disease-free intervals between nephrectomy and metastasis diagnosis. After propensity score weighting for these differences and adjusting for immortal time bias, the favorable association between metastasectomy and OS became much weaker (HR = 0.62, 95%CI: 0.39-1.00, P = .050). Propensity-score-weighted 5-year OS estimates were 24% and 20% in the metastasectomy and medical therapy group, respectively (log-rank P = .001). In exploratory analyses, the benefit of metastasectomy was confined to patients who achieved complete resection of all known metastases. CONCLUSION: Within the limitations of an observational study, these findings support the concept of metastasectomy being associated with an OS benefit in mRCC patients. Metastasectomies not achieving complete resection of all known lesions are likely without OS benefit.

Periprosthetic fractures of hip and knee-A morbidity and mortality analysis.

BACKGROUND: Periprosthetic fractures (PPF) following total knee (TKA) and hip arthroplasty (THA) have become more common over the years. The aim of the present study was to assess morbidity and mortality following surgery for PPF of hip and knee. PATIENTS AND METHODS: Altogether, 124 patients (mean age: 77 years; 77.4% female) with PPF of the hip (n=97) and knee (n=27), treated between 2005 and 2017 at a level-1 trauma centre, were retrospectively included. In order to assess risk factors for postoperative morbidity, Fine and Gray's model was used to compensate for death as the competing event. Risk factors for mortality were estimated with uni- and multivariate Cox-regression models. RESULTS: Vancouver B2 fractures were most common (n=39; 42.4%), followed by B1 fractures (n=23; 25.0%). Lewis-Rorabeck Type I fractures (n=14; 51.9%) were most frequent in PPF of the knee. Overall complication rates were 44.0% and 29.9% for PPF of the knee and hip, respectively, with three patients having both early and late complications, 25 patients developing early complications and 19 patients undergoing surgery for implant-related, late complications. In the multivariate Fine and Gray model, advanced patient age (HR: 0.956; 95%CI: 0.922-0.991; p=0.014) and prosthesis exchange (vs. ORIF; HR: 0.242, 95%CI: 0.068-0.859; p=0.028) were associated with lower risk of implant-related complications, irrespective of gender (p=0.450) and a surgical delay > 2 days (p=0.411). One- and 5-year overall survival-rates were 97.9% and 93.1%, respectively. Gender, type of fixation (ORIF vs. prosthesis exchange), surgical delay > 2 days, BMI and age at surgery were neither in the univariate, nor multivariate Cox-regression model associated with an increased mortality rate. CONCLUSION: Postoperative morbidity caused by implant-related complications is higher in younger patients and those receiving ORIF. With the statistical approach used, potential underestimation of actual complication rates may have been avoided, taking into account death as the competing event. Despite being based on a retrospective, heterogenous patient collective treated at a level-1 trauma centre, our results indicate that careful planning of the surgical procedure beyond 2 days, taking into consideration both patient's age and activity level, has no negative effect on patient outcome.

Influence of tumor-infiltrating immune cells on local control rate, distant metastasis, and survival in patients with soft tissue sarcoma.

Soft tissue sarcomas (STS) are considered non-immunogenic, although distinct entities respond to anti-tumor agents targeting the tumor microenvironment. This study's aims were to investigate relationships between tumor-infiltrating immune cells and patient/tumor-related factors, and assess their prognostic value for local recurrence (LR), distant metastasis (DM), and overall survival (OS). One-hundred-eighty-eight STS-patients (87 females [46.3%]; median age: 62.5 years) were retrospectively analyzed. Tissue microarrays (in total 1266 cores) were stained with multiplex immunohistochemistry and analyzed with multispectral imaging. Seven cell types were differentiated depending on marker profiles (CD3+, CD3+ CD4+ helper, CD3+ CD8+ cytotoxic, CD3+ CD4+ CD45RO+ helper memory, CD3+ CD8+ CD45RO+ cytotoxic memory T-cells; CD20 + B-cells; CD68+ macrophages). Correlations between phenotype abundance and variables were analyzed. Uni- and multivariate Fine&Gray and Cox-regression models were constructed to investigate prognostic variables. Model calibration was assessed with C-index. IHC-findings were validated with TCGA-SARC gene expression data of genes specific for macrophages, T- and B-cells. B-cell percentage was lower in patients older than 62.5 years (p = .013), whilst macrophage percentage was higher (p = .002). High B-cell (p = .035) and macrophage levels (p = .003) were associated with increased LR-risk in the univariate analysis. In the multivariate setting, high macrophage levels (p = .014) were associated with increased LR-risk, irrespective of margins, age, gender or B-cells. Other immune cells were not associated with outcome events. High macrophage levels were a poor prognostic factor for LR, irrespective of margins, B-cells, gender and age. Thus, anti-tumor, macrophage-targeting agents may be applied more frequently in tumors with enhanced macrophage infiltration.

Diabetes mellitus is independently associated with adverse clinical outcome in soft tissue sarcoma patients.

Diabetes mellitus (DM) and hyperglycemia are known predictors of adverse outcome in different tumor entities. The present study investigated the effect of DM and pre-surgery blood glucose levels on cancer specific survival (CSS), overall survival (OS), and disease-free survival (DFS) in non-metastatic soft tissue sarcoma (STS) patients. A total of 475 STS patients who underwent curative resection were included in this retrospective study. CSS, DFS, and OS were assessed using Kaplan-Meier curves. The association between pre-existing DM as well as mean pre-surgery blood glucose levels and all 3 survival endpoints was analyzed using Cox-hazard proportional (for OS and DFS) and competing risk regression models (for CSS). In unadjusted analysis, DM was significantly associated with adverse CSS (sub-hazard ratio [SHR]: 2.14, 95% confidence interval [CI] 1.18-3.90, p = 0.013) and OS (hazard ratio [HR]: 2.05, 95% CI 1.28-3.28) and remained significant after adjusting for established prognostic factors (CSS: adjusted SHR 2.33, 95% CI 1.21-4.49, p = 0.012; OS: adjusted HR 1.96, 95% CI 1.17-3.28, p = 0.010), respectively. There was no significant association of DM with DFS (p = 0.149). The mean pre-surgery glucose levels were not significantly associated with inferior outcome (CSS: p = 0.510, OS: p = 0.382 and DFS: p = 0.786). This study shows, that DM represents a negative prognostic factor for clinical outcome in STS patients after curative resection.