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Purpose The aim of this study was to determine the change in the long leg axis according to the preoperative knee phenotype using the mechanically aligned extension-first technique in total knee arthroplasty. The hypothesis of this study was that the knee phenotype would have an impact on the postoperative leg axis. Methods This was a retrospective comparative study comprising 224 whole-leg radiographs of 112 patients. The leg axes of the pre- and postoperative radiographs were measured and categorized into three preoperative limb phenotypes (based on the hip-knee-ankle angle [HKA]) according to Hirschmann et al. (varus—HKA 181.5°). Additionally, femoral phenotypes (based on the femoral mechanical angle [FMA], i.e., the mechanical medial distal femoral angle [mMDFA], as well as the tibial phenotypes [based on the tibial mechanical angle, i.e., the medial proximal tibial angle (MPTA)] was calculated. The change in the long leg axis was analyzed and compared with the preoperative limb phenotype. Results Significantly more patients with preoperative varus alignment shifted to neutral alignment (46.3%, n = 31) than did patients with preoperative valgus alignment (38.9%; n = 14). Moreover, 43.3% of patients (n = 29) with the varus phenotype remained in a varus alignment, compared with the 58.3% of patients with preoperative valgus phenotype (n = 21) remaining in valgus alignment. These findings were similar for both females (p p = 0.015). Conclusion Using an extension-first mechanically aligned surgical technique, varus phenotypes predominantly result in neutral leg axes or remain varus, neutral phenotypes remain neutral, and valgus phenotypes remain valgus or change to neutral phenotypes. This study showed that preoperative knee phenotypes in valgus knees influence this technique more strongly than estimated in previous investigations, which is in line with modern alignment philosophies for TKA. Level of evidence Level IV, retrospective comparative study.

Introduction High BMI is associated with increased risk for knee osteoarthritis, ultimately necessitating total knee arthroplasty (TKA). The aim of this retrospective study was to (1) analyse the amount of postoperative long-term weight loss as reflected by BMI change in TKA patients, (2) identify factors associated with increased change in BMI, and to (3) compare changes with BMI trends of a general population. Materials and methods Overall, 298 TKA patients [198 females; mean age: 65.1 ± 7.9 years, median follow-up 8.8 (interquartile range: 5.9–10.8 years)] were included in the final evaluation and compared with an age group-matched control group from the general population regarding weight trends between 2006 and 2014. Main variable of interest in both cohorts was body mass index (BMI). Linear regression analyses were performed to assess changes in weight and BMI over time between TKA patients and the general population. Furthermore, mixed linear-effects models were constructed to analyse the potential change in BMI independent from age and gender. Results In TKA patients, a significant drop in BMI by 0.8 ± 3.2 points from postoperative to final follow-up was observed (p p = 0.382), gender (p = 0.310), or revision surgery (p = 0.195). In the general population, likewise a significant BMI-decrease by 0.7 ± 6.1 points was observed between 2006 and 2014, with younger people (p = 0.004) and females (p p = 0.734). Notably, patients with initially higher BMI were significantly more likely to lose weight postoperatively than normal-weight patients (p Conclusions Our results point against the notion that TKA patients lose a considerable amount of weight in comparison to the general population as soon as improved joint function and pain relief have been achieved. Thus, individualized patient education programmes should be reinforced, promoting a healthy lifestyle.

Zusammenfassung Hintergrund Atypische chondrogene Tumoren (ACT) der kurzen und langen Röhrenknochen, früher als Chondrosarkome G1 bezeichnet, verhalten sich lokal aggressiv, haben aber ein sehr geringes Metastasierungspotenzial. Die Abgrenzung zu benignen Enchondromen ist aus klinischer, radiologischer und histopathologischer Sicht komplex. Ziel der Arbeit Epidemiologie, Diagnostik und Therapie von ACT unter besonderer Berücksichtigung der Abgrenzung zu Enchondromen werden dargestellt. Material und Methoden Es erfolgt die Zusammenfassung der internationalen Fachliteratur zu ACT und Enchondromen. Ergebnisse Die Inzidenz von Enchondromen, und mehr noch von ACT, ist über die Jahre angestiegen, was auf häufiger werdende Diagnostik hinweist. Im Gegensatz zu Enchondromen können ACT mit Schmerzen verbunden sein und radiologische Zeichen aggressiven Wachstums, wie tiefes endosteales Scalloping, aufweisen. Die alleinige Biopsie zur Differenzierung zwischen Enchondromen und ACT ist oft nicht hilfreich, da aufgrund der punktuellen Probegewebsentnahme ein „sampling error“ resultieren kann. Die definitive operative Therapie von ACT der langen und kurzen Röhrenknochen hat sich über die letzten Jahre gewandelt, weg von einer radikalen Tumorentfernung hin zu intraläsionaler Kürettage. Ein Zuwarten ist bei radiologischem Verdacht auf das Vorliegen eines Enchondroms regelmäßigen Verlaufskontrollen mittels Magnetresonanztomographie (MRT) möglich. Schlussfolgerungen ACT weisen im Gegensatz zu Enchondromen radiologische Zeichen eines aggressiven Wachstums auf. Die heutzutage bevorzugte Therapie besteht aus einer intraläsionalen Kürettage. Sowohl Diagnostik als auch Therapie und Nachsorge von kartilaginären Tumoren sollten an einem spezialisierten Tumorzentrum erfolgen.

The aim of this systematic review and meta-analysis was to assess risk for iatrogenic radial nerve palsy (iRNP), non-union, and post-operative infection in humeral shaft fractures. A PubMed search including original articles comparing different treatments for humeral shaft fractures published since January 2000 was performed. Random effect models with relative risks (RR) and 95% CIs were calculated for treatment groups and outcomes. Of the 841 results, 43 studies were included in the meta-analysis (11 level II, 5 level III, 27 level IV). Twenty-seven compared intramedullary nailing (IM) with ORIF, nine conservative with operative treatment, four ORIF with minimally invasive plate osteosynthesis (MIPO), and three anterior/anterolateral with posterior approach. iRNP risk was higher for ORIF vs IM (18 studies; RR: 1.80; P = 0.047), ORIF vs MIPO (4 studies; RR: 5.60; P = 0.011), and posterior vs anterior/anterolateral approach (3 studies; RR: 2.68; P = 0.005). Non-union risk was lower for operative vs conservative therapy (six studies; RR: 0.37; P < 0.001), but not significantly different between ORIF and IM (21 studies; RR: 1.00; P = 0.997), or approaches (two studies; RR: 0.36; P = 0.369). Post-operative infection risk was higher for ORIF vs IM (14 studies; RR: 1.84; P = 0.004) but not different between approaches (2 studies; RR: 0.95; P = 0.960). Surgery appears to be the method of choice when aiming to secure bony union, albeit risk for iRNP has to be considered, particularly in case of ORIF vs IM or MIPO, and posterior approach. Due to the limited number of randomised studies, evidence on the best treatment option remains moderate, though.

Introduction In total knee arthroplasty (TKA), tibial obliquity-restoration using kinematic alignment (KA) poses a major difference to conventional mechanical alignment. This study aimed at analysing the accuracy of conventional instrumentation (CI) versus patient-specific instrumentation (PSI) to restore anatomic tibial obliquity measured by the medial proximal tibial angle (MPTA) on conventional X-rays. Materials and Methods One-hundred patients were randomized to receive CI (n = 50) or PSI (n = 50) for TKA. Further 100 patients received CI without randomisation, resulting in 200 patients in total (127 women, mean age: 70.7 (range: 48–90 years). Pre- and postoperative X-rays were measured twice by two observers with a 2-week break in-between. Inter- and intraclass correlations were calculated and postoperative tibial obliquity compared to preoperative anatomy. Results In 150 patients with CI, no case with tibial obliquity-deviation greater than 2° was found, whilst 21.3% (n = 32) and 0.7% (n = 1) of cases and had a deviation of 0°–1°, and 1°–2°, respectively. In the remaining 78.0% (n = 117), tibial obliquity was restored. In 50 patients with PSI, no single case with a deviation greater than 1° was found. Sixty percent (n = 30) had a deviation of 0°–1°. In the remaining 40.0% (n = 20), no deviation from preoperative measurements was found. Consequently, CI resulted in a significantly smaller change in tibial obliquity from preoperative to postoperative than PSI (p 0.90). Conclusion Both conventional and patient-specific instrumentation revealed adequate results with respect to restoring tibial obliquity in kinematically aligned TKA, with conventional instrumentation achieving superior results.

Quantifying the phenotypic features of rare diseases such as inborn errors of immunity (IEI) helps clinicians make diagnoses, classify disorders, and objectify the disease severity at its first presentation as well as during therapy and follow-up. Furthermore, it may allow cross-sectional and cohort comparisons and support treatment decisions such as an evaluation for transplantation. On the basis of a literature review, we provide a descriptive comparison of ten selected scores and measures frequently used in IEI and divide these into three categories: (1) diagnostic tools (for Hyper-IgE syndrome, hemophagocytic lymphohistiocytosis, and Wiskott-Aldrich syndrome), (2) morbidity and disease activity measures (for common variable immune deficiency [CVID], profound combined immune deficiency, CTLA-4 haploinsufficiency, immune deficiency and dysregulation activity [IDDA], IPEX organ impairment, and the autoinflammatory disease activity index), and (3) treatment stratification scores (shown for hypogammaglobulinemia). The depth of preclinical and statistical validations varies among the presented tools, and disease-inherent and user-dependent factors complicate their broader application. To support a comparable, standardized evaluation for prospective monitoring of diseases with immune dysregulation, we propose the IDDA2.1 score (comprising 22 parameters on a 2–5-step scale) as a simple yet comprehensive and powerful tool. Originally developed for use in a retrospective study in LRBA deficiency, this new version may be applied to all IEI with immune dysregulation. Reviewing published aggregate cohort data from hundreds of patients, the IDDA kaleidoscope function is presented for 18 exemplary IEI as an instructive phenotype–pattern visualization tool, and an unsupervised, hierarchically clustered heatmap mathematically confirms similarities and differences in their phenotype expression profiles.

Summary 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 x‑rays for diagnosis than lesions at other sites (p = 0.026). A typical nidus could be detected in only 23/37 of x‑rays (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 x‑rays, osteoid osteoma should be considered as differential diagnosis.

This systematic review and meta-analysis aimed to analyse negative effects of smoking in orthopaedic and trauma patients. A PubMed search was carried out for studies published until July 2020 regarding effects of smoking on fracture risk, nonunion, infection after orthopaedic surgery, and persisting nonunion after scaphoid nonunion surgery. Random effects models calculated for outcome parameters, and relative risks (RR) with 95% confidence intervals are provided. No adjustments for covariates were made. Heterogeneity was assessed with Higgins’ I2, publication bias with Harbord’s p (Hp), sensitivity analysis performed on funnel plots and quality of studies was analysed using the Newcastle-Ottawa Scale. Of 3362 retrieved entries, 69 were included in the final analysis. Unadjusted RR for smokers to develop vertebral (six studies, seven entries; RR: 1.61; p = 0.008; I2 = 89.4%), hip (11 studies, 15 entries; RR: 1.28; p = 0.007; I2 = 84.1%), and other fractures (eight studies, 10 entries; RR: 1.75; p = 0.019; I2 = 89.3%) was significantly higher. Postoperative infection risk was generally higher for smokers (21 studies; RR: 2.20; p < 0.001; I2 = 58.9%), and remained upon subgroup analysis for elective spinal (two studies; RR: 4.38; p < 0.001; I2 = 0.0%) and fracture surgery (19 studies; RR: 2.10; p < 0.001; I2 = 58.5%). Nonunion risk after orthopaedic (eight studies; RR: 2.15; p < 0.001; I2 = 35.9%) and fracture surgery (11 studies; RR: 1.85; p < 0.001; I2 = 39.9%) was significantly higher for smokers, as was persisting nonunion risk after surgery for scaphoid nonunion (five studies; RR: 3.52; p < 0.001; I2 = 0.0%). Sensitivity analysis for each model reduced heterogeneity whilst maintaining significance (all I2 < 20.0%). Smoking has a deleterious impact on fracture incidence, and (subsequent) development of nonunions and postoperative infections. Cite this article: EFORT Open Rev 2021;6:1006-1019. DOI: 10.1302/2058-5241.6.210058

In the last decade, new tumor entities have been described, including

Introduction: The aim of this study was to externally validate the 2013-SPRING model, a survival prediction tool for patients treated surgically for bone metastases in a retrospective patient cohort from a single institution. Moreover, subgroup analyses on patients treated with (A) endoprostheses or (B) osteosynthesis, as well as (C) upper limb and (D) lower limb metastases, were performed. Methods: Altogether, 303 cancer patients (mean age: 67.6 ± 11.1 years; 140 males (46.2%)) with bone metastases to the extremities, treated surgically between March 2000 and June 2018 at a single tertiary sarcoma centre, were retrospectively included. Median follow-up amounted to 6.3 (interquartile range (IQR): 2.3–21.8) months, with all patients followed-up for at least one year or until death. The 2013-SPRING model was applied to assess the prognostication accuracy at 3, 6 and 12 months. Models were validated with area under the curve receiver operator characteristic (AUC ROC; the higher the better), as well as Brier score. Results: Of the 303 patients, 141 had been treated with osteosynthesis (46.5%), and the remaining 162 patients with endoprosthesis (53.5%). Sixty-five (21.5%) metastases were located in the upper limbs, and two hundred and thirty-eight (78.5%) in the lower limbs. Using the 2013-SPRING model for the entire cohort, the accuracy of risk of death prediction at 3, 6 and 12 months, determined by the AUC ROC, was 0.782 (95% CI: 0.729–0.843), 0.810 (95% CI: 0.763–0.858) and 0.802 (95% CI: 0.751–0.854), respectively. Corresponding Brier scores were 0.170, 0.178 and 0.169 at 3, 6 and 12 months. In the subgroup analyses, predictive accuracy of the 2013-SPRING model was likewise encouraging, albeit being slightly higher in the osteosynthesis subgroup as compared with the endoprosthesis subgroup, and also higher in the upper limb in comparison to the lower limb metastasis subgroup. Conclusions: The current validation study of the 2013-SPRING model shows that this model is clinically relevant to use in an external cohort, also after stratification for surgical procedure and metastasis location.

Purpose The aims of this study were to (1) analyze the impact of an artificial intelligence (AI)-based computer system on the accuracy and agreement rate of board-certified orthopaedic surgeons (= senior readers) to detect X-ray features indicative of knee OA in comparison to unaided assessment and (2) compare the results to those of senior residents (= junior readers). Methods One hundred and twenty-four unilateral knee X-rays from the OAI study were analyzed regarding Kellgren–Lawrence grade, joint space narrowing (JSN), sclerosis and osteophyte OARSI grade by computerized methods. Images were rated for these parameters by three senior readers using two modalities: plain X-ray (unaided) and X-ray presented alongside reports from a computer-assisted detection system (aided). After exclusion of nine images with incomplete annotation, intraclass correlations between readers were calculated for both modalities among 115 images, and reader performance was compared to ground truth (OAI consensus). Accuracy, sensitivity and specificity were also calculated and the results were compared to those from a previous study on junior readers. Results With the aided modality, senior reader agreement rates for KL grade (2.0-fold), sclerosis (1.42-fold), JSN (1.37-fold) and osteophyte OARSI grades (3.33-fold) improved significantly. Reader specificity and accuracy increased significantly for all features when using the aided modality compared to the gold standard. On the other hand, sensitivity only increased for OA diagnosis, whereas it decreased (without statistical significance) for all other features. With aided analysis, senior readers reached similar agreement and accuracy rates as junior readers, with both surpassing AI performance. Conclusion The introduction of AI-based computer-aided assessment systems can increase the agreement rate and overall accuracy for knee OA diagnosis among board-certified orthopaedic surgeons. Thus, use of this software may improve the standard of care for knee OA detection and diagnosis in the future. Level of evidence Level II.

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

SummarySoft tissue sarcomas (STS) represent a small group of adult solid malignancies, with risk factors such as environmental factors, genetic predisposition, and prior radiotherapy. In STS patients with a novel swelling, differential diagnoses include recurrence, second primary cancer, metastasis from unknown primary cancer, and radiation-associated STS, the latter usually occurring approximately 10 years after radiotherapy. We present the case of a 64-year-old male patient with pleomorphic rhabdomyosarcoma, who underwent resection and radiotherapy. The patient presented again 5 years later with painful swelling in the area of the prior sarcoma, raising suspicion of recurrence. Resection was performed and a diagnosis of pleomorphic sarcoma (not otherwise specified [NOS]) was made. The patient was treated with radiotherapy and remained sarcoma-free for the following 7 years. A molecular analysis of both neoplasms, using RNA next-generation sequencing, did not detect any specific fusions. Due to the lack of rhabdomyoblastic differentiation in the second sarcoma and the low likelihood of a second primary in the same previously irradiated location, the diagnosis of a radiation-associated STS was suggested. This short report illustrates the difficult diagnostic work-up of a presumably radiation-associated STS, as these neoplasms lack characteristic morphological and immunohistochemical features. In our case, the suggested diagnosis may have pointed against another course of radiotherapy in an already irradiation-harmed region. Therefore, a relatively low latency period between surgery, radiotherapy, and diagnosis of another STS should not automatically point towards recurrence and may prompt further in-depth investigation.

Background Extra-abdominal desmoid tumor fibromatosis (DTF) is a rare, locally aggressive soft tissue tumour. The best treatment modality for this patient cohort is still object of debate. Questions/purpose This paper aimed to (1) to compare the outcomes of DTF after different treatment modalities, (2) to assess prognostic factors for recurrence following surgical excision, and (3) to assess prognostic factors for progression during observation. Methods This was a retrospective multicenter study under the patronage of the European Musculoskeletal Oncology Society (EMSOS). All seven centres involved were tertiary referral centres for soft tissue tumours. Baseline demographic data was collected for all patients as well as data on the diagnosis, tumour characteristics, clinical features, treatment modalities and whether they had any predisposing factors for DTF. Results Three hundred eighty-eight patients (240 female, 140 male) with a mean age of 37.6 (±18.8 SD, range: 3–85) were included in the study. Two hundred fifty-seven patients (66%) underwent surgical excision of ADF, 70 patients (18%) were observed without therapy, the residual patients had different conservative treatments. There were no significant differences in terms of tumour recurrence or progression between the different treatment groups. After surgical excision, younger age, recurrent disease and larger tumour size were risk factors for recurrence, while tumours around the shoulder girdle and painful lesions were at risk of progression in the observational group. Conclusion Local recurrence rate after surgery was similar to progression rates under observation. Hence, observation in DTF seems to be justified, considering surgery in case of dimensional progression in 2 consecutive controls (3 and 6 months) and in painful lesions, with particular attention to lesions around the shoulder girdle.

Return to work (RTW) has been specifically identified as a high priority in patients undergoing total hip arthroplasty (THA). This investigation sought to assess the effect of the stem design on patients’ RTW. Secondly, the study aimed to identify risk factors that lead to a delayed RTW. Questionnaires inquiring about RTW, employment history, educational level, type of work, physical demands and joint awareness were administered by post. Further data were collected from patients’ hospital records. 176 patients who underwent THA using a short-stem and 97 patients using a straight-stem design were compared. The median return to work time was 10 weeks [IQR 7–14 weeks], with no significant difference between the two groups (short stems vs. straight stems; 10 [IQR 7–14] vs. 11 [7.5–13.5] weeks; p = 0.693). In the multivariate linear regression analysis, self-employment vs. employee (p = 0.001), dimension of preoperative workload (p = 0.001), preoperative sick leave (p

Recent retrospective studies suggested that early postoperative infections might be associated with a survival benefit for extremity osteosarcoma patients, but the reported results have been conflicting. The files of 437 patients with a newly diagnosed, high-grade osteosarcoma of the extremities treated at 5 referral centers in Germany and Austria between 1989 and 2016 were retrospectively evaluated. All patients underwent multi-agent chemotherapy and limb-sparing tumor excision, followed by endoprothetic replacement. We used the Kaplan–Meier method to calculate survival curves, which we compared with the log-rank test. With a median follow-up of 100 months (interquartile range, 49–155 months), local recurrence (LR) probability, event-free survival (EFS), and disease-specific survival (DSS) after 5 years in this selected patient cohort amounted to 5%, 67%, and 79%, respectively, and 46 patients (10.5%) developed an early postoperative infection. We found no significant differences in LR, EFS, or DSS between patients with and without early infections, and there were no differences in known prognostic factors between the two groups. However, in subgroup analyses patients with a poor response to neoadjuvant chemotherapy and an early infection had a better DSS compared to patients without early infections (93% vs. 62% after 5 years, p = 0.044). Provided that our findings can be validated in separate patient cohorts, we believe that patient outcome after adjuvant immunomodulatory treatments in osteosarcoma patients should be evaluated and reported separately for good and poor responders to neoadjuvant chemotherapy in future studies.

Summary Background Wound healing deficits and subsequent surgical site infections are potential complications after surgical procedures, resulting in increased morbidity and treatment costs. Closed-incision negative-pressure wound therapy (ciNPWT) systems seem to reduce postoperative wound complications by sealing the wound and reducing tensile forces. Materials and methods We conducted a collaborative English literature review in the PubMed database including publications from 2009 to 2020 on ciNPWT use in five surgical subspecialities (orthopaedics and trauma, general surgery, plastic surgery, cardiac surgery and vascular surgery). With literature reviews, case reports and expert opinions excluded, the remaining 59 studies were critically summarized and evaluated with regard to their level of evidence. Results Of nine studies analysed in orthopaedics and trauma, positive results of ciNPWT were reported in 55.6%. In 11 of 13 (84.6%), 13 of 15 (86.7%) and 10 of 10 (100%) of studies analysed in plastic, vascular and general surgery, respectively, a positive effect of ciNPWT was observed. On the contrary, only 4 of 12 studies from cardiac surgery discovered positive effects of ciNPWT (33.3%). Conclusion ciNPWT is a promising treatment modality to improve postoperative wound healing, notably when facing increased tensile forces. To optimise ciNPWT benefits, indications for its use should be based on patient- and procedure-related risk factors.

Purpose In many cases, the diagnosis of a periprosthetic joint infection (PJI) consisting of the clinical appearance, laboratory tests, and other diagnostic tools remains a difficult task. Single serum biomarkers are easy to collect, are suitable for periodical assessment, and are a crucial tool in PJI diagnosis, but limited sensitivity or specificity is reported in literature. The aim of this study was to combine the best-performing single serum biomarkers into a multi-biomarker model aiming to improve the diagnostic properties. Methods Within a 27-month period, 124 surgical procedures (aseptic or septic revision total knee arthroplasty (TKA) or total hip arthroplasty (THA)) were prospectively included. The serum leukocyte count, C-reactive protein (CRP), interleukin-6, procalcitonin, interferon alpha, and fibrinogen were assessed 1 day prior to surgery. Logistic regression with lasso-regularization was used for the biomarkers and all their ratios. After randomly splitting the data into a training (75%) and a test set (25%), the multi-biomarker model was calculated and validated in a cross-validation approach. Results CRP (AUC 0.91, specificity 0.67, sensitivity 0.90, p value 0.03) and fibrinogen (AUC 0.93, specificity 0.73, sensitivity 0.94, p value 0.02) had the best single-biomarker performances. The multi-biomarker model including fibrinogen, CRP, the ratio of fibrinogen to CRP, and the ratio of serum thrombocytes to CRP showed a similar performance (AUC 0.95, specificity 0.91, sensitivity 0.72, p value 0.01). Conclusion In this study, multiple biomarkers were tested for their diagnostic performance, with CRP and fibrinogen showing the best results regarding the AUC, accuracy, sensitivity, and specificity. It was not possible to further increase the diagnostic accuracy by combining multiple biomarkers using sophisticated statistical methods.

ZusammenfassungChordome sind maligne Knochentumoren, die mit einer jährlichen Inzidenz von 0,08 pro 100.000 Personen auftreten. Sie zeigen eine notochordale Differenzierung mit einer nukleären Expression von Brachyury (TBXT). Hauptlokalisation ist das axiale Skelett vom Clivus bis zum Sakrum und dem Os coccygis. Chordome wachsen langsam und lange nur lokal destruierend. Sie werden daher oft erst spät diagnostiziert. Putative Vorläuferläsionen sind Chordareste und der benigne notochordale Zelltumor. Dabei handelt es sich um zumeist mikroskopisch kleine, intraossäre Läsionen. Bei Chordomen werden unterschiedliche histologische Subtypen differenziert, welche sich prognostisch unterscheiden. Wiederkehrende genetische Veränderungen als Tumorauslöser sind nicht bekannt. Brachyury scheint eine noch nicht im Detail geklärte Schlüsselfunktion in der Entstehung von Chordomen zu besitzen. Die chirurgische En-bloc-Resektion mit negativen Resektionsrändern ist die einzige kurative Behandlungsoption. Die Hochdosisbestrahlung, speziell mit Protonen und Carbonionen, ist eine therapeutische Alternative in inoperablen Fällen. Medikamentöse Therapien sind für Chordome derzeit nicht zugelassen. Erste klinische Studien zu neuen Therapiemodalitäten laufen.

Background Despite the fact that about one third of patients with primary localized extremity soft tissue sarcoma (eSTS) will develop metastatic disease, abdominal metastases (AM) and retroperitoneal metastases (RM) constitute rare events. There is no clear consensus on how to achieve follow-up on patients with primary localized eSTS following curative resection, especially regarding the surveillance of potential AM/RM. Aim To systematically analyse incidence, diagnosis, treatment and outcome of AM/RM in eSTS patients. Methods In this systematic review, 899 studies available in PubMed and published between 2000 and 2018 were screened, identifying 17 original articles focused on AM or RM in eSTS. Article selection was based on the PRISMA guidelines, using the search terms (abdominal metastasis AND soft tissue sarcoma) and (soft tissue sarcoma metastasis abdomen). All studies published between January 1, 2000 and December 31, 2018 were screened. Further articles were identified by cross-searching article references, with the final search date being February 18, 2019. Due to limited data and the different reporting techniques used, the present review focused on descriptive analysis of the included studies. Results Of the 17 studies included, six original articles reported on incidence ± diagnosis, therapy and outcome in AM and RM, whilst three original and eight case reports focused on diagnostic pathway, therapeutic procedures or outcomes without allowing conclusions regarding incidence of AM and RM. According to the former six studies, incidence of AM ranged from 0.9%-5.6% in patients with miscellaneous histological subtypes, and up to 12.1% in patients with myxoid liposarcoma. The most common histological subtypes that developed AM or RM were (myxoid) liposarcoma and leiomyosarcoma, but also rare subtypes such as epithelioid sarcoma, myxofibrosarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumour had been reported to develop AM/RM. Surgery for AM/RM was performed in five of eight case-reports (62.5%) and in 20.8%-100.0% of original articles. In particular, patients with hepatic metastases undergoing metastasectomy had a survival benefit compared to patients treated with chemotherapy or best supportive care (> 3 years vs Conclusion Patients with eSTS should undergo surveillance with abdominal ultrasonography/computed tomography, or even whole-body-magnetic resonance imaging to detect AM/RM at an early stage.

Perioperatively administered (leukocyte reduced) allogeneic red blood cell transfusions (lrRBCTs) may lead to transfusion-related immunomodulation and reduced overall survival (OS) in cancer patients. Herein, the effect of lrRBCT on local recurrence (LR), distant metastasis (DM), and OS in soft tissue sarcoma (STS) patients was analysed.Retrospective study on 432 STS patients (mean age: 60.0 ± 17.8 years; 46.1% female), surgically treated at a tertiary tumour centre. Uni- and multivariate survival models were calculated to analyse impact of perioperative lrRBCTs on LR, DM, OS.Perioperatively, 75 patients (17.4%) had received lrRBCTs. Older patients, deep, large, lower limb STS rather required lrRBCTs (all p 0.05). No significant association between lrRBCT administration and LR- (p = 0.582) or DM-risk (p = 0.084) was observed. LrRBCT was associated with worse OS in univariate analysis (HR: 2.222; p 0.001), with statistical significance lost upon multivariate analysis (HR: 1.658; p = 0.059; including age, histology, size, grading, amputation, depth). Adding preoperative haemoglobin in subgroup of 220 patients with laboratory parameters revealed significant negative impact of low haemoglobin on OS (p = 0.014), whilst effect of lrRBCT was further diminished (p = 0.167).Unfavourable prognostic factors prevail in STS patients requiring lrRBCTs. Low haemoglobin levels rather than lrRBCT seem to reduce OS.

This retrospective study aimed at analyzing the impact of metastasectomy on post-metastasis survival (PMS) in bone sarcoma patients with lung metastases. Altogether, 47 bone sarcoma patients (24 males, median age at diagnosis of lung metastases: 21.8 (IQR: 15.6–47.3) years) with primary (n = 8) or secondary (n = 39) lung metastases treated at a single university hospital were retrospectively included. Based on a propensity score, inverse probability of treatment weight (IPTW) was calculated to account for selection bias whether patients had undergone metastasectomy or not. The most common underlying histology was osteosarcoma (n = 37; 78.7%). Metastasectomy was performed in 39 patients (83.0%). Younger patients (p = 0.025) with singular (p = 0.043) and unilateral lesions (p = 0.024), as well as those with an interval ≥ 9 months from primary diagnosis to development of lung metastases (p = 0.024) were more likely to undergo metastasectomy. Weighted 1- and 3-year PMS after metastasectomy was 80.8% and 58.3%, compared to 88.5% and 9.1% for patients who did not undergo metastasectomy. Naive Cox-regression analysis demonstrated a significantly prolonged PMS for patients with metastasectomy (HR: 0.142; 95%CI: 0.045–0.450; p = 0.001), which was confirmed after IPTW-weighting (HR: 0.279; 95%CI: 0.118–0.662; p = 0.004), irrespective of age, time to metastasis, and the number of lesions. In conclusion, metastasectomy should be considered in bone sarcoma patients with lung metastases, after carefully considering the individual risks, to possibly improve PMS.

Cementless calcar-guided femoral short stems in total hip arthroplasty (THA) have become increasingly popular over the years. Early distal migration of femoral stems measured by Einzel-Bild-Roentgen Analyse, Femoral Component Analyse (EBRA-FCA) has been reported to be a risk factor for aseptic loosening. The aim of this study was to analyse axial migration behavior and subsidence of a new short stem (launched in 2015) over a follow-up period of 3 years. According to the study protocol, 100 hip osteoarthritis patients who consecutively received an unilateral cementless calcar-guided short stem (ANA.NOVA proxy) at a single department were prospectively included in this mid-term follow-up study. Thirteen patients were lost to follow-up, resulting in 87 patients with unilateral THA who fulfilled the criteria for migration analysis with EBRA-FCA. The cohort comprised 41 males (mean age: 60 ± 16.5; mean BMI (Body Mass Index): 30 ± 13) and 46 females (mean age: 61 ± 15.5; mean BMI: 27 ± 10). Seven standardized radiographs per patient were analyzed with EBRA-FCA. An average migration of 2.0 mm (0.95–3.35) was observed within the first 3 years. The median increase during the first year was higher than in the second and third year (1.2 mm [IQR: 0.5–2.15] vs. 0.3 mm [IQR: 0.1–0.6 mm] vs. 0.25 mm [IQR: 0.1–0.5 mm]. Detected migration did not lead to stem loosening, instability, dislocation, or revision surgery in any patient. A higher risk for subsidence was observed in male and heavyweight patients, whereas the female gender was associated with a lower risk. No correlation between migration and revision could be observed. Although moderate subsidence was detectable, the performance of the short stem ANA.NOVA proxy is encouraging. Yet, its use may be re-considered in overweight and male patients due to more pronounced subsidence.

The aims of this study were to (1) assess reliability of leg length discrepancy (LLD) measurements at different anatomical landmarks, (2) longitudinally investigate LLD in patients within the first year following total hip arthroplasty (THA) and to (3) correlate changes in LLD with functional outcome. Ninety-nine patients with short stem THA (53.3% males, mean age: 61.0 ± 8.1 years) were prospectively included. Upright pelvic anteroposterior (a.p.) radiographs taken at 6 timepoints (preoperatively, discharge, 6, 12, 24, 52 weeks postoperatively) were used to assess LLD at 5 anatomical landmarks (iliac crest, upper sacroiliac joint, lower sacroiliac joint, tear drop figure, greater trochanter). WOMAC and Harris Hip Score (HHS) were obtained preoperatively and at 6 and 52 weeks. LLD measures significantly increased in the initial phase following THA, from discharge to 6 weeks postoperatively and remained constant thereafter. Documentation of LLDs is dependent on measurement site: LLDs varied significantly between trochanter and iliac crest to tear drop figure (p p = 0.252); HHS (p = 0.798)]. Radiographic assessment of LLD following THA may not be performed early postoperatively, as measurements appear to inaccurately reflect actual LLDs at this time, potentially due incomplete leg extension and/or inhibited weight-bearing.

Fragestellung: Die Implantation einer Hüfttotalendoprothese etablierte sich als eine der Operationen des letzten Jahrhunderts in der Orthopädie & Traumatologie. Lebensqualität und Funktion sind nicht nur Schlagwörter, sondern Umstände welche ein zufriedenstellendes und [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Fragestellung: Implantation von Kurzschaftprothesen gewinnt seit ein paar Jahren zunehmend an Popularität. Im Zuge dessen wurde 2015 das Kurzschaftsystem ANA.NOVA® Alpha Schaft Proxy® am Markt eingeführt. Um die Performance dieses System beurteilen zu können, wurde eine prospektive [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Background: Molecular diagnosis has become an established tool in the characterisation of adult soft-tissue sarcomas (STS). FoundationOne® Heme analyses somatic gene alterations in sarcomas via DNA and RNA-hotspot sequencing of tumour-associated genes. Methods: We evaluated FoundationOne® Heme testing in 81 localised STS including 35 translocation-associated and 46 complex-karyotyped cases from a single institution. Results: Although FoundationOne® Heme achieved broad patient coverage and identified at least five genetic alterations in each sample, the sensitivity for fusion detection was rather low, at 42.4%. Nevertheless, potential targets for STS treatment were detected using the FoundationOne® Heme assay: complex-karyotyped sarcomas frequently displayed copy-number alterations of common tumour-suppressor genes, particularly deletions in TP53, NF1, ATRX, and CDKN2A. A subset of myxofibrosarcomas (MFS) was amplified for HGF ( n = 3) and MET ( n = 1). PIK3CA was mutated in 7/15 cases of myxoid liposarcoma (MLS; 46.7%). Epigenetic regulators (e.g. MLL2 and MLL3) were frequently mutated. Conclusions: In summary, FoundationOne® Heme detected a broad range of genetic alterations and potential therapeutic targets in STS (e.g. HGF/MET in a subset of MFS, or PIK3CA in MLS). The assay’s sensitivity for fusion detection was low in our sample and needs to be re-evaluated in a larger cohort.

Tumour endoprostheses have facilitated limb-salvage procedures in primary bone and soft tissue sarcomas, and are increasingly being used in symptomatic metastases of the long bones. The objective of the present review was to analyse articles published over the last three years on tumour endoprostheses and to summarize current knowledge on this topic. The NCBI PubMed webpage was used to identify original articles published between January 2015 and April 2018 in journals with an impact factor in the top 25.9% of the respective category (orthopaedics, multidisciplinary sciences). The following search-terms were used: tumour endoprosthesis, advances tumour endoprosthesis, tumour megaprosthesis, prosthetic reconstruction AND tumour. We identified 347 original articles, of which 53 complied with the abovementioned criteria. Articles were categorized into (1) tumour endoprostheses in the shoulder girdle, (2) tumour endoprostheses in the proximal femur, (3) tumour endoprostheses of the knee region, (4) tumour endoprostheses in the pelvis, (5) (expandable) prostheses in children and (6) long-term results of tumour endoprostheses. The topics of interest covered by the selected studies largely matched with the main research questions stated at a consensus meeting, with survival outcome of orthopaedic implants being the most commonly raised research question. As many studies reported on the risk of deep infections, research in the future should also focus on potential preventive methods in endoprosthetic tumour reconstruction. Cite this article: EFORT Open Rev 2019;4:445-459. DOI: 10.1302/2058-5241.4.180081

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; p0.001), 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 p0.05). 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.

Background Total hip arthroplasty (THA) is the most successful orthopaedic surgery of the past century. The current study aimed to compare the accuracy of digital planning using 2D versus 3D templating. Materials and methods Ninety-five THAs in 90 patients were included in the current study. Pre- and post-operative X-rays (in two planes) and low-dose rotation computed tomography scans from hip to foot were performed. Paired t-test and regression analyses were conducted to compare 2D and 3D templating accuracy of the definitive implant. Results Cup size planned both with 2D (p p = 0.012) templating was significantly different from the definitively used cup size. The difference between the 2D-planned and implanted stem size (p p = 0.181). Three-dimensional templating showed significantly higher accuracy than 2D templating in terms of cup size (1.1 ± 1.4 versus 1.7 ± 1.8; p = 0.007) and stem size (0.3 ± 0.6 versus 0.7 ± 0.7; p With increasing body mass index (BMI), 2D templating of the stem became more inaccurate (p = 0.041). Remarkably, 3D templating remained accurate for all components (stem, p = 0.533; cup, p = 0.479) despite increasing BMI. Conclusion Despite extended planning time and increased exposure to radiation, 3D-based planning showed higher accuracy than 2D templating, especially in obese patients. On the basis of our results, we believe that 3D-based pre-operative planning in THA is justifiable and beneficial in patients with increased BMI. Level of Evidence III.

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.

In patients with metastatic or unresectable soft tissue and bone sarcoma of extremities and pelvis, survival is generally poor. The aim of the current systematic review was to analyse recent publications on treatment approaches in patients with inoperable and/or metastatic sarcoma. Original articles published between 1st January 2011 and 2nd May 2020, using the search terms ‘unresectable sarcoma’, ‘inoperability AND sarcoma’, ‘inoperab* AND sarcoma’, and ‘treatment AND unresectable AND sarcoma’ in PubMed, were potentially eligible. Out of the 839 initial articles (containing 274 duplicates) obtained and 23 further articles identified by cross-reference checking, 588 were screened, of which 447 articles were removed not meeting the inclusion criteria. A further 54 articles were excluded following full-text assessment, resulting in 87 articles finally being analysed. Of the 87 articles, 38 were retrospective (43.7%), two prospective (2.3%), six phase I or I/II trials (6.9%), 22 phase II non-randomized trials (27.6%), nine phase II randomized trials (10.3%) and eight phase III randomized trials (9.2%). Besides radio/particle therapy, isolated limb perfusion and conventional chemotherapy, novel therapeutic approaches, including immune checkpoint inhibitors and tyrosine kinase inhibitors were also identified, with partially very promising effects in advanced sarcomas. Management of inoperable, advanced or metastatic sarcomas of the pelvis and extremities remains challenging, with the optimal treatment to be defined individually. Besides conventional chemotherapy, some novel therapeutic approaches have promising effects in both bone and soft tissue subtypes. Considering that only a small proportion of studies were randomized, the clinical evidence currently remains moderate and thus calls for further large, randomized clinical trials. Cite this article: EFORT Open Rev 2020;5:799-814. DOI: 10.1302/2058-5241.5.200069