A Lightweight Browser-Based Tool for Collaborative and Blinded Image Analysis.

Collaborative manual image analysis by multiple experts in different locations is an essential workflow in biomedical science. However, sharing the images and writing down results by hand or merging results from separate spreadsheets can be error-prone. Moreover, blinding and anonymization are essential to address subjectivity and bias. Here, we propose a new workflow for collaborative image analysis using a lightweight online tool named Tyche. The new workflow allows experts to access images via temporarily valid URLs and analyze them blind in a random order inside a web browser with the means to store the results in the same window. The results are then immediately computed and visible to the project master. The new workflow could be used for multi-center studies, inter- and intraobserver studies, and score validations.

Time-Dependent Prediction Models for Individual Prognosis of Chronic Postsurgical Pain following Knee Replacement Based on an Extensive Multivariable Data Set.

(1) Background: Clinically useful prediction models for chronic postsurgical pain (CPSP) in knee replacement (TKA) are lacking. (2) Methods: In our prospective, multicenter study, a wide-ranging set of 91 variables was collected from 933 TKA patients at eight time points up to one year after surgery. Based on this extensive data pool, simple and complex prediction models were calculated for the preoperative time point and for 6 months after surgery, using least absolute shrinkage and selection operator (LASSO) 1se and LASSO min, respectively. (3) Results: Using preoperative data only, LASSO 1se selected age, the Revised Life Orientation Test on pessimism, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-subscore pain and the Timed "Up and Go" Test for prediction, resulting in an area under the curve (AUC) of 0.617 and a Brier score of 0.201, expressing low predictive power only. Using data up to 6 months after surgery, LASSO 1se included preoperative Patient Health Questionnaire-4, Knee Injury and Osteoarthritis Outcome Score (KOOS)-subscore pain (pain) 3 months after surgery (month), WOMAC pain 3 and 6 months, KOOS subscore symptoms 6 months, KOOS subscore sport 6 months and KOOS subscore Quality of Life 6 months. This improved the predictive power to an intermediate one (AUC 0.755, Brier score 0.168). More complex models computed using LASSO min did little to further improve the strength of prediction. (4) Conclusions: Even using multiple variables and complex calculation methods, the possibility of individual prediction of CPSP after TKA remains limited.

Enhancing biomechanical machine learning with limited data: generating realistic synthetic posture data using generative artificial intelligence.

Objective: Biomechanical Machine Learning (ML) models, particularly deep-learning models, demonstrate the best performance when trained using extensive datasets. However, biomechanical data are frequently limited due to diverse challenges. Effective methods for augmenting data in developing ML models, specifically in the human posture domain, are scarce. Therefore, this study explored the feasibility of leveraging generative artificial intelligence (AI) to produce realistic synthetic posture data by utilizing three-dimensional posture data. Methods: Data were collected from 338 subjects through surface topography. A Variational Autoencoder (VAE) architecture was employed to generate and evaluate synthetic posture data, examining its distinguishability from real data by domain experts, ML classifiers, and Statistical Parametric Mapping (SPM). The benefits of incorporating augmented posture data into the learning process were exemplified by a deep autoencoder (AE) for automated feature representation. Results: Our findings highlight the challenge of differentiating synthetic data from real data for both experts and ML classifiers, underscoring the quality of synthetic data. This observation was also confirmed by SPM. By integrating synthetic data into AE training, the reconstruction error can be reduced compared to using only real data samples. Moreover, this study demonstrates the potential for reduced latent dimensions, while maintaining a reconstruction accuracy comparable to AEs trained exclusively on real data samples. Conclusion: This study emphasizes the prospects of harnessing generative AI to enhance ML tasks in the biomechanics domain.

Calcar-guided short-stem total hip arthroplasty in fractures of the femoral neck: a prospective observational study of 68 hips.

INTRODUCTION: The indications for cementless short-stem total hip arthroplasty (THA) have been expanded due to encouraging results. However, no evidence in cases of femoral neck fractures (FNFs) is available. We aimed to prospectively obtain data on the safety and the clinical outcomes of a cementless calcar-guided short stem in patients with FNFs. MATERIALS AND METHODS: We conducted a prospective observational study of 68 patients diagnosed with FNFs who underwent short-stem THA between 2016 and 2019 with a calcar-guided stem. Complications during follow-up leading to revision were documented, and patient reported outcome measurements recorded. Stem migration was analyzed using the Einzel-Bild-Röntgen-Analysis Femoral Component Analysis software. RESULTS: The mean follow-up was 33.8 ± 14.8 months. The patient mortality at last follow-up was 10.6%. Two patients required stem revision, due to periprosthetic fracture and late aseptic loosening, respectively, corresponding to 96.2% stem survival. Survivorship for the endpoint of revision for any reason was 91.1% at 6 years. All revisions occurred in females. The mean Harris Hip Score at the last follow-up was 93.0 ± 8.9. The mean axial migration at last follow-up was 1.90 ± 1.81 mm. No significant influence on migration was found regarding gender, age, weight, and body mass index. CONCLUSIONS: The clinical and radiological findings were satisfying and most patients benefited from the minimally invasive procedure. However, as for conventional THA as well, implant survivorship and mortality were markedly worse compared to results regarding osteoarthritis. Especially in elderly female patients with FNF, cementless short-stem THA is a concern and a cemented THA should be the first choice.

Functional outcomes after intramedullary nailing (C-Nail®) of severe calcaneal fractures with mean follow-up of 36 months.

PURPOSE: Calcaneal fractures (CFs) are rare but potentially debilitating injuries. Apart from the open, far lateral or sinus tarsi approach, operative treatment can be performed minimally invasive and percutaneously with intramedullary nailing. In this study, we sought to investigate the functional outcome of severe CFs treated with the C-Nail® implant. METHODS: Twenty-two CFs (9 × Sanders III and 8 × Sanders IV), operated between 2016 and 2019, were followed up with a mean duration of 36 (± 11) months. The AOFAS score, pre- and postoperative Böhler angles, wound healing disorders, and patient-reported outcome measures (PROMs) like pain levels and return to work/sport levels were assessed. RESULTS: The mean AOFAS score was 72.0 (± 9.8). Four patients sustained wound healing disorders, yet no implant-associated surgical revision was required. Fifty percent of patients were pain-free within 1 year. Within 1 year, about 50% of the patients could return to sports, and about 80% of the patients could return to work. PROMs and functional results align with those from other implants reported in the literature. CONCLUSION: Intramedullary nailing of severe CFs with the C-Nail® implant can be considered a safe treatment alternative that yields acceptable results at mid-terms.

[Treatment of symptomatic end-stage osteoarthritis of the ankle with anterolateral approach and an anatomical plate]. / Sprunggelenkarthrodese über einen anterolateralen Zugang mit einer anatomischen Platte.

OBJECTIVE: The aim of this paper is to describe the anterolateral approach using an anatomical plate for ankle arthrodesis and to present the first mid-term results with this technique in a high-risk population. INDICATIONS: The indication for arthrodesis of the ankle joint with this described technique is moderate to severe osteoarthritis of the ankle. CONTRAINDICATIONS: In addition to the general contraindications typical of any operation, there is a specific contraindication in cases of active infection of the soft tissues and accompanying osteomyelitis at the ankle. SURGICAL TECHNIQUE: The incision is made along the course of the peroneus tertius muscle. After that, the mobilization of the peroneus superficialis nerve is carried out, followed by the mobilization of the long extensor tendons, especially the extensor digitorum muscle in a medial direction opening the capsule and removal of the residual cartilage on the distal tibia and talus. Subsequently, the subchondral sclerosis is opened, and the implantation of a suitable osteosynthesis material, e.g., an anatomical angle-stable plate, is carried out. Finally, wound closure is performed involving the muscle belly of the extensor digitorum muscle covering the plate. POSTOPERATIVE MANAGEMENT: Immobilization of the ankle for 5-7 days in a dorsal knee-high splint. Retention in a walker after decongestion for another 5 weeks. Increased loading can be done after X­ray/computed tomography (CT) control from the 6th week. RESULTS: In all, 11 patients were observed retrospectively for an average of 14 months. There were no complications. The European Foot and Ankle Society (EFAS) score improved significantly from 3.3 to 17.8 points. All patients were subjectively satisfied with the result and would have the operation again.

An isoelastic monoblock cup versus a modular metal-back cup: a matched-pair analysis of clinical and radiological results using Einzel-Bild-Röntgen-Analyse software.

INTRODUCTION: Bone preservation and long-term survival are the main challenges in cementless total hip arthroplasty (THA). A good bone stock is especially important for adequate anchorage of the cup in revision cases. However, the optimal acetabular cup design for preserving good bone stock is still unclear. We aimed to compare clinical outcome, radiological alterations, migration, and wear at mid-term for two different cup types. MATERIALS AND METHODS: This retrospective matched-pair study was performed using the data for 98 THA cases treated with a monoblock cup composed of vitamin E-blended highly cross-linked polyethylene (VEPE; monoblock group) or a modular cup composed of a highly cross-linked polyethylene (HXLPE) without an antioxidant (modular group). Clinical results were evaluated using the Harris Hip Score (HHS). The obtained radiographs were analyzed for radiological alterations, migration, and wear using Einzel-Bild-Röntgen-Analyse (EBRA) software. RESULTS: The mean follow-up duration was 73.2 ± 19.2 months (range: 32-108 months) and 60.5 ± 12.2 months (range: 20-84 months) in the monoblock and modular groups, respectively. HHS improved to 95.7 points in the monoblock group and 97.6 points in the modular group, without significant differences (p = 0.425). EBRA measurements were obtained in all cases. Acetabular bone alterations were not detected on radiological assessments. Mean cup migration was 1.67 ± 0.92 mm (range: 0.46-3.94 mm) and 1.24 ± 0.87 mm (range: 0.22-3.62 mm) in the monoblock and modular groups. The mean wear rate was 0.21 ± 0.18 mm (range: 0.00-0.70 mm) and 0.20 ± 0.13 mm (range: 0.00-0.50 mm) in the monoblock and modular groups. Both migration and wear pattern showed no significant differences (p = 0.741 and 0.243). None of the cases required revision surgery, yielding an implant survival rate of 100% in both groups. CONCLUSION: The isoelastic press-fit monoblock VEPE cup and modular metal-back HXLPE cup showed equivalent mid-term wear and cup migration. Long-term studies are required to determine the effects of modularity, isoelasticity, and polyethylene stabilization with vitamin E on cup loosening and survival rates.

[Disproportionately increased incidence of proximal femoral fractures in a level one trauma center : Epidemiological analysis from 2016 to 2022]. / Überproportional angestiegene Inzidenz proximaler Femurfrakturen in einem Level-One-Traumazentrum : Epidemiologische Analyse von 2016 bis 2022.

BACKGROUND: Proximal femoral fractures represent the most frequent fracture entity in Germany accounting for more than 20% of all fractures. According to a decision of the Federal Joint Committee from 2019, proximal femoral fractures also have to be surgically treated within 24 h. In order to quantify a subjectively perceived increase in workload in trauma surgery at a supraregional trauma center, a retrospective analysis of the number of surgically treated proximal femoral fractures was performed. Proximal femoral fractures were chosen due to their high incidence and homogeneous treatment. METHODS: Using ICD-10 codes, all surgically treated proximal femoral fractures from 2016 to 2022, including the patient's zip code, were retrieved from the database of the trauma center. RESULTS: The number of surgically treated proximal femoral fractures doubled from 2016 to 2022. The highest increase (60%) was recorded from 2020 to 2022. Heat maps show an increase in the catchment area radius as well. CONCLUSION: When compared (inter)nationally, a disproportionate increase in the amount of surgically treated proximal femoral fractures was recorded at the trauma center studied. The increase of the catchment area radius and the number of patients treated in the urban area show that less and less hospitals participate in emergency treatment. Possible explanations are a lack of resources aggravated by the recent COVID-19 pandemic and a lack of qualified personnel, interface problems between the federal states or the strict requirements of the Federal Joint Committee in the treatment of proximal femoral fractures. It must be assumed that there is a clearly increased workload for all professions involved in the trauma center investigated, although the infrastructure has remained unchanged.

Can we separately measure glenoid vs. humeral lateralization and distalization in reverse shoulder arthroplasty?

BACKGROUND: Lateralization and distalization in reverse shoulder arthroplasty (RSA) can be measured on anteroposterior (AP) radiographs using 2 previously described angles: lateralization shoulder angle (LSA) and distalization shoulder angle (DSA). However, these 2 angles measure global lateralization and distalization but do not allow to differentiate how much lateralization or distalization are attributable to the glenoid and the humerus. We hypothesized that new angles could allow us to separately measure glenoid vs. humeral lateralization and distalization. A more precise understanding of independent glenoid and humeral contributions to lateralization and distalization may be beneficial in subsequent clinical research. METHOD: Retrospective analysis of postoperative AP radiographs of 100 patients who underwent primary RSA for cuff-tear arthropathy, massive cuff tear, or glenohumeral osteoarthritis were analyzed. The new angles that we proposed use well-known bony landmarks (the acromion, glenoid, and humerus) and the most lateral point of the glenosphere, which we termed the "glenoid pivot point" (GPP). For lateralization, we used the GPP to split LSA into 2 new angles: glenoid lateralization angle (GLA) and humeral lateralization angle (HLA). For distalization, we introduced the modified distalization shoulder angle (mDSA) that can also be split into 2 new angles: glenoid distalization angle (GDA) and humeral distalization angle (HDA). Three orthopedic surgeons measured the new angles, using the online tool Tyche. Mean values with overall and individual standard deviations as well as intraclass correlation coefficients (ICCs) were calculated. RESULTS: Because the angles form a triangle, the following equations can be made: LSA = GLA + HLA, and mDSA = GDA + HDA. All angles showed excellent inter- and intraobserver reliability (ICC = 0.92-0.97) with low means of individual standard deviations that indicate a precision of 2° for each angle. CONCLUSION: Use of the most lateral part of the glenosphere (termed glenoid pivot point) allows us to separately measure glenoid vs. humeral lateralization and distalization. The 4 new angles (HLA, GLA, GDA, HDA) described in the present study can be used on true AP radiographs, routinely obtained after shoulder replacement, and the measured angles may be used with all types of reverse prostheses available.

Influence of Lateral Sitting Wedges on the Rasterstereographically Measured Scoliosis Angle in Patients Aged 10-18 Years with Adolescent Idiopathic Scoliosis.

Adolescent idiopathic scoliosis (AIS) is a three-dimensional axial deviation of the spine diagnosed in adolescence. Despite a long daily sitting duration, there are no studies on whether scoliosis can be positively influenced by sitting on a seat wedge. For the prospective study, 99 patients with AIS were measured with the DIERS formetric III 4D average, in a standing position, on a level seat and with three differently inclined seat wedges (3°, 6° and 9°). The rasterstereographic parameters 'scoliosis angle' and 'lateral deviation RMS' were analysed. The side (ipsilateral/contralateral) on which the optimal correcting wedge was located in relation to the lumbar/thoraco-lumbar convexity was investigated. It was found that the greatest possible correction of scoliosis occurred with a clustering in wedges with an elevation on the ipsilateral side of the convexity. This clustering was significantly different from a uniform distribution (p < 0.001; chi-square = 35.697 (scoliosis angle); chi-square = 54.727 (lateral deviation RMS)). It should be taken into account that the effect of lateral seat wedges differs for individual types of scoliosis and degrees of severity. The possibility of having a positive effect on scoliosis while sitting holds great potential, which is worth investigating in follow-up studies.

The effect of losartan on the development of post-traumatic joint stiffness in a rat model.

Post-traumatic joint stiffness (PTJS) is accompanied by a multidimensional disturbance of joint architecture. Pharmacological approaches represent promising alternatives as the traumatic nature of current therapeutic standards may lead to PTJS' progression. Losartan is an auspicious candidate, as it has demonstrated an antifibrotic effect in other organs. Forty-eight Sprague Dawley rats were randomized into equally sized losartan or control groups. After a standardized knee trauma, the joint was immobilized for either 2 weeks (n = 16), 4 weeks (n = 16) or 4 weeks with re-mobilization for an additional 4 weeks (n = 16). Pharmacotherapy with losartan or placebo (30 mg/kg/day) was initiated on the day of trauma and continued for the entire course. Joint contracture was measured alongside histological and molecular biological assessments. There were no significant biomechanical changes in joint contracture over time, comparing short-term (2 weeks) with long-term losartan therapy (4 weeks). However, comparing the formation of PTJS with that of the control, there was a trend toward improvement of joint mobility of 10.5° (p 0.09) under the influence of losartan. During the re-mobilization phase, no significant effect of losartan on range of motion (ROM) was demonstrated. At a cellular level, losartan significantly reduced myofibroblast counts by up to 72 % (4 weeks, p ≤ 0.001) without effecting the capsular configuration. Differences in expression levels of profibrotic factors (TGF-ß, CTGF, Il-6) were most pronounced at week 4. The antifibrotic properties of losartan are not prominent enough to completely prevent the development of PTJS after severe joint injury.

A new 3D-printed polylactic acid-bioglass composite for bone tissue engineering induces angiogenesis in vitro and in ovo.

Large bone defects such as those that occur after trauma or resections due to cancer still are a challenge for surgeons. Main challenge in this area is to find a suitable alternative to the gold-standard therapy, which is highly risky, and a promising option is to use biomaterials manufactured by 3D printing. In former studies, we demonstrated that the combination of polylactic acid (PLA) and bioglass (BG) resulted in a stable 3D-printable material, and porous and finely structured scaffolds were printed. These scaffolds exhibited osteogenic and anti-inflammatory properties. This 3D-printed material fulfills most of the requirements described in the diamond concept of bone healing. However, the question remains as to whether it also meets the requirements concerning angiogenesis. Therefore, the aim of this study was to analyze the effects of the 3D-printed PLA-BG composite material on angiogenesis. In vitro analyses with human umbilical vein endothelial cells (HUVECs) showed a positive effect of increasing BG content on viability and gene expression of endothelial markers. This positive effect was confirmed by an enhanced vascular formation analyzed by Matrigel assay and chicken chorioallantoic membrane (CAM) assay. In this work, we demonstrated the angiogenic efficiency of a 3D-printed PLA-BG composite material. Recalling the osteogenic potential of this material demonstrated in former work, we manufactured a mechanically stable, 3D-printable, osteogenic and angiogenic material, which could be used for bone tissue engineering.

Dynamic surface topography data for assessing intra- and interindividual variation of vertebral motion.

Spinal function is substantially related to the motion of the particular vertebrae and the spine as a whole. For systematic assessment of individual motion, data sets are required which cover the kinematics comprehensively. Additionally, the data should enable a comparison of inter- and intraindividual variation of vertebral orientation in dedicated motion tasks like gait. For this purpose, this article provides surface topography (ST) data which were acquired while the individual test persons were walking on a treadmill at three different speed levels (2 km/h, 3 km/h, 4 km/h). In each recording, ten full walking cycles were included per test case to enable a detailed analysis of motion patterns. The provided data reflects asymptomatic and pain-free volunteers. Each data set contains the vertebral orientation in all three motion directions for the vertebra prominens down to L4 as well as the pelvis. Additionally, spinal parameters like balance, slope, and lordosis / kyphosis parameters as well as an assignment of the motion data to single gait cycles are included. The complete raw data set without any preprocessing is provided. This allows to apply a broad range of further signal processing and evaluation steps in order to identify characteristic motion patterns as well as intra- and inter-individual variation of vertebral motion.

Creation and Evaluation of a Severity Classification of Hyperkyphosis and Hypolordosis for Exercise Therapy.

The rise in the occurrence of musculoskeletal disorders, such as thoracic hyperkyphosis (THK) or lumbar hypolordosis (LHL), is a result of demographic changes. Exercise therapy is an effective approach that can reduce related disabilities and costs. To ensure successful therapy, an individualized exercise program adapted to the severity of the disorder is expedient. Nevertheless, appropriate classification systems are scarce. This project aimed to develop and evaluate a severity classification focused on exercise therapy for patients with THK or LHL. A multilevel severity classification was developed and evaluated by means of an online survey. Reference limits of spinal shape angles were established by data from video rasterstereography of 201 healthy participants. A mean kyphosis angle of 50.03° and an average lordosis angle of 40.72° were calculated as healthy references. The strength of the multilevel classification consisting of the combination of subjective pain and objective spinal shape factors was confirmed by the survey (70% agreement). In particular, the included pain parameters were considered relevant by 78% of the experts. Even though the results of the survey provide important evidence for further analyses and optimization options of the classification system, the current version is still acceptable as therapeutic support.

Optimism and pessimism are antithetically associated with post-operative knee function in patients' undergoing total knee arthroplasty.

PURPOSE: Personality traits, such as dispositional optimism and pessimism, have impact on a variety of health-related problems. Influence on outcome in total knee arthroplasty (TKA) could only be shown for other personality trait concepts, but not for dispositional optimism/pessimism. This study aims to examine the association of dispositional optimism/pessimism with pre-operative joint function and post-operative outcome in TKA. METHODS: Data were acquired in a multicentre, cross-sectoral, prospective study (the PROMISE Trial). Patients were followed for 12 months post-operatively. Dispositional optimism/pessimism was measured pre-operatively via the revised Life Orientation Test (LOT-R), pre- and post-operative function was measured via the 12 Item Knee-osteoarthritis outcome Scores (KOOS-12). Log-linear regression models considering known confounders and t-test were carried out to show the association of LOT-R scores with pre- and post-operative KOOS-12 scores. RESULTS: 740 patients were analyzed. Optimistic LOT-R was significantly positively associated to the mean scores of KOOS-12 pre- and post-operative, while pessimistic LOT-R was significantly associated negatively (pre-operative: optimistic p = 0.001, pessimistic p = 0.001; post-operative optimistic: 3M p = 0.001, 6M p = 0.001, 12M p = 0.001; post-operative pessimistic: 3M p = 0.01, 6M p = 0.004, 12M p = 0.001). CONCLUSION: Optimism was positively associated with pre-operative joint function and, more importantly, post-operative functional outcome in TKA, while pessimism was associated with the opposite. Assessing patients' general personality traits prior to surgery to identify pessimistic patients, hence being at risk for poor outcome in TKA, should be considered to react to the patients' special needs and possible pessimistic expectations, i.e., through a cognitive-behavioral intervention, to potentially increase optimism and hereby post-operative outcome in TKA. LEVEL OF EVIDENCE: Prognostic Level III.

The Controversial Definition of Normal Toe Alignment.

"Normal" and "abnormal" are frequently used in surgical planning and to evaluate surgical results of the forefoot. However, there is no objectifiable value of metatarsophalangeal angles (MTPAs) 2-5 in the dorsoplantar (DP) view with which to objectively evaluate lesser toe alignment. We aimed to determine which angles are considered to be "normal" by orthopedic surgeons and radiologists. Thirty anonymized radiographs of feet were submitted twice in randomized order to determine the respective MTPAs 2-5. After six weeks, the anonymized radiographs and photographs of the same feet without apparent affiliation were presented again. The terms "normal," "borderline normal," and "abnormal" were assigned by the observers. Viewers considered MTP-2 alignment from 0° to -20° to be normal, and below -30° abnormal; MTP-3, 0° to -15° to be normal and below -30° abnormal; MTP-4, 0° to -10° normal and below -20° abnormal. Between 5° valgus and 15° varus was the range of MTP-5 recognized as normal. High intra-observer but low interobserver reliability with overall low correlation of clinical and radiographic aspects was observed. The assessment of the terms "normal" or "abnormal" are subject to a high degree of variation. Therefore, these terms should be used cautiously.

Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies - (lessons learned from) a prospective study.

This prospective cohort study aimed to characterise the impact of oxaliplatin-based chemotherapy and its neurotoxic side effects (i.e., chemotherapy-induced neuropathy) on functional fall-risk and falls. Twenty chemotherapy-naïve participants (mean age, 59 years; 16 males) were consecutively included. A multimodal fall risk assessment was performed at four time points within 6 months. Polyneuropathy was assessed using the Neurologic Disability Scale; the fall risk was assessed by functional tests (Tinetti Test, Chair-Rising Test, and Timed up and Go Test). Patient-reported outcomes comprised the Hospitality Anxiety and Depression Scale (HADS), the Falls Efficacy Scale - International (FES-I) to assess the fear of falling, and the Physical Activity for the Elderly (PASE) questionnaire. Three falls occurred during the study. All fallen participants had a high fall risk-index (≥4 more risk factors) compared to only 30% of the non-fallen participants (p = 0.03) and suffered more frequently from pre-existing mild polyneuropathy (p = 0.049). Study discontinuation (n = 12) was associated with a higher rate of polypharmacy (p = 0.045), anxiety (HADS-A, p = 0.03), and specific fear of falling (FES-I, p = 0.025). In contrast, study completers (n = 8) reported an improvement in physical activity (PASE) (p = 0.018). In summary, pre-existing fall-risk factors impacted more falls than chemotherapy. A fall risk index offers a time-efficient screening option in an outpatient oncological setting.

Simultaneous bilateral TKA in the context of fast track surgery - Do patients meet discharge criteria as anticipated?

BACKGROUND: The efficacy and safety of enhanced recovery after surgery (ERAS) protocols for patients undergoing total knee arthroplasty (TKA) have been generally proven. Previous studies investigating patients undergoing simultaneous bilateral TKA (SBTKA) focused on complications, mortality, and pain and did not examine patients' functional limitations. Therefore, the aim of this study was to investigate to what extent patients undergoing SBTKA are able to meet functional discharge criteria originally designed for their counterparts undergoing unilateral TKA (UTKA) in an ERAS setting. MATERIALS AND METHODS: All patients who received primary SBTKA between June 2015 and December 2018 were included in this retrospective analysis. For comparison, UTKA patients were matched 1:1 to SBTKA patients using Propensity Score Matching based on age, gender, and BMI. The times to achieving the rehabilitation checkpoints of walking 150 m, walking a flight of stairs, and 90° knee flexion were evaluated. RESULTS: 63 (SBTKA group) and 64 (UTKA group) patients were included. Due to the Propensity-Score-Matching there were no differences regarding age, gender, and BMI. The mean length of stay (LOS) was 9.1 days in the SBTKA and 7.6 days in the UTKA group (p = 0.003). On average, it took SBTKA patients 5.4 days to achieve an uninterrupted walking distance of at least 150 m, while it took UTKA patients 4.1 days (p < 0.001). Mean time to walking a flight of stairs was 6.3 days for SBTKA patients and 4.7 days for UTKA patients (p < 0.001). 90° flexion was achieved after 4.1 days by SBTKA patients and 3.5 days by UTKA patients (p = 0.241). CONCLUSION: The vast majority of SBTKA patients were able to achieve functional discharge criteria within their inpatient stay when allowed about 30% extra time. Therefore, functional discharge criteria in ERAS protocols designed for UTKA can be considered appropriate for SBTKA patients. LEVEL OF EVIDENCE: Therapeutic Level III.

Gene expression variability in long-term survivors of childhood cancer and cancer-free controls in response to ionizing irradiation.

BACKGROUND: Differential expression analysis is usually adjusted for variation. However, most studies that examined the expression variability (EV) have used computations affected by low expression levels and did not examine healthy tissue. This study aims to calculate and characterize an unbiased EV in primary fibroblasts of childhood cancer survivors and cancer-free controls (N0) in response to ionizing radiation. METHODS: Human skin fibroblasts of 52 donors with a first primary neoplasm in childhood (N1), 52 donors with at least one second primary neoplasm (N2 +), as well as 52 N0 were obtained from the KiKme case-control study and exposed to a high (2 Gray) and a low dose (0.05 Gray) of X-rays and sham- irradiation (0 Gray). Genes were then classified as hypo-, non-, or hyper-variable per donor group and radiation treatment, and then examined for over-represented functional signatures. RESULTS: We found 22 genes with considerable EV differences between donor groups, of which 11 genes were associated with response to ionizing radiation, stress, and DNA repair. The largest number of genes exclusive to one donor group and variability classification combination were all detected in N0: hypo-variable genes after 0 Gray (n = 49), 0.05 Gray (n = 41), and 2 Gray (n = 38), as well as hyper-variable genes after any dose (n = 43). While after 2 Gray positive regulation of cell cycle was hypo-variable in N0, (regulation of) fibroblast proliferation was over-represented in hyper-variable genes of N1 and N2+. In N2+, 30 genes were uniquely classified as hyper-variable after the low dose and were associated with the ERK1/ERK2 cascade. For N1, no exclusive gene sets with functions related to the radiation response were detected in our data. CONCLUSION: N2+ showed high degrees of variability in pathways for the cell fate decision after genotoxic insults that may lead to the transfer and multiplication of DNA-damage via proliferation, where apoptosis and removal of the damaged genome would have been appropriate. Such a deficiency could potentially lead to a higher vulnerability towards side effects of exposure to high doses of ionizing radiation, but following low-dose applications employed in diagnostics, as well.

Bone Sialoprotein Immobilized in Collagen Type I Enhances Angiogenesis In Vitro and In Ovo.

Bone fracture healing is a multistep process, including early immunological reactions, osteogenesis, and as a key factor, angiogenesis. Molecules inducing osteogenesis as well as angiogenesis are rare, but hold promise to be employed in bone tissue engineering. It has been demonstrated that the bone sialoprotein (BSP) can induce bone formation when immobilized in collagen type I, but its effect on angiogenesis still has to be characterized in detail. Therefore, the aim of this study was to analyse the effects of BSP immobilized in a collagen type I gel on angiogenesis. First, in vitro analyses with endothelial cells (HUVECs) were performed detecting enhancing effects of BSP on proliferation and gene expression of endothelial markers. A spheroid model was employed confirming these results. Finally, the inducing impact of BSP-collagen on vascular density was proved in a yolk sac membrane assay. Our results demonstrate that BSP is capable of inducing angiogenesis and confirm that collagen type I is the optimal carrier for this protein. Taking into account former results, and literature showing that BSP also induces osteogenesis, one can hypothesize that BSP couples angiogenesis and osteogenesis, making it a promising molecule to be used in bone tissue regeneration.