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Intensive farming has severe impacts on the chemical status of groundwater and streams and consequently on the ecological status of dependent ecosystems. Eutrophication is a widespread problem in lakes and marine waters. Common problems are hypoxia, algal blooms, fish kills, and loss of water clarity, underwater vegetation, biodiversity and recreational value. In this paper we evaluate the nitrogen (N) and phosphorus (P) concentrations of groundwater and surface water in a coastal catchment, the loadings and sources of N and P, and their effect on the ecological status of an estuary. We calculate the necessary reductions in N and P loadings to the estuary for obtaining a good ecological status, which we define based on the number of days with N and P limitation, and the corresponding stream and groundwater threshold values assuming two different management options. The calculations are performed by the combined use of empirical models and a physically based 3-D integrated hydrological model of the whole catchment. The assessment of the ecological status indicates that the N and P loads to the investigated estuary should be reduced to levels corresponding to 52 and 56% of the current loads, respectively, to restore good ecological status. Model estimates show that threshold total N (TN) concentrations should be in the range of 2.9 to 3.1 mg l−1 in inlet freshwater (streams) to Horsens estuary and 6.0 to 9.3 mg l−1 in shallow aerobic groundwater (∼ 27–41 mg l−1 of nitrate), depending on the management measures implemented in the catchment. The situation for total P (TP) is more complex, but data indicate that groundwater threshold values are not needed. The stream threshold value for TP to Horsens estuary for the selected management options is 0.084 mg l−1. Regional climate models project increasing winter precipitation and runoff in the investigated region resulting in increasing runoff and nutrient loads to the Horsens estuary and many other coastal waters if present land use and farming practices continue. Hence, lower threshold values are required in many coastal catchments in the future to ensure good status of water bodies and ecosystems.

Wound healing as a result of a skin injury involves a series of dynamic physiological processes, leading to wound closure, re-epithelialization, and the remodeling of the extracellular matrix (ECM). The primary scar formed by the new ECM never fully regains the original tissue's strength or flexibility. Moreover, in some cases, due to dysregulated fibroblast activity, proliferation, and differentiation, the normal scarring can be replaced by pathological fibrotic tissue, leading to hypertrophic scars or keloids. These disorders can cause significant physical impairment and psychological stress and represent significant challenges in medical management in the wound-healing process. The present study aimed to investigate the therapeutic effects of exogenously applied carbon dioxide (CO 2 ) on fibroblast behavior, focusing on viability, proliferation, migration, and differentiation to myofibroblasts. We found that CO 2 exposure for up to 60 min did not significantly affect fibroblast viability, apoptosis rate, or proliferation and migration capacities. However, a notable finding was the significant reduction in α-smooth muscle actin (α-SMA) protein expression, indicative of myofibroblast differentiation inhibition, following CO 2 exposure. This effect was specific to CO 2 and concentration as well as time-dependent, with longer exposure durations leading to greater reductions in α-SMA expression. Furthermore, the inhibition of myofibroblast differentiation correlated with a statistically significantly reduced glycolytic and mitochondrial energy metabolism, and as a result, with a reduced ATP synthesis rate. This very noticeable decrease in cellular energy levels seemed to be specific to CO 2 exposure and could not be observed in the control cultures using nitrogen (N 2 )-saturated solutions, indicating a unique and hypoxia-independent effect of CO 2 on fibroblast metabolism. These findings suggest that exogenously applied CO 2 may possess fibroblast differentiation-reducing properties by modulating fibroblast's energy metabolism and could offer new therapeutic options in the prevention of scar and keloid development.

Background/Objectives : The aim was to investigate diagnostic, treatment and preventive options to establish an overview of the existing evidence on hemorrhage in pelvic fractures in older adults. Methods : A systematic review was conducted. Due to the rarity of this complication, only case reports and series with individuals older than 55 years with a pelvic ring fracture that is caused by a low-energy trauma or no apparent trauma, along with hemorrhage, were eligible. A search was performed on four databases. The CARE checklist was used to investigate the reporting integrity of the included studies. Analysis was performed narratively, and this study was registered on the Open Science Framework. Results : 21 patients from 19 studies were included (17 females and 4 males) with an average age of 82.1 years. The 21 patients suffered a total of 29 fractures. Pubic ramus fractures were present in 48.3% of all fractures. In 42.9%, an active hemorrhage was reported. Arterial vessels were injured in direct anatomical relationship to the fracture. Abdominal pain and hemorrhagic instability were the main red flag symptoms reported. Active arterial hemorrhage was diagnosed by CT with angiogram and treated by embolization with or without additional surgery. Conclusions : Clinically relevant hemorrhage in pelvic fractures due to low-energy trauma is rare. However, these fractures, combined with clinically relevant hemorrhage, account for an increased mortality and morbidity in elderly people. This systematic review was able to create a clinical decision tree for hemorrhage in ramus pubic fractures.

Osteoporosis is a progressive metabolic bone disease characterized by decreased bone density and microarchitectural deterioration, leading to an increased risk of fracture, particularly in postmenopausal women and the elderly. Increasing evidence suggests that inflammatory processes play a key role in the pathogenesis of osteoporosis and are strongly associated with the activation of osteoclasts, the cells responsible for bone resorption. In the present study, we investigated, for the first time, the influence of proinflammatory cytokines on the osteogenic differentiation, proliferation, and metabolic activity of primary human osteoblast-like cells (OBs) derived from the femoral heads of elderly patients. We found that all the proinflammatory cytokines, IL-1β, TNF-α, IL-6, and IL-8, enhanced the extracellular matrix mineralization of OBs under differentiation-induced cell culture conditions. In the cases of IL-1β and TNF-α, increased mineralization was correlated with increased osteoblast proliferation. Additionally, IL-1β- and TNF-α-increased osteogenesis was accompanied by a rise in energy metabolism due to improved glycolysis or mitochondrial respiration. In conclusion, we show here, for the first time, that, in contrast to findings obtained with cell lines, mesenchymal stem cells, or animal models, human OBs obtained from patients exhibited significantly enhanced osteogenesis upon exposure to proinflammatory cytokines, probably in part via a mechanism involving enhanced cellular energy metabolism. This study significantly contributes to the field of osteoimmunology by examining a clinically relevant cell model that can help to develop treatments for inflammation-related metabolic bone diseases.

Objectives: Proximal humeral fractures (PHFs) show a high incidence in aged patients. While nondisplaced fractures achieve good results by conservative treatment, surgical procedures are discussed controversially. Next to open reduction and internal fixation (ORIF), the primary use of reverse shoulder arthroplasty (RSA) has become increasingly important. The aim of this study was to investigate the clinical function, activities of daily living (ADL), as well as pain assessment in patients with PHFs, treated by ORIF or RSA., Methods: A retrospective comparison study was assessed. From November 2011 to March 2016, 34 patients (17 matched pairs) that had undergone either ORIF or RSA of the proximal humerus, were included in this study. Pain was measured by numeric rating scale (NRS). ADL were obtained by Katz-Index and SF-12. Moreover, shoulder function was assessed using the Oxford Shoulder Score (OSS). The maximum range of motion (ROM) was also recorded. From November 2011 to March 2016, 34 patients (17 matched pairs) that had undergone either ORIF (Figure or RSA of the proximal humerus) were included in this study. For statistical analyses, Student's t-test, Wilcoxon test, and Chi-Quadrat test were used. Statistical significance was indicated with p < 0.05., Results: Totally 34 patients with an average age of 76.6 years were included. Surgical treatment was performed on average 5.2 days after diagnosis, differing significantly between the two groups (RSA/ORIF: 6.9/3.5 days) The operation time of RSA (97 min) was significantly longer than for ORIF (78 min). Pain assessment, as well as the Katz-Index and the SF-12, showed no significant differences. Moreover, clinical shoulder function showed no significant discrepancies between the two surgical techniques., Conclusions: Aged patients with PHFs treated with RSA display similar results regarding clinical function, ADL as well as pain perception compared with ORIF. However, revision surgery rate was lower in patients who underwent RSA. Thus, the surgical treatment of PHFs by RSA represents an excellent alternative, especially with regard to an aging patient population., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Background/Objectives: Postoperative delirium is a prevalent and serious complication among elderly patients following surgical procedures. Prior research indicates that reduced competence in daily living, as evidenced by limitations in performing Activities of Daily Living (ADL), is directly associated with reduced patient mobility. This study aimed to investigate the potential role of preoperative mobility as a risk factor for the development of postoperative delirium. Methods: To assess preoperative mobility, a comprehensive geriatric evaluation of daily living competence was conducted. This included the Katz Index of Independence in ADL, which assessed basic daily activities over the preceding 14 days, and the Instrumental Activities of Daily Living Scale (IADL). Postoperatively, delirium monitoring was performed twice daily for seven days using validated delirium screening tools, including the Nursing Delirium Screening Scale, the Confusion Assessment Method, and the 4ATest. Results: A significant correlation was observed between the incidence of delirium and the IADL scores in all patients, with p < 0.001 for men and p = 0.001 for women. Among emergency patients, the Katz Index scores significantly differed between those who developed delirium and those who did not ( p = 0.015). Additionally, a significant correlation was found between the Katz Index and the incidence of delirium in both groups ( p < 0.001). Conclusions: The findings of this study emphasize the necessity of preoperative geriatric assessment using tools such as the Katz Index or IADL to identify patients at risk of delirium. The results confirm the importance of enhanced postoperative monitoring for potential delirium. For elective patients, prehabilitation should be considered when reduced daily living competence is identified. For emergency patients, immediate postoperative interventions, including intensive mobilization and orthogeriatric co-management, are recommended.

Purpose: To compare anterior plate fixation (SP fixation) both alone and in combination with an additional posterior sacroiliac screw (SP+SIS fixation) as a treatment for pelvic ring injuries with widening of the pubic symphysis and disruption to the anterior sacroiliac ligaments., Methods: To find studies with pelvic ring injuries (APC II; B2.3d) and SP or SP+SIS fixation, a systematic literature review was conducted by searching four databases. A protocol was published a priori at Open Science Framework (https://doi.org/10.17605/OSF.IO/3YHAV). Exclusion criteria included perineal injuries, chronic instability of the symphysis, complete sacroiliac separation, and pediatric patients (age <18 years). Primary outcomes of interest were defined as implant failure, health-related quality of life, and revision rate., Results: Altogether, 1861 studies were screened, and 40 studies qualified for full-text analysis. In total, 14 studies (two surveys, six biomechanical studies, and six retrospective clinical studies) were included. The surveys revealed that surgeons who had more recently begun practicing were more likely to use posterior fixation (SP+ISS). The biomechanical studies were heterogenous and did not yield a uniform pattern. In clinical studies, 117 patients (45%) received SP fixation, and 142 patients (55%) received SP+SIS fixation. Complications occurred in 31 SP patients (30%) and in five SP+SIS patients (3.5%)., Conclusion: A high risk of bias was uncovered, and reporting was found to be incomplete. SP+SIS may have the potential to improve outcomes, but the evidence remains too inconclusive to draw reliable recommendations.

Background: Thromboelastometry like ROTEM ® is a point-of-care method used to assess the coagulation status of patients in a rapid manner being particularly useful in critical care settings, such as trauma, where quick and accurate assessment of coagulation can guide timely and appropriate treatment. Currently, this method is not yet comprehensively available with sparse data on its effectiveness in resuscitation rooms. The aim of this study was to assess the effect of early thromboelastometry on the probability of mass transfusions and mortality of severely injured patients. Methods: The TraumaRegister DGU ® was retrospectively analyzed for severely injured patients (2011 until 2020) with information available regarding blood transfusions and Trauma-Associated Severe Hemorrhage (TASH) score components. Patients with an estimated risk of mass transfusion >2% were included in a matched-pair analysis. Cases with and without use of ROTEM ® diagnostic were matched based on risk categories for mass transfusion. A total of 1722 patients with ROTEM ® diagnostics could be matched with a non-ROTEM ® patient with an identical risk category. Adult patients (≥16) admitted to a trauma center in Germany, Austria, or Switzerland with Maximum Abbreviated Injury Scale severity ≥3 were included. Results: A total of 83,798 trauma victims were identified after applying the inclusion and exclusion criteria. For 7740 of these patients, the use of ROTEM ® was documented. The mean Injury Severity Score (ISS) in patients with ROTEM ® was 24.3 compared to 19.7 in the non-ROTEM ® group. The number of mass transfusions showed no significant difference (14.9% ROTEM ® group vs. 13.4% non-ROTEM ® group, p = 0.45). Coagulation management agents were given significantly more often in the ROTEM ® subgroup. Mortality in the ROTEM ® group was 4.1% less than expected (estimated mortality based on RISC II 34.6% vs. observed mortality 30.5% (n = 525)). In the non-ROTEM ® group, observed mortality was 1.6% less than expected. Therefore, by using ROTEM ® analysis, the expected mortality could be reduced by 2.5% (number needed to treat (NNT) 40; SMR of ROTEM ® group: 1:0.88; SMR of non-ROTEM ® group: 1:0.96; p = 0.081). Conclusions: Hemorrhage is still one of the leading causes of death of severely injured patients in the first hours after trauma. Early thromboelastometry can lead to a more targeted coagulation management, but is not yet widely available. This study demonstrated that ROTEM ® was used for the more severely injured patients and that its use was associated with a less than expected mortality as well as a higher utilization of hemostatic products.

Background: Surgical correction of adolescent idiopathic scoliosis from the posterior approach can be performed by the "all screws" technique; hybrid technique with screws and hooks; hybrid technique or with screws, hooks, and tapes; or selective fusion (SF) or nonselective fusion (NSF). The aim of the present investigation was to analyze the influence from different operative techniques on frontal curve correction and sagittal profile in patients with adolescent idiopathic scoliosis., Methods: We conducted a retrospective analysis on 55 consecutive patients with scoliosis who had been treated by posterior instrumented fusion. We collected demographic data and analyzed pre- and postoperative radiographs. Statistical analysis was performed using SPSS version 25. Because data showed normal distribution, t tests were performed., Results: Twenty-two patients were treated using the hybrid technique with screws and hooks; 25 were treated using the hybrid technique with screws, hooks, and tape; and 8 were treated using the all screws technique. An SF was performed in 32 patients and NSF in 23 patients. There was no significant difference with regard to curve correction of the main curve between the different techniques. Correction of the minor curve was significantly higher in NSF than in SF patients. In SF, there was a correction of the minor curve of 43.9%. Impact on sagittal balance showed no significant differences between NSF and SF., Conclusion: The different operative techniques did not show a difference with regard to the correction of the main curve. NSF showed a significantly higher degree of correction of the minor curve than SF. However, we still found a correction of 43.9% of the noninstrumented minor curve in SF. Thus, SF and hybrid techniques do not lead to inferior radiographic outcome., Clinical Relevance: SF and hybrid techniques are safe and effective techniques that could be used as an alternative to NSF and all screw fixation in the operative treatment for scoliosis., Competing Interests: Declaration of Conflicting Interests : M.R.K. reports paid lectures for Globus Medical and Depuy Synthes. The other authors declare no conflict of interest relevant to this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2024 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: Clinical trials investigating acetabular fractures are heterogeneous in their investigated outcomes and their corresponding measurements. Standardization may facilitate comparability and pooling of research results, which would lead to an increase in knowledge about the optimal treatment of acetabular fractures, resulting in long-term evidence-based treatment decisions and improvements in patient care. The aim of this systematic review is to identify the reported outcomes and their measurements from studies on treatments for acetabular fractures to develop a core outcome set which contains the most relevant outcome measures to be included in future studies., Methods: Studies published in English and German including patients aged 16 years and older, with a surgically treated acetabular fracture, will be included. Studies with nonsurgical treatment, pathologic fractures, polytraumatized patients, and patients younger than 16 years of age will be excluded because other outcomes may be of interest in these cases. Any prospective and retrospective study will be included. Systematic reviews will be excluded, but their included studies will be screened for eligibility. The literature will be searched on MEDLINE, CENTRAL, Web of Science, ClinicalTrials.gov, and WHO ICTRP. Risk of selective reporting of outcomes will be assessed using the Outcome Reporting Bias in Trials classification system. Heterogeneously defined outcomes that measure the same outcome will be grouped and subsequently categorized into outcome domains using the taxonomy of the Core Outcome Measures in Effectiveness Trials Initiative., Discussion: It is expected that a high number of studies will be included, and many outcomes will be identified using different definitions and measurement instruments. A limitation of this systematic review is that only previously investigated outcomes will be detected, thus disregarding potentially relevant outcomes., Systematic Review Registration: PROSPERO CRD42022357644., (© 2024. The Author(s).)

Non-muscle invasive bladder cancer is a common tumour in men and women. In case of resistance to the standard therapeutic agents, gemcitabine can be used as off-label instillation therapy into the bladder. To reduce potential side effects, continuous efforts are made to optimise the therapeutic potential of drugs, thereby reducing the effective dose and consequently the pharmacological burden of the medication. We recently demonstrated that it is possible to significantly increase the therapeutic efficacy of mitomycin C against a bladder carcinoma cell line by exposure to non-toxic doses of blue light (453 nm). In the present study, we investigated whether the therapeutically supportive effect of blue light can be further enhanced by the additional use of the wavelength-specific photosensitiser riboflavin. We found that the gemcitabine-induced cytotoxicity of bladder cancer cell lines (BFTC-905, SW-1710, RT-112) was significantly enhanced by non-toxic doses of blue light in the presence of riboflavin. Enhanced cytotoxicity correlated with decreased levels of mitochondrial ATP synthesis and increased lipid peroxidation was most likely the result of increased oxidative stress. Due to these properties, blue light in combination with riboflavin could represent an effective therapy option with few side effects and increase the success of local treatment of bladder cancer, whereby the dose of the chemotherapeutic agent used and thus the chemical load could be significantly reduced with similar or improved therapeutic success., Competing Interests: The authors whose names are listed above certify that they neither actually nor potentially have any kind of affiliations with or involvement in any organisation or entity with any financial interest (such as honoraria; educational grants; participation in speakers&rsquo; bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Introduction: When needed operative treatment of sacral fractures is mostly performed with percutaneous iliosacral screw fixation. The advantage of navigation in insertion of pedicle screws already could be shown by former investigations. The aim of this investigation was now to analyze which influence iliosacral screw placement guided by navigation has on duration of surgery, radiation exposure and accuracy of screw placement compared to the technique guided by fluoroscopy., Methods: 68 Consecutive patients with sacral fractures who have been treated by iliosacral screws were inclouded. Overall, 85 screws have been implanted in these patients. Beside of demographic data the duration of surgery, duration of radiation, dose of radiation and accuracy of screw placement were analyzed., Results: When iliosacral screw placement was guided by navigation instead of fluoroscopy the dose of radiation per inserted screw (155.0 cGy*cm 2 vs. 469.4 cGy*cm 2 p < 0.0001) as well as the duration of radiation use (84.8 s vs. 147.5 s p < 0.0001) were significantly lower. The use of navigation lead to a significant reduction of duration of surgery (39.0 min vs. 60.1 min p < 0.01). The placement of the screws showed a significantly higher accuracy when performed by navigation (0 misplaced screws vs 6 misplaced screws-p < 0.0001)., Conclusion: Based on these results minimal invasive iliosacral screw placement guided by navigation seems to be a safe procedure, which leads to a reduced exposure to radiation for the patient and the surgeon, a reduced duration of surgery as well as a higher accuracy of screw placement., (© 2024. The Author(s).)

Introduction: This retrospective cohort study aimed to evaluate the impact of kick-off time on the risk of injury for professional soccer players in the first German Bundesliga. It was hypothesized that late kick-off times would have a negative effect on muscle and ligament injuries to the ankle and knee., Methods: Kick-off times and injury data were collected over 5 consecutive seasons (1530 matches; 2014-2019) from two media-based registries (transfermarkt.de ® und kicker.de ® ). The kick-off times were assorted into three groups: Afternoon kick-off between prior to 3:30 pm (988 matches), evening kick-off between 5:30 to 6:30 pm (303 matches), and night kick-off after 8 pm (239 matches)., Results: A total of 1327 match injuries were recorded over 5 seasons in 510 different male elite soccer players. The injuries affected muscles in 32.1%, ankle ligaments in 7.8%, and knee ligaments in 5.6%. There was no significant difference in injury rates when comparing different kick-off time groups (p > 0.05), however, the mean of time attributed to muscle and ankle ligament injuries suffered in games with a late kick-off time was significantly longer (p < 0.05)., Conclusion: This study shows that there is no significant (p > 0.05) association between three different kick-off time groups and injury risk in the first German Bundesliga. However, significant (p < 0.05) differences in the lay-off times attributed to muscle and ankle ligament injuries differed with different kick-off times assorted into the three groups. Reasons for this observation could be found in the circadian muscle rhythms and muscle fatigue., (© The Authors, published by EDP Sciences, 2024.)

Purpose: The current study aimed to investigate the correlation between the grade of radiographic hip osteoarthritis (OA) and the fracture pattern observed in fragility fractures of the proximal femur. The information may help in cases of occult hip fractures., Methods: In this retrospective study all 448 patients treated with fragility fractures of the proximal femur in the years 2014-2018 were included. Patients were allocated into two groups: Group I) intracapsular (femoral neck) fractures and Group II) extracapsular (pertrochanteric and subtrochanteric) femoral fractures. The radiographic grade of OA was determined according to Kellgren and Lawrence's classification. One single observer examined all radiographs., Results: Patients' age ranged between 52 and 104 years with a mean of 80.0 years. There was a significant difference in mean age between the two groups (76.9 years intracapsular vs. 83.1 years extracapsular fractures). A total of 250 (55.8%) fractures were intracapsular (femoral neck) and 198 (44.2%) were located extracapsular (pertrochanteric, subtrochanteric). A significant correlation between the degree of OA to fracture pattern was observed: Higher degrees of OA were related to extracapsular fractures and lower degrees of OA to intracapsular fractures., Conclusion: The results of this study support the hypothesis that hip osteoarthritis affects the fracture pattern in proximal femur fractures. More severe hip OA is associated with extracapsular fractures that can be treated surgically with lower complication rates compared to intracapsular fractures., (© The Authors, published by EDP Sciences, 2024.)

Background: Soft tissue swelling assessment benefits from a reproducible and easy to use measurement method. Monitoring of the injured lower extremity is of clinical import during staged soft tissue management. Portable 3D scanners offer a novel and precise option to quantify and contrast the shapes and volumes of the injured and contralateral uninjured limbs. This study determined three regions of interest (ROI) within the lower extremity (lower leg, ankle and foot), that can be used to evaluate 3D volumetric assessment for staged soft tissue management in orthopedic and trauma surgery., Methods: Twelve healthy volunteers (24 legs) were included in this cohort study. Scans of all three ROI were recorded with a portable 3D scanner (Artec, 3D scanner EVA) and compared between the right and left leg using the software Artec Studio (Arctec Group, Luxemburg)., Results: Mean volume of the right leg was 1926.64 ± 308.84 ml (mean ± SD). ROI: lower leg: 931.86 ± 236.15 ml; ankle: 201.56 ± 27.88 ml; foot: 793.21 ± 112.28 ml. Mean volume of the left leg was 1937.73 ± 329.51 ml. ROI: lower leg: 933.59 ± 251.12 ml; ankle: 201.53 ± 25.54 ml; foot: 802.62 ± 124.83 ml. There was no significant difference of the overall volume between right and left leg (p > 0.05; overall volume: △ difference: 29.5 ± 7.29 ml, p = 0.8; lower leg: △ difference: 21.5 ± 6.39 ml, p = 0.8; ankle: △ difference: 5.3 ± 2.11 ml, p = 0.4; △ difference: 16.33 ± 4.45 ml, p = 0.8., Conclusion: This pilot study defines three regions of interest of the lower leg and demonstrates no difference between the right and left side. Based on these ROI, further studies are needed to evaluate the clinical applicability of the scanner., (© 2023. The Author(s).)

Background: The field of orthopedics seeks effective, safer methods for evaluating articular cartilage regeneration. Despite various treatment innovations, non-invasive, contrast-free full quantitative assessments of hyaline articular cartilage's regenerative potential using compositional magnetic resonance (MR) sequences remain challenging. In this context, our aim was to investigate the effectiveness of different MR sequences for quantitative assessment of cartilage and to compare them with the current gold standard delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC) measurements., Methods: We employed ex vivo imaging in a preclinical minipig model to assess knee cartilage regeneration. Standardized osteochondral defects were drilled in the proximal femur of the specimens (n=14), which were divided into four groups. Porcine collagen scaffolds seeded with autologous adipose-derived stromal cells (ASC), autologous bone marrow stromal cells (BMSC), and unseeded scaffolds (US) were implanted in femoral defects. Furthermore, there was a defect group which received no treatment. After 6 months, the specimens were examined using different compositional MR methods, including the gold standard dGEMRIC as well as T 1 , T 2 , T 2 *, and T 1ρ techniques. The statistical evaluation involved comparing the defect region with the uninjured tibia and femur cartilage layers and all measurements were performed on a clinical 3T MR Scanner., Results: In the untreated defect group, we observed significant differences in the defect region, with dGEMRIC values significantly lower (404.86±64.2 ms, P=0.018) and T 2 times significantly higher (44.24±2.75 ms, P<0.001). Contrastingly, in all three treatment groups (ASC, BMSC, US), there were no significant differences among the three regions in the dGEMRIC sequence, suggesting successful cartilage regeneration. However, T 1 , T 2 *, and T 1ρ sequences failed to detect such differences, highlighting their lower sensitivity for cartilage regeneration., Conclusions: As expected, dGEMRIC is well suited for monitoring cartilage regeneration. Interestingly, T 2 imaging also proved to be a reliable cartilage imaging technique and thus offers a contrast agent-free alternative to the former gold standard for subsequent in vivo studies investigating the cartilage regeneration potential of different treatment modalities., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-570/coif). VG, PJ and JW report that the study was supported by the Deutsche Arthrose-Hilfe grant number: P460-A335-Windolf-EP2-jung1-knie-op-I-25k-2019-20. VG reports that this study was supported by collagen scaffolds from Matricel GmbH. The other authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Dupuytren's disease (DD) is a fibroproliferative disorder affecting the palmar fascia, causing functional restrictions of the hand and thereby limiting patients' daily lives. The disturbed and excessive myofibroblastogenesis, causing DD, is mainly induced by transforming growth factor (TGF)-β1. But, the extent to which impaired TGF-β1 release or TGF-β signal degradation is involved in pathologically altered myofibroblastogenesis in DD has been barely examined. Therefore, the complex in which TGF-β1 is secreted in the extracellular matrix to elicit its biological activity, and proteins such as plasmin, integrins, and matrix metalloproteinases (MMPs), which are involved in the TGF-β1 activation, were herein analyzed in DD-fibroblasts (DD-FBs). Additionally, TGF-β signal degradation via caveolin-1 was examined with 5-fluoruracil (5-FU) in detail. Gene expression analysis was performed via Western blot, PCR, and immunofluorescence analyses. As a surrogate parameter for disturbed myofibroblastogenesis, 𝛼-smooth-muscle-actin (𝛼-SMA) expression was evaluated. It was demonstrated that latency-associated peptide (LAP)-TGF-β and latent TGF-β-binding protein (LTBP)-1 involved in TGF-β-complex building were significantly upregulated in DD. Plasmin a serinprotease responsible for the TGF-β release was significantly downregulated. The application of exogenous plasmin was able to inhibit disturbed myofibroblastogenesis, as measured via 𝛼-SMA expression. Furthermore, a reduced TGF-β1 degradation was also involved in the pathological phenotype of DD, because caveolin-1 expression was significantly downregulated, and if rescued, myofibroblastogenesis was also inhibited. Therefore, our study demonstrates that a deficient release and degradation of TGF-β1 are important players in the pathological phenotype of DD and should be addressed in future research studies to improve DD therapy or other related fibrotic conditions.

Background: Patients with muscle-invasive bladder cancer face a poor prognosis due to rapid disease progression and chemoresistance. Thus, there is an urgent need for a new therapeutic treatment. The tumor microenvironment (TME) has crucial roles in tumor development, growth, progression, and therapy resistance. TME cells may also survive standard treatment of care and fire up disease recurrence. However, whether specific TME components have tumor-promoting or tumor-inhibitory properties depends on cell type and cancer entity. Thus, a deeper understanding of the interaction mechanisms between the TME and cancer cells is needed to develop new cancer treatment approaches that overcome therapy resistance. Little is known about the function and interaction between mesenchymal stromal cells (MSC) or fibroblasts (FB) as TME components and bladder cancer cells., Methods: We investigated the functional impact of conditioned media (CM) from primary cultures of different donors of MSC or FB on urothelial carcinoma cell lines (UCC) representing advanced disease stages, namely, BFTC-905, VMCUB-1, and UMUC-3. Underlying mechanisms were identified by RNA sequencing and protein analyses of cancer cells and of conditioned media by oncoarrays., Results: Both FB- and MSC-CM had tumor-promoting effects on UCC. In some experiments, the impact of MSC-CM was more pronounced. CM augmented the aggressive phenotype of UCC, particularly of those with epithelial phenotype. Proliferation and migratory and invasive capacity were significantly increased; cisplatin sensitivity was reduced. RNA sequencing identified underlying mechanisms and molecules contributing to the observed phenotype changes. NRF2 and NF-κB signaling was affected, contributing to improved cisplatin detoxification. Likewise, interferon type I signaling was downregulated and regulators of epithelial mesenchymal transition (EMT) were increased. Altered protein abundance of CXCR4, hyaluronan receptor CD44, or TGFβ-signaling was induced by CM in cancer cells and may contribute to phenotypical changes. CM contained high levels of CCL2/MCP-1, MMPs, and interleukins which are well known for their impact on other cancer entities., Conclusions: The CM of two different TME components had overlapping tumor-promoting effects and increased chemoresistance. We identified underlying mechanisms and molecules contributing to the aggressiveness of bladder cancer cells. These need to be further investigated for targeting the TME to improve cancer therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Frerichs, Frerichs, Petzsch, Köhrer, Windolf, Bittersohl, Hoffmann and Grotheer.)

Background: Antibiotic treatment of spondylodiscitis is influenced by antibiotic stewardship; specifically, empirical antibiotic therapy is avoided in favor of-delayed-targeted antibiotic therapy after microbiological diagnosis. Only patients with neurological deficits or clinical signs of sepsis should be treated by empirical antibiotic therapy. However, the level of evidence for this treatment concept is weak., Purpose: The aim of this study was to investigate whether patients who were treated with a nontargeted antibiotic therapy show a worse outcome than patients who were exclusively treated with targeted antibiotic therapy., Study Design/setting: A retrospective single-center data analysis., Patient Sample: We included 201 patients with spondylodiscitis who were treated at the authors' institution between 2013 and 2020., Outcome Measures: Mortality rate, time in hospital, development of laboratory parameters, and development of pain (visual analog scale)., Methods: We performed a retrospective data analysis of patients who were treated for spondylodiscitis from January 2013 to March 2020. Clinical and demographic data as well as outcome and complications were recorded and analyzed. We investigated whether patients who were treated by a nontargeted antibiotic therapy had a worse outcome than patients who were exclusively treated by targeted antibiotic therapy and which other clinical factors had an impact on clinical outcome., Results: A total of 201 patients were included, 37 of whom developed sepsis during their hospital stay, and 14 of these 37 patients died. The 14 patients who died represented (10.0%) of the subgroup who received an empirical antibiotic treatment before the targeted antibiotic therapy ( n = 141). There were 0 deaths in the subgroup who did not receive an empirical antibiotic treatment ( P < 0.05). The time to diagnosis since admission to the hospital was 10.5 (2.2) days in patients with sepsis; in patients without sepsis, it was 5.2 (0.9) days ( P < 0.05)., Conclusions: Based on the results of this investigation, the authors recommend delaying antibiotic therapy until targeted antibiotic therapy is possible. Furthermore, early diagnosis of spondylodiscitis and prevention and early detection of sepsis are essential to reduce the mortality rate of patients with spondylodiscitis., Competing Interests: Declaration of Conflicting Interests : M.R.K. reports personal fees from Globus Medical outside the submitted work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Cold atmospheric plasmas (CAPs) generated by dielectric barrier discharge (DBD), particularly those containing higher amounts of nitric oxide (NO) or NO derivates (NOD), are attracting increasing interest in medical fields. In the present study, we, for the first time, evaluated DBD-CAP-induced NOD accumulation and therapeutically relevant NO release in calcified bone tissue. This knowledge is of great importance for the development of new therapies against bacterial-infectious complications during bone healing, such as osteitis or osteomyelitis. We found that by modulating the power dissipation in the discharge, it is possible (1) to significantly increase the uptake of NODs in bone tissue, even into deeper regions, (2) to significantly decrease the pH in CAP-exposed bone tissue, (3) to induce a long-lasting and modulable NO production in the bone samples as well as (4) to significantly protect the treated bone tissue against bacterial contaminations, and to induce a strong bactericidal effect in bacterially infected bone samples. Our results strongly suggest that the current DBD technology opens up effective NO-based therapy options in the treatment of local bacterial infections of the bone tissue through the possibility of a targeted modulation of the NOD content in the generated CAPs.

Adipose tissue-derived stromal cells (ASCs) play an important role in various therapeutic approaches to bone regeneration. However, such applications become challenging when the obtained cells show a functional disorder, e.g., an impaired osteogenic differentiation potential (ODP). In addition to ASCs, human adipose tissue is also a source for another cell type with therapeutic potential, the dedifferentiated fat cells (DFATs), which can be obtained from mature adipocytes. Here, we for the first time compared the ODPs of each donors ASC and DFAT obtained from the same adipose tissue sample as well as the role of oxidative stress or antioxidative catalase on their osteogenic outcome. Osteogenic potential of ASC and DFAT from nine human donors were compared in vitro. Flow cytometry, staining for calcium accumulation with alizarin red, alkaline phosphatase assay and Western blots were used over an osteogenic induction period of up to 14 days. H 2 O 2 was used to induce oxidative stress and catalase was used as an antioxidative measure. We have found that ASC and DFAT cultures' ODPs are nearly identical. If ASCs from an adipose tissue sample showed good or bad ODP, so did the corresponding DFAT cultures. The inter-individual variability of the donor ODPs was immense with a maximum factor of about 20 and correlated neither with the age nor the sex of the donors of the adipose tissue. Oxidative stress in the form of exogenously added H 2 O 2 led to a significant ODP decrease in both cell types, with this ODP decrease being significantly lower in DFAT cultures than in the corresponding ASC cultures. Regardless of the individual cell culture-specific ODP, however, exogenously applied catalase led to an approx. 2.5-fold increase in osteogenesis in the ASC and DFAT cultures. Catalase appears to be a potent pro-osteogenic factor, at least in vitro. A new finding that points to innovative strategies and therapeutic approaches in bone regeneration. Furthermore, our results show that DFATs behave similarly to ASCs of the same adipose tissue sample with respect to ODPs and could therefore be a very attractive and readily available source of multipotent stem cells in bone regenerative therapies.

Background: The Calcaneus is the largest bone of the foot and the most frequent tarsal bone to be fractured. Overall, it causes round about 10 cases per 100,000 residents per year mainly in men. Especially displaced intra-articular calcaneus fractures often have early and late complications and its associated disability. There are various strategies for the treatment of displaced intra-articular calcaneus fractures, but the gold standard is still subject of a long-standing controversy. Minimally invasive procedures became more common in an attempt to reduce the high rate of complications associated with open reduction and internal fixation. With the increase in minimally invasive techniques, screw fixation also gained in significance. The current literature does not sufficiently elucidate whether the screw fixation is superior to other treatment options especially in relation to adverse events, health-related quality of life and postoperative pain. This study aims to investigate benefits and harms of treating displaced intra-articular calcaneus fractures (types II, III and IV according to Sanders) with screw fixation in adults., Methods: A systematic review will be conducted based on the principles described in the Cochrane Handbook. We will include adults with displaced intra-articular calcaneus fractures of Sanders type II, III and IV. The surgical method of screw fixation shall be compared to other surgical interventions to stabilise calcaneus fractures. Primary outcomes are serious adverse events, health-related quality of life and postoperative pain level. MEDLINE, CENTRAL, CINAHL, Web of Science and bibnet.org, ClinicalTrial.gov and the World Health Organization International Clinical Trials Registry Platform (ICTR) will be searched. Screening and data extraction will be performed by two authors independently. A third author will arbitrate disputes. Risk of Bias will be assessed with the Cochrane tool. Meta-analysis will be performed if participants, interventions, comparisons and outcomes are sufficiently similar to ensure a result that is clinically meaningful., Discussion: Due to the increasing use of minimally invasive techniques and the increasing use of screw fixation instead of open reduction and plate fixation, it is important to analyse the benefits and harms of screw fixation for calcaneus fractures. Screw fixation could, in the future, help to operate in a less invasive and tissue preserving manner while still achieving an adequate functional result for the patient SYSTEMATIC REVIEW REGISTRATION: CRD42021244695., (© 2022. The Author(s).)

Objective: To evaluate radiological outcomes following the use of xenogeneic bone graft substitute (BGS) in patients undergoing multisegmental spinal fusion., Summery of Background Data: Data exists for single level and short segment fusions, there presently is a paucity of data on fusion rate after bone augmentation with BGS in multisegmental posterior spinal fusion (PSF). The leading concern is pseudarthrosis, which often leads to a loss of correction after PSF. Therefore, the bone graft is an essential aspect of PSF., Methods: We retrospectively analysed the radiological data of a consecutive cohort of patients who had been treated for adolescent idiopathic scoliosis (AIS) via multisegmental spinal fusion, in whom a bovine derived BGS had been used and had a complete dataset of 24 months follow-up. The Cobb angle of the main curve was measured pre-operatively and then at 6, 12 and 24 months post-operatively. Loosening of the screws was recorded at the same post-operative time points., Results: After applying inclusion and exclusion criteria, 28 patients were included. We found no significant change of the cobb angle from the main curve as well as the cobb angle from the thoracic kyphosis during the 24 months of follow up. No patient showed a lack of bony fusion. There was 1 revision surgery, which was due to trauma., Conclusion: In this cohort, all patients showed successful bone fusion during a 24-month follow-up. Additionally, there was no change in the Cobb angle during the 2-year post-operative period. Our data indicates that the use of bovine-derived BGS supports bone fusion after multisegmental posterior instrumented fusion of the spine., Competing Interests: MRK reports personal fees from Globus Medical, outside the submitted work. The other authors declare no conflict of interest relevant to this work.

Background: The aim of this study was to characterize three regions of interest (ROI) around the knee with a portable 3D scanner (Artec 3D scanner EVA). Soft tissue topography assessment with an optimized, precise, and reproducible method may assist surgeons when managing soft tissue swelling in the post traumatic setting., Methods: 12 healthy volunteers (24 legs, 7 women, 5 man) were included in this study. The patient cohort showed a mean age of 27.1 years (SD±3), a mean weight of 70 kg (SD±13) and a mean height of 171 cm (SD±8.8). All scans were recorded by the same examiner in the same room and with the same scanner (Artec, 3 D scanner EVA). Three volume regions of interest (ROI) were defined: the distal femur (circumference measured between the of superior extent of the patella to 10 cm proximal), the knee joint (measured from the top of the patella to the tibial tuberosity) and the proximal tibia (tibial tuberosity to 10 cm distal)., Results: The mean volume of the right leg was 3.901 l (I. distal femur: 1.63 l, knee joint: 1.33 l, proximal tibia: 1.10 l) and mean volume of the left leg was 3.910 l (I. distal femur: 1.66 l, knee joint: 1.34 l, proximal tibia: 1.12 l). The volume difference between the right and left leg was 0.094 l (SD ± 0.083 l) The Wilcoxon-Mann-Whitney test showed no significant differences of the volumes between the right and left leg., Conclusions: This study demonstrates that portable 3D scanning could be an accurate and reliable tool for orthopedics and trauma surgeons. Based on the ROIs of this pilot study, further studies are needed to test the significance for clinical applications for patients with an injured knee., Competing Interests: The authors have declared that no competing interests exist.

Mesenchymal stromal cells (MSCs) play a pivotal role in modern therapeutic approaches of bone defect regeneration. A complication that is steadily increasing due to demographic population developments is an age-related disorder of the osteogenic differentiation potential (ODP) of MSCs. In the present in vitro study we have evaluated the impact of reactive oxygen species (ROS) and antioxidants on ODP of "normal healthy" as well as osteogenetically compromised human adipose tissue-derived stromal cells (ASC). We show that although ASC exhibit a marked ODP, a significant number of ASC cultures showed a retarded osteogenesis. These so-called "non-responder"-ASC cultures (NR-ASC) expressed an antigenic phenotype identical to that of the well osteogenically differentiating "responder"-ASCs (R-ASC), but NR-ASC significantly correlated with the older age of their donors as well as with a significantly higher intracellular generation of ROS. Furthermore, we found that treatment of the cell cultures with low concentration of H 2 O 2 seemed to promote osteogenic differentiation but higher H 2 O 2 concentration strongly reduced osteogenesis in all ASC cultures. Additionally, we found that exogenously applied superoxide dismutase (SOD) or catalase completely restored the impaired ODP of NR-ASC, whereas ascorbate, glutathione, N-acetylcysteine or a water soluble vitamin E derivate did not show any relevant effects. Our results suggest that aging-related increases in oxidative stress, especially due to H 2 O 2 , can severely impair the ODP of ASC whereas SOD or catalase almost completely corrected this disorder. Our findings point to novel osteo-therapeutic aspects of catalase and SOD and open up new approaches to ASC-based regeneration of bone defects., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: We (1) collected instruments that assess health-related quality of life (HRQoL), activities of daily living (ADL) and social participation during follow-up after polytrauma, (2) described their use and (3) investigated other relevant patient-reported outcomes (PROs) assessed in the studies., Design: Systematic Review using the Preferred Reporting Items for Systematic Review and Meta-Analysis guideline., Data Sources: MEDLINE, Embase, CINAHL, PsycINFO, CENTRAL, as well as the trials registers ClinicalTrials.gov and WHO ICTRP were searched from January 2005 to April 2018., Eligibility Criteria: All original empirical research published in English or German including PROs of patients aged 18-75 years with an Injury Severity Score≥16 and/or an Abbreviated Injury Scale≥3. Studies with defined injuries or diseases (e.g. low-energy injuries) and some text types (e.g. grey literature and books) were excluded. Systematic reviews and meta-analyses were excluded, but references screened for appropriate studies., Data Extraction and Synthesis: Data extraction, narrative content analysis and a critical appraisal (e.g. UK National Institute for Health and Care Excellence) were performed by two reviewers independently., Results: The search yielded 3496 hits; 54 publications were included. Predominantly, HRQoL was assessed, with Short Form-36 Health Survey applied most frequently. ADL and (social) participation were rarely assessed. The methods most used were postal surveys and single assessments of PROs, with a follow-up period of one to one and a half years. Other relevant PRO areas reported were function, mental disorders and pain., Conclusions: There is a large variation in the assessment of PROs after polytrauma, impairing comparability of outcomes. First efforts to standardise the collection of PROs have been initiated, but require further harmonisation between central players. Additional knowledge on rarely reported PRO areas (e.g. (social) participation, social networks) may lead to their consideration in health services provision., Prospero Registration Number: CRD42017060825., Competing Interests: Competing interests: JS was executive secretary of the Academy for Trauma Surgery GmbH (AUC). The authors declare that they have no competing interests., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Clinical Magnetic Resonance Imaging (MRI) of joints is limited to mere morphologic evaluation and fails to directly visualize joint or ligament function. In this controlled laboratory study, we show that knee joint functionality may be quantified in situ and as a function of graded posterior cruciate ligament (PCL)-deficiency by combining MRI and standardized loading. 11 human knee joints underwent MRI under standardized posterior loading in the unloaded and loaded (147 N) configurations and in the intact, partially, and completely PCL-injured conditions. For each specimen, configuration, and condition, 3D joint models were implemented to analyse joint kinematics based on 3D Euclidean vectors and their projections on the Cartesian planes. Manual 2D measurements served as reference. With increasing PCL deficiency, vector projections increased significantly in the anteroposterior dimension under loading and manual measurements demonstrated similar patterns of change. Consequently, if combined with advanced image post-processing, stress MRI is a powerful diagnostic adjunct to evaluate ligament functionality and joint laxity in multiple dimensions and may have a role in differentiating PCL injury patterns, therapeutic decision-making, and treatment monitoring., (© 2021. The Author(s).)

T2 mapping assesses tissue ultrastructure and composition, yet the association of imaging features and tissue functionality is oftentimes unclear. This study aimed to elucidate this association for the posterior cruciate ligament (PCL) across the micro- and macroscale and as a function of loading. Ten human cadaveric knee joints were imaged using a clinical 3.0T scanner and high-resolution morphologic and T2 mapping sequences. Emulating the posterior drawer test, the joints were imaged in the unloaded (δ 0 ) and loaded (δ 1 ) configurations. For the entire PCL, its subregions, and its osseous insertion sites, loading-induced changes were parameterized as summary statistics and texture variables, i.e., entropy, homogeneity, contrast, and variance. Histology confirmed structural integrity. Statistical analysis was based on parametric and non-parametric tests. Mean PCL length (37.8 ± 1.8 mm [δ 0 ]; 44.0 ± 1.6 mm [δ 1 ] [ p < 0.01]), mean T2 (35.5 ± 2.0 ms [δ 0 ]; 37.9 ± 1.3 ms [δ 1 ] [ p = 0.01]), and mean contrast values (4.0 ± 0.6 [δ 0 ]; 4.9 ± 0.9 [δ 1 ] [ p = 0.01]) increased significantly under loading. Other texture features or ligamentous, osseous, and meniscal structures remained unaltered. Beyond providing normative T2 values across various scales and configurations, this study suggests that ligaments can be imaged morphologically and functionally based on joint loading and advanced MRI acquisition and post-processing techniques to assess ligament integrity and functionality in variable diagnostic contexts.

Dupuytren's disease (DD) is a fibroproliferative disorder of the palmar aponeurosis, which is characterized by a compound myofibrogenesis and evidenced by an increased expression of α-smooth muscle actin (α-SMA). In Dupuytren's tissue, higher levels of reactive oxygen species (ROS) are documented, stimulating the proliferation and differentiation of myofibroblasts. Our preliminary study demonstrates that α-SMA-expression is significantly inhibited by blue light irradiation in DD. The objective of this study was to investigate the beneficial effect of blue light irradiation and to elucidate the influence of ROS on myofibrogenesis in the pathogenesis of DD. Therefore, an in-vitro model of human DD fibroblasts was used. DD fibroblasts and control fibroblasts isolated from carpal tunnel syndrome (CTS) were daily irradiated with 40 J/cm2 (λ = 453 nm, 38 mW/cm2). Protein expression of ROS-modulating enzymes (Catalase, NOX4, SOD1, MnSOD) and α-SMA were determined, and additionally analysed after a pharmacological inhibition of the TGF-β1-signaling with SB431542. Furthermore, the protein expression of α-SMA as surrogate parameter for myofibrogenesis was evaluated after applying different concentrations of long-lasting ROS. It could be determined that the beneficial blue light irradiation, which inhibited myofibrogenesis, is mediated by a significant inhibition of catalase protein expression. This effect should be accompanied with an increased intracellular ROS level. Proof of evidence was an H2O2-application on DD fibroblasts, also leading to a decreased myofibrogenesis. Furthermore, it could be demonstrated that endogenous MnSOD was significantly downregulated in resting DD fibroblasts. If DD fibroblasts were treated with the pharmacological inhibitor SB431542, myofibrogenesis was inhibited, but MnSOD expression was simultaneously elevated, which ought to affect ROS level by raising intracellular H2O2 amount. Blue light irradiation as well as the pharmacological action of SB431542 in consequence mediates their beneficial effect on disturbed myofibrogenesis in DD by further increasing ROS level. The present study demonstrates the importance of intracellular ROS homeostasis in DD and illuminates the beneficial effect of blue light as a promising therapy option for DD., Competing Interests: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

The need for an autologous cell source for bone tissue engineering and medical applications has led researchers to explore multipotent mesenchymal stromal cells (MSC), which show stem cell plasticity, in various human tissues. However, MSC with different tissue origins vary in their biological properties and their capability for osteogenic differentiation. Furthermore, MSC-based therapies require large-scale ex vivo expansion, accompanied by cell type-specific replicative senescence, which affects osteogenic differentiation. To elucidate cell type-specific differences in the osteogenic differentiation potential and replicative senescence, we analysed the impact of BMP and TGF-β signaling in adipose-derived stromal cells (ASC), fibroblasts (FB), and dental pulp stromal cells (DSC). We used inhibitors of BMP and TGF-β signaling, such as SB431542, dorsomorphin and/or a supplemental addition of BMP-2. The expression of high-affinity binding receptors for BMP-2 and calcium deposition with alizarin red S were evaluated to assess osteogenic differentiation potential. Our study demonstrated that TGF-β signaling inhibits osteogenic differentiation of ASC, DSC and FB in the early cell culture passages. Moreover, DSC had the best osteogenic differentiation potential and an activation of BMP signaling with BMP-2 could further enhance this capacity. This phenomenon is likely due to an increased expression of activin receptor-like kinase-3 and -6. However, in DSC with replicative senescence (in cell culture passage 10), osteogenic differentiation sharply decreased, and the simultaneous use of BMP-2 and SB431542 did not result in further improvement of this process. In comparison, ASC retain a similar osteogenic differentiation potential regardless of whether they were in the early (cell culture passage 3) or later (cell culture passage 10) stages. Our study elucidated that ASC, DSC, and FB vary functionally in their osteogenic differentiation, depending on their tissue origin and replicative senescence. Therefore, our study provides important insights for cell-based therapies to optimize prospective bone tissue engineering strategies.

Background: Hip fracture caused by fall is a common injury of the elderly. The risk of sustaining a contralateral hip fracture has been reported to be 5-10%. Aging society heightens the need of efficient prevention tools. To be able to cope with this demand, understanding of biomechanics of hip fractures are mandatory. Previous studies suggest that geometry of the proximal femur could play an important role for fracture probability and fracture type. Thus, analysis of hip geometry could play an important role in the prediction and prevention of bilateral hip fractures. Aim of this study was to elucidate the influence of caput collum diaphyseal angle on the fracture type of proximal femur., Material and Methods: In a retrospective analysis, data of patients with an acute hip fracture who underwent surgical treatment within five years were included. Data was separated into two groups: (I) intra capsular femur fracture (femoral neck fractures) and (II) extra capsular femur fracture (inter- and subtrochanteric femur fractures). Occurrence of a bilateral fracture, age, gender, weight, height and caput collum diaphyseal angle (standardized measurement of the opposite joint on preoperative digital x-rays) of each group were further analyzed., Results: Data of 448 patients were included ((I): 250 vs. (II): 198 patients). Group (I) showed a significant higher mean caput collum diaphyseal angle of 133.9 ± 7.0° (mean ± standard deviation) compared to group (II) with 127.6 ± 6.1° (F (1, 451) = 106.5, p = 0.00). In group (I) 0 patients had a caput collum diaphyseal angle <120° (varus), 214 patients (86%) 120°-140° and 35 patients (14%) angle>140° (valgus). In contrast, in group (II) 21 patients (10%) had a caput collum diaphyseal angle <120° (varus), 175 patients (86%) 120°-140° and 7 patients (4%) >140° (valgus). 52 patients had a bilateral hip fracture. 36 patients (69%) sustained a bilateral hip fracture of the same fracture type., Conclusion: Patients with an intra capsular proximal femur fracture showed a significantly higher caput collum diaphyseal angle compared to patients with an extra capsular proximal femur fracture. Moreover, intra capsular femur fractures are correlated with an indifferent (120-140°) or valgus (>140°) femoral neck configuration. Extra capsular femur fractures correlate with an indifferent (120-140°) or varian femoral neck configuration (<120°). The results support the assumption that the caput collum diaphyseal angle has an influence on fracture type of the proximal femur. This could possibly be a predictor for the fracture type of the contralateral hip (second fracture). Based on this, present data may benefit prosthetists in developing new and more efficient hip protectors., Level of Evidence: Level III. Retrospective comparative study., (© 2021 Published by Elsevier B.V. on behalf of Professor P K Surendran Memorial Education Foundation.)

Introduction  The range of motion of the carpometacarpal (CMC) joints is difficult to assess in clinical practice. Materials and Methods  The purpose of this study was to measure a precise range of motion measurement of the metacarpal arc during maximum palmar flexion of the fifth CMC joint in healthy persons with three different methods: optical, electrogoniometrical, and sonographical. Results  The metacarpal arc motion measured with the optical technique was 24.9 degrees (standard deviation [SD]: 6.2 degrees), with the electrogoniometric technique was 24.3 degrees (SD: 3.6 degrees) and with sonography was 25.1 degrees (SD: 3.5 degrees), with no differences between left and right hand for all methods. Conclusion  This study shows that different techniques can be used for the measurement of the metacarpal arc motion. With these techniques, it is possible to assess the metacarpal arc in patients with fractures to the CMC joints to evaluate posttraumatic function und rehabilitation progress. This study shows level of evidence as III., Competing Interests: Conflict of Interest None declared. Ethical Approval The present study was approved by the local research ethics committee of the Heinrich-Heine-University Düsseldorf (no. 4716)., (Society of Indian Hand & Microsurgeons. This article is published by Thieme.)

Purpose: When revision surgery is needed in total knee arthroplasty (TKA) the most frequent reasons are aseptic loosening (AL) and periprosthetic joint infection (PJI). However preoperative distinction between AL and PJI remains challenging. Aim of this study is to determine the incidence of PJI in patients with suspected AL after TKA and to evaluate a diagnostic algorithm for reliable differential diagnosis., Methods: In this study a total of 149 symptomatic patients with radiographic signs of prosthetic loosening and suspected AL were included. Preoperatively all patients underwent a standardized diagnostic algorithm. For each patient demographics, as well as the results of laboratory and microbiological testing were collected from the medical records., Results: Of the included patients 117 (78.5%) were diagnosed with AL and 32 (21.5%) with PJI. The latency period from primary arthroplasty to the presentation with symptomatic implant loosening was significantly shorter for PJI compared to AL (p < 0.05). The initial CRP values were significantly higher in patients with PJI compared to patients with AL (p < 0.05). Elevated count of white blood cells or percentage of neutrophils within the synovial fluid support the diagnosis of PJI. The sensitivity of synovial cell count (CC) count for PJI in patients with radiographic signs of loosening was 0.84 (CI 0.81-0.87) with a specificity of 0.96 (CI 0.92-0.98). The single best measure for the diagnosis of PJI was synovial fluid cultures with a specificity of 1, however this measure provides poor sensitivity., Conclusion: Patients with radiographic signs of loosening in TKA need thorough diagnostics. Information about primary TKA, serological testing, and results of joint aspiration can rule out a PJI in most cases., (© 2019 Delhi Orthopedic Association. All rights reserved.)

Purpose: Aim of this retrospective study was to evaluate the impact of the patient related factors body mass index (BMI), urinary tract infection, current smoking, gender, and American Society of Anesthesiologists (ASA) classification on the incidence of acute and chronic deep periprosthetic joint infections (PJI) in total knee arthroplasty (TKA)., Methods: All patients undergoing revision surgery for a deep PJI of primary TKA between July 2012 and December 2016 were included in this study. All relevant data was collected from the medical records. Acute deep PJI was defined when PJI was diagnosed within the first 6 weeks after primary TKA, chronic PJI was defined when patients demonstrated PJI later than 6 weeks after primary TKA., Results: A total of 57 patients was included in this study with 13 cases of acute PJI and 44 of chronic PJI. Overweight patients (BMI > 25 kg/m 2 ) represent a significantly larger proportion in both PJI groups (p < 0.05). Current smokers had an significantly increased risk for acute and chronic PJI (p < 0.05). In the acute PJI group 46.2% patients had an postoperative urinary tract infection., Conclusion: An elevated BMI (>25 kg/m 2 ), current smoking and urinary tract infection are possible risk factors for acute and chronic deep PJI. After primary TKA screening for urinary tract infection is recommendable to prevent predominantly acute deep PJI., Competing Interests: None., (© 2019 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Autologous bone marrow concentrate (BMC) and mesenchymal stem cells (MSCs) have beneficial effects on the healing of bone defects. To address the shortcomings associated with the use of primary MSCs, induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) have been proposed as an alternative. The aim of this study was to investigate the bone regeneration potential of human iMSCs combined with calcium phosphate granules (CPG) in critical-size defects in the proximal tibias of mini-pigs in the early phase of bone healing compared to that of a previously reported autograft treatment and treatment with a composite made of either a combination of autologous BMC and CPG or CPG alone. iMSCs were derived from iPSCs originating from human fetal foreskin fibroblasts (HFFs). They were able to differentiate into osteoblasts in vitro, express a plethora of bone morphogenic proteins (BMPs) and secrete paracrine signaling-associated cytokines such as PDGF-AA and osteopontin. Radiologically and histomorphometrically, HFF-iMSC + CPG transplantation resulted in significantly better osseous consolidation than the transplantation of CPG alone and produced no significantly different outcomes compared to the transplantation of autologous BMC + CPG after 6 weeks. The results of this translational study imply that iMSCs represent a valuable future treatment option for load-bearing bone defects in humans., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2019.)

Introduction: Proximal femoral fractures (PFF) are among the most frequent fractures in older people. However, the situation of people with a PFF after hospital discharge is poorly understood. Our aim is to (1) analyse healthcare provision, (2) examine clinical and patient-reported outcomes (PROs), (3) describe clinical and sociodemographic predictors of these and (4) develop an algorithm to identify subgroups with poor outcomes and a potential need for more intensive healthcare., Methods and Analysis: This is a population-based prospective study based on individually linked survey and statutory health insurance (SHI) data. All people aged minimum 60 years who have been continuously insured with the AOK Rheinland/Hamburg and experience a PFF within 1 year will be consecutively included (SHI data analysis). Additionally, 700 people selected randomly from the study population will be consecutively invited to participate in the survey. Questionnaire data will be collected in the participants' private surroundings at 3, 6 and 12 months after hospital discharge. If the insured person considers themselves to be only partially or not at all able to take part in the survey, a proxy person will be interviewed where possible. SHI variables include healthcare provision, healthcare costs and clinical outcomes. Questionnaire variables include information on PROs, lifestyle characteristics and socioeconomic status. We will use multiple regression models to estimate healthcare processes and outcomes including mortality and cost, investigate predictors, perform non-responder analysis and develop an algorithm to identify vulnerable subgroups., Ethics and Dissemination: The study was approved by the ethics committee of the Faculty of Medicine, Heinrich-Heine-University Düsseldorf (approval reference 6128R). All participants including proxies providing written and informed consent can withdraw from the study at any time. The study findings will be disseminated through scientific journals and public information., Trial Registration Number: DRKS00012554., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Overall Total hip arthroplasty (THA) is a very successful procedure. However, in case of complication dedicated management is required. Two major complications of THA failures are aseptic loosening (AL) and periprosthetic joint infection (PJI). The primary hypothesis of this study was that joint aspirations in patients with signs of loosening after THA are capable to detect PJI in suspected AL with negative serologic testing., Methods: In this study a total of 108 symptomatic patients with radiographic signs of prosthetic loosening and hip pain in THA were included. Based on a standardized algorithm all patients underwent serological testing followed by joint aspiration preoperatively. Intraoperatively harvested samples were subjected to microbiological testing and served as the gold standard in differential diagnosis. Demographics, as well as the results of serologic and microbiological testing were collected from the medical records., Results: Of the included patients 85 were finally diagnosed with an AL and 23 with PJI. Within the patients with PJI 13 (56%) patients demonstrated elevated CRP and WBC counts, as well as positive synovial cultures after joint aspiration. In ten patients (44%) diagnosed with PJI neither CRP nor WBC were abnormal., Conclusion: The diagnosis of PJI can be difficult in THA with radiographic signs of loosening. Clinical features including pain, fever, and local sings of infection are uncommon especially a long period after index operation. First-line screening testing relies on serological evaluation of CRP and WBC. However, normal CRP and WBC values cannot rule out a PJI. These cases can be detected by joint aspiration and synovial cultures reliably.

Purpose: Aseptic loosening (AL) has been reported to be one of the most frequent complications in Total Knee Arthroplasty (TKA) and Total Hip Arthroplasty (THA). The aim of this study was to identify the effects of gender, current tobacco use and BMI on the incidence of AL and implant survival time in THA and TKA., Methods: Between July 2012 and December 2016 all patients that were diagnosed with an AL of a primary THA or primary TKA and underwent revision surgery at a single institution were retrospectively reviewed for this study. For each patient gender, current tobacco use, BMI, and implant survival time were obtained from the medical records., Results: 202 patients with 85 THA and 117 TKA were included in this study. There was no impact of the gender on implant survival times (p > 0.05) in THA and TKA. In the TKA group current tobacco use was associated with a significant shorter implant survival time (p < 0.05). For THA and TKA with cemented stem fixation a significant increase of AL was seen in overweight compared to normal weight patients (p < 0.05) and in obese compared to normal weight patients (p < 0.05)., Conclusion: The results demonstrate that current tobacco use and elevated BMI are associated with increased rates of AL in TKA. Also, in THA with cemented stem fixation an elevated BMI is associated with an increased incidence of AL.

Objective: Leg length discrepancy (LLD) could be a predisposing factor for early degeneration of lumbar intervertebral discs (IVD). The purpose of this study was to elucidate the molecular effect of LLD on IVDs., Methods: IVDs of Eleven patients (25.6 ± 4.3years) with LLD (>10 mm) and 14 control subjects (23.9 ± 3.5years) were compared using a 3T-MR scanner. Morphological T2-weighted and glycosaminoglycan-chemical-exchange-saturation-transfer (gagCEST) sequences were performed., Results: No differences in morphological Pfirrmann grading were found (p > 0.05). In contrast, nucleus-pulposus-gagCEST-values of L5/S1 were significantly lower (p = 0.0008)., Conclusion: Our results suggest that LLD is a predisposing factor for molecular IVD alterations, which are detectable even before morphological pathologies could be found.