Publications by authors named "Siegmund Lang"

62 Publications

Managing periprosthetic joint infection-a qualitative analysis of nursing staffs' experiences.

BMC Nurs 2022 Jul 18;21(1):190. Epub 2022 Jul 18.

Department for Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.

Background: Periprosthetic joint infection represents a major complication in orthopaedics and trauma surgery. For an ideal management approach, it is important to understand the distinct challenges for all persons involved in the treatment. Therefore, it was aimed at investigating (1) the impact of periprosthetic joint infection (PJI) on the well-being of nursing staff to (2) identify challenges, which could be improved facilitating the management of PJI.

Methods: This is a qualitative interview study. In total, 20 nurses of a German university orthopedic trauma center specialized on infectious complications were recruited using a purposive sampling strategy. Content analysis was performed on transcripts of individual in-person interviews conducted between March 2021 and June 2021.

Results: Three major themes could be extracted including (i) feelings associated with the management of PJI and the need for emotional support, illustrating the negative emotional impact on nurses, whereby receiving collegial support was perceived as an important coping strategy, (ii) patients' psychological burden, highlighting the nurses' lack of time to address mental issues adequately and, (iii) realization of the severity of PJI and compliance problems.

Conclusion: Identified facilitating factors for PJI management include strengthening of mental care in the treatment of PJI, providing opportunities for exchange among multidisciplinary team members and implementing compliance-enhancing strategies. The findings of this study can be beneficial for improving professionals' satisfaction, optimising the work environment, creating organizational structures which enhance opportunities for exchange and preventing mental health issues among the nursing team.
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http://dx.doi.org/10.1186/s12912-022-00978-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294832PMC
July 2022

[Antibiotic use for prophylaxis and empirical therapy of fracture-related infections in Germany : A survey of 44 hospitals].

Unfallchirurgie (Heidelb) 2022 Jun 24. Epub 2022 Jun 24.

Klinik und Poliklinik für Unfallchirurgie, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Deutschland.

Background: Antibiotics play an important role in the prophylaxis and treatment of infections in orthopedic trauma surgery; however, there seems to be remarkable differences in the clinical antibiotic practice between hospitals, particularly for open fractures and for the empirical therapy of fracture-related infections (FRI).

Methods: Therefore, we intended to evaluate the current clinical praxis in university and workers' compensation hospitals in Germany with a questionnaire on prophylaxis and empirical treatment of FRI. The results were compared with the resistance profile of 86 FRI patients in order to analyze the hypothetical effectiveness of the empirical treatment.

Results: A total of 44 hospitals (62.0%) responded. A homogeneous antibiotic prophylaxis (95.5% of all hospitals) with cephalosporins was reported for perioperative prophylaxis of internal fixation of closed fractures. For open fractures, eight different monotherapy and combination treatment concepts were reported. In empirical treatment of FRI, 12 different therapeutic concepts were reported, including aminopenicillins/beta lactamase inhibitors (BLI) (31.8%), cephalosporins (31.8%), and ampicillin/sulbactam + vancomycin (9.1%). In terms of the hypothetical effectiveness of these antibiotic regimes, low sensitivity rates of 65.1% and 74.4% for cephalosporins and aminopenicillins/BLI, respectively, were found. For the combination vancomycin + meropenem, the highest hypothetical sensitivity (91.9%) was detected.

Discussion: Based on the existing, institution-specific pathogen spectrum, the combination therapy including meropenem and vancomycin seems to be of value but should be restricted to patients with multiple revision procedures or a septic course of infection in order to prevent the selection of highly resistant pathogens.
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http://dx.doi.org/10.1007/s00113-022-01200-0DOI Listing
June 2022

Incidence and treatment of intracapsular femoral neck fractures in Germany.

Arch Orthop Trauma Surg 2022 Jun 23. Epub 2022 Jun 23.

Department of Trauma Surgery, University Medical Centre Regensburg, Franz‑Josef‑Strauss Allee 11, 93053, Regensburg, Germany.

Introduction: Intracapsular femoral neck fractures are one of the most common fractures in Germany. Nevertheless, the epidemiology and treatment modalities are not described comprehensively. For this reason, this study highlights the epidemiology of femoral neck fractures in different age groups and summarizes treatment strategies within the period from 2009 to 2019 based on nationwide data.

Materials And Methods: In this retrospective cohort study all cases of intracapsular femoral neck fractures (ICD-10: S72.0) between 2009 and 2019 in Germany were analyzed with regard to epidemiology, incidence and treatment. Operation and procedure classification system (OPS)- codes in combination with intracapsular femoral neck fracture as main diagnosis were taken to investigation. Data was provided by the Federal Statistical Office of Germany (Destatis).

Results: A total of 807,834 intracapsular femoral neck fractures with a mean incidence of 110.0 per 100,000 inhabitants annually was detected within eleven years. In 68.8% of all fractures patients were female. Most patients were older than 70 years (82.4%), and 56.7% were older than 80 years. The overall increase of fracture numbers between 2009 and 2019 was 23.2%. Joint replacement has been most often performed (80.4%). Hemiarthroplasty (56.8%) and total hip arthroplasty (22.8%) were the most common procedures with an increase of 27.1 and 38.6%, respectively. The proportion of cemented hemiarthroplasties was 86.2% while 51.3% of all total hip arthroplasties were totally or partially cemented. Osteosyntheses were mainly conducted using dynamic compression screws (34.0%), conventional screws (31.3%) and nails (22.2%).

Conclusion: The incidence of intracapsular femoral neck fractures in Germany has been increasing continuously within the last decade. In particular, patients over 80 years suffered predominantly from this type of fracture. The majority was treated with a joint replacement procedure, mainly cemented hemiarthroplasty.
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http://dx.doi.org/10.1007/s00402-022-04504-3DOI Listing
June 2022

Antibiotic Prophylaxis and Empirical Antibiotic Therapy in Primary Arthroplasty and Periprosthetic Joint Infections: Current Practice and Need for Therapy Optimization.

Z Orthop Unfall 2022 Apr 25. Epub 2022 Apr 25.

Klinik und Poliklinik für Unfallchirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland.

The aim of the present work was to survey the situation of healthcare regarding the use of prophylactic and empirical antibiotics in primary arthroplasty and treatment of periprosthetic joint infections (PJI). For this purpose, a survey was conducted at German university and occupational accident hospitals. Survey data was compared to previously published data on the antimicrobial regimes of PJI (n=81) patients (n=81) treated in our department between 2017 and 2020. A homogeneous picture emerged for the prophylactic administration of antibiotics in the context of primary arthroplasty. In 93.2% (elective) and 88.6% (fracture treatment) of the hospitals, first or second generation cephalosporins were administered perioperatively for infection prophylaxis in primary hip arthroplasty. The empirical antibiotic treatment of PJIs showed a clearly inhomogeneous therapeutic picture. Monotherapy with an aminopenicillin plus a beta-lactamase inhibitor is used most frequently (38.7%); first and second generation cephalosporins are used second most frequently as monotherapy (18.2%). In light of the global problem of antibiotic multi-resistance, clinical use of antibiotics has to be reasonable and effective. The present results highlight the further need to improve awareness and following existing guidelines in the administration of empirical antibiotic therapy in PJI.
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http://dx.doi.org/10.1055/a-1773-1382DOI Listing
April 2022

[Current practice of empiric antibiotic treatment for spondylodiscitis].

Orthopadie (Heidelb) 2022 Jul 7;51(7):540-546. Epub 2022 Apr 7.

Klinik und Poliklinik für Unfallchirurgie, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Deutschland.

Background And Research Question: In pyogenic spondylodiscitis, infections with coagulase-negative staphylococci must be given increasing importance. Empirical antibiosis is particularly necessary in patients with severe or progressive neurological deficits or hemodynamic instability, as well as in the case of culture-negative spondylodiscitis. It is unclear whether uniform empirical antibiosis standards adapted to the resistance profiles exist in Germany.

Study Design And Methods: A survey on the empirical antibiotic therapy for pyogenic spondylodiscitis was conducted at German university and Berufsgenossenschaft clinics, each in the departments of orthopedics and trauma surgery. The survey results were applied to the resistance profiles of pathogens in 45 spondylodiscitis patients treated in our department between 2013 and 2020. Thus, the potential susceptibility and resistance rates were calculated for the indicated antibiotic therapies.

Results: Of the 71 clinics queried, a total of 44 (62.0%) responded. Sixteen different antibiotic therapies were reported as standard regimes. Among these, 14 different combination therapies were reported. The most commonly reported empirical antibiotics, namely amoxicillin/clavulanic acid or ampicillin/sulbactam (29.5%) and cephalosporins (18.2%) showed high potential resistance rates of 20.0% and 35.6%, respectively, in relation to the previously published resistance profile. The highest potential susceptibility rates were achieved with a combination of vancomycin + ampicillin/sulbactam (91.1% sensitive pathogens), vancomycin + piperacillin/tazobactam (91.1% sensitive pathogens), and ampicillin/sulbactam + teicoplanin (95.6% sensitive pathogens). One out of these combinations was reported as standard regime by three clinics (6.8%).

Conclusion: The nationwide survey of empiric antibiotic treatment for pyogenic spondylodiscitis revealed a large heterogeneity in the standard of care. A combination of a broad-spectrum-β-lactam antibiotic with an additional glycopeptide antibiotic may be justified.
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http://dx.doi.org/10.1007/s00132-022-04240-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249703PMC
July 2022

Fibronectin Adherent Cell Populations Derived From Avascular and Vascular Regions of the Meniscus Have Enhanced Clonogenicity and Differentiation Potential Under Physioxia.

Front Bioeng Biotechnol 2021 28;9:789621. Epub 2022 Jan 28.

Laboratory for Experimental Trauma Surgery, Department of Trauma Surgery, University Regensburg Medical Centre, Regensburg, Germany.

The meniscus is composed of an avascular inner region and vascular outer region. The vascular region has been shown to contain a progenitor population with multilineage differentiation capacity. Strategies facilitating the isolation and propagation of these progenitors can be used to develop cell-based meniscal therapies. Differential adhesion to fibronectin has been used to isolate progenitor populations from cartilage, while low oxygen or physioxia (2% oxygen) enhances the meniscal phenotype. This study aimed to isolate progenitor populations from the avascular and vascular meniscus using differential fibronectin adherence and examine their clonogenicity and differentiation potential under hyperoxia (20% oxygen) and physioxia (2% oxygen). Human vascular and avascular meniscus cells were seeded onto fibronectin-coated dishes for a short period and monitored for colony formation under either hyperoxia or physioxia. Non-fibronectin adherent meniscus cells were also expanded under both oxygen tension. Individual fibronectin adherent colonies were isolated and further expanded, until approximately ten population doublings (passage 3), whereby they underwent chondrogenic, osteogenic, and adipogenic differentiation. Physioxia enhances clonogenicity of vascular and avascular meniscus cells on plastic or fibronectin-coated plates. Combined differential fibronectin adhesion and physioxia isolated a progenitor population from both meniscus regions with trilineage differentiation potential compared to equivalent hyperoxia progenitors. Physioxia isolated progenitors had a significantly enhanced meniscus matrix content without the presence of collagen X. These results demonstrate that combined physioxia and fibronectin adherence can isolate and propagate a meniscus progenitor population that can potentially be used to treat meniscal tears or defects.
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http://dx.doi.org/10.3389/fbioe.2021.789621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831898PMC
January 2022

Antibiotic cement coating in orthopedic surgery: a systematic review of reported clinical techniques.

J Orthop Traumatol 2021 Dec 23;22(1):56. Epub 2021 Dec 23.

Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.

Background: Antibiotic-containing cement and bone graft substitute-coated orthopedic implants provide the advantages of simultaneous local antibiotic delivery and internal stable fixation, aiding in both infection eradication and osseous healing. Standardized protocols pertaining to implant coating techniques in various clinical and particularly intraoperative settings are scarce, and available literature is limited. This systematic review aims to provide a summary of the available current literature reporting on custom-made coating techniques of orthopedic implants, indications, outcomes, and associated complications in clinical use.

Methods: A systematic search of the literature in PubMed, Medline, Embase, and Cochrane Library databases was performed in accordance with PRISMA guidelines. Articles reporting specifically on custom-made coating techniques of orthopedic implants in a clinical setting were eligible.

Results: A total of 41 articles with a cumulative total number of 607 cases were included. Indications for treatment mostly involved intramedullary infections after previous plate osteosynthesis or nailing. A variety of implants ranging from intramedullary nails, plates, wires, and rods served as metal cores for coating. Polymethylmethacrylate (PMMA) bone cement was most commonly used, with vancomycin as the most frequently added antibiotic additive. Chest tubes and silicone tubes were most often used to mold. Common complications are cement debonding and breakage of the metallic implant.

Conclusion: Adequate coating techniques can reduce the burden of treatment and be associated with favorable outcomes. Lack of general consensus and heterogeneity in the reported literature indicate that the perfect all-in-one implant coating method is yet to be found. Further efforts to improve implant coating techniques are warranted.

Level Of Evidence: III.
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http://dx.doi.org/10.1186/s10195-021-00614-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8702599PMC
December 2021

[Fracture-related infections after intramedullary nailing : Diagnostics and treatment].

Unfallchirurg 2022 Jan 18;125(1):50-58. Epub 2021 Dec 18.

Klinik und Poliklinik für Unfallchirurgie, Universitätsklinikum Regensburg (UKR), Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Deutschland.

Intramedullary nailing is the treatment of choice for a large number of fractures requiring surgery. In cases of fracture-related infections (FRI) the treatment of nail infections requires special attention due to the closed situation of the osteosynthesis material in the intramedullary canal. This article gives an overview of the general principles and diagnostic criteria for FRI after nail fixation and discusses the treatment recommendations based on three case examples. In cases of acute implant infections, an implant-retaining procedure is principally possible for both periprosthetic joint infections and FRI; however, after intramedullary nailing the nail should also be exchanged in cases of acute nail infections as a sufficient debridement of the nail is impossible due to its intramedullary location. In chronic FRI after intramedullary nailing a one-stage or two-stage procedure can be followed. In cases of adequate soft tissue coverage, good fracture reduction and an expected bone healing without critical bony substance defects, a one-stage procedure with nail exchange should be preferred. If a chronic infection with soft tissue and bone defects develops after intramedullary nailing, a two-stage procedure analogous to the treatment of osteomyelitis should be considered. In this case a multidisciplinary team approach with specialists in plastic surgery, microbiology and infectious diseases is necessary. The use of local antibiotics and antimicrobial-coated implants is deemed to be advantageous.
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http://dx.doi.org/10.1007/s00113-021-01117-0DOI Listing
January 2022

Is There a Difference in Clinical Features, Microbiological Epidemiology and Effective Empiric Antimicrobial Therapy Comparing Healthcare-Associated and Community-Acquired Vertebral Osteomyelitis?

Antibiotics (Basel) 2021 Nov 18;10(11). Epub 2021 Nov 18.

Department of Trauma Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.

Background: Empiric antibiotic therapy for suspected vertebral osteomyelitis (VO) should be initiated immediately in severely ill patients, and might be necessary for culture-negative VO. The current study aimed to identify differences between community-acquired (CA) and healthcare-associated (HA) VO in terms of clinical presentation, causative pathogens, and antibiotic susceptibility.

Methods: Cases of adult patients with VO treated at a German university orthopaedic trauma center between 2000 and 2020 were retrospectively reviewed. Patient history was used to distinguish between CA and HA VO. Susceptibility of antibiotic regimens was assessed based on antibiograms of the isolated pathogens.

Results: A total of 155 patients (with a male to female ratio of 1.3; and a mean age of 66.1 ± 12.4 years) with VO were identified. In 74 (47.7%) patients, infections were deemed healthcare-associated. The most frequently identified pathogens were (HAVO: 51.2%; CAVO: 46.8%), and Coagulase-negative Staphylococci (CoNS, HAVO: 31.7%; CAVO: 21.3%). Antibiograms of 45 patients (HAVO: = 22; CAVO: = 23) were evaluated. Significantly more methicillin-resistant isolates, mainly CoNS, were found in the HAVO cohort (27.3%). The highest rate of resistance was found for cefazolin (HAVO: 45.5%; CAVO: 26.1%). Significantly higher rates of resistances were seen in the HAVO cohort for mono-therapies with meropenem (36.4%), piperacillin-tazobactam (31.8%), ceftriaxone (27.3%), and co-amoxiclav (31.8%). The broadest antimicrobial coverage was achieved with either a combination of piperacillin-tazobactam + vancomycin (CAVO: 100.0%; HAVO: 90.9%) or meropenem + vancomycin (CAVO: 100.0%; HAVO: 95.5%).

Conclusion: Healthcare association is common in VO. The susceptibility pattern of underlying pathogens differs from CAVO. When choosing an empiric antibiotic, combination therapy must be considered.
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http://dx.doi.org/10.3390/antibiotics10111410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615006PMC
November 2021

Terminology of bone and joint infection.

Bone Joint Res 2021 Nov;10(11):742-743

Department of Trauma Surgery, University Medical Center Regensburg, Regensburg, Germany.

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http://dx.doi.org/10.1302/2046-3758.1011.BJR-2021-0371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636293PMC
November 2021

The Tibial Plateau Map: Fracture Line Morphology of Intra-Articular Proximal Tibial Fractures.

Biomed Res Int 2021 24;2021:9920189. Epub 2021 Aug 24.

Department of Trauma Surgery, University Medical Centre Regensburg, Regensburg, Germany.

The purpose of this study was to characterize the patterns of a large series of tibial plateau fractures with the use of fracture mapping, with regard to different fracture types using the OTA/AO and Schatzker classification. Patients with intra-articular fractures of the tibial plateau were evaluated, using the OTA/AO and Schatzker classification on CT scans. For fracture mapping, the axial slice that completely displayed the tibial joint plane was first identified, then matched to a template congruently, and the fracture lines were identified and reproduced. In addition to epidemiological data (age and gender), the trauma mechanism (high-energy, low-energy, and pathological fracture) was recorded. In total, 271 patients with 278 intra-articular fractures of the tibial head were analyzed, including seven patients with both sides affected. The mean age was 49.1 years (men 46.3 years, women 53.5 years). The majority of fractures was caused by high-energy trauma. No significant difference could be shown with respect to trauma mechanism and resulting fracture type in terms of OTA/AO ( = 0.352) or Schatzker classification ( = 0.884). A significant difference could be found with respect to gender and resulting fracture type in terms of OTA/AO ( = 0.031). 170 (61.2%) were OTA/AO type B fractures, and 108 (38.8%) were type C fractures. Using the Schatzker classification, we found 53 type I (19.1%), 60 type II (21.6%), 27 type III (9.7%), 32 type IV (11.5%), 16 type V (5.8%), and 90 type VI (32.4%) fractures. The main affection was found in the lateral and intermedial column of the tibial plateaus, concerning both OTA/AO and Schatzker classification. The variability of intra-articular tibial head fractures is very high. In consequence, an individual analysis of fracture patterns and therapy planning by using CT scans is crucial.
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http://dx.doi.org/10.1155/2021/9920189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408007PMC
October 2021

Radiological and mid- to long-term patient-reported outcome after stabilization of traumatic thoraco-lumbar spinal fractures using an expandable vertebral body replacement implant.

BMC Musculoskelet Disord 2021 Aug 30;22(1):744. Epub 2021 Aug 30.

Clinic of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.

Background: For the treatment of unstable thoraco-lumbar burst fractures, a combined posterior and anterior stabilization instead of a posterior-only instrumentation is recommend in the current literature due to the instability of the anterior column. Data on restoring the bi-segmental kyphotic endplate angle (BKA) with expandable vertebral body replacements (VBR) and on the mid- to long-term patient-reported outcome measures (PROM) is sparse.

Methods: A retrospective cohort study of patients with traumatic thoraco-lumbar spinal fractures treated with an expandable VBR implant (Obelisc™, Ulrich Medical, Germany) between 2001 and 2015 was conducted. Patient and treatment characteristics were evaluated retrospectively. Radiological data acquisition was completed pre- and postoperatively, 6 months and at least 2 years after the VBR surgery. The BKA was measured and fusion-rates were assessed. The SF-36, EQ-5D and ODI questionnaires were evaluated prospectively.

Results: Ninety-six patients (25 female, 71 male; age: 46.1 ± 12.8 years) were included in the study. An AO Type A4 fracture was seen in 80/96 cases (83.3%). Seventy-three fractures (76.0%) were located at the lumbar spine. Intraoperative reduction of the BKA in n = 96 patients was 10.5 ± 9.4° (p < 0.01). A loss of correction of 1.0 ± 2.8° at the first follow-up (t1) and of 2.4 ± 4.0° at the second follow-up (t2) was measured (each p < 0.05). The bony fusion rate was 97.9%. The total revision rate was 4.2%. Fifty-one patients (53.1% of included patients; age: 48.9 ± 12.4 years) completed the PROM questionnaires after 106.4 ± 44.3 months and therefore were assigned to the respondent group. The mean ODI score was 28.2 ± 18.3%, the mean EQ-5D VAS reached 60.7 ± 4.1 points. Stratified SF-36 results (ISS < and ≥ 16) were lower compared to a reference population.

Conclusion: The treatment of traumatic thoraco-lumbar fractures with an expandable VBR implant lead to a high rate of bony fusion. A significant correction of the BKA could be achieved and no clinically relevant loss of reduction occurred during the follow-up. Even though health related quality of life did not reach the normative population values, overall satisfactory results were reported.
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http://dx.doi.org/10.1186/s12891-021-04585-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407019PMC
August 2021

Football-related injuries are the major reason for the career end of professional male football players.

Knee Surg Sports Traumatol Arthrosc 2021 Nov 9;29(11):3560-3568. Epub 2021 Aug 9.

Department of Trauma Surgery, University Medical Centre Regensburg, Regensburg, Germany.

Purpose: Little is known about the consequences of injuries on professional male football players' career and retirement period. The aim of this study is to investigate the impact of injuries that male professional football players endure during their career, reasons for the end of their career and the post-career phase of retirement.

Methods: In a retrospective cross-sectional cohort study, retired male professional football players of the German Bundesliga were investigated by a standardised questionnaire to analyse the history of injuries sustained during their professional football career, the reasons for ending their career, their current health status and their suggestions for future prevention strategies.

Results: Most of the 116 analysed players (n = 73 (62.9%)) stated an injury as the reason for ending their professional career. Relevant injuries were mainly located in the lower extremities (n = 587 (61.3%)) with a focus on the knee (p < 0.001) and ankle (p < 0.001). A significant majority of the participants who had retired due to injury described degenerative symptoms, such as pain or instability, and were diagnosed with osteoarthritis after retirement (p < 0.001). These players had also often been affected by symptoms of depression during their career, which had decreased significantly after retirement. Moreover, players who had not retired due to injury had significantly better overall health status and quality of life after retirement.

Conclusion: Football-related injuries have a significant impact on the career end of professional male football players and their health status after retirement. Future prevention strategies need to particularly address injuries to the knees and ankles and to implement measures for preventing osteoarthritis after retirement.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1007/s00167-021-06684-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514381PMC
November 2021

Decision-making to stop or continue playing after football injuries - a systematic video analysis of 711 injury situations in amateur football.

Eur J Sport Sci 2021 Jul 5:1-7. Epub 2021 Jul 5.

Department of Trauma Surgery, University Medical Centre Regensburg, Regensburg, Germany.

Scientific injury registration via video analysis is lacking in amateur football. The purpose of this study was to analyse match injury situations with a focus on the decisions made by players and referees after sustaining a football trauma. In a retrospective cohort study, traumatic injuries sustained in any of the 305 matches of the highest amateur level (4th league) in Germany in the 2015-16 season were assessed by means of video analysis and a standardised video protocol. In total, 711 traumatic incidents at 919 different body regions had been recorded. The three most frequently injured body regions were the ankles (34.1%), the head (17.5%) and the knees (17.0%). 90% (= 156) of head injuries were direct contact injuries, this percentage was significantly higher than that of contact injuries on ankle (68.4%; 0.001) or knee (52.6%; = 0.001). Referees decided on foul play significantly more often in case of knee injuries (57.1%; = 0.002) or ankle injuries (64.5%; 0.001) than in head injuries (39.8%). Only 26.1% of players with a head injury opted for substitution, which was lower than after ankle (27.8%; = 0.78) and knee injuries (34.0%; = 0.13). In conclusion, amateur football is associated with a considerable number of injury situations that are followed by match interruptions and the substitution of players. Players and referees decided to continue playing more often after a head injury than after an injury to other body regions. An advanced education programme on the risks and management of head injuries in football is required to prevent long-term health consequences.
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http://dx.doi.org/10.1080/17461391.2021.1943717DOI Listing
July 2021

The Incidence of Fractures Among the Adult Population of Germany–an Analysis From 2009 through 2019

Dtsch Arztebl Int 2021 10;118(40):665-669

Department of Trauma Surgery, Regensburg University Medical Center, Germany; Department for Psychosomatic Medicine, Regensburg University Medical Center, Germany.

Background: Detailed analyses of epidemiological data on fractures are an impor - tant resource for persons and institutions providing health care services, as they yield information on the effects of current treatment strategies and on the need for preventive measures. The epidemiology of fractures in Germany, however, is unknown. The goal of this study is to determine the nationwide fracture burden from 2009 through 2019, as a function of anatomical site, age, and sex.

Methods: Annual compilations of ICD-10 diagnosis codes for the years 2009-2019 were made available to us by the German Federal Statistical Office. The prevalence and incidence of fractures at 30 different sites were quantified, and standardized sex and age distributions were calculated.

Results: A total of 688 403 fractures was registered in 2019. From 2009 to 2019, the incidence of fractures rose by 14%, to 1014 fractures per 100 000 persons per year. The most common fracture types were femoral neck fractures (120 per 100 000 persons per year), pertrochanteric femoral fractures (109 per 100 000 persons per year), and distal radius fractures (106 per 100 000 persons per year). All types were more common in women, with incidences that rose with age. The highest incidence was of pertrochanteric femoral fractures in women over age 90, with an incidence of 2550 per 100 000 persons per year. The largest rises in incidence were seen with regard to acetabular fractures (+ 58%) and clavicular fractures (+ 44%).

Conclusion: The increasing frequency of fractures, particularly among the elderly, presents a challenge to the health care system. Given the high frequency of geriatric fractures, prophylactic measures against fractures ought to be intensified.
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http://dx.doi.org/10.3238/arztebl.m2021.0238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727861PMC
October 2021

The epidemiology of fracture-related infections in Germany.

Sci Rep 2021 05 17;11(1):10443. Epub 2021 May 17.

Department for Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.

The epidemiology of fracture-related infection (FRI) is unknown, which makes it difficult to estimate future demands and evaluate progress in infection prevention. Therefore, we aimed to determine the nationwide burden's development over the last decade as a function of age group and gender. FRI prevalence as a function of age group and gender was quantified based on annual ICD-10 diagnosis codes from German medical institutions between 2008 through 2018, provided by the Federal Statistical Office of Germany (Destatis). The prevalence of FRI increased by 0.28 from 8.4 cases per 100,000 inhabitants to 10.7 cases per 100,000 inhabitants between 2008 and 2018. The proportion of fractures resulting in FRI increased from 1.05 to 1.23%. Gender distribution was equal. Patients aged 60-69 years and 70-79 years comprised the largest internal proportion with 20.2% and 20.7%, respectively, whereby prevalence increased with age group. A trend towards more diagnoses in older patients was observed with a growth rate of 0.63 for patients older than 90 years. Increasing rates of fracture-related infection especially in older patients indicate an upcoming challenge for stakeholders in health care systems. Newly emerging treatment strategies, prevention methods and interdisciplinary approaches are strongly required.
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http://dx.doi.org/10.1038/s41598-021-90008-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128870PMC
May 2021

[Infections of the spine : Pyogenic spondylodiscitis and implant-associated vertebral osteomyelitis].

Unfallchirurg 2021 Jun 10;124(6):489-504. Epub 2021 May 10.

Klinik und Poliklinik für Unfallchirurgie, Universitätsklinikum Regensburg (UKR), Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Deutschland.

Pyogenic (unspecific) spondylodiscitis and implant-associated vertebral osteomyelitis (IAVO) are important diseases with the risk of neurological and septic complications. An early diagnosis is essential in which magnetic resonance imaging (MRI), histopathology and microbiological identification of the pathogen play key roles. The goals of conservative treatment in uncomplicated spondylodiscitis are antibiotic infection control and pain management. In the case of sepsis, neurological deficits, segmental instability or epidural abscesses surgical treatment of the infection with stabilization of the spine should be considered. In IAVO the formation of a mature biofilm represents the transition from acute to chronic infection. Acute infections can be treated by extensive debridement in combination with biofilm-active antibiotic treatment while retaining the implant. In chronic infections implant removal or exchange in combination with several weeks of antibiotic treatment is often necessary.
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http://dx.doi.org/10.1007/s00113-021-01002-wDOI Listing
June 2021

[Use of video-assisted thoracoscopy in dorsoventral stabilization of osteodestructive pyogenic spondylodiscitis of the thoracic spine].

Unfallchirurg 2021 06 3;124(6):505-511. Epub 2021 May 3.

Klinik und Poliklinik für Unfallchirurgie, Universitätsklinikum Regensburg (UKR), Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Deutschland.

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http://dx.doi.org/10.1007/s00113-021-01000-yDOI Listing
June 2021

Influence of Oral Anticoagulation and Antiplatelet Drugs on Outcome of Elderly Severely Injured Patients.

J Clin Med 2021 Apr 13;10(8). Epub 2021 Apr 13.

Department of Trauma Surgery, University Medical Centre Regensburg, D-93053 Regensburg, Germany.

Introduction: Severely injured elderly patients have a poorer prognosis and higher mortality rates after severe trauma compared with younger patients. The aim of this study was to correlate the influence of pre-existing oral anticoagulation (OAC) and antiplatelet drugs (PAI) on the outcome of severely injured elderly patients.

Methods: Using a prospective cohort study model over an 11-year period, severely injured elderly patients (≥65 years and ISS ≥ 16) were divided into two groups (no anticoagulation/platelet inhibitors: nAP and OAC/PAI). A comparison of the groups was conducted regarding injury frequency, trauma mechanism, severity of head injuries, and medication-related mortality.

Results: In total, 254 out of 301 patients were analyzed (nAP: = 145; OAC/PAI: = 109, unknown data: = 47). The most relevant injury was falling from low heights (<3 m), which led to a significantly higher number of severe injuries in patients with OAC/PAI. Patients with pre-existing OAC/PAI showed a significantly higher overall mortality rate compared to the group without (38.5% vs. 24.8%; = 0.019). The severity of head injuries in OAC/PAI was also higher on average (AIS 3.7 ± 1.6 vs. 2.8 ± 1.9; = 0.000).

Conclusion: Pre-existing oral anticoagulation and/or platelet aggregation inhibitors are related to a higher mortality rate in elderly polytrauma patients. Low-energy trauma can lead to even more severe head injuries due to pre-existing medication than is already the case in elderly patients without OAC/PAI.
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http://dx.doi.org/10.3390/jcm10081649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069499PMC
April 2021

Iliac Bone Corridors to Host the Transiliac Internal Fixator-An Experimental CT Based Analysis.

J Clin Med 2021 Apr 4;10(7). Epub 2021 Apr 4.

Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.

Background: The transiliac internal fixator (TIFI) is a novel minimally invasive surgical procedure to stabilize posterior pelvic ring fractures. Two bone corridors with different lengths, widths, and angulations are suitable to host screws in the posterior iliac wing. While the length and the width have been described previously, the angulation has not been determined yet.

Methods: We created a computer tomography-based 3D-model of 40 patients (20 women, 20 men). The possible bone corridors to host the ilium screws for the TIFIcc (cranio-caudal) and the TIFIdv (dorso-ventral) procedure were identified. After reaching the optimal position, the angles in relation to the sagittal and axial plane were measured. The anterior pelvic plane was chosen as the reference plane.

Results: The mean angle of the TIFIcc screws related to the axial plane was 63.4° (±1.8°) and to the sagittal plane was 12.3° (±1.5°). The mean angle of the TIFIdv screws related to the axial plane was 16.1° (±1.2°) and to the sagittal plane was 20.1° (±2.0°). In each group, a high constancy was apparent irrespective of the age or physical dimension of the patient, although a significant gender-dependent difference was observed".

Conclusions: Due to a high inter-individual constancy in length, width, and angulation, bone corridors in the posterior iliac wing are reliable to host screws for posterior pelvic ring fixation irrespective of each individual patient's anatomy.
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http://dx.doi.org/10.3390/jcm10071500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038471PMC
April 2021

Does Dynamic Anterior Plate Fixation Provide Adequate Stability for Traumatic Subaxial Cervical Spine Fractures at Mid-Term Follow-Up?

J Clin Med 2021 Mar 12;10(6). Epub 2021 Mar 12.

Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.

Background: It remains questionable if the treatment of cervical fractures with dynamic plates in trauma surgery provides adequate stability for unstable fractures with disco-ligamentous injuries. The primary goal of this study was to assess the radiological and mid-term patient-reported outcome of traumatic subaxial cervical fractures treated with different plate systems.

Patients And Methods: Patients, treated with anterior cervical discectomy and fusion (ACDF) between 2001 and 2015, using either a dynamic plate (DP: Mambo™, Ulrich, Germany) or a rigid locking plate (RP: CSLP™, Depuy Synthes, USA), were identified. For radiological evaluation, the sagittal alignment, the sagittal anterior translation and the bony consolidation were evaluated. After at least two years, the patient-reported outcome measures (PROM) were evaluated using the German Short-Form 36 (SF-36), Neck Disability Index (NDI) and the EuroQol in 5 Dimensions (EQ-5D) scores.

Results: 33 patients met the inclusion criteria (DP: 13; RP:20). Twenty-six patients suffered from AO Type B or C fractures. Both the sagittal alignment and the sagittal translation could be sufficiently improved in both groups ( ≥ 0.05). No significant loss of reduction could be observed at the follow-up in both groups ( ≥ 0.05). Bony consolidation could be observed in 30 patients (DP: 12/13 (92%); RP: 18/20 (90%); ( ≥ 0.05)). In 20 patients, PROMs could be evaluated (follow-up: 71.2 ± 25.5 months). The whole cohort showed satisfactory PROM results (EQ-5D: 72.0 ± 4.9; SF-36 PCS: 41.9 ± 16.2, MCS: 45.4 ± 14.9; NDI: 11.0 ± 9.1). without significant differences between the DP and RP group ( ≥ 0.05) Conclusion: The dynamic plate concept provides enough stability without a difference in fusion rates in comparison to rigid locking plates in a population that mostly suffered fragile fractures.
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http://dx.doi.org/10.3390/jcm10061185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999148PMC
March 2021

Are There Any Red Flag Injuries in Severely Injured Patients in Older Age?

J Clin Med 2021 Jan 7;10(2). Epub 2021 Jan 7.

Department of Trauma Surgery, University Medical Centre Regensburg, 93053 Regensburg, Germany.

Introduction: Severely injured elderly patients pose a significant burden to trauma centers and, compared with younger patients, have worse prognoses and higher mortality rates after major trauma. The objective of this study was to identify the etiological mechanisms that are associated with severe trauma in elderly patients and to detect which injuries correlate with high mortality in elderly patients.

Methods: Using a prospect cohort study model over an 11-year period, severely injured patients (ISS ≥ 16) were divided into two age groups (Group 1: 18-64; Group 2: 65-99 years). A comparison of the groups was conducted regarding injury frequency, trauma mechanism, distribution of affected body parts (AIS and ISS regions) and injury related mortality.

Results: In total, 1008 patient were included (Group 1: = 771; Group 2: = 237). The most relevant injury in elderly patients was falling from low heights (<3 m) in contrast to traffic accident in young patients. Severely injured patients in the older age group showed a significantly higher overall mortality rate compared to the younger group (37.6% vs. 11.7%; = 0.000). In both groups, the 30-day survival for patients without head injuries was significantly better compared to patients with head injuries (92.7% vs. 85.3%; = 0.017), especially analyzing elderly patients (86.6% vs. 58.6%; = 0.003). The relative risk of 30-day mortality in patients who suffered a head injury was also higher in the elderly group (OR: Group 1: 4.905; Group 2: 7.132).

Conclusion: In contrast to younger patients, falls from low heights (<3 m) are significant risk factors for severe injuries in the geriatric collective. Additionally, elderly patients with an ISS ≥ 16 had a significantly higher mortality rate compared to severe injured younger patients. Head injuries, even minor head traumata, are associated with a significant increase in mortality. These findings will contribute to the development of more age-related therapy strategies in severely injured patients.
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http://dx.doi.org/10.3390/jcm10020185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825590PMC
January 2021

Two-Dimensional Visualization of the Three-Dimensional Planned Sacroiliac Screw Corridor with the Slice Fusion Method.

J Clin Med 2021 Jan 6;10(2). Epub 2021 Jan 6.

Department of Trauma Surgery, Regensburg University Medical Center, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.

Insertion of sacro-iliac (SI) screws for stabilization of the posterior pelvic ring without intraoperative navigation or three-dimensional imaging can be challenging. The aim of this study was to develop a simple method to visualize the ideal SI screw corridor, on lateral two-dimensional images, corresponding to the lateral fluoroscopic view, used intraoperatively while screw insertion, to prevent neurovascular injury. We used multiplanar reconstructions of pre- and postoperative computed tomography scans (CT) to determine the position of the SI corridor. Then, we processed the dataset into a lateral two-dimensional slice fusion image (SFI) matching head and tip of the screw. Comparison of the preoperative SFI planning and the screw position in the postoperative SFI showed reproducible results. In conclusion, the slice fusion method is a simple technique for translation of three-dimensional planned SI screw positioning into a two-dimensional strict lateral fluoroscopic-like view.
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http://dx.doi.org/10.3390/jcm10020184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825576PMC
January 2021

Management and Mid-Term Outcome After "Real SCIWORA" in Children and Adolescents.

Global Spine J 2022 Jul 7;12(6):1208-1213. Epub 2021 Jan 7.

Department of Trauma, Regensburg University Medical Center, Regensburg, Germany.

Study Design: Retrospective analysis.

Objective: The SCIWORA Syndrome (Spinal Cord Injury Without Radiographic Abnormalities) is a rare but potentially severe injury with a peak in childhood and adolescence. With a better understanding of injury patterns and advances in MRI, there is ongoing discussion regarding the "Real SCIWORA" syndrome, a clinical picture of neurologic deficits on clinical examination but absence of radiographic pathologies even on MRI. The purpose of this study was to evaluate mid-term clinical outcome and the psychological impact of the "Real SCIWORA."

Methods: In this retrospective analysis, we evaluated 32 patients treated for "Real SCIWORA" between 2007-2019. Inclusion criteria were: neurologic deficit after trauma, no other cerebral or skeletal injury and a lack of pathological findings in spinal MRI. All patients were followed until complete recovery from initial symptoms. 25/32 patients were re-evaluated after 6.9 years (1-14 years) using the Oswestry Disability Index, the Frankel Score, the EQ-5D score, and the Breslau Short Screening Scale for PTSD.

Results: Initial neurologic presentation ranged from Frankel Grade A-D. All patients recovered neurologically during 1-13 days to a Frankel Grade E. The analysis of HR-QoL revealed no difference between the cohort of SCIWORA patients and the German population norm, Oswestry Disability Index showed only minimal disabilities. 4/25 patients showed signs of PTSD.

Conclusions: The "Real SCIWORA" syndrome is a diagnosis per exclusionem requiring a full spinal MRI to ensure exclusion of structural and potentially serious reasons of the neurologic impairment. Further clinical re-evaluation, psychological support seems to be essential.

Level Of Evidence: IV-retrospective study.
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http://dx.doi.org/10.1177/2192568220979131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210218PMC
July 2022

Physioxia Expanded Bone Marrow Derived Mesenchymal Stem Cells Have Improved Cartilage Repair in an Early Osteoarthritic Focal Defect Model.

Biology (Basel) 2020 Aug 17;9(8). Epub 2020 Aug 17.

Laboratory of Experimental Trauma Surgery, Department of Trauma Surgery, University Hospital Regensburg, Franz Josef Strauss Allee 11, 93053 Regensburg, Germany.

Focal early osteoarthritis (OA) or degenerative lesions account for 60% of treated cartilage defects each year. The current cell-based regenerative treatments have an increased failure rate for treating degenerative lesions compared to traumatic defects. Mesenchymal stem cells (MSCs) are an alternative cell source for treating early OA defects, due to their greater chondrogenic potential, compared to early OA chondrocytes. Low oxygen tension or physioxia has been shown to enhance MSC chondrogenic matrix content and could improve functional outcomes of regenerative therapies. The present investigation sought to develop a focal early OA animal model to evaluate cartilage regeneration and hypothesized that physioxic MSCs improve in vivo cartilage repair in both, post-trauma and focal early OA defects. Using a rabbit model, a focal defect was created, that developed signs of focal early OA after six weeks. MSCs cultured under physioxia had significantly enhanced in vitro MSC chondrogenic GAG content under hyperoxia with or without the presence of interleukin-1β (IL-1β). In both post-traumatic and focal early OA defect models, physioxic MSC treatment demonstrated a significant improvement in cartilage repair score, compared to hyperoxic MSCs and respective control defects. Future investigations will seek to understand whether these results are replicated in large animal models and the underlying mechanisms involved in in vivo cartilage regeneration.
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http://dx.doi.org/10.3390/biology9080230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463623PMC
August 2020

Attenuation of Hypertrophy in Human MSCs via Treatment with a Retinoic Acid Receptor Inverse Agonist.

Int J Mol Sci 2020 Feb 20;21(4). Epub 2020 Feb 20.

Regensburg University Medical Center, Department of Trauma Surgery, 93053 Regensburg, Germany.

In vitro chondrogenically differentiated mesenchymal stem cells (MSCs) have a tendency to undergo hypertrophy, mirroring the fate of transient "chondrocytes" in the growth plate. As hypertrophy would result in ossification, this fact limits their use in cartilage tissue engineering applications. During limb development, retinoic acid receptor (RAR) signaling exerts an important influence on cell fate of mesenchymal progenitors. While retinoids foster hypertrophy, suppression of RAR signaling seems to be required for chondrogenic differentiation. Therefore, we hypothesized that treatment of chondrogenically differentiating hMSCs with the RAR inverse agonist, BMS204,493 (further named BMS), would attenuate hypertrophy. We induced hypertrophy in chondrogenic precultured MSC pellets by the addition of bone morphogenetic protein 4. Direct activation of the RAR pathway by application of the physiological RAR agonist retinoic acid (RA) further enhanced the hypertrophic phenotype. However, BMS treatment reduced hypertrophic conversion in hMSCs, shown by decreased cell size, number of hypertrophic cells, and collagen type X deposition in histological analyses. BMS effects were dependent on the time point of application and strongest after early treatment during chondrogenic precultivation. The possibility of modifing hypertrophic cartilage via attenuation of RAR signaling by BMS could be helpful in producing stable engineered tissue for cartilage regeneration.
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http://dx.doi.org/10.3390/ijms21041444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073129PMC
February 2020

Controversies in regenerative medicine: Should intervertebral disc degeneration be treated with mesenchymal stem cells?

JOR Spine 2019 Mar 1;2(1):e1043. Epub 2019 Mar 1.

Department of Physiology, Anatomy and Genetics University of Oxford Oxford UK.

Low back pain (LBP) can significantly reduce the quality of life of patients, and has a considerable economic and social impact worldwide. It is commonly associated with disc degeneration, even though many people with degenerate discs are asymptomatic. Degenerate disc disease (DDD), is thus a common term for intervertebral disc (IVD) degeneration associated with LBP. Degeneration is thought to lead to LBP because of nerve ingrowth into the degenerate disc, inflammation, or because degradation of extracellular matrix (ECM) alters spinal biomechanics inappropriately. Thus, while the objectives of some interventions for LBP are to control pain intensity, other interventions aim to deal with the consequences of disc degeneration through stabilizing the disc surgically, by inserting artificial discs or by repairing the disc biologically and preventing progressive IVD degeneration. Despite tremendous research efforts, treatment of LBP through the use of regenerative interventions aiming to repair the IVD is still controversial. The use of mesenchymal stem cells for IVD regeneration in a patient-based case will be discussed by an ensemble of clinicians and researchers.
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http://dx.doi.org/10.1002/jsp2.1043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711491PMC
March 2019

Phenotypic Characterization of Bone Marrow Mononuclear Cells and Derived Stromal Cell Populations from Human Iliac Crest, Vertebral Body and Femoral Head.

Int J Mol Sci 2019 Jul 14;20(14). Epub 2019 Jul 14.

AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos Platz, Switzerland.

(1) In vitro, bone marrow-derived stromal cells (BMSCs) demonstrate inter-donor phenotypic variability, which presents challenges for the development of regenerative therapies. Here, we investigated whether the frequency of putative BMSC sub-populations within the freshly isolated mononuclear cell fraction of bone marrow is phenotypically predictive for the in vitro derived stromal cell culture. (2) Vertebral body, iliac crest, and femoral head bone marrow were acquired from 33 patients (10 female and 23 male, age range 14-91). BMSC sub-populations were identified within freshly isolated mononuclear cell fractions based on cell-surface marker profiles. Stromal cells were expanded in monolayer on tissue culture plastic. Phenotypic assessment of in vitro derived cell cultures was performed by examining growth kinetics, chondrogenic, osteogenic, and adipogenic differentiation. (3) Gender, donor age, and anatomical site were neither predictive for the total yield nor the population doubling time of in vitro derived BMSC cultures. The abundance of freshly isolated progenitor sub-populations (CD45-CD34-CD73+, CD45-CD34-CD146+, NG2+CD146+) was not phenotypically predictive of derived stromal cell cultures in terms of growth kinetics nor plasticity. BMSCs derived from iliac crest and vertebral body bone marrow were more responsive to chondrogenic induction, forming superior cartilaginous tissue in vitro, compared to those isolated from femoral head. (4) The identification of discrete progenitor populations in bone marrow by current cell-surface marker profiling is not predictive for subsequently derived in vitro BMSC cultures. Overall, the iliac crest and the vertebral body offer a more reliable tissue source of stromal progenitor cells for cartilage repair strategies compared to femoral head.
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http://dx.doi.org/10.3390/ijms20143454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678175PMC
July 2019

Bone Marrow Aspirate Concentrate for the Treatment of Avascular Meniscus Tears in a One-Step Procedure-Evaluation of an In Vivo Model.

Int J Mol Sci 2019 Mar 5;20(5). Epub 2019 Mar 5.

Department of Trauma Surgery, University Medical Centre Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.

Avascular meniscus tears show poor intrinsic regenerative potential. Thus, lesions within this area predispose the patient to developing knee osteoarthritis. Current research focuses on regenerative approaches using growth factors or mesenchymal stem cells (MSCs) to enhance healing capacity within the avascular meniscus zone. The use of MSCs especially as progenitor cells and a source of growth factors has shown promising results. However, present studies use bone-marrow-derived BMSCs in a two-step procedure, which is limiting the transfer in clinical praxis. So, the aim of this study was to evaluate a one-step procedure using bone marrow aspirate concentrate (BMAC), containing BMSCs, for inducing the regeneration of avascular meniscus lesions. Longitudinal meniscus tears of 4 mm in size of the lateral New Zealand White rabbit meniscus were treated with clotted autologous PRP (platelet-rich plasma) or BMAC and a meniscus suture or a meniscus suture alone. Menisci were harvested at 6 and 12 weeks after initial surgery. Macroscopical and histological evaluation was performed according to an established Meniscus Scoring System. BMAC significantly enhanced regeneration of the meniscus lesions in a time-dependent manner and in comparison to the PRP and control groups, where no healing could be observed. Treatment of avascular meniscus lesions with BMAC and meniscus suturing seems to be a promising approach to promote meniscus regeneration in the avascular zone using a one-step procedure.
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http://dx.doi.org/10.3390/ijms20051120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429139PMC
March 2019

TGF- Signalling is Suppressed under Pro-Hypertrophic Conditions in MSC Chondrogenesis Due to TGF- Receptor Downregulation.

Int J Stem Cells 2019 Mar;12(1):139-150

Laboratory of Experimental Trauma Surgery, Department of Trauma Surgery, University Regensburg Medical Centre, Regensburg, Germany.

Background And Objectives: Mesenchymal stem cells (MSCs) become hypertrophic in long term despite chondrogenic differentiation following the pathway of growth plate chondrocytes. This terminal differentiation leads to phenotypically unstable cartilage and was mirrored in vitro by addition of hypertrophy inducing medium. We investigated how intrinsic TGF- signaling is altered in pro-hypertrophic conditions.

Methods And Results: Human bone marrow derived MSC were chondrogenically differentiated in 3D culture. At day 14 medium conditions were changed to 1. pro-hypertrophic by addition of T3 and withdrawal of TGF- and dexamethasone 2. pro-hypertrophic by addition of BMP 4 and withdrawal of TGF- and dexamethasone and 3. kept in prochondrogenic medium conditions. All groups were treated with and without TGF-type-1-receptor inhibitor SB431542 from day 14 on. Aggregates were harvested for histo- and immunohistological analysis at d14 and d28, for gene expression analysis (rt-PCR) on d1, d3, d7, d14, d17, d21 and d28 and for Western blot analysis on d21 and d28. Induction of hypertrophy was achieved in the pro-hypertrophic groups while expression of TGF-type-1- and 2-receptor and Sox 9 were significantly downregulated compared to pro-chondrogenic conditions. Western blotting showed reduced phosphorylation of Smad 2 and 3 in hypertrophic samples, reduced TGF--1 receptor proteins and reduced SOX 9. Addition of SB431542 did not initiate hypertrophy under pro-chondrogenic conditions, but was capable of enhancing hypertrophy when applied simultaneously with BMP-4.

Conclusions: Our results suggest that the enhancement of hypertrophy in this model is a result of both activation of pro-hypertrophic BMP signaling and reduction of anti-hypertrophic TGF signaling.
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http://dx.doi.org/10.15283/ijsc18088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457698PMC
March 2019
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