Leukocyte-reduced platelet-rich plasma stimulates the in vitro proliferation of adipose-tissue derived mesenchymal stem cells depending on PDGF signaling.

BACKGROUND Platelet-rich Plasma (PRP) is suggested as xenoprotein-free cell-culture medium replacement for animalderived supplements. OBJECTIVE The aim of this study was to investigate PRP-triggered signaling in adipose derived mesenchymal stem cells (ASCs). Leukocyte- reduced PRP might be an alternative to bovine standard culture media additives. METHODS PRP was obtained from 4 male patients. We incubated hASCs in alpha-MEM with 10% or 20% pooled PRP or 20% fetal calf serum (FCS) for 6, 12, 24, 48 and 72 hours prior to determination of the S-phase fraction (SPF). The influence of 10ng/µl recombinant Platelet derived growth factor (PDGF) subtypes AA, AB and BB on the proliferation of hASCs was measured after 48 hours. To investigate the influence of PDGF signaling on ASCs, 3 µM PDGF receptor-beta inhibitor was added, followed by α-MEM with 20% FCS or 20% PRP for 48 hours. Afterwards the proliferation and protein expression of ASCs was measured again. RESULTS ASCs exposed to 20% PRP, PDGF-AB and –BB demonstrated significant higher SPF in comparison to PDGF-AA and 20% FCS after 48 hours (all P < 0.05). PDGF receptor-beta inhibition diminished the PRP-induced SPF increase of ASCs significantly after 48 hours (P < 0.01). ASCs with PDGF receptor-beta inhibition showed significant higher PDGF receptor-beta and significant lower c-MYC expression compared to untreated cells in presence of 20% PRP after 48 hours (both P < 0.05). CONCLUSIONS The proliferation promoting effect of PRP on ASCs is mediated by PDGF signaling and is associated with c-MYC overexpression

The epidemiology of fracture-related infections in 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

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

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

Antibiotikaeinsatz zu Prophylaxe und empirischer Therapie von frakturassoziierten Infektionen in Deutschland

Hintergrund Antibiotika (AB) spielen eine wichtige Rolle in der Prophylaxe und Behandlung von Infektionen in der Unfallchirurgie. Dennoch scheint es gerade bei der Infektionsprophylaxe nach offenen Frakturen und auch bei der empirischen Therapie von frakturassoziierten Infektionen (FRI) große Unterschiede zwischen einzelnen Kliniken zu geben. Methodik An deutschen Universitäts- und berufsgenossenschaftlichen Kliniken wurde eine Umfrage zu Prophylaxe und empirischer AB-Therapie von FRI durchgeführt. Die AB-Regime wurden mit dem Resistenzprofil der Erreger bei 86 FRI-Patienten verglichen, um die theoretische Wirksamkeit der jeweiligen Therapien zu ermitteln. Ergebnisse Von 71 Kliniken antworteten insgesamt 44 (62,0 %). Bei geschlossenen Frakturen zeigte sich mit der Verwendung von Cephalosporinen in 95,5 % der Kliniken ein einheitliches Bild. Für offene Frakturen wurden 8 verschiedene AB-Regime berichtet, wobei Aminopenicilline/β-Lactamase-Inhibitor (BLI) (31,8 %) am häufigsten genannt wurden. Für die empirische Therapie der FRI wurden 12 verschiedene AB-Regime angegeben, am häufigsten Aminopenicilline/BLI (31,8 %), Cephalosporine (31,8 %) und Ampicillin/Sulbactam + Vancomycin (9,1 %). Hinsichtlich der empirischen Therapie der FRI zeigten sich niedrige Sensibilitätsraten für Cephalosporine (65,1 %) bzw. Aminopenicillinen/BLI (74,4 %). Für die Kombination Vancomycin + Meropenem ergab sich mit 91,9 % die höchste hypothetische Sensibilität. Diskussion Im Abgleich mit dem vorliegenden, einrichtungsspezifischen Keimspektrum erscheint die Kombinationstherapie Vancomycin + Meropenem für die empirische Therapie sinnvoll, sollte jedoch Patienten mit mehrfachen Revisionseingriffen oder septischen Infektionsverläufen vorbehalten bleiben, um die Selektion hochresistenter Keime zu vermeiden

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

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

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

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 (p ≥ 0.05). No significant loss of reduction could be observed at the follow-up in both groups (p ≥ 0.05). Bony consolidation could be observed in 30 patients (DP: 12/13 (92%); RP: 18/20 (90%); (p ≥ 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 (p ≥ 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

Phenotypic characterization of bone marrow mononuclear cells and derived stromal cell populations from human lliac crest, vertebral body and femoral head

(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

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

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

Treatment of Periprosthetic Joint Infection and Fracture-Related Infection With a Temporary Arthrodesis Made by PMMA-Coated Intramedullary Nails – Evaluation of Technique and Quality of Life in Implant-Free Interval

Background: Antimicrobial coating of intramedullary nails with polymethyl methacrylate (PMMA) bone cement promises infection control and stabilization for subsequent bone healing. However, when removing the implant, bone cement can debond and remain in the medullary cavity of the long bones, representing a nidus for reinfection. This work presents a technique comprising reinforcement of PMMA-coated intramedullary nails with cerclage wire to prevent such problems in patients treated for fracture-related infection (FRI) or knee periprosthetic joint infection (PJI) with a static spacer as temporary arthrodesis allowing weight-bearing in the implant-free interval. Outcomes of this surgical treatment were evaluated in terms of (i) associated complications and (ii) patient-reported quality of life. Methods: In this retrospective case series, 20 patients with PJI (n = 14, 70%) and FRI (n = 6, 30%) treated with PMMA-coated intramedullary nails reinforced with cerclage wire between January 2021 and July 2021 were included. Quality of life during the implant-free interval was evaluated with the EQ-5D, SF-36, and an ICD-10 based psychological symptom rating and compared with previously analyzed cohorts of successfully treated PJI and FRI patients in whom eradication of infection and stable bone consolidation was achieved. Results: Complications during the implant-free interval comprised a broken nail in one case (5.0%) and a reinfection in one case (5.0%). Coating-specific side effects and cement debonding during removal did not occur. The mean physical health component score of SF-36 was 26.1 ± 7.6, and the mean mental health component score reached a value of 47.1 ± 18.6. The mean EQ-5D index value was 0.36 ± 0.32 and the mean EQ-5D visual analogue scale rating was 47.4 ± 19.4. The scores were significantly lower than those in the successfully treated FRI cohort but not in the PJI cohort. The mean ICD-10-based symptom rating scores revealed psychological symptom burden on the depression scale and enhanced levels of anxiety in comparison with healed FRI and PJI patients. Conclusion: Reinforcement of PMMA bone cement-coated implants seems to be a reasonable treatment option to create a temporary arthrodesis, preventing detachment of the bone cement when the implant was removed. Level of Evidence: IV

Increased incidence of vertebral fractures in German adults from 2009 to 2019 and the analysis of secondary diagnoses, treatment, costs, and in-hospital mortality

The aim of this cross-sectional study was to present the nationwide rates of hospitalized patients with vertebral fractures over one decade and to comprehensively analyze the treatment characteristics and direct costs incurred in 2019. Therefore, the trends in the incidence rate were quantified based on annual ICD-10 diagnosis codes from all German medical facilities between 2009 and 2019, provided by the Federal Statistical Office (Destatis). The ICD-10 Codes “S12.0-2; S22.0-; S32.0-, and S32.1-2” were evaluated. The relative change from 2009 through 2019 was determined. Using data from the Institute for Hospital Remuneration Systems (InEK) for 2019 the secondary diagnoses, OPS-codes, intensive care unit (ICU) treatment, in-hospital mortality, the proportion of G-DRGs and cumulative costs were evaluated. The documented number of vertebral fractures increased by 45.6% between 2009 and 2019 to an incidence of 150.7 per 100,000 inhabitants. The lumbar spine was most commonly affected with an incidence of 70.5/100,000 inhabitants in 2019 (46.8% of all vertebral fractures). The highest increases were seen in the numbers of subaxial cervical fractures (+ 121.2%) and sacral fractures (+ 306.6%). Of all vertebral fractures in 2019, 63.7% were diagnosed in women and 69.0% in patients aged 70 years or older. Osteoporosis was documented in 17.9% of cases as a concomitant diagnosis. In 10.1% of all cases, an ICU treatment was documented. The in-hospital mortality was 2.0% in 2019. I68D was the most frequently used G-DRG code, accounting for 33.3% of cases. The total direct costs for inpatient treatment in 2019 amounted to €589,205,715. The evaluation of 955,091 vertebral fractures showed a sharp increase in the nation-wide incidence rate. The presented age and sex distribution, the comorbidity profile and the in-hospital mortality rate indicate the importance of comprehensive geriatric assessment and emphasize the need for spinal care centers to be established