Publications by authors named "Matthias Schürmann"

18 Publications

  • Page 1 of 1

Chronic inflammation of middle ear cholesteatoma promotes its recurrence via a paracrine mechanism.

Cell Commun Signal 2021 Feb 24;19(1):25. Epub 2021 Feb 24.

Department of Otolaryngology, Head and Neck Surgery, Medical School OWL Campus Klinikum Bielefeld, Bielefeld University, Teutoburger Str. 50, 33604, Bielefeld, Germany.

Background: Cholesteatoma disease is an expanding lesion in the middle ear. Hearing loss and facial paralysis alongside with other intracranial complications are found. No pharmaceutical treatment is available today and recurrence after surgical extraction occurs. We investigated possible TLR4-based mechanisms promoting recurrence and explore possible treatments strategies.

Methods: We isolated fibroblasts and epidermal stem cells from cholesteatoma tissue and healthy auditory canal skin. Subsequently, their expression under standard culture conditions and after stimulation with LPS was investigated by RT-qPCR. Cell metabolism and proliferation were analysed upon LPS treatment, with and without TLR4 antagonist. An indirect co-culture of fibroblasts and epidermal stem cells isolated from cholesteatoma tissue was utilized to monitor epidermal differentiation upon LPS treatment by RT-qPCR and immunocytochemistry.

Results: Under standard culture conditions, we detected a tissue-independent higher expression of IL-1β and IL-8 in stem cells, an upregulation of KGF and IGF-2 in both cell types derived from cholesteatoma and higher expression of TLR4 in stem cells derived from cholesteatoma tissue. Upon LPS challenge, we could detect a significantly higher expression of IL-1α, IL-1β, IL-6 and IL-8 in stem cells and of TNF-a, GM-CSF and CXCL-5 in stem cells and fibroblasts derived from cholesteatoma. The expression of the growth factors KGF, EGF, EREG, IGF-2 and HGF was significantly higher in fibroblasts, particularly when derived from cholesteatoma. Upon treatment with LPS the metabolism was elevated in stem cells and fibroblasts, proliferation was only enhanced in fibroblasts derived from cholesteatoma. This could be reversed by the treatment with a TLR4 antagonist. The cholesteatoma fibroblasts could be triggered by LPS to promote the epidermal differentiation of the stem cells, while no LPS treatment or LPS treatment without the presence of fibroblasts did not result in such a differentiation.

Conclusion: We propose that cholesteatoma recurrence is based on TLR4 signalling imprinted in the cholesteatoma cells. It induces excessive inflammation of stem cells and fibroblasts, proliferation of perimatrix fibroblasts and the generation of epidermal cells from stem cells thru paracrine signalling by fibroblasts. Treatment of the operation site with a TLR4 antagonist might reduce the chance of cholesteatoma recurrence. Video Abstract.
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http://dx.doi.org/10.1186/s12964-020-00690-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903614PMC
February 2021

Imaging of SARS-CoV-2 infected Vero E6 cells by helium ion microscopy.

Beilstein J Nanotechnol 2021 2;12:172-179. Epub 2021 Feb 2.

Physics of Supramolecular Systems and Surfaces, Faculty of Physics, Bielefeld University, Bielefeld, Germany.

Helium ion microscopy (HIM) offers the opportunity to obtain direct views of biological samples such as cellular structures, virus particles, and microbial interactions. Imaging with the HIM combines sub-nanometer resolution, large depth of field, and high surface sensitivity. Due to its charge compensation capability, the HIM can image insulating biological samples without additional conductive coatings. Here, we present an exploratory HIM study of SARS-CoV-2 infected Vero E6 cells, in which several areas of interaction between cells and virus particles, as well as among virus particles, were imaged. The HIM pictures show the three-dimensional appearance of SARS-CoV-2 and the surface of Vero E6 cells at a multiplicity of infection of approximately 1 with great morphological detail. The absence of a conductive coating allows for a distinction between virus particles bound to the cell membrane and virus particles lying on top of the membrane. After prolonged imaging, it was found that ion-induced deposition of hydrocarbons from the vacuum renders the sample sufficiently conductive to allow for imaging even without charge compensation. The presented images demonstrate the potential of the HIM in bioimaging, especially for the imaging of interactions between viruses and their host organisms.
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http://dx.doi.org/10.3762/bjnano.12.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871036PMC
February 2021

Stem Cell-Induced Inflammation in Cholesteatoma is Inhibited by the TLR4 Antagonist LPS-RS.

Cells 2020 01 14;9(1). Epub 2020 Jan 14.

Department of Cell Biology, University of Bielefeld, 33619 Bielefeld, Germany.

Cholesteatoma is a severe non-cancerous lesion of the middle ear characterized by massive inflammation, tissue destruction, and an abnormal growth of keratinized squamous epithelium. We recently demonstrated the presence of pathogenic stem cells within cholesteatoma tissue, unfortunately their potential roles in regulating disease-specific chronic inflammation remain poorly understood. In the presented study, we utilized our established human in vitro cholesteatoma stem cell model for treatments with lipopolysaccharides (LPS), tumor necrosis factor α (TNFα), and the TLR4-antagonist LPS from LPS-RS) followed by qPCR, western blot, and immunocytochemistry. Middle ear cholesteatoma stem cells (ME-CSCs) showed a significantly increased expression of TLR4 accompanied by a significantly enhanced LPS-dependent pro-inflammatory gene expression pattern of TNFα, IL-1α, IL-1ß, IL-6, and IL-8 compared to non-pathogenic control cells. LPS-dependent pro-inflammatory gene expression in ME-CSCs was driven by an enhanced activity of NF-B p65 leading to a TNFα-mediated feed-forward-loop of pro-inflammatory NF-B target gene expression. Functional inactivation of TLR4 via the TLR4-antagonist LPS-RS blocked chronic inflammation in ME-CSCs, resulting in a nearly complete loss of IL-1ß, IL-6, and TNFα expression. In summary, we determined that ME-CSCs mediate the inflammatory environment of cholesteatoma via TLR4-mediated NF-B-signaling, suggesting a distinct role of ME-CSCs as drivers of cholesteatoma progression and TLR4 on ME-CSCs as a therapeutic target.
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http://dx.doi.org/10.3390/cells9010199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017370PMC
January 2020

The Therapeutic Effect of 1,8-Cineol on Pathogenic Bacteria Species Present in Chronic Rhinosinusitis.

Front Microbiol 2019 22;10:2325. Epub 2019 Oct 22.

Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, Bielefeld, Germany.

Chronic rhinosinusitis (CRS) is marked by an inflamed mucosa of sinuses and is accompanied by a significantly reduced quality of live. Since no guidelines for the treatment of CRS are available, long lasting clinical histories with health care costs adding up to dozens of billion $ annually are caused by CRS. The progression of CRS is often induced by bacterial infections and/or a shift in microbiome as well as biofilm formation. The exact microbiome alterations are still unclear and the impenetrable biofilm renders the treatment with common antibiotics ineffective. This study focuses on characterizing the microbiome changes in CRS and investigating the inhibition of biofilm growth by 1,8-Cineol, a small, non-polar and hence biofilm penetrating molecule with known antimicrobial potential. We performed MALDI-TOF MS based characterization of the microbiomes of healthy individuals and CRS patients ( = 50). The microbiome in our test group was shifted to pathogens (, , and ). In contrast to published studies, solely based on cell culture techniques, we could not verify the abundance of in CRS. The inhibition of bacterial proliferation and biofilm growth by 1,8-Cineol was measured for these three pathogens. Interestingly, , the most prominent germ in CRS, showed a biofilm inhibition not simply correlated to its inhibition of proliferation. RT-qPCR confirmed that this was due to the downregulations of major key players in biofilm generation (agrA, SarA and σ) by 1,8-Cineol. Furthermore we verified this high biofilm inhibition potential in a model host system consisting out of biofilm grown on mature respiratory epithelium. A second host model, comprising organotypic slices, was utilized to investigate the reaction of the innate immune system present in the nasal mucosa upon biofilm formation and treatment with 1,8-Cineol. Interestingly , the cause of very common catheter infections, possesses a biofilm generation pathway very similar to and might be treatable in a similar fashion. The two presented model systems might be transferred to combinations of every biofilm forming bacterial with most kind of epithelium and mucosa.
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http://dx.doi.org/10.3389/fmicb.2019.02325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821979PMC
October 2019

An Effective Primary Head and Neck Squamous Cell Carcinoma In Vitro Model.

Cells 2019 06 7;8(6). Epub 2019 Jun 7.

Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, Teutoburger Str. 50, 33604 Bielefeld, Germany.

Head and neck squamous cell carcinoma is a highly malignant disease and research is needed to find new therapeutic approaches. Faithful experimental models are required for this purpose. Here, we describe the specific cell culture conditions enabling the efficient establishment of primary cell culture models. Whereas a classical 10% serum-containing medium resulted in the growth of fibroblast-like cells that outcompeted epithelial cells, we found that the use of specific culture conditions enabled the growth of epithelial tumor cells from HPV+ and HPV- head and neck cancer tissue applicable for research. EpCAM and high Thy-1 positivity on the cell surface were mutually exclusive and distinguished epithelial and fibroblast-like subpopulations in all primary cultures examined and thus can be used to monitor stromal contamination and epithelial cell content. Interestingly, cells of an individual patient developed tumor spheroids in suspension without the use of ultra-low attachment plates, whereas all other samples exclusively formed adherent cell layers. Spheroid cells were highly positive for ALDH1A1 and hence displayed a phenotype reminiscent of tumor stem cells. Altogether, we present a system to establish valuable primary cell culture models from head and neck cancer tissue at high efficiency that might be applicable in other tumor entities as well.
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http://dx.doi.org/10.3390/cells8060555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628367PMC
June 2019

Specific Targeting of Oncogenes Using CRISPR Technology.

Cancer Res 2018 10 7;78(19):5506-5512. Epub 2018 Sep 7.

Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, Bielefeld, Germany.

In recent decades, tools of molecular biology have enabled researchers to genetically modify model organisms, including human cells. RNAi, zinc-finger nucleases, transcription activator-like effector nucleases, CRISPR-Cas9 (clustered regularly-interspaced short palindromic repeats and CRISPR-associated protein 9), retro- or lentiviral gene transfer, and many other methods can be utilized to remove genes, add genes, or change their expression. Within the same timeframe, survival rates for many highly malignant tumor diseases have not improved substantially. If modern medicine could apply even a subset of research methods in clinical management, which are already well established and controllable in basic research laboratories, this could strongly impact patients' prognosis. CRISPR-Cas9 is a method to precisely target and manipulate genomic loci and recent studies have attempted to use this method as a genetic treatment for Duchenne muscular dystrophy, blood disorders, autosomal-dominant hearing loss, and cancer. Some of these approaches target mutant genomic sequences specifically and try to avoid affecting the respective normal loci. Considering obvious genetic risks opposing the objected benefits, data are needed to show whether CRISPR technology is suitable as a future cancer therapy approach or not. Here, we develop strategies for the specific targeting of viral cancer drivers and oncogenes activated by mutation, using the latest CRISPR technology. .
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http://dx.doi.org/10.1158/0008-5472.CAN-18-0571DOI Listing
October 2018

Stem cells in middle ear cholesteatoma contribute to its pathogenesis.

Sci Rep 2018 04 18;8(1):6204. Epub 2018 Apr 18.

Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, 33604, Bielefeld, Germany.

Cholesteatoma is a potentially life-threatening middle ear lesion due to the formation of an inflamed ectopic mass of keratinizing squamous epithelium. Surgical removal remains the only treatment option, emphasizing the need to gain a better understanding of this severe disease. We show for the first time that stem cells residing in cholesteatoma tissue contribute to disease progression. Cells expressing the "stemness" markers Nestin and S100B were detected in middle ear cholesteatoma and auditory canal skin. Isolated Nestin + /S100B + -cells showed the capability for self-renewal, neurosphere formation and differentiation into mesodermal and ectodermal cell types. Compared to auditory canal skin stem cells middle ear cholesteatoma-derived stem cells displayed an enhanced susceptibility to inflammatory stimuli, and this suggested a possible contribution to the inflammatory environment in cholesteatoma tissue. Cholesteatoma derived stem cells were able to differentiate into keratinocyte-like cells using factors mimicking the microenvironment of cholesteatoma. Our findings demonstrate a new perspective on the pathogenesis of cholesteatoma and may lead to new treatment strategies for this severe middle ear lesion.
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http://dx.doi.org/10.1038/s41598-018-24616-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906547PMC
April 2018

Technical feasibility study for production of tailored multielectrode arrays and patterning of arranged neuronal networks.

PLoS One 2018 23;13(2):e0192647. Epub 2018 Feb 23.

Center for Spinelectronic Materials and Devices, Physics Department, Bielefeld University, Bielefeld, Germany.

In this manuscript, we first reveal a simple ultra violet laser lithographic method to design and produce plain tailored multielectrode arrays. Secondly, we use the same lithographic setup for surface patterning to enable controlled attachment of primary neuronal cells and help neurite guidance. For multielectrode array production, we used flat borosilicate glass directly structured with the laser lithography system. The multi layered electrode system consists of a layer of titanium coated with a layer of di-titanium nitride. Finally, these electrodes are covered with silicon nitride for insulation. The quality of the custom made multielectrode arrays was investigated by light microscopy, electron microscopy and X-ray diffraction. The performance was verified by the detection of action potentials of primary neurons. The electrical noise of the custom-made MEA was equal to commercially available multielectrode arrays. Additionally, we demonstrated that structured coating with poly lysine, obtained with the aid of the same lithographic system, could be used to attach and guide neurons to designed structures. The process of neuron attachment and neurite guidance was investigated by light microscopy and charged particle microscopy. Importantly, the utilization of the same lithographic system for MEA fabrication and poly lysine structuring will make it easy to align the architecture of the neuronal network to the arrangement of the MEA electrode.. In future studies, this will lead to multielectrode arrays, which are able to specifically attach neuronal cell bodies to their chemically defined electrodes and guide their neurites, gaining a controlled connectivity in the neuronal network. This type of multielectrode array would be able to precisely assign a signal to a certain neuron resulting in an efficient way for analyzing the maturation of the neuronal connectivity in small neuronal networks.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192647PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825013PMC
April 2018

Identification of a Novel High Yielding Source of Multipotent Adult Human Neural Crest-Derived Stem Cells.

Stem Cell Rev Rep 2018 Apr;14(2):277-285

Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld, Teutoburger Straße 50, 33604, Bielefeld, Germany.

Due to their extraordinarily broad differentiation potential and persistence during adulthood, adult neural crest-derived stem cells (NCSCs) are highly promising candidates for clinical applications, particularly when facing the challenging treatment of neurodegenerative diseases or complex craniofacial injuries. Successful application of human NCSCs in regenerative medicine and pharmaceutical research mainly relies on the availability of sufficient amounts of tissue for cell isolation procedures. Facing this challenge, we here describe for the first time a novel population of NCSCs within the middle turbinate of the human nasal cavity. From a surgical point of view, high amounts of tissue are routinely and easily removed during nasal biopsies. Investigating the presence of putative stem cells in obtained middle turbinate tissue by immunohistochemistry, we observed Nestin/p75/S100/α smooth muscle actin (αSMA) cells, which we successfully isolated and cultivated in vitro. Cultivated middle turbinate stem cells (MTSCs) kept their expression of neural crest and stemness markers Nestin, p75 and S100 and showed the capability of sphere formation and clonal growth, indicating their stem cell character. Application of directed in vitro differentiation assays resulted in successful differentiation of MTSCs into osteogenic and neuronal cell types. Regarding the high amount of tissue obtained during surgery as well as their broad differentiation capability, MTSCs seem to be a highly promising novel neural crest stem cell population for applications in cell replacement therapy and pharmacological research.
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http://dx.doi.org/10.1007/s12015-017-9797-2DOI Listing
April 2018

Label-free nonlinear optical microscopy detects early markers for osteogenic differentiation of human stem cells.

Sci Rep 2016 05 26;6:26716. Epub 2016 May 26.

Cell Biology, University of Bielefeld, D-33501 Bielefeld, Germany.

Tissue engineering by stem cell differentiation is a novel treatment option for bone regeneration. Most approaches for the detection of osteogenic differentiation are invasive or destructive and not compatible with live cell analysis. Here, non-destructive and label-free approaches of Raman spectroscopy, coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) microscopy were used to detect and image osteogenic differentiation of human neural crest-derived inferior turbinate stem cells (ITSCs). Combined CARS and SHG microscopy was able to detect markers of osteogenesis within 14 days after osteogenic induction. This process increased during continued differentiation. Furthermore, Raman spectroscopy showed significant increases of the PO4(3-) symmetric stretch vibrations at 959 cm(-1) assigned to calcium hydroxyapatite between days 14 and 21. Additionally, CARS microscopy was able to image calcium hydroxyapatite deposits within 14 days following osteogenic induction, which was confirmed by Alizarin Red-Staining and RT- PCR. Taken together, the multimodal label-free analysis methods Raman spectroscopy, CARS and SHG microscopy can monitor osteogenic differentiation of adult human stem cells into osteoblasts with high sensitivity and spatial resolution in three dimensions. Our findings suggest a great potential of these optical detection methods for clinical applications including in vivo observation of bone tissue-implant-interfaces or disease diagnosis.
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http://dx.doi.org/10.1038/srep26716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880889PMC
May 2016

Helium Ion Microscopy Visualizes Lipid Nanodomains in Mammalian Cells.

Small 2015 Nov 5;11(43):5781-9. Epub 2015 Oct 5.

Faculty of Physics, Bielefeld University, 33501, Bielefeld, Germany.

Cell membranes are composed of 2D bilayers of amphipathic lipids, which allow a lateral movement of the respective membrane components. These components are arranged in an inhomogeneous manner as transient micro- and nanodomains, which are believed to be crucially involved in the regulation of signal transduction pathways in mammalian cells. Because of their small size (diameter 10-200 nm), membrane nanodomains cannot be directly imaged using conventional light microscopy. Here, direct visualization of cell membrane nanodomains by helium ion microscopy (HIM) is presented. It is shown that HIM is capable to image biological specimens without any conductive coating and that HIM images clearly allow the identification of nanodomains in the ultrastructure of membranes with 1.5 nm resolution. The shape of these nanodomains is preserved by fixation of the surrounding unsaturated fatty acids while saturated fatty acids inside the nanodomains are selectively removed. Atomic force microscopy, fluorescence microscopy, 3D structured illumination microscopy, and direct stochastic optical reconstruction microscopy provide additional evidence that the structures in the HIM images of cell membranes originate from membrane nanodomains. The nanodomains observed by HIM have an average diameter of 20 nm and are densely arranged with a minimal nearest neighbor distance of ≈ 15 nm.
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http://dx.doi.org/10.1002/smll.201501540DOI Listing
November 2015

Interaction of adult human neural crest-derived stem cells with a nanoporous titanium surface is sufficient to induce their osteogenic differentiation.

Stem Cell Res 2014 Jul 9;13(1):98-110. Epub 2014 May 9.

Molecular Neurobiology, Faculty of Biology, University of Bielefeld, 33615 Bielefeld, Germany. Electronic address:

Osteogenic differentiation of various adult stem cell populations such as neural crest-derived stem cells is of great interest in the context of bone regeneration. Ideally, exogenous differentiation should mimic an endogenous differentiation process, which is partly mediated by topological cues. To elucidate the osteoinductive potential of porous substrates with different pore diameters (30 nm, 100 nm), human neural crest-derived stem cells isolated from the inferior nasal turbinate were cultivated on the surface of nanoporous titanium covered membranes without additional chemical or biological osteoinductive cues. As controls, flat titanium without any topological features and osteogenic medium was used. Cultivation of human neural crest-derived stem cells on 30 nm pores resulted in osteogenic differentiation as demonstrated by alkaline phosphatase activity after seven days as well as by calcium deposition after 3 weeks of cultivation. In contrast, cultivation on flat titanium and on membranes equipped with 100 nm pores was not sufficient to induce osteogenic differentiation. Moreover, we demonstrate an increase of osteogenic transcripts including Osterix, Osteocalcin and up-regulation of Integrin β1 and α2 in the 30 nm pore approach only. Thus, transplantation of stem cells pre-cultivated on nanostructured implants might improve the clinical outcome by support of the graft adherence and acceleration of the regeneration process.
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http://dx.doi.org/10.1016/j.scr.2014.04.017DOI Listing
July 2014

Sympathetic dysfunction in long-term complex regional pain syndrome.

Clin J Pain 2010 Feb;26(2):128-31

Department of Orthopedic Surgery, University of Bochum, Germany.

Objective: Malfunction of the sympathetic nervous system (SNS) is common in early complex regional pain syndrome type I (CRPS I). This study was designed to evaluate the function of the SNS in patients with chronic CRPS I and to correlate the obtained data with hand function measurements.

Materials And Methods: Thirty-two patients of both the sexes in whom the diagnosis of CRPS I of the upper extremity had been established for at least 3 years before they were included in the study. Besides a hand outcomes questionnaire [Michigan Hand Outcome Questionnaire, (MHQ)] the patients underwent a standardized testing of the peripheral sympathetic nervous system (pSNS) using laser Doppler flowmetry (LDF).

Results: Mean time since initial diagnosis was 4.6+/-2.1 years. The mean MHQ score of the affected limb was 57.3+/-17 compared with 69.4+/-13.7 for the unaffected hand (P=0.002). Twenty patients (62.5%) still demonstrated pathologic results regarding the pSNS function (mean sympathetic reflex 0.18+/-0.11, normal range>0.38). We found no statistically significant correlation between pSNS function either with the clinical outcome as measured by MHQ (r=0.246; P=0.175), or with the level of pain (r=0.132; P=0.473).

Conclusions: Even 5 years after the diagnosis of CRPS I of the upper extremity we detected significant impairments of the pSNS in nearly two thirds of our patients. Patients still have pain and present with a significant deterioration of their hand function in comparison with the not affected hand. In our study we could not identify any correlation between pSNS function and clinical outcome as measured by MHQ.
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http://dx.doi.org/10.1097/AJP.0b013e3181b5effcDOI Listing
February 2010

Analysis of efficacy and failure in proximal humerus fractures treated with locking plates.

J Orthop Trauma 2007 Nov-Dec;21(10):676-81

Department of Orthopaedic Surgery, Denver Health Medical Center, University of Colorado School of Medicine, Denver, CO 80204, USA.

Objective: The purpose of this study was to determine the efficacy of proximal humerus locking plates (PHLP) and to clarify predictors of loss of fixation.

Design: Retrospective review of patients with proximal humerus fractures fixed with a PHLP.

Setting: Five Level 1 trauma centers.

Patients: One hundred fifty-three patients (111 female, 42 male) 18 years or older with a displaced fracture or fracture-dislocation of the proximal humerus treated with a PHLP between January 1, 2001 and July 31, 2005.

Intervention: Demographic data, trauma mechanism, surgical approach, and perioperative complications were collected from the medical records. Fracture classification according to the AO/OTA, radiographic head-shaft angle, and screw tip-articular surface distance in true anteroposterior (AP) and axillary lateral radiographs of the shoulder were measured postoperatively. Varus malreduction was defined as a head-shaft angle of <120 degrees.

Main Outcome Measurements: Statistical analysis was done to establish correlations between loss of fixation and postoperative head-shaft angle in the true AP radiograph, patient age, fracture type, trauma mechanism, number of locking head screws, and type of plate.

Results: The mean age was 62.3 +/- 15.4 years (22-92) and the mean injury severity score (ISS) was 9.5 +/- 10.16 (4-57; n = 73). The surgical approach was deltopectoral (90.2%) or transdeltoid (9.8%). No intraoperative complications were reported. The mean postoperative head-shaft angle was 130 degrees (95 degrees to 160 degrees; SD = 13). The overall incidence of loss of fixation was 13.7%. There was a statistically significant association between varus reduction (<120 degrees) and loss of fixation (30.4% when the head-shaft angle was <120 degrees versus 11% when the head-shaft angle was > or =120 degrees; P = 0.02).

Conclusion: This series presents the experience using PHLP in 5 Level 1 trauma centers. There were no intraoperative complications related to the locking plate systems. Despite the use of fixed-angle devices, loss of fixation occurred, primarily in the presence of varus malreduction. Our findings suggest that avoiding varus should substantially decrease the risk of postoperative failures.
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http://dx.doi.org/10.1097/BOT.0b013e31815bb09dDOI Listing
February 2008

Early diagnosis in post-traumatic complex regional pain syndrome.

Orthopedics 2007 06;30(6):450-6

Department of Traumatology and Orthopedic Surgery, University of Erlangen, Sana Klinikum Hof, Hof, Germany.

Since prospective studies confirmed an incidence of >10% of complex regional pain syndrome complication in patients after distal radial fracture, early diagnosis is important. Therapy should be commenced immediately with a systematic approach to avoid chronicity of the disease. Despite this, epidemiological studies revealed an extreme delay in effective treatment among complex regional pain syndrome patients, who were repeatedly referred to different physicians and often treated inadequately before being referred to specialized pain clinics. In post-traumatic patients, the clinical examination still is preferred to establish the diagnosis of complex regional pain syndrome. First, possible differential diagnoses must be excluded. Next the clinical criteria of the consensus definition should be checked and documented, if possible with the help of verifying procedures. Imaging methods could be applied; however, they are not useful for early diagnosis since sensitivity is low and the consequences of trauma may interfere with potential complex regional pain syndrome findings. In questionable cases repeated examinations after short periods detect the presence of complex regional pain syndrome in orthopedic patients, particularly if symptoms are progressive or an expected improvement does not occur.
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http://dx.doi.org/10.3928/01477447-20070601-01DOI Listing
June 2007

Imaging in early posttraumatic complex regional pain syndrome: a comparison of diagnostic methods.

Clin J Pain 2007 Jun;23(5):449-57

Department of Trauma and Orthopedic Surgery, Sana Klinikum Hof, University of Erlangen-Nürnberg, Eppenreuther Strasse 9, 95035 Hof, Germany.

Objectives: The complex regional pain syndrome type I (CRPS I) still is difficult to diagnose in posttraumatic patients. As CRPS I is a clinical diagnosis the characteristic symptoms have to be differentiated from normal posttraumatic states. Several diagnostic procedures are applied to facilitate an early diagnosis, although their value for diagnosing posttraumatic CRPS I is unclear.

Methods: One hundred fifty-eight consecutive patients with distal radial fracture were followed up for 16 weeks after trauma. To assess the diagnostic value of the commonly applied methods a detailed clinical examination was carried out 2, 8, and 16 weeks after trauma in conjunction with bilateral thermography, plain radiographs of the hand skeleton, three phase bone scans (TPBSs), and contrast-enhanced magnetic resonance imaging (MRI). All imaging procedures were assessed blinded.

Results: At the end of the observation period 18 patients (11%) were clinically identified as having CRPS I and 13 patients (8%) revealed an incomplete clinical picture which were defined as CRPS borderline cases. The sensitivity of all diagnostic procedures used was poor and decreased between the first and the last examinations (thermography: 45% to 29%; TPBS: 19% to 14%; MRI: 43% to 13%; bilateral radiographs: 36%). In contrast a high specificity was observed in the TPBS and MRI at the eighth and sixteenth-week examinations (TPBS: 96%, 100%; MRI: 78%, 98%) and for bilateral radiographs 8 weeks after trauma (94%). The thermography presented a fair specificity that improved from the second to the sixteenth week (50% to 89%).

Discussion: The poor sensitivity of all tested procedures combined with a reasonable specificity produced a low positive predictive value (17% to 60%) and a moderate negative predictive value (79% to 86%). These results suggest, that those procedures cannot be used as screening tests. Imaging methods are not able to reliably differentiate between normal posttraumatic changes and changes due to CRPS I. Clinical findings remain the gold standard for the diagnosis of CRPS I and the procedures described above may serve as additional tools to establish the diagnosis in doubtful cases.
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http://dx.doi.org/10.1097/AJP.0b013e31805c9e66DOI Listing
June 2007

Sympathetic dysfunction as a temporary phenomenon in acute posttraumatic CRPS I.

Clin Auton Res 2005 Feb;15(1):29-34

Chirurgische Klinik und Poliklinik der Universität Rostock, Abteilung Unfall- und Wiederherstellungschirurgie, Rostock, Germany.

Objective: Sympathetic testing was carried out in patients in the acute phase of "complex regional pain syndrome type I" (CRPS I) shortly after trauma to the upper limb. Repeated measurements were used to detect changes in peripheral sympathetic function during the course of the disease.

Material And Methods: In a busy trauma center, 10 consecutive patients who developed CRPS I following trauma or surgery of the upper limb were diagnosed according to the 1999 modified IASP diagnostic criteria for CRPS I. Clinical signs and symptoms and bilateral hand temperature (infrared thermometry) were recorded. Vasoconstrictor response to sympathetic provocation (inspiratory gasp, contralateral cooling) at the tip of the middle finger of both hands was measured employing laser Doppler flowmetry (LDF). Sympathetic reaction was quantified by the magnitude of blood flow decrease after provocation (SRF parameter).

Results: The diagnosis CRPS I could be established 63 days (46-72 days) post-injury. The mean follow-up time after diagnosis was 83+/-15 days. Pain measured by a visual analog scale (VAS 0-10) showed an average of 5.0+/-2.0 at the time of diagnosis and decreased to 1.7+/-1.9 at the last examination. Edema and active range of motion improved substantially during the follow-up period. On the ipsilateral hand marked sympathetic dysfunction was seen early after the onset of CRPS I (mean SRF parameter: 0.14+/-0.01), slowly returning to normal sympathetic reaction three months after the onset of symptoms (mean SRF parameter: 0.42+/-0.21). Diminished sympathetic function was seen even on the contralateral hand.

Conclusions: Sympathetic dysfunction is regularly seen at the onset of CRPS I and normalizes during the course of the disease. This temporary phenomenon suggests a posttraumatic sympathetic deficit playing a decisive role in the genesis of CRPS I.
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http://dx.doi.org/10.1007/s10286-005-0237-zDOI Listing
February 2005

MR imaging of ulnocarpal impaction after fracture of the distal radius.

AJR Am J Roentgenol 2003 Jul;181(1):195-8

Department of Clinical Radiology, Ludwig Maximilians University, Klinikum Grosshadern, Marchioninistr. 15, D-81377 Munich, Germany.

Objective: The purpose of our study was to evaluate the incidence of ulnocarpal impaction after distal radius fracture using MR imaging and to correlate imaging findings with those of radiography and clinical findings.

Conclusion: Ulnocarpal impaction is a common finding after distal radius fracture. MR imaging can detect characteristic bone marrow changes of the lunate early after the trauma. A significant correlation exists between MR imaging findings and the extent of posttraumatic ulnar variance and pain levels.
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http://dx.doi.org/10.2214/ajr.181.1.1810195DOI Listing
July 2003