Nils T. Veith

Plantar Fibromatosis—Topical Review:

Morbus Ledderhose is a rare hyperproliferative disease of the plantar fascia, leading to the formation of nodules. Its origin is unknown. No causal therapy is available, and treatment remains symptomatic. Various therapeutic strategies to alleviate symptoms are available and are adapted to the severity of the disease. In early stages, conservative therapy including nonpharmacological, physical, and pharmacological treatments is applied. If the disease progresses, irradiation of the plantar surface, injections of steroids, shock wave therapy, and partial or complete fasciectomy as an ultimate therapy may be indicated. Novel experimental treatment options including application of fibrinolytic agents are currently being tested, but no controlled, randomized long-term studies are available. This review aims to provide a systematic overview of current established procedures and outlines novel experimental strategies for the treatment of morbus Ledderhose, including future avenues to treat this rare disease.

How to detect a dwarf: in vivo imaging of nanoparticles in the lung

UNLABELLED Nanotechnology is a rapidly developing field in science and industry. The exposure to nanoparticles (NPs) will steadily grow in the future and there is thus an urgent need to study potential impacts of the interaction between NPs and the human body. The respiratory tract is the route of entry for all accidentally inhaled NPs. Moreover, NPs may intentionally be delivered into the lung as contrast agents and drug delivery systems. The present review provides an overview of currently used techniques for the in vivo imaging of NPs in the lung, including x-ray imaging, computed tomography, gamma camera imaging, positron emission tomography, magnetic resonance imaging, near-infrared imaging, and intravital fluorescence microscopy. Studies based on these techniques may contribute to the development of novel NP-based drug delivery systems and contrast agents. In addition, they may provide completely new insights into nanotoxicological processes. FROM THE CLINICAL EDITOR Nanoparticles are rapidly gaining ground in various therapeutic and diagnostic applications. This review provides an overview of current in vivo imaging techniques of NPs in the lung, including x-ray, CT, gamma camera imaging, PET, MRI, near-infrared imaging, and intravital fluorescence microscopy, aiding the development of novel NP-based techniques and nanotoxicology.

A novel tool for continuous fracture aftercare – Clinical feasibility and first results of a new telemetric gait analysis insole

Weight bearing after lower extremity fractures still remains a highly controversial issue. Even in ankle fractures, the most common lower extremity injury no standard aftercare protocol has been established. Average non weight bearing times range from 0 to 7 weeks, with standardised, radiological healing controls at fixed time intervals. Recent literature calls for patient-adapted aftercare protocols based on individual fracture and load scenarios. We show the clinical feasibility and first results of a new, insole embedded gait analysis tool for continuous monitoring of gait, load and activity. Ten patients were monitored with a new, independent gait analysis insole for up to 3 months postoperatively. Strict 20 kg partial weight bearing was ordered for 6 weeks. Overall activity, load spectrum, ground reaction forces, clinical scoring and general health data were recorded and correlated. Statistical analysis with power analysis, t-test and Spearman correlation was performed. Only one patient completely adhered to the set weight bearing limit. Average time in minutes over the limit was 374 min. Based on the parameters load, activity, gait time over 20 kg weight bearing and maximum ground reaction force high and low performers were defined after 3 weeks. Significant difference in time to painless full weight bearing between high and low performers was shown. Correlation analysis revealed a significant correlation between weight bearing and clinical scoring as well as pain (American Orthopaedic Foot and Ankle Society (AOFAS) Score rs=0.74; Olerud-Molander Score rs=0.93; VAS pain rs=-0.95). Early, continuous gait analysis is able to define aftercare performers with significant differences in time to full painless weight bearing where clinical or radiographic controls could not. Patient compliance to standardised weight bearing limits and protocols is low. Highly individual rehabilitation patterns were seen in all patients. Aftercare protocols should be adjusted to real-time patient conditions, rather than fixed intervals and limits. With a real-time measuring device high performers could be identified and influenced towards optimal healing conditions early, while low performers are recognised and missing healing influences could be corrected according to patient condition.

Direct visualisation of microparticles in the living lung.

Microparticles (MP) and fibres can be inhaled and cause inflammatory lung diseases. So far MP and fibres have not observed directly in the lung of living animals. A direct visualisation of particles and fibres would be important to study interactions with local and immigration host cells. In this methodical report latex beads were used as model particles for, e.g. nanoparticles, dusts, pollen or bacteria and were investigated using intravital fluorescence microscopy. Intravital fluorescence microscopy of the lung periphery is challenging because of the constant movement of the lung tissue and the heart. Chest window techniques have been described for investigation of lung vessels. For investigation of MP in larger areas of the lung surface this study presents an open chest-technique. Fluorescent MP were instilled into the trachea and could be observed in the alveoli of the right lung. Abundant numbers of MP were found within alveolar macrophages indicating that they are actively engulfed. Using the same setup also fluorescence labelled bacteria and its phagocytosis could be observed as shown in preliminary experiments. In conclusion, we present a method to analyse MP/fibres and its interaction with local and immigrating host cells in the living lung.

Surfactant protein A mediates pulmonary clearance of Staphylococcus aureus

Surfactant protein A has been shown to enhance opsonization and clearance of Staphylococcus aureus in vitro. Here, the phagocytosis of alveolar S. aureus was investigated in vivo using intravital microscopy. Fluorescence labelled S. aureus Newman cells were intratracheally administered to anesthetized mice and the alveolar surface was observed for fifteen minutes. Confirming previously reported in vitro data, surfactant protein A-deficient mice showed a significantly reduced uptake of bacteria compared to wild-type mice.

Obesity does not affect the healing of femur fractures in mice.

Obesity is reported to be both protective and deleterious to bone. Lipotoxicity and inflammation might be responsible for bone loss through inhibition of osteoblasts and activation of osteoclasts. However, little is known whether obesity affects the process of fracture healing. Therefore, we studied the effect of high fat diet-induced (HFD) obesity on callus formation and bone remodelling in a closed femur fracture model in mice. Thirty-one mice were fed a diet containing 60kJ% fat (HFD) for a total of 20 weeks before fracture and during the entire postoperative observation period. Control mice (n=31) received a standard diet containing 10kJ% fat. Healing was analyzed using micro-CT, biomechanical, histomorphometrical, immunohistochemical, serum and protein biochemical analysis at 2 and 4 weeks after fracture. HFD-fed mice showed a higher body weight and increased serum concentrations of leptin and interleukin-6 compared to controls. Within the callus tissue Western blot analyses revealed a higher expression of transcription factor peroxisome proliferator-activated receptor y (PPARy) and a reduced expression of runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein (BMP)-4. However, obesity did not affect the expression of BMP-2 and did not influence the receptor activator of nuclear factor κB (RANK)/RANK ligand/osteoprotegerin (OPG) pathway during fracture healing. Although the bones of HFD-fed animals showed an increased number of adipocytes within the bone marrow, HFD did not increase callus adiposity. In addition, radiological and histomorphometric analysis could also not detect significant differences in bone formation between HFD-fed animals and controls. Accordingly, HFD did not affect bending stiffness after 2 and 4 weeks of healing. These findings indicate that obesity does not affect femur fracture healing in mice.

The importance of surfactant proteins—New aspects on macrophage phagocytosis

Surfactant and its components have multiple functions. The so called collectins are surfactant proteins which opsonize bacteria and improve pulmonary host defense via the phagocytosis and clearance of microorganisms and particles. In this special issue of the Annals of Anatomy a new surfactant protein, Surfactant Associated 3, is highlighted. As outlined in this mini review Surfactant Associated 3 is regarded as an enhancer of phagocytosis. In addition, the role played by SP-A is updated and open research questions raised.

Fracture healing redefined

It is well established that local mechanical conditions and interfragmentary movement are important factors for successful bone healing and may vary dramatically with patient fracture-load and activity. Up until now however it was technically impossible to use these key influence parameters in the aftercare treatment process of human lower extremity fractures. We propose a theory that with state of the art sensor technology these biomechanical influences can not only be monitored in vivo, but also used for individualized therapy protocols. Local measurement systems for fracture healing are available but remain research tools, due to various technical issues. To investigate the biomechanical influences on healing right away surrogate sensor tools are needed. Various gait characteristics have been proposed as surrogate measures. Currently available sensor tools could be modified with the appropriate support structure to allow such measurements continuously over the course of a fracture healing. Interdisciplinary work between clinicians, software engineers with computer and biomechanical simulations is needed. Through such a sensor system human boundary conditions for fracture healing could not only be defined for the first time, but also used for a unique, extendible aftercare system. With this tool critical healing situations would be detected much earlier and could be prevented with easy activity modifications, reducing patient and socioeconomic burden of disease. The hypothesis, necessary tools and support structures are presented.

Talusfrakturen – ein Update

Background: Talus fractures are rare and often result from axial trauma. As most of the talus surface is covered by cartilage, the blood supply is limited. Thus talus fractures are seen as one of the most severe fractures and often lead to significant long-term complications. Several studies suggest that the initial fracture classification can lead to correct treatment and that this can influence the long-term outcome. The aim of the current study was to investigate the importance of the initial fracture classification in respect to the radiological outcome in a large patient cohort. Patients and Methods: Over a span of 12 years, 61 patients with talus fractures were treated at our institution. Overall 45 patients were available for a retrospective analysis. Correlation analysis was performed between the initial fracture severity and the radiological outcome. Results: The average follow-up was 17.3 months (range 6-68). Significant correlations were found between the Marti-Weber Classification and Bargon Score (rs = 0.78; p < 0.0001), as well as between the Hawkins Classification and the Bargon Score (rs = 0.80; p < 0.0001). Conclusions: Precise prediction of the expected radiological outcome of talar neck and body fractures is possible through the initial fracture classification alone. Computed tomography is the accepted standard to determine the exact diagnosis and extent of injury.

Polytrauma in the elderly: a review

Although the field of geriatric trauma is – ironically – young, care for the elderly trauma patient is increasingly recognised as an important challenge, considering the worldwide trend towards increasing longevity. Increasing age is associated with physiological changes and resulting comorbidities that present multiple challenges to the treating physician. Even though polytrauma is less likely with increasing age, lower-energy trauma can also result in life-threatening injuries due to the reduced physiological reserve. Mechanisms of injury and resulting injury patterns are markedly changed in the elderly population and new management strategies are needed. From initial triage to long-term rehabilitation, these patients require care that differs from the everyday standard. In the current review, the special requirements of this increasing patient population are reviewed and management options discussed. With the increase in orthogeriatrics as a speciality, the current status quo will almost certainly shift towards a more tailored treatment approach for the elderly patient. Further research expanding our current knowledge is needed to reduce the high morbidity and mortality rate. Cite this article: Braun BJ, Holstein J, Fritz T, Veith NT, Herath S, Mörsdorf P, Pohlemann T. Polytrauma in the elderly: a review. EFORT Open Rev 2016;1:146-151. DOI: 10.1302/2058-5241.1.160002.