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Pain due to osteoarthritis (OA) is one of the most frequent causes of chronic pain. However, the mechanisms of OA pain are poorly understood. This review addresses the mechanisms which are thought to be involved in OA pain, derived from studies on pain mechanisms in humans and in experimental models of OA. Three areas will be considered, namely local processes in the joint associated with OA pain, neuronal mechanisms involved in OA pain, and general factors which influence OA pain. Except the cartilage all structures of the joints are innervated by nociceptors. Although the hallmark of OA is the degradation of the cartilage, OA joints show multiple structural alterations of cartilage, bone and synovial tissue. In particular synovitis and bone marrow lesions have been proposed to determine OA pain whereas the contribution of the other pathologies to pain generation has been studied less. Concerning the peripheral neuronal mechanisms of OA pain, peripheral nociceptive sensitization was shown, and neuropathic mechanisms may be involved at some stages. Structural changes of joint innervation such as local loss and/or sprouting of nerve fibers were shown. In addition, central sensitization, reduction of descending inhibition, descending excitation and cortical atrophies were observed in OA. The combination of different neuronal mechanisms may define the particular pain phenotype in an OA patient. Among mediators involved in OA pain, nerve growth factor (NGF) is in the focus because antibodies against NGF significantly reduce OA pain. Several studies show that neutralization of interleukin-1β and TNF may reduce OA pain. Many patients with OA exhibit comorbidities such as obesity, low grade systemic inflammation and diabetes mellitus. These comorbidities can significantly influence the course of OA, and pain research just began to study the significance of such factors in pain generation. In addition, psychologic and socioeconomic factors may aggravate OA pain, and in some cases genetic factors influencing OA pain were found. Considering the local factors in the joint, the neuronal processes and the comorbidities, a better definition of OA pain phenotypes may become possible. Studies are under way in order to improve OA and OA pain monitoring.

The steady progress in medical diagnosis and treatment of diseases largely hinges on the steady development and improvement of modern imaging modalities. Raman spectroscopy has attracted increasing attention for clinical applications as it is label-free, non-invasive, and delivers molecular fingerprinting information of a sample. In combination with fiber optic probes, it also allows easy access to different body parts of a patient. However, image acquisition with fiber optic probes is currently not possible. Here, we introduce a fiber optic probe-based Raman imaging system for the real-time molecular virtual reality data visualization of chemical boundaries on a computer screen and the physical world. The approach is developed around a computer vision-based positional tracking system in conjunction with photometric stereo and augmented and mixed chemical reality, enabling molecular imaging and direct visualization of molecular boundaries of three-dimensional surfaces. The proposed approach achieves a spatial resolution of 0.5 mm in the transverse plane and a topology resolution of 0.6 mm, with a spectral sampling frequency of 10 Hz, and can be used to image large tissue areas in a few minutes, making it highly suitable for clinical tissue-boundary demarcation. A variety of applications on biological samples, i.e., distribution of pharmaceutical compounds, brain-tumor phantom, and various types of sarcoma have been characterized, showing that the system enables rapid and intuitive assessment of molecular boundaries.A fiber optic probe-based Raman imaging system with real-time molecular virtual reality data visualization of chemical boundaries for clinical tissue-boundary demarcation.

Background The number of people living with soft-tissue and bone sarcomas is increasing due to improved individual therapy and changes in demographics. At present, there are no recommendations for psychological co-treatment, occupational and social reintegration following the treatment of soft tissue and bone sarcomas. Methods Seventy-four patients, 42 males and 32 females, aged between 18 and 80 years (54.58 ± 16.99 yr.) with soft-tissue (62) and bone sarcomas (12) were included to answer five standardized and one personal questionnaire regarding quality of life, function, reintegration and participation after surgical treatment. Results A number of tumour-specific and patient-specific factors were identified that affected the therapeutic outcome. Patients with sarcoma of the lower extremity described poorer mobility. Patients who underwent amputation reported a higher anxious preoccupation. Patients with a higher range of education were less fatalistic and avoiding. The size of tumours or additive radiation therapy did not affect the post-therapeutic quality of life, coping and function. There was a good correlation between anxiety and depression with occupational reintegration, function, quality of life and coping. Conclusion Patients with sarcomas of the lower limb have a higher demand for postoperative rehabilitation and need more help in the postoperative occupational reintegration. Furthermore patients that underwent limb-preserving operations reported better postoperative function and quality of life. Risk assessment using patient-specific factors and an intensive psychological co-treatment may have a large role in the co-treatment of patients from the beginning of their cancer therapy.

Purpose Both high tibial valgus osteotomy (HTO) and unicompartmental medial knee arthroplasty (UKA) are established methods for the treatment for moderate stages of OA. This is the first global meta-analysis to compare the long-term effects of both methods regarding survival, outcomes and complications of total arthroplasty. Methods Literature research was performed using established medical databases: MEDLINE (via PubMed), EMBASE (via OVID) and the Cochrane register. Criteria for inclusion were as follows: English or German papers, a clinical trial with a clear description of survival, an outcome evaluation using a well-described knee score and a follow-up >5 years. Statistical analysis was performed using the special meta-analysis software called “Comprehensive Meta Analysis” (version 2.0; Biostat, Englewood, NJ, USA). Results Final meta-analysis after the full-text review included 46 studies about valgus HTO and 43 studies about medial UKA. There were no significant differences between valgus HTO and medial UKA in terms of the number of total required replacements. After a 5- to 8-year follow-up, 91.0% of the valgus HTO patients and 91.5% of medial UKA patients did not need a total replacement. This value was 84.4% for valgus HTOs and 86.9% for medial UKAs after a 9- to 12-year follow-up. Mean survival time to TKA was 9.7 years after valgus HTO and 9.2 years after medial UKA. Clinical outcome was significantly better after medial UKA in a 5- to 12-year follow-up. After more than 12 years, results were comparable in both groups. No significant differences were seen in the complication rates. Conclusions This meta-analysis aimed to find the advantages and disadvantages of two established methods for the treatment for medial compartment knee osteoarthritis. Valgus HTO is more appropriate for younger patients who accept a slight decrease in their physical activity. Medial UKA is appropriate for older patients obtaining sufficient pain relief but with reduced physical activity. Level of evidence II.

Background Metastatic bone disease (MBD) and its complications have a significant impact on patients’ quality of life. Pathological fractures are a particular problem as they affect patient mobility and pose a high risk of non-union. The pelvis is frequently affected by MBD and its fixation is challenging. We present a case series of three pathological sacral fractures treated with a new minimally invasive bilateral fixed angle locking system. Case presentation Case 1 and 2 suffered a pathological transforaminal sacral fracture without adequate trauma in stage 4 carcinomas (gastric cancer and breast cancer). Both were initially treated with non-surgical treatment, which had only a limited effect and led to imminent immobility. Both were operated on with fluoroscopic navigation and underwent transsacral SACRONAIL ® stabilisation according to CT morphology (S1 + S2 and S1 respectively). Immediately after the operation, pain decreased and mobilisation improved. Case 3 had a pathological transalar sacral fracture during the 2nd cycle of chemotherapy due to non-Hodgkin’s lymphoma. He soon became immobile and could only move in a wheelchair. The operation was performed with CT navigation due to the very small corridors and an implant was inserted in S1 and S2. The patient reported immediate pain relief and his ability to walk improved over the following months. Despite continued chemotherapy, no wound complications occurred. Conclusions The cases show the advantages of the minimally invasive bilateral fixed angle locking system SACRONAIL ® in the treatment of patients with pathological sacral fractures. It allows immediate full weight bearing and the risk of secondary surgical complications is low. All cases showed an improvement in pain scores and mobility.

Background Spondylodiscitis is a chameleon among infectious diseases due to the lack of specific symptoms with which it is associated. It is nevertheless a serious infection, with 7% mortality of hospitalized patients, in large part because of delayed diagnosis. The aim of this study was to develop a diagnosis and course-of-disease index to optimize its treatment. Material and methods Through analysis of 296 patients between January 1998 and December 2013, we developed a scoring system for spondylodiscitis, which we term SponDT (Spondylodiscitis Diagnosis and Treatment) based on three traits: (1) the inflammatory marker C-reactive protein (CRP) (mg/dl), (2) pain according to a numeric rating scale (NRS) and (3) magnetic resonance imaging (MRI), to monitor its progression following treatment. Results The number of patients receiving treatment increased over the past 15 years of our study. We also found an increasing age of patients at the point of diagnosis across the study, with an average age of 67.7 years. In 34% of patients, spondylodiscitis developed spontaneously. Almost 70% of them did not receive treatment until the first diagnosis using SponDT. Following treatment against spondylodiscitis, pain intensity decreased from 6.0 to 3.1 NRS. The inflammatory markers also decreased (CRP from 119.2 to 46.7 mg/dl). Similarly, MRI revealed a regression in inflammation following treatment. By employing SponDT, patients were diagnosed and entered into treatment with a score of 5.6 (severe spondylodiscitis) and discharged with a score of 2.4 (light/healed spondylodiscitis). Conclusion SponDT can be used to support the diagnosis of spondylodiscitis, particularly in patients suffering from back pain and elevated levels of inflammation, and can be used during the course of treatment to optimize control of therapy. Level of evidence IIa—evidence from at least one well-designed controlled trial which is not randomized

Introduction The NUT midline carcinoma is a rare tumor mostly reported in the midline of upper aerodigestive tract and mediastinum. Children as well as adolescents are affected without a gender distribution. A standard treatment is not established. So far, there exists no reported case of a pregnant female suffering from NUT midline carcinoma with musculoskeletal manifestation. Case presentation A 34-year-old woman was referred to our outpatient clinic by the general practitioner during her 31st week of pregnancy suffering from shoulder pain and dyspnea. So far, dyspnea was interpreted as a typical pregnancy-related symptom. However, a chest X-ray showed a tumor mass in the right lung in close relation to the scapula. Further examinations found metastases in different areas of the body. No pregnancy-related complications were detected by obstetric examination. After an interdisciplinary perinatal case discussion, cesarean section was directly followed by an open biopsy of the right side scapula tumor lesion. A NUT midline carcinoma was diagnosed by immunohistochemistry. Due to disseminated tumor disease in multiple non-resectable locations, a palliative systemical chemotherapy was started by the oncological outpatient clinic. Conclusion This report presents the case of the very rare NUT midline carcinoma under pregnancy which made interdisciplinary case discussions indispensable for therapy planning.

Several studies have found changes in the organization of the primary somatosensory cortex (SI) after amputation. This SI reorganization was mainly investigated by stimulating neighboring areas to amputation. Unexpectedly, the somatosensory representation of the deafferented limb has rarely been directly tested. We stimulated the truncated peroneal nerve in 24 unilateral transtibial amputees and 15 healthy controls. The stimulation intensity was adjusted to make the elicited percept comparable between both stimulation sides. Neural sources of the somatosensory-evoked magnetic fields (SEFs) to peroneal stimulation were localized in the contralateral foot/leg areas of SI in 19 patients and 14 healthy controls. We demonstrated the activation of functionally preserved cortical representations of amputated lower limbs. None of the patients reported evoked phantom limb pain (PLP) during stimulation. Stimulation that evoked perceptions in the foot required stronger intensities on the amputated side than on the intact side. In addition to this, stronger stimulation intensities were required for amputees than for healthy controls. Exploratorily, PLP intensity was neither associated with stimulation intensity nor dipole strength nor with differences in Euclidean distances (between SEF sources of the healthy peroneus and mirrored SEF sources of the truncated peroneus). Our results provide hope that the truncated nerve may be used to establish both motor control and somatosensory feedback via the nerve trunk when a permanently functional connection between the nerve trunk and the prosthesis becomes available.

Background Autologous chondrocyte implantation (ACI) is a therapy for articular cartilage and osteochondral lesions that relies on notch- or trochlea-derived primary chondrocytes. An alternative cell source for ACI could be osteochondritis dissecans (OCD) fragment-derived chondrocytes. Assessing the potential of these cells, we investigated their characteristics ex vivo and after monolayer expansion, as monolayer expansion is an integral step of ACI. However, as monolayer expansion can induce de-differentiation, we asked whether monolayer-induced de-differentiation can be reverted through successive alginate bead culture. Methods Chondrocytes were isolated from the OCD fragments of 15 patient knees with ICRS grades 3–4 lesions for ex vivo analyses, primary alginate bead culture, monolayer expansion, and alginate bead culture following monolayer expansion for attempting re-differentiation. We determined yield, viability, and the mRNA expression of aggrecan and type I, II, and X collagen. Results OCD fragment-derived chondrocyte isolation yielded high numbers of viable cells with a low type I:II collagen expression ratio (< 1) and a relatively high aggrecan and type II and X collagen mRNA expression, indicating chondrogenic and hypertrophic characteristics. As expected, monolayer expansion induced de-differentiation. Alginate bead culture of monolayer-expanded cells significantly improved the expression profile of all genes investigated, being most successful in decreasing the hypertrophy marker type X collagen to 1.5% of its ex vivo value. However, the chondrogenic phenotype was not fully restored, as the collagen type I:II expression ratio decreased significantly but remained > 1. Conclusion OCD fragment derived human chondrocytes may hold not yet utilized clinical potential for cartilage repair.

Background Screw fixation of pelvic ring fractures is a common, but demanding procedure and navigation techniques were introduced to increase the precision of screw placement. The purpose of this case series was the evaluation of screw misplacement rate and functional outcome of percutaneous screw fixation of pelvic ring disruptions using a 2D navigation system. Methods Between August 2004 and December 2007, 44 of 442 patients with pelvic injuries were included for closed reduction and percutaneous screw fixation of disrupted pelvic ring lesions using an optoelectronic 2D-fluoroscopic based navigation system. Operating and fluoroscopy time were measured, as well as peri- and postoperative complications documented. Screw position was assessed by postoperative CT scans. Quality of live was evaluated by SF 36-questionnaire in 40 of 44 patients at mean follow up 15.5 ± 1.2 month. Results 56 iliosacral- and 29 ramus pubic-screws were inserted (mean operation time per screw 62 ± 4 minutes, mean fluoroscopy time per screw 123 ± 12 seconds). In post-operative CT-scans the screw position was assessed and graded as follows: I. secure positioning, completely in the cancellous bone (80%); II. secure positioning, but contacting cortical bone structures (14%); III. malplaced positioning, penetrating the cortical bone (6%). The malplacements predominantly occurred in bilateral overlapping screw fixation. No wound infection or iatrogenic neurovascular damage were observed. Four re-operations were performed, two of them due to implant-misplacement and two of them due to implant-failure. Conclusion 2D-fluoroscopic navigation is a safe tool providing high accuracy of percutaneous screw placement for pelvic ring fractures, but in cases of a bilateral iliosacral screw fixation an increased risk for screw misplacement was observed. If additional ramus pubic screw fixations are performed, the retrograde inserted screws have to pass the iliopubic eminence to prevent an axial screw loosening.