Importance of IL-6 trans-signaling and high autocrine IL-6 production in human osteoarthritic chondrocyte metabolism.

OBJECTIVE: Neutralization of Interleukin (IL)-6-signaling by antibodies is considered a promising tool for the treatment of osteoarthritis (OA). To gain further insight into this potential treatment, this study investigated the effects of IL-6-signaling and IL-6 neutralization on chondrocyte metabolism and the release of IL-6-signaling-related mediators by human chondrocytes. DESIGN: Chondrocytes were collected from 49 patients with advanced knee/hip OA or femoral neck fracture. Isolated chondrocytes were stimulated with different mediators to analyze the release of IL-6, soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130). The effect of IL-6 and IL-6/sIL-6R complex as well as neutralization of IL-6-signaling on the metabolism was analyzed. RESULTS: OA chondrocytes showed high basal IL-6 production and release, which was strongly negatively correlated with the production of cartilage-matrix-proteins. Chondrocytes produced and released sIL-6R and sgp130. The IL-6/sIL-6R complex significantly increased nitric oxide, prostaglandin E2 and matrix metalloproteinase 1 production, decreased Pro-Collagen Type II and mitochondrial ATP production, and increased glycolysis in OA chondrocytes. Neutralization of IL-6-signaling by antibodies did not significantly affect the metabolism of OA chondrocytes, but blocking of glycoprotein 130 (gp130)-signaling by SC144 significantly reduced the basal IL-6 release. CONCLUSION: Although IL-6 trans-signaling induced by IL-6/sIL-6R complex negatively affects OA chondrocytes, antibodies against IL-6 or IL-6R did not affect chondrocyte metabolism. Since inhibition of gp130-signaling reduced the enhanced basal release of IL-6, interfering with gp130-signaling may ameliorate OA progression because high cellular release of IL-6 correlates with reduced production of cartilage-matrix-proteins.

Biomechanical Comparison of Cannulated Screw Osteosynthesis With Tension-Band Wiring for Proximal Fractures of the Fifth Metatarsal (Jones Fracture).

Jones fractures, which lie at the junction of the diaphysis to the metaphysis of the fifth metatarsal, are a well-described clinical issue. There are various surgical approaches, including the commonly performed cannulated screw osteosyntheses, and the less frequently used tension-band approach. The aim is to compare the biomechanical stability of these osteosyntheses. We performed an osteotomy on 16 fresh frozen fifth metatarsal bones from body donors representing a Jones fracture. The fractures were treated pairwise with screw osteosynthesis or tension-band wiring. This was followed by cyclic axial bending until osteosynthesis failure. Stability under axial bending force was higher in the screw osteosynthesis (mean: 70.0 ± 66.5 N) compared to the tension-band wiring (mean: 35.7 ± 23.3 N) group although not reaching statistical significance (p = .116). The study shows no statistically significant difference in biomechanical stability under axial loading between screw osteosynthesis and tension band wiring. Based on the data obtained, no differences can be observed from a biomechanical point of view. The study supports the established method of treating Jones fractures primarily with screw osteosynthesis. In addition, the data suggest that tension band wiring may be a good alternative osteosynthesis, for example, after failed casting treatment or failure of primary osteosynthesis.

[Local spinal profile following operative treatment of thoracolumbar and lumbar fractures : Impact of reduction technique and bone quality]. / Lokales Wirbelsäulenprofil nach operativer Behandlung thorakolumbaler und lumbaler Frakturen : Einfluss von Repositionstechnik und Knochenqualität.

BACKGROUND: The goal of surgery for spinal injuries is fracture reduction, fixation and stable healing in a physiological position. Several open and minimally invasive surgical techniques are available. OBJECTIVE: The extent of open reduction and the fixation potential achieved by the AOSpine (AT) and Kluger (KT) techniques were compared. The influence of fracture morphology, age, sex, and bone quality on fracture reduction and secure fixation was investigated. MATERIAL AND METHODS: In this monocentric retrospective cohort study data of patients with traumatic thoracolumbar and lumbar fractures treated by AT or KT were analyzed. The bisegmental kyphotic angle (bGDW) of each injured spinal segment was determined. Normal bGDW values were extrapolated from the literature. The change of bGDW over time was analyzed under consideration of the bone quality in Hounsfield units (HU), injury severity according to the AOSpine classification, gender and age of patients. RESULTS: A total of 151 data sets were evaluated. The AT and KT methods achieved a similar extent of reduction (AT 10 ± 6°, KT 11 ± 8°; p = 0.786). In follow-up a mean reduction loss of -5 ± 4° was seen. The technique had no influence on this (p = 0.998). The fracture morphology just managed to achieve a significant influence (p = 0.043). Low HU correlated significantly but weakly with lower extent of reduction (r = 0.241, p < 0.003) and greater reduction loss (r = 0.272, p < 0.001). In the age group 50-65 years 21% of men and 43% of women had bone quality of < 110 HU. Age and HU were significantly correlated (r = -0.701, p < 0.001). CONCLUSION: The AT and KT are equivalent in terms of reduction and secure fixation properties. The high proportion of male and female patients with HU < 110 in the age group under 65 years and the influence on reduction and secure fixation emphasize the need for preoperative bone densitometry.

Iatrogenic Damage to Neurovascular and Soft Tissue Structures During Lateral Release of Hallux Valgus: A Comparative Anatomical Study of Minimally Invasive Versus Open Surgical Techniques.

Lateral release is often an integral step in surgical correction of hallux valgus and can be performed using open or minimally invasive techniques. We investigated whether these techniques cause iatrogenic damage to arteries, nerves, tendons, or joint capsules. In this cadaver study, lateral release was performed on 9 pairs of specimens by a specialized foot surgeon. The specimens were randomly assigned to each group. The operations were followed by anatomical preparation, data collection, photo documentation, and statistical analysis. Iatrogenic damage to arteries, nerves, tendons, or joint capsules was rare, regardless of the surgical technique used. However, with the minimally invasive technique, the tendon of the extensor hallucis longus muscle and the sensitive terminal branches of the fibular nerve were at risk due to their anatomical proximity to the access portal. The deep transverse metatarsal ligament was potentially at risk if the adductor hallucis muscle was completely detached from the lateral sesamoid. When the deep transverse metatarsal ligament was transected there was risk of damaging the underlying plantar neurovascular structures. Both surgical techniques are safe in terms of the risk of injury to neighboring neurovascular and soft tissue structures.

Inhibition of Inducible Nitric Oxide Synthase Prevents IL-1ß-Induced Mitochondrial Dysfunction in Human Chondrocytes.

Interleukin (IL)-1ß is an important pro-inflammatory cytokine in the progression of osteoarthritis (OA), which impairs mitochondrial function and induces the production of nitric oxide (NO) in chondrocytes. The aim was to investigate if blockade of NO production prevents IL-1ß-induced mitochondrial dysfunction in chondrocytes and whether cAMP and AMP-activated protein kinase (AMPK) affects NO production and mitochondrial function. Isolated human OA chondrocytes were stimulated with IL-1ß in combination with/without forskolin, L-NIL, AMPK activator or inhibitor. The release of NO, IL-6, PGE2, MMP3, and the expression of iNOS were measured by ELISA or Western blot. Parameters of mitochondrial respiration were measured using a seahorse analyzer. IL-1ß significantly induced NO release and mitochondrial dysfunction. Inhibition of iNOS by L-NIL prevented IL-1ß-induced NO release and mitochondrial dysfunction but not IL-1ß-induced release of IL-6, PGE2, and MMP3. Enhancement of cAMP by forskolin reduced IL-1ß-induced NO release and prevented IL-1ß-induced mitochondrial impairment. Activation of AMPK increased IL-1ß-induced NO production and the negative impact of IL-1ß on mitochondrial respiration, whereas inhibition of AMPK had the opposite effects. NO is critically involved in the IL-1ß-induced impairment of mitochondrial respiration in human OA chondrocytes. Increased intracellular cAMP or inhibition of AMPK prevented both IL-1ß-induced NO release and mitochondrial dysfunction.

Factors influencing quality of life, function, reintegration and participation after musculoskeletal tumour operations.

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.

NUT midline carcinoma in a young pregnant female: a case report.

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.

Irreducible Ankle Fracture Due to Incarceration of the Long Flexor Tendons Together With the Neurovascular Bundle in the Tibial Fibular Interosseous Space: A Case Report and Short Literature Review.

Ankle fracture dislocations with frustrating attempts at closed reduction are a rare traumatic entity. We present a case of an irreducible ankle fracture due to incarceration of all the flexor tendons including the neurovascular bundle in the tibial fibular interosseous space; to date, only one such case has been published in the literature. A computed tomography scan in both bone and soft tissue windows was necessary to clarify the structures that were inhibiting repositioning. The decisive step for surgical treatment was removal of the trapped structures from the tibial fibular interosseous space by a dorsomedial approach. The malleolar joint was then reconstructed anatomically. After 12 weeks, the patient was fully mobile without restrictions in his daily professional activities.

Acute atraumatic carpal tunnel syndrome due to flexor tendon rupture following palmar plate osteosynthesis in a patient taking rivaroxaban.

INTRODUCTION: Few case reports describe the development of a hematoma under oral anticoagulation as the cause of an atraumatic carpal tunnel syndrome. CASE REPORT: A 76 years old woman presented an acute atraumatic carpal tunnel syndrome of her left hand under oral anticoagulation with rivaroxaban due to atrial fibrillation. 12 years ago, palmar plate osteosynthesis of a distal radius fracture had been performed on the affected wrist. Open decompression of the carpal canal was performed due to persistent severe pain under intense pain therapy and progressive neurological symptoms. The cause of the pain was a hematoma due to a rupture of the flexor pollicis longus and the second flexor digitorum profundus tendon with concomitant synovitis at the plate's distal rim. After decompression, pain relieved and neurological deficits improved rapidly. DISCUSSION: Ruptures of the flexor tendons occur in palmar plate osteosynthesis in up to 1.5% in the long term postoperative course. Very distal plate positions, like in this case, increase that risk. Under anticoagulation, the rupture induced a hematoma increasing local pressure resulting in an acute carpal tunnel syndrome. Acute nerve compression syndromes should be treated surgically without delay. CONCLUSION: Therapy with anticoagulants may increase hematoma after tendon rupture, thus supporting the development of an atraumatic acute carpal tunnel syndrome and complicating the surgical therapy. Hardware removal after fracture healing should be advised in patients with Soong grade 2 plate positions especially those taking anticoagulants.

Referred cramping phantom hand pain elicited in the face and eliminated by peripheral nerve block.

Phantom limb pain is a restricting condition for a substantial number of amputees with quite different characteristics of pain. Here, we report on a forearm amputee with constant phantom pain in the hand, in whom we could regularly elicit the rare phenomenon of referred cramping phantom pain by touching the face. To clarify the underlying mechanisms, we followed the cramp during the course of an axillary blockade of the brachial plexus. During the blockade, both phantom pain and the referred cramp were abolished, while a referred sensation of "being touched at the phantom" persisted. Furthermore, to identify the cortical substrate, we elicited the cramp during functional magnetic imaging. Imaging revealed that referred cramping phantom limb pain was associated with brain activation of the hand representation in the primary sensorimotor cortex. The results support the hypothesis that referred cramping phantom limb pain in this case is associated with a substantial brain activation in the hand area of the deafferented sensorimotor cortex. However, this alone is not sufficient to elicit referred cramping phantom limb pain. Peripheral inputs, both, from the arm nerves affected by the amputation and from the skin in the face at which the referred cramp is evoked, are a precondition for referred cramping phantom limb pain to occur, at least in this case.

Dermatomal Organization of SI Leg Representation in Humans: Revising the Somatosensory Homunculus.

Penfield and Rasmussen's homunculus is the valid map of the neural body representation of nearly each textbook of biology, physiology, and neuroscience. The somatosensory homunculus places the foot representation on the mesial surface of the postcentral gyrus followed by the representations of the lower leg and the thigh in superio-lateral direction. However, this strong homuncular organization contradicts the "dermatomal" organization of spinal nerves. We used somatosensory-evoked magnetic fields and source analysis to study the leg's neural representation in the primary somatosensory cortex (SI). We show that the representation of the back of the thigh is located inferior to the foot's representation in SI whereas the front of the thigh is located laterally to the foot's representation. This observation indicates that the localization of the leg in SI rather follows the dermatomal organization of spinal nerves than the typical map of neighboring body parts as depicted in Penfield and Rasmussen's illustration of the somatosensory homunculus.

Hounsfield units as predictor for cage subsidence and loss of reduction: following posterior-anterior stabilization in thoracolumbar spine fractures.

STUDY DESIGN: A retrospective, longitudinal cohort study. OBJECTIVE: The purpose of this study was to examine whether Hounsfield units (HUs), as an alternative bone mineral density measurement to dual-energy X-ray absorptiometry and quantitative computed tomography, which lead to additional radiation exposure for patients, has an effect on the maintenance of reduction in bisegmental Cobb angle (CA) and cage subsidence in patients who receive bisegmental spine stabilization after traumatic thoracolumbar spine fractures. METHODS: A total of 81 patients with a mean follow-up of 12 months were analyzed. CAs and cage subsidence were measured intraoperatively and at follow-up. HU was measured, and patients were subsequently assigned based on HU to three HU subgroups (group 1: HU < 110 [poor bone quality (BQ)]; group 2: HU 180-110 [diminished BQ]; group 3: HU > 180 [good BQ]). RESULTS: Following anterior stabilization, loss of reduction and cage subsidence differed between patients with poor and diminished BQ but not significantly, and both groups showed significantly more loss of reduction and cage subsidence than patients with good BQ. CONCLUSION: BQ, estimated with HU, had significant effects on cage subsidence and loss of reduction. We recommend measuring HU before surgery and applying additional treatment strategies, such as polymethylmethacrylate augmentation of endplates or anterior plates, for patients with HU < 180. These slides can be retrieved under Electronic Supplementary Material.

Human osteochondritis dissecans fragment-derived chondrocyte characteristics ex vivo, after monolayer expansion-induced de-differentiation, and after re-differentiation in alginate bead culture.

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.

Tissue engineering-relevant characteristics of ex vivo and monolayer-expanded chondrocytes from the notch versus trochlea of human knee joints.

PURPOSE: The aim was to analyse the biological characteristics of chondrocytes from the two biopsy sites notch vs. trochlea of human knee joints. The question was whether tissue engineering-relevant characteristics such as viability and mRNA expression profile would be comparable ex vivo and after monolayer expansion, as these are parts of routine autologous chondrocyte implantation (ACI). METHODS: Biopsies from the intercondylar notch and the lateral aspect of the trochlea from 20 patients with ICRS grades 3 and 4 cartilage defects were harvested during arthroscopy. Collagen types 1, 2, and 10 mRNA were quantified by polymerase chain reaction. RESULTS: Compared with notch chondrocytes, ex vivo trochlea chondrocytes had comparable cell numbers, vitality and aggrecan, collagen types 1, -2 and -10 mRNA expression. After monolayer expansion both notch and trochlea chondrocyte characteristics were comparably altered, regardless of their biopsy origin, and no significant differences in viability and mRNA expression were noted. CONCLUSIONS: Collectively, these findings suggest that tissue engineering-relevant characteristics of notch and trochlea chondrocytes are comparable ex vivo and after monolayer expansion. Thus, trochlea chondrocytes promise clinical potential and chondrocytes for ACI could potentially be generated from both notch and trochlea biopsy sites.

Differences in type II collagen turnover of osteoarthritic human knee and ankle joints.

PURPOSE: We analysed hyaline cartilage of human knee and ankle joints for collagen and proteoglycan turnover in order to find differences in the metabolism and biochemical content of the extracellular matrix that could explain the higher prevalence of osteoarthritis (OA) in the knee joint, compared to the ankle joint. METHODS: Cartilage tissue from ankle and knee joints of OA patients were assessed for total collagen and proteoglycan content. For turnover, the aggrecan 846-epitope (CS 846), the type II collagen C-propeptide (CP2) and the collagenase-generated intrahelical cleavage neoepitope (C2C) were quantified. RESULTS: Molecular analyses showed that type II collagen turnover (CP2 and C2C) was significantly elevated in the ankle, whereas aggrecan turnover (CS 846), total proteoglycan and total collagen were comparable between both joints. Analysis of the inter-relationships in the components of cartilage matrix turnover showed a significant positive correlation of C2C vs CP2. CONCLUSIONS: The data suggest an increased type II collagen turnover in ankle vs knee OA cartilage but a comparable aggrecan turnover and comparable contents of type II collagen and proteoglycan. These findings point towards a focused attempt in advanced OA cartilage to structurally repair the collagen network that was more pronounced in the ankle joint and may explain in part the higher prevalence of OA in the knee as compared to the ankle joint.

Risk factors for cartilage damage and osteoarthritis of the elbow joint: case-control study and systematic literature review.

INTRODUCTION: This case-control study compares patients with healthy elbows to a group of symptomatic patients with cartilage damage/osteoarthritis. MATERIALS AND METHODS: The control group (n = 126) was recruited during routine medical examinations of patients (general medical offices). Included in the case group were a total of 92 patients who were undergoing arthroscopy as a result of chronic elbow discomfort. All patients were questioned with regard to occupational stress and athletic stress. RESULTS: A significantly increased risk of cartilage damage/osteoarthritis was found with subjectively perceived increased stress in occupational settings: OR = 3.8 (95% CI 2.1-6.7); p < 0.001; for the individual stresses of the elbow joint in occupational settings, the following severities in effects were found: Exposure to heavy work OR = 3.9 (95% CI 2.2-6.8); Force OR = 3.7 (95% CI 2.1-6.5); Vibration OR = 4.6 (95% CI 2.5-8.5); Repetition OR = 9.2 (95% CI 3.6-23.3); p < 0.001. Elbow-stressing sport types represent a potential risk factor for the development of cartilage damage/osteoarthritis of the elbow joint: OR = 2.5 (95% CI 1.3-4.7); p = 0.003. CONCLUSIONS: Cartilage damage/radiographic osteoarthritis of the elbow joint are rare with respect to the overall prevalence of osteoarthritis. In the large number of patients with cartilage damage/radiographic osteoarthritis of the elbow joint, occupational or athletic stress factors and injuries sustained, in addition to other causes (rheumatism, gout), can prove as possible causes of these as secondary to symptomatic forms of osteoarthritis.

The frequency of cartilage lesions in non-injured knees with symptomatic meniscus tears: results from an arthroscopic and NIR- (near-infrared) spectroscopic investigation.

INTRODUCTION: Are symptomatic tear injuries to the menisci of the knee frequently or always associated with cartilage damage to the corresponding articular surfaces and other joint surfaces, respectively? METHODS: A total of 137 patients (medial n = 127; lateral n = 10) underwent a meniscus resection. These patients showed no signs of a clear radiographic arthrosis and no MRI-detectable cartilage lesions > grade II. Traumatic injury was ruled out with a thorough medical history. The indication for operation was made exclusively on the basis of distinct, clinically apparent meniscus signs. In addition to the ICRS classification, all articular surfaces were examined spectroscopically (NIRS, near-infrared spectroscopy). RESULTS: In 76.6% (n = 105) of all knees examined, clear cartilage damage (ICRS-grade III/IV) was found. For 43.8%, these were in the area of the patella, while for 34.3% they were in the area of the medial femur, and for 17.5%, in the area of the medial tibial plateau. More rarely, this damage was localized to the area of the trochlea (8.8%) or the lateral joint compartment (femoral 2.2%, tibial 15.3%). There were no significant differences between patients with medial or lateral meniscus lesions with respect to the distribution pattern of the joint injuries. During spectroscopic examination, pathological values were demonstrated (objective evidence of cartilage degeneration) in at least one of the examined articular surfaces (media n = 6, range 1-6). CONCLUSION: Through our investigations, a high, if not complete, concomitance of degenerative cartilage lesions and degenerative meniscus damage was demonstrated. From this it can be concluded that the entity of "isolated degenerative meniscus damage" clearly does not exist in practice. It is therefore highly probable that degenerative meniscus lesions, as a part of general joint degeneration, are to be interpreted in the context of the development of arthrosis. The practical consequences still are unclear. Patients after partial meniscectomy need a longer follow-up to detect potential cartilage lesions as well as an OA progression.

Transsacral Osseous Corridor Anatomy Is More Amenable To Screw Insertion In Males: A Biomorphometric Analysis of 280 Pelves.

BACKGROUND: Percutaneous iliosacral screw placement is the standard procedure for fixation of posterior pelvic ring lesions, although a transsacral screw path is being used more frequently in recent years owing to increased fracture-fixation strength and better ability to fix central and bilateral sacral fractures. However, biomorphometric data for the osseous corridors are limited. Because placement of these screws in a safe and effective manner is crucial to using transsacral screws, we sought to address precise sacral anatomy in more detail to look for anatomic variation in the general population. QUESTIONS/PURPOSES: We asked: (1) What proportion of healthy pelvis specimens have no transsacral corridor at the level of the S1 vertebra owing to sacral dysmorphism? (2) If there is no safe diameter for screw placement in the transsacral S1 corridor, is an increased and thus safe diameter of the transsacral S2 corridor expected? (3) Are there sex-specific differences in sacral anatomy and are these correlated with known anthropometric parameters? METHODS: CT scans of pelves of 280 healthy patients acquired exclusively for medical indications such as polytrauma (20%), CT angiography (70%), and other reasons (10%), were segmented manually. Using an advanced CT-based image analysis system, the mean shape of all segmented pelves was generated and functioned as a template. On this template, the cylindric transsacral osseous corridor at the level of the S1 and S2 vertebrae was determined manually. Each pelvis then was registered to the template using a free-form registration algorithm to measure the maximum screw corridor diameters on each specimen semiautomatically. RESULTS: Thirty of 280 pelves (11%) had no transsacral S1 corridor owing to sacral dysmorphism. The average of maximum cylindrical diameters of the S1 corridor for the remaining 250 pelves was 12.8 mm (95% CI, 12.1-13.5 mm). A transverse corridor for S2 was found in 279 of 280 pelves, with an average of maximum cylindrical diameter of 11.6 mm (95% CI, 11.3-11.9 mm). Decreasing transsacral S1 corridor diameters are correlated with increasing transsacral S2 corridor diameters (R value for females, -0.260, p < 0.01; for males, -0.311, p < 0.001). Female specimens were more likely to have sacral dysmorphism (defined as a pelvis without a transsacral osseous corridor at the level of the S1 vertebra) than were male specimens (females, 16%; males, 7%; p < 0.003). Furthermore female pelves had smaller-corridor diameters than did male pelves (females versus males for S1: 11.7 mm [95% CI, 10.6-12.8 mm] versus 13.5 mm [95% CI, 12.6-14.4 mm], p < 0.01; and for S2: 10.6 mm [95% CI, 10.1-11.1 mm] versus 12.2 mm [95% CI, 11.8-12.6 mm ], p < 0.0001). CONCLUSIONS: Narrow corridors and highly individual, sex-dependent variance of morphologic features of the sacrum make transsacral implant placement technically demanding. Individual preoperative axial-slice CT scan analyses and orthogonal coronal and sagittal reformations are recommended to determine the prevalence of sufficient-sized osseous corridors on both levels for safe screw placements, especially in female patients, owing to their smaller corridor diameters and higher rate of sacral dysmorphism.

Neuronal prostaglandin E2 receptor subtype EP3 mediates antinociception during inflammation.

The pain mediator prostaglandin E2 (PGE2) sensitizes nociceptive pathways through EP2 and EP4 receptors, which are coupled to Gs proteins and increase cAMP. However, PGE2 also activates EP3 receptors, and the major signaling pathway of the EP3 receptor splice variants uses inhibition of cAMP synthesis via Gi proteins. This opposite effect raises the intriguing question of whether the Gi-protein-coupled EP3 receptor may counteract the EP2 and EP4 receptor-mediated pronociceptive effects of PGE2. We found extensive localization of the EP3 receptor in primary sensory neurons and the spinal cord. The selective activation of the EP3 receptor at these sites did not sensitize nociceptive neurons in healthy animals. In contrast, it produced profound analgesia and reduced responses of peripheral and spinal nociceptive neurons to noxious stimuli but only when the joint was inflamed. In isolated dorsal root ganglion neurons, EP3 receptor activation counteracted the sensitizing effect of PGE2, and stimulation of excitatory EP receptors promoted the expression of membrane-associated inhibitory EP3 receptor. We propose, therefore, that the EP3 receptor provides endogenous pain control and that selective activation of EP3 receptors may be a unique approach to reverse inflammatory pain. Importantly, we identified the EP3 receptor in the joint nerves of patients with painful osteoarthritis.