Incidence of postoperative complications in patellar fractures related to different methods of osteosynthesis procedures - a retrospective cohort study.

BACKGROUND: Patellar fractures have a comparatively low incidence compared to all fracture frequencies of the musculoskeletal system. However, surgical management is crucial to prevent postoperative complications that affect the knee joint. The purpose of the present study was to evaluate the incidence of postoperative complications and onset of postoperative osteoarthritis related to the chosen technique of patellar fracture management. METHODS: In a retrospective cohort study consecutive managed, isolated patella fractures were reviewed for demographic data, trauma mechanism, patella fracture type, fixation technique and postoperative complications. The results were documented radiographically and clinically and analysed statistically. The reporting followed the STROBE guidelines. RESULTS: A total of 112 patients were eligible for data evaluation. Surgical management of comminuted patellar fractures with small fragment screws showed significant fewer postoperative complications compared to other fixation techniques (8%, p < 0.043). The incidence of posttraumatic infection was significantly higher following the hybrid fixation technique with cannulated screws and tension wire than following the other analysed techniques (p = 0.024). No postoperative wound infection was observed after screw fixation or locking plate fixation. Symptomatic hardware was most frequently seen after tension-band fixation. Onset of posttraumatic osteoarthritis was most often found after the hybrid fixation technique (55%). CONCLUSION: Surgical management of patellar fractures remains crucial but fracture fixation using plating systems or small fragment screws is least associated with postoperative complications. TRIAL REGISTRATION: Trial registration number (DRKS):00027894.

Decision-making, therapy, and outcome in lateral compression fractures of the pelvis - analysis of a single center treatment.

BACKGROUND: Pelvic lateral compression fractures are the most stable of the unstable fractures. Therefore, decision making regarding operative or non-operative therapy is still a matter of debate. METHODS: Factors, influencing decision making for therapy, were explored based on prospectively collected register data of a single Level-1 trauma center. The analysis included epidemiological records such as age and gender, and injury characterizing parameters such as degree of displacement and the Injury Severity Score (ISS). In-hospital mortality and complications served as short-term outcome variables. After matching for relevant confounders, long-term results were compared between operatively and non-operatively treated patients, evaluating the Merle d'Aubigne and the EQ. 5D-3 L scores. RESULTS: Over an 11-year period (2004-14), 134 patients suffered from lateral compression fractures out of 567 pelvic fractures (33%). After excluding patients with clear indications for operation (complex pelvic fractures and pubic symphysis ruptures) and pediatric fractures, 114 patients could be included in the analysis. Sixty-one patients were treated conservatively (54%), 53 with an operation (46%). The operated patients were younger (43.7 vs 58.3 years), had higher ISS (19.9 vs 15.5 points) and fracture displacements (2.3 vs 4.9 mm) (p < 0.001 for all). The length of hospital stay was shorter in the conservatively treated group (12.7 vs 17.3 days, p < 0.02). Although the types of complications were different, the incidence was not. The mortality was less in the operated group (1.9% vs. 6.6%), however, a logistic regression analysis showed that only the ISS was an independent risk factor, but not the type of therapy. Merle d'Aubigne and EQ. 5D-3 L scores were not different in the matched cohorts. CONCLUSION: Decision-making for operative therapy was favored in severely injured young patients with high displacement. However, short- and long-term outcomes showed no difference between operatively and non-operatively treated patients. TRIAL REGISTRATION: DRKS, no. 00000488 . Registered 14th July 2010 - Retrospectively registered.

Current status of anti-inflammatory therapy for posttraumatic osteoarthritis.

Although there is ample evidence that intra-articular injuries are associated with the up-regulation of pro-inflammatory cytokines, the success of anti-inflammatory, disease-modifying treatments to prevent posttraumatic osteoarthritis (PTOA) remain uncertain. To summarize the current status of anti-inflammatory therapy for PTOA, we conducted a systematic review. 9 clinical studies in humans were identified applying anti-inflammatory agents to prevent or treat PTOA. A total of 347 patients aged an average 41 ±â€ˆ14 years were included in this review. 5 studies had comparable designs with randomized allocation. Those studies of course had a statistically significant higher Coleman Methodology Score (65 ±â€ˆ6) than the case-control studies (39 ±â€ˆ13, p = 0.013). The most frequently reported main outcome parameter was pain assessed by different scales (n = 7), the most examined joint the knee (n = 7). The majority of the analyses (n = 6) focused on the intra-articular (IA) application of hyaluronic acid (HA) reporting mainly positive effects. One study stated positive results following IA administration of Interleukin 1 receptor antagonist in -patients presenting rupture of the anterior cruciate ligament. Platelet-rich plasma was also used to relieve symptoms following acute injury, but the study quality was too low to conclude any effects. Although the initial data, especially regarding IA HA injection, are encouraging, study designs differ substantially. Therefore, current data does not allow us to conclude that anti-inflammatory therapy following acute injuries has beneficial effects on short- or long-term outcomes.

Autologous chondrocyte implantation in children and adolescents.

PURPOSE: Autologous chondrocyte implantation (ACI) is a well-established treatment method for cartilage defects in knees. Age-related grouping was based on expression data of cartilage-specific markers. Specificities of ACI in the different populations were analysed. METHODS: Two hundred and sixty-seven patients undergoing ACI in the knee between 2006 and 2010 were included in this analysis. Cell characteristics and expression data of cartilage-specific surface markers as CD44, aggrecan and collagen type II were statistically analysed for age association. Epidemiological data of the defined groups were compared. Course of treatment was evaluated using MRI. RESULTS: A correlation analysis showed statistically significant associations between age and aggrecan or collagen type II expression in all patients <30 years. A cluster analysis could predict age-dependent expression of these markers separating groups with an average age of 18.1 ± 2.3 and 23.6 ± 4.2 years, respectively (p < 0.02). Discriminance analysis suggested the age border between adults and juveniles at about 20 years. There was no influence of age on cell characteristics or CD44 expression. In the 19 of 267 patients with an age ≤18 years, gender distribution was not different compared to adults, but patella was significantly more affected. Cartilage lesions were mainly caused by osteochondritis dissecans (OCD) and trauma. The Knee Osteoarthritis Scoring System in MRI reached 4.8 ± 2.3 points before, declining to 3.3 ± 2.3 points 6 and 12 months after the operation. CONCLUSIONS: Age-related expression of cartilage-specific markers allows definition of adolescents in cartilage regenerating surgery. Chondromalacia in these patients is mainly caused by OCD or trauma. LEVEL OF EVIDENCE: Case series, Level IV.

Fracture dislocation of the humerus with intrathoracic humeral head fragment - A case report and review of the literature.

We present a rare case of humeral fracture dislocation with intrathoracic humeral head fragment. A 74-year old female was transferred to a major trauma facility after falling on her arm while gardening. An intrathoracic humeral head fragment was diagnosed after initial imaging. In correspondence with the department of thoracic surgery, the decision was made to remove the intrathoracic fragment thoracoscopically and succeed with a reverse total shoulder arthroplasty.

Incisional negative pressure wound therapy to reduce surgical-site infections in major limb amputations: a meta-analysis.

Purpose: Incisional negative pressure wound therapy (iNPWT) has shown effectiveness in the treatment of high-risk surgical wounds. Especially patients with diabetes-induced peripheral arterial disease undergoing major limb amputation have a high intrinsic risk for post-surgical wound infections. While normal gauze wound dressings do not cause stimulation of microvasculature, iNPWT might improve wound healing and reduce wound complications. The purpose of this study was to systematically review the literature for rates of wound complications and readmissions, as well as post-surgical 30-day mortality. Methods: We conducted a systematic review searching the Cochrane, PubMed, and Ovid databases. Inclusion criteria were the modified Coleman methodology Score >60, non-traumatic major limb amputation, and adult patients. Traumatic amputations and animal studies were excluded. Relevant articles were reviewed independently by referring to the title and abstract. In a meta-analysis, we compared 3 studies and 457 patients. Results: A significantly overall lower rate of postoperative complications is associated with usage of iNPWT (odds ratio (OR) = 0.52; 95% CI: 0.30-0.89; P = 0.02). There was no significant improvement for 30-day mortality, when iNPWT was used (OR= 081; 95% CI: 0.46 - 1.45; P = 0.48). Nevertheless, we did not note a significant difference in the readmission rate or revision surgery between the two groups. Conclusion: Overall, the usage of iNPWT may reduce the risk of postoperative wound complications in major lower limb amputations but does not improve 30-day mortality rates significantly. However, to anticipate surgical-site infection, iNPWT has shown effectiveness and thus should be used whenever applicable.

Protective effects of C5a blockade in sepsis.

Sepsis in humans is a difficult condition to treat and is often associated with a high mortality rate. In this study, we induced sepsis in rats using cecal ligation and puncture (CLP). In rats depleted of the complement factor C3, CLP led to very short survival times (about 4 days). Of the rats that underwent CLP ('CLP rats') that were C3-intact and treated with preimmune IgG, most (92%) were dead by 7 days. Blood neutrophils from these rats contained on their surfaces the powerful complement activation product C5a. This group had high levels of bacteremia, and their blood neutrophils when stimulated in vitro had greatly reduced production of H2O2, which is known to be essential for the bactericidal function of neutrophils. In contrast, when companion CLP rats were treated with IgG antibody against C5a, survival rates were significantly improved, levels of bacteremia were considerably reduced, and the H2O2 response of blood neutrophils was preserved. Bacterial colony-forming units in spleen and liver were very high in CLP rats treated with preimmune IgG and very low in CLP rats treated with IgG antibody against C5a, similar to values obtained in rats that underwent 'sham' operations (without CLP). These data indicate that sepsis causes an excessive production of C5a, which compromises the bactericidal function of neutrophils. Thus, C5a may be a useful target for the treatment of sepsis.

Clinical outcome after surgical treatment of transitional fractures of the distal tibia in children.

PURPOSE OF THE STUDY: Fractures affecting a partially closed physis are described as transitional fractures. The distal tibia is one of the most common locations for transitional fractures second only to the distal radius. Aim of this retrospective study was to evaluate the clinical and radiological results after surgical treatment of transitional fractures of the distal tibia. PATIENTS AND METHODS: From May 2003 to March 2009 24 children (median age 14 years) received surgical treatment for transitional fractures of the distal tibia. 89% (21/24) of patients were followed up after 27.5 (range 6 to 72) months to assess functional out come (using the AO Foot and Ankle Score). RESULTS: Nine girls and 15 boys were included in the study with the girls being younger on average (12.4 ± 0.9 vs. 14.3 ± 1.1 years, p = 0.00013). Two-plane fractures were present in 4 cases, 15 and 5 children sustained tri-plane I and II fractures, respectively. Median preoperative fracture displacement was measured at 4 mm (range 3 to 11 mm). Traumatic supination of the ankle joint during sports activities was the predominant injury mechanism (18/24 cases) followed by bicycle or motorbike accidents (6/24). A satisfactory reduction (1 mm or less) was achieved in all but one patient. In this case revision surgery was necessary to restore anatomical reduction. No perioperative complications occurred in the remaining 23 cases. Metal implants were removed upon fracture consolidation after 8.2 ± 6.7 months. At the time of follow-up none of the children were impaired in activities of daily living and there were no restrictions in sporting activity. All patients sco- red good or excellent results on the AO Foot and Ankle Score. DISCUSSION: Surgical stabilization can be recommended as a safe and effective treatment strategy in displaced transitional fractures of the distal tibia and will lead to good or excellent mid term results.

Humerus shaft fractures - where are we today?

Humeral shaft fractures account for about 1-3% of all fractures. These fractures are regarded as the domain of non-surgical management. This is certainly still the contemporary view but there is an obvious trend towards surgical stabilization. Surgical treatment of humeral shaft fractures has nonetheless been greatly facilitated by the development of new implants. In particular, a new generation of nails that general permit immediate mobilization have become available for improved management of longitudinal and multi-segmental fractures. Retrograde and antegrade nails have advantages and disadvantages and selection procedure is often based on the distal or proximal location of the fracture. Plates also offer an alternative for certain indications and have advantages at the proximal and distal shaft in particular. If there is primary lesion of the radial nerve, exploration is not very advisable, but in the absence of remission exploration can be conducted after several months with the same degree of success. Since the published literature offers no comparative studies with a high level of evidence, our statement can only be regarded as an up-to-date recommendation in the hope that future prospective randomized studies will address this issue.

Surgical treatment of supracondylar humerus fractures in children.

PURPOSE OF THE STUDY: Surgical techniques for the treatment of supracondylar fractures in children are repeatedly the subject of discussion. The aim of the present study was to compare experience with the technique of crossed Kirschner wires at our own hospital with current literature. PATIENTS AND METHODS: In the period from 2000-2006 a total of 86 children aged 1.7 to 12.7 years were treated by means of crossed K-wire osteosynthesis. Follow up was conducted at an average of 32 months. Outcomes were evaluated based on von Laer's criteria. RESULTS: Reported complications were migration of the K-wires in 7% of cases and secondary dislocation and re-operation in 4% of cases. Lesion of the radial nerve was diagnosed postoperatively in two cases. Hospital stay was 1.5 days on average. Postoperative immobilization in an upper arm splint and implant removal after 6 weeks on average. 57% of the children received physiotherapy during the course of treatment. Slight varization was found in 11% of children and an unsatisfactory range of motion in 13%. Satisfactory outcomes were recorded for 83% of patients. CONCLUSION: K-wire osteosynthesis is associated with a low complication rate and continues to be a safe standard procedure for the stabilization of supracondylar humerus fractures. Key words: supracondylar humerus fracture, Kirschner wires, paediatric fractures.

Treatment, recurrence rates and follow-up of Tenosynovial Giant Cell Tumor (TGCT) of the foot and ankle-A systematic review and meta-analysis.

BACKGROUND: The tenosynovial giant cell tumor (TGCT) is a usually benign lesion which arises from the synovium. It affects joints, tendon sheaths and bursae. The clinical course is often unpredictable, and local recurrences frequently occur. The aim of this study was to describe different treatment options, surgical complications, and to develop a follow-up regime based on a systematic literature review and meta-analysis of foot and ankle lesions. METHODS AND RESULTS: 1284 studies published between 01/1966 and 06/2021 were identified. 25 met the inclusion criteria, with a total of 382 patients. Of these, 212 patients had a diffuse (dTGCT) and 170 a localized (lTGCT) TGCT. Patients with a dTGCT had a mean age of 36.6±8.2 years, and 55% were female. The overall complication rate was 24% in dTGCT, irrespective of the therapeutic procedure; the mean follow-up was 37.9±27.4 months with a recurrence rate of 21%, and recurrences occurred between 3 and 144 months, the vast majority (86%) within the first 5 years following intervention. Patients with a lTGCT had a mean age of 31.2±5.7 years, and 53% were female. Complications occurred in 12%. The mean follow-up was 51.1±24.6 months, the recurrence rate was 7%, and recurrence occurred between 1 and 244 months after intervention. CONCLUSION: Diffuse TGCTs of the foot and ankle region have a remarkable recurrence rate irrespective of therapeutic procedures, and most lesions reoccurred within 5, with more than half of these in the first 2 years. The lTGCTs are well treatable lesions, with a low recurrence and a moderate complication rate. Based on these findings, we propose a follow-up regime for the dTGCT including a clinical survey and MR imaging 3 months after surgical intervention (baseline), followed by twice-yearly intervals for the first 2 years, yearly intervals up to the fifth year, and further individual follow-up due to the fact that recurrences can even occur for years later. For the lTGCT a clinical survey and MRT is proposed after 3-6 months after intervention (baseline), followed by annual clinical examination for 3 years, and in case of symptoms MR-imaging. Larger prospective multi-center studies are necessary to confirm these results and recommendations.

Evaluation of the influence of platelet-rich plasma (PRP), platelet lysate (PL) and mechanical loading on chondrogenesis in vitro.

The aim of this work is to investigate the capability of PRP as an adjuvant therapy to autologous chondrocyte implantation (ACI) in combination with multi-axial load with respect to cartilage regeneration. Articular cartilage shows poor repair capacity and therapies for cartilage defects are still lacking. Well-established operative treatments include ACI, and growing evidence shows the beneficial effects of PRP. Platelets contain numerous growth factors, among them transforming growth factor beta (TGF-ß). Dynamic mechanical loading is known to be essential for tissue formation, improving extracellular matrix (ECM) production. For our ACI model monolayer expanded human chondrocytes were seeded into polyurethane scaffolds and embedded in fibrin (hChondro), in PRP-Gel (PRP), or in fibrin with platelet lysate (PL), which was added to the media once a week with a concentration of 50 vol%. The groups were either exposed to static conditions or multi-axial forces in a ball-joint bioreactor for 1 h per day over 2 weeks, mimicking ACI under physiological load. The culture medium was collected and analyzed for glycosaminoglycan (GAG), nitrite and transforming growth factor beta 1 (TGF-ß1) content. The cell-scaffold constructs were collected for DNA and GAG quantification; the expression of chondrogenic genes, TGF-ß and related receptors, as well as inflammatory genes, were analyzed using qPCR. Loading conditions showed superior chondrogenic differentiation (upregulation of COL2A1, ACAN, COMP and PRG4 expression) than static conditions. PRP and PL groups combined with mechanical loading showed upregulation of COL2A1, ACAN and COMP. The highest amount of total TGF-ß1 was quantified in the PL group. Latent TGF-ß1 was activated in all loaded groups, while the highest amount was found in the PL group. Load increased TGFBR1/TGFBR2 mRNA ratio, with further increases in response to supplements. In general, loading increased nitrite release into the media. However, over time, the media nitrite content was lower in the PL group compared to the control group. Based on these experiments, we conclude that chondrogenic differentiation is strongest when simulated ACI is performed in combination with dynamic mechanical loading and PRP-gel or PL supplementation. An inflammatory reaction was reduced by PRP and PL, which could be one of the major therapeutic effects. Loading presumably can enhance the action of TGF-ß1, which was predominantly activated in loaded PL groups. The combination of load and PRP represents an effective and promising synergy concerning chondrocyte-based cartilage repair.

Injury patterns in polytraumatized children and consequences for the emergency room management.

INTRODUCTION: The effective initial treatment in the emergency room of polytraumatized children requires a sound knowledge of com- mon injury patterns, incidence, mortality, and consequences. The needed initial radiological imaging remains controversial and should be adapted to the expected injury pattern. PATIENTS AND METHODS: In this retrospective study, the injury patterns of 56 polytraumatized paediatric patients (age ≤ 16 years) in the period from December 2001 to May 2009 were evaluated. All children were initially diagnosed with a whole body CT scan. The cause of accident, the localization including the detailed diagnose, the lethality and the severity of the injuries were analyzed. The AIS (Abbreviated Injury Scale) and ISS (Injury Severity Score) were used to classify the severity of injuries in different body regions. Moreover the number and the kind of operation as a consequence of the initial made diagnoses were investigated. RESULTS: The mean ISS was 30 ± 13 in 38 boys and 18 girls with a mean age of 10 years. The lethality was 13% and 4% in the first 24 hours. The most severe and most frequent injury was craniocerebral trauma in 89% with an AIS ≥ 3 in 80%. Surgical intervention of the head was done in 41%. Thorax injuries were found in 63% with 57% with an AIS ≥ 3 and in 11% a thoracic drainage was needed. Abdominal trauma was found in 34% (surgery 4%) with an AIS ≥ 3 in 32%. Fractures of the spine occurred in 14% (surgery 5%) with an AIS ≥ 3 in 4% and pelvic injuries were diagnosed in 16% (surgery 4%) with an AIS ≥ 3 in 14%. Injuries of the upper extremity were found in 23% (surgery 11%) with an AIS ? 3 in 5% and of the lower extremity in 32% (surge- ry 16%) with an AIS ≥ 3 in 13%. CONCLUSION: The authors recommend a whole body CT scan in children who are potentially polytraumatized because of the detected high percentage of head and thorax injuries in polytraumatized children and the needed head surgery. The quickest imaging with a high sensitivity is the whole body CT scan which provides the clinicians with relevant information to initiate life-saving therapy.

Immunohistochemical analysis of sensory corpuscles in human transplants of the anterior cruciate ligament.

BACKGROUND: Sensory nerve endings in ligaments play an important role for the proprioceptive function. Clinical trials show that the sense of body position does not fully recover in the knee joint after reconstructive surgery of the ruptured anterior cruciate ligament. The aim of this study is to identify sensory corpuscles in autogenous and allogenous transplants of the ligament and to compare their quantity between the used allografts and autografts. METHODS: Thirty-three patients were included in this study. Three patellar tendon allografts, 14 patellar tendon autografts and 12 semitendinosus autografts were harvested during revision surgery after traumatic rerupture of the graft. The control consisted of 4 healthy anterior cruciate ligaments after fresh rupture. After haematoxylin staining, immunohistochemical analysis was performed using antibodies against S100, p75 and PGP9.5. Microscopical examination was carried out, and the number of mechanoreceptors was counted. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: Two types of mechanoreceptors were identified in each graft: Ruffini corpuscles and free nerve endings. The number of Ruffini corpuscles per square centimeter was the highest in the control. Comparing the grafts, the highest number of receptors could be detected in the semitendinosus autograft. The amount of free nerve endings was higher in the semitendinosus and patellar tendon autografts than in the control; the allografts showed the lowest number of receptors. With increasing time after reconstruction, the number of both types of receptors showed a decrease in the semitendinosus graft, whereas it increased in the patellar tendon graft and allograft. The number of mechanoreceptors in the semitendinosus and patellar tendon graft decreased over time after graft-failure, whereas it increased slightly in the allograft. CONCLUSION: This study was the first to identify mechanoreceptors in human transplants of the anterior cruciate ligament. The partial increase in the number of receptors over time after reconstruction could indicate a reinnervation of the grafts.

Survival of human mesenchymal stromal cells from bone marrow and adipose tissue after xenogenic transplantation in immunocompetent mice.

INTRODUCTION: Mesenchymal stromal cells (MSC) represent an attractive cell population for tissue engineering purposes. As MSC are described as immunoprivileged, non-autologous applications seem possible. A basic requirement is the survival of MSC after transplantation in the host. The purpose of the current paper was to evaluate the survival of undifferentiated and osteogenically induced human MSC from different origins after transplantation in immunocompetent mice. METHODS: Human MSC were isolated from bone marrow (BMSC) and adipose tissue (ASC). After cultivation on mineralized collagen, MSC were transplanted subcutaneously into immunocompetent mice (n=12). Undifferentiated MSC (group A) were compared with osteogenic-induced MSC (group B). Human-specific in situ hybridization and anti-vimentin staining was used to follow MSC after transplantation. Quantitative evaluation of lymphocytes and macrophages was performed as a measure of immunologic rejection. Unloaded scaffolds served as controls (group C). Specimens were harvested at 4 and 8 weeks. RESULTS: Undifferentiated BMSC and ASC were detected in the majority of cases after xenogenic transplantation (group A, a total of 22 out of 24 cases), while osteogenic-induced MSC (group B) could be detected in only three of 24 cases. Quantification of lymphocytes and macrophages revealed significantly higher cell numbers in group B compared with group A (P<0.05). DISCUSSION: Our results suggest that undifferentiated MSC are candidates for non-autologous cell transplantation, while osteogenic-induced MSC seem to be eliminated by the host's immune system. This observation seems independent of the origin of MSC and applies to BMSC and ASC.

Evaluation of strategies for the treatment of type B and C pelvic fractures: results from the German Pelvic Injury Register.

Aims: The best method of treating unstable pelvic fractures that involve the obturator ring is still a matter for debate. This study compared three methods of treatment: nonoperative, isolated posterior fixation and combined anteroposterior stabilization. Patients and Methods: The study used data from the German Pelvic Trauma Registry and compared patients undergoing conservative management (n = 2394), surgical treatment (n = 1345) and transpubic surgery, including posterior stabilization (n = 730) with isolated posterior osteosynthesis (n = 405) in non-complex Type B and C fractures that only involved the obturator ring anteriorly. Calculated odds ratios were adjusted for potential confounders. Outcome criteria were intraoperative and general short-term complications, the incidence of nerve injuries, and mortality. Results: Operative stabilization reduced mortality by 36% (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.42 to 0.98) but the incidence of complications was twice as high (OR 2.04, 95% CI 1.57 to 2.64). Mortality and the incidence of neurological deficits at discharge were no different after isolated posterior or combined anteroposterior fixation. However, the odds of both surgical (98%, OR 1.98, 95%CI 1.22 to 3.22) and general complications (43%, OR 1.43, 95% CI 1.02 to 2.00) were higher in the group with the more extensive surgery. Conclusion: Operative stabilization is recommended for non-complex unstable pelvic fractures. The need for anterior fixation of obturator ring fractures should, however, be considered critically. Cite this article: Bone Joint J 2018;100-B:973-83.

Protective effects of an aptamer inhibitor of neutrophil elastase in lung inflammatory injury.

Neutrophils play an important part in the development of acute inflammatory injury. Human neutrophils contain high levels of the serine protease elastase, which is stored in azurophilic granules and is secreted in response to inflammatory stimuli. Elastase is capable of degrading many components of extracellular matrix [1-4] and has cytotoxic effects on endothelial cells [5-7] and airway epithelial cells. Three types of endogenous protease inhibitors control the activity of neutrophil elastase, including alpha-1 protease inhibitor (alpha-1PI), alpha-2 macroglobulin and secreted leukoproteinase inhibitor (SLPI) [8-10]. A disturbed balance between neutrophil elastase and these inhibitors has been found in various acute clinical conditions (such as adult respiratory syndrome and ischemia-reperfusion injury) and in chronic diseases. We investigated the effect of NX21909, a selected oligonucleotide (aptamer) inhibitor of elastase, in an animal model of acute lung inflammatory disease [11-14]. This inhibitor was previously selected from a hybrid library of randomized DNA and a small-molecule irreversible inhibitor of elastase (a valine diphenyl ester phosphonate, Fig. 1), by the blended SELEX process [15]. We show that NX21909 inhibits lung injury and neutrophil influx in a dose-dependent manner, the first demonstration of efficacy by an aptamer in an animal disease model.

Seizure-induced muscle force can caused lumbar spine fracture.

Patients suffering form epilepsy have an increased risk for fractures. Beside fractures caused by fall or accident muscles forces alone generated during tonic-clonic seizure can result in severe musculoskeletal injury. Contractions of strong paraspinal muscles can lead to compression fracture of the mid-thoracic spine. We report a patient who had suffered from a tonic-clonic seizure during early morning hours. After a cracking sound the patient woke up in a state of post-ictal disorientation, loss of urine and tongue bite. He was admitted to our facilities with the suspected vertebral fracture albeit he just reported of mild lower back pain. Native X-rays and computer-tomography scans showed instable burst fractures of L2 and L4. The fractures were stabilised with a dorsally instrumented internal fixator from L1 to L5 followed by hemi-laminectomy and ventral spondylodesis. Muscle force alone can result in severe skeletal trauma including vertebral fractures. This example emphasizes the importance of critical examination of patients after grand mal seizures. Seizures-induced injuries can appear clinically asymptomatic and can easily be overseen due to absence of trauma and post-ictal impairment of consciousness.

Mesenchymal stem cells maintain TGF-beta-mediated chondrogenic phenotype in alginate bead culture.

This article addresses the stability of chondrogenic phenotype and the transdifferentiation potential of bone marrow-derived mesenchymal stem cells (MSCs) at distinct stages of differentiation. Differentiated MSCs were expected to maintain cartilage-like gene expression pattern in the absence of any chondrogenic growth factor or in the presence of osteogenic signals. MSCs encapsulated in alginate beads were treated with transforming growth factor (TGF)-beta 3 for 3, 6, or 14 days and then cultured in absence of TGF-beta for the remainder of the 2-week culture period. Additionally, cells were cultured in osteogenic medium after TGF-beta-mediated chondroinduction. Gene expression of col2a1, aggrecan, COMP, alkaline phosphatase (AP), and correlating protein synthesis was analyzed. After short-term stimulation with TGF-beta, MSCs maintained a chondrogenic phenotype. Chondrogenic gene expression and protein synthesis directly correlated with the extent of stimulation time and the concentration of TGF-beta. Pretreatment with TGF-beta could prevent AP mRNA expression of encapsulated MSCs. TGF- beta stimulation within the first 3 days of culture seems to be crucial for the expression of a chondrogenic phenotype. Fully differentiated and encapsulated MSCs are not able to transdifferentiate into osteoblasts. These findings give rise to a better understanding of the behavior of cartilage grafts affected by local factors of osteochondral transplantation sites in vivo.

Differential expression pattern of extracellular matrix molecules during chondrogenesis of mesenchymal stem cells from bone marrow and adipose tissue.

Adipose-derived adult stem cells (ADASCs) or bone marrow-derived mesenchymal stem cells (BMSCs) are considered as alternative cell sources for cell-based cartilage repair due to their ability to produce cartilage-specific matrix. This article addresses the differential expression pattern of extracellular matrix (ECM) molecules in BMSCs or ADASCs following chondrogenic differentiation. Human BMSCs or ADASCs were encapsulated in alginate and cultured in TGF-beta1-containing medium for 2 or 3 weeks. Chondrospecific mRNA expression was analyzed and alternative splicing of alpha(1)-procollagen type II mRNA was monitored via reverse transcriptase-polymerase chain reaction (RT-PCR). Corresponding ECM synthesis was demonstrated using immunohistochemistry. After chondroinduction, expression of collagen type II, type X, COMP and aggrecan mRNA was 3-15-fold higher than in ADASCs. The type IIA splicing form of alpha(1)-procollagen type II was expressed in both populations, and the type IIB splicing form was exclusively detected in BMSCs. In response to TGF-beta, collagen type II and X were secreted more strongly by BMSCs than by ADASCs. BMSCs express a more mature phenotype than ADASCs after chondroinduction. TGF-beta1 induces alternative splicing of the alpha(1)-procollagen type II transcript in BMSCs, but not in ADASCs. These findings may direct the development of a cell-specific culture environment either to prevent hypertrophy in BMSCs or to promote chondrogenic maturation in ADASCs.