Development of a local controlled release system for therapeutic proteins in the treatment of skeletal muscle injuries and diseases.

The present study aims to develop and characterize a controlled-release delivery system for protein therapeutics in skeletal muscle regeneration following an acute injury. The therapeutic protein, a membrane-GPI anchored protein called Cripto, was immobilized in an injectable hydrogel delivery vehicle for local administration and sustained release. The hydrogel was made of poly(ethylene glycol)-fibrinogen (PEG-Fibrinogen, PF), in the form of injectable microspheres. The PF microspheres exhibited a spherical morphology with an average diameter of approximately 100 micrometers, and the Cripto protein was uniformly entrapped within them. The release rate of Cripto from the PF microspheres was controlled by tuning the crosslinking density of the hydrogel, which was varied by changing the concentration of poly(ethylene glycol) diacrylate (PEG-DA) crosslinker. In vitro experiments confirmed a sustained-release profile of Cripto from the PF microspheres for up to 27 days. The released Cripto was biologically active and promoted the in vitro proliferation of mouse myoblasts. The therapeutic effect of PF-mediated delivery of Cripto in vivo was tested in a cardiotoxin (CTX)-induced muscle injury model in mice. The Cripto caused an increase in the in vivo expression of the myogenic markers Pax7, the differentiation makers eMHC and Desmin, higher numbers of centro-nucleated myofibers and greater areas of regenerated muscle tissue. Collectively, these results establish the PF microspheres as a potential delivery system for the localized, sustained release of therapeutic proteins toward the accelerated repair of damaged muscle tissue following acute injuries.

Surgical stabilisation in equivocal pelvic ring injuries - Into the grey zone.

Pelvic ring injuries comprise a spectrum of bony, ligamentous and muscular injuries, described by several common classification systems. However, the majority of injuries lie in areas of intermediate severity, where complexity and variable nature make it extremely hard to define in detail. This fact and associated injuries make it extremely difficult to conduct randomised control trials, with purpose to direct treatment guidelines. Thus, special interest and expertise are required by pelvic trauma surgeons, while surgical indications and fixation methods rely on their experience, at least in part. Namely, a significant grey zone of indication exists. As fixation methods evolve, specifically percutaneous fixation using osseous fixation pathways, some injuries in which morbidity bound with surgical fixation was considered too high relative to its benefits, may be considered eligible for surgical treatment nowadays. Moreover, due to significant progress in the treatment of the acute polytrauma casualties, the survival rate increased over the years, emphasizing the effect of long-term morbidity and functional outcome of pelvic ring injuries. The purpose of this manuscript is to describe the equivocal areas of controversies, hence "the grey zone", and to provide the readership with up-to-date published data. We aimed to collect and detail clinical and radiological clues in the diagnosis of intermediate unstable anterior-posterior compression and lateral compression injuries, and for the selection of treatment methods and sequence. Recent publications have provided some insights into specific injury features that are correlated with increased chance of instability, pain and delay in ambulation. Specific focus is given to the utility of examination under anaesthesia in selected cases. Other publications surveyed the shared experience of pelvic trauma surgeons as for the classification, indication and treatment sequence of pelvic ring injuries. Although the data hasn't matured yet to a comprehensive treatment algorithm, it may serve clinicians well when making treatment decisions in the grey zone of pelvic ring injuries, and serve as a basis for future prospective studies.

A combined cell and growth factor delivery for the repair of a critical size tibia defect using biodegradable hydrogel implants.

The ability to repair critical-sized long-bone injuries using growth factor and cell delivery was investigated using hydrogel biomaterials. Physiological doses of the recombinant human bone morphogenic protein-2 (rhBMP2) were delivered in a sustained manner from a biodegradable hydrogel containing peripheral human blood-derived endothelial progenitor cells (hEPCs). The biodegradable implants made from polyethylene glycol (PEG) and denatured fibrinogen (PEG-fibrinogen, PF) were loaded with 7.7 µg/ml of rhBMP2 and 2.5 × 106 cells/ml hEPCs. The safety and efficacy of the implant were tested in a rodent model of a critical-size long-bone defect. The hydrogel implants were formed ex-situ and placed into defects in the tibia of athymic nude rats and analyzed for bone repair after 13 weeks following surgery. The hydrogels containing a combination of 7.7 µg/ml of rhBMP2 and 2.5 × 106 cells/ml hEPCs were compared to control hydrogels containing 7.7 µg/ml of rhBMP2 only, 2.5 × 106 cells/ml hEPCs only, or bare hydrogels. Assessments of bone repair include histological analysis, bone formation at the site of implantation using quantitative microCT, and assessment of implant degradation. New bone formation was detected in all treated animals, with the highest amounts found in the treatments that included animals that combined the PF implant with rhBMP2. Moreover, statistically significant increases in the tissue mineral density (TMD), trabecular number and trabecular thickness were observed in defects treated with rhBMP2 compared to non-rhBMP2 defects. New bone formation was significantly higher in the hEPC-treated defects compared to bare hydrogel defects, but there were no significant differences in new bone formation, trabecular number, trabecular thickness or TMD at 13 weeks when comparing the rhBMP2 + hEPCs-treated defects to rhBMP2-treated defects. The study concludes that the bone regeneration using hydrogel implants containing hEPCs are overshadowed by enhanced osteogenesis associated with sustained delivery of rhBMP2.

Interobserver and intraobserver agreement for Letournel acetabular fracture classification system using 3-dimensional printed solid models.

BACKGROUND: Acetabular fractures pose diagnostic and surgical challenges. They are classified using the Judet-Letournel system, which is based solely on X-ray. However, computed tomography (CT) imaging is now more widely utilized in diagnosing these injuries. The emergence of 3-dimensional (3-D) printing technology in varying orthopedic fields has provided surgeons a solid model that improves their spatial understanding of complex fractures and ability to plan pre-operatively. AIM: To evaluate the reliability of the Judet-Letournel classification system of acetabular fractures, when using either CT imaging or 3-D printed models. METHODS: Seven patients with acetabular fractures underwent pelvic CT imaging, which was then used to create solid, 3-D printed models. Eighteen orthopaedic trauma surgeons responded to questionnaires regarding fracture classification and preferred surgical approach. The same questionnaire was completed using only CT imaging, and two weeks later, using only 3-D printed models. The inter- and intra-observer agreement rates were then analyzed. RESULTS: Inter-observer agreement rates based on CT imaging or 3-D printed models were moderate for fracture classification: κ = 0.44, κ = 0.55, respectively (P < 0.001) and fair for preferred surgical approach: κ = 0.34, κ = 0.29, respectively (P < 0.005). Intra-observer agreement rates for fracture classification and preferred surgical approach comparing CT imaging or 3-D printed models were moderate: κ = 0.48, κ = 0.41, respectively. No significant difference in intra-observer agreement was detected when comparing orthopedic pelvic specialists to general orthopedic traumatologists. CONCLUSION: The Judet-Letournel classification demonstrated only moderate rates of agreement. The use of 3-D printed models increased the inter-observer agreement rates with respect to fracture classification, but decreased it with respect to the preferred surgical approach. This study highlights the role of 3-D printed models in acetabular fractures by improving spatial understanding of these complex injuries, thus providing more reliable fracture diagnoses and alternative viewpoints for pre-operative planning.

Heparan sulfate chains contribute to the anticoagulant milieu in malignant pleural effusion.

BACKGROUND: While malignant pleural effusion (MPE) is a common and significant cause of morbidity in patients with cancer, current treatment options are limited. Human heparanase, involved in angiogenesis and metastasis, cleaves heparan sulfate (HS) side chains on the cell surface. AIMS: To explore the coagulation milieu in MPE and infectious pleural effusion (IPE) focusing on the involvement of heparanase. METHODS: Samples of 30 patients with MPE and 44 patients with IPE were evaluated in comparison to those of 33 patients with transudate pleural effusions, using heparanase ELISA, heparanase procoagulant activity assay, thrombin and factor Xa chromogenic assays and thromboelastography. A cell proliferation assay was performed. EMT-6 breast cancer cells were injected to the pleural cavity of mice. A peptide inhibiting heparanase activity was administered subcutaneously. RESULTS: Levels of heparanase, factor Xa and thrombin were significantly higher in exudate than transudate. Thromboelastography detected almost no thrombus formation in the whole blood, mainly on MPE addition. This effect was completely reversed by bacterial heparinase. Direct measurement revealed high levels of HS chains in pleural effusions. Higher proliferation was observed in tumour cell lines incubated with exudate than with transudate and it was reduced when bacterial heparinase was added. The tumour size in the pleural cavity of mice treated with the heparanase inhibitor were significantly smaller compared with control (p=0.005). CONCLUSIONS: HS chains released by heparanase form an anticoagulant milieu in MPE, preventing local thrombosis and enabling tumour cell proliferation. Inhibition of heparanase might provide a therapeutic option for patients with recurrent MPE.

Growth Factor Delivery for the Repair of a Critical Size Tibia Defect Using an Acellular, Biodegradable Polyethylene Glycol-Albumin Hydrogel Implant.

Growth factor delivery using acellular matrices presents a promising alternative to current treatment options for bone repair in critical-size injuries. However, supra-physiological doses of the factors can introduce safety concerns that must be alleviated, mainly by sustaining delivery of smaller doses using the matrix as a depot. We developed an acellular, biodegradable hydrogel implant composed of poly(ethylene glycol) (PEG) and denatured albumin to be used for sustained delivery of bone morphogenic protein-2 (BMP2). In this study, poly(ethylene glycol)-albumin (PEG-Alb) hydrogels were produced and loaded with 7.7 µg/mL of recombinant human BMP2 (rhBMP2) to be tested for safety and performance in a critical-size long-bone defect, using a rodent model. The hydrogels were formed ex situ in a 5 mm long cylindrical mold of 3 mm diameter, implanted into defects made in the tibia of Sprague-Dawley rats and compared to non-rhBMP2 control hydrogels at 13 weeks following surgery. The hydrogels were also compared to the more established PEG-fibrinogen (PEG-Fib) hydrogels we have tested previously. Comprehensive in vitro characterization as well as in vivo assessments that include: histological analyses, including safety parameters (i.e., local tolerance and toxicity), assessment of implant degradation, bone formation, as well as repair tissue density using quantitative microCT analysis were performed. The in vitro assessments demonstrated similarities between the mechanical and release properties of the PEG-Alb hydrogels to those of the PEG-Fib hydrogels. Safety analysis presented good local tolerance in the bone defects and no signs of toxicity. A significantly larger amount of bone was detected at 13 weeks in the rhBMP2-treated defects as compared to non-rhBMP2 defects. However, no significant differences were noted in bone formation at 13 weeks when comparing the PEG-Alb-treated defects to PEG-Fib-treated defects (with or without BMP2). The study concludes that hydrogel scaffolds made from PEG-Alb containing 7.7 µg/mL of rhBMP2 are effective in accelerating the bridging of boney defects in the tibia.

Depletion of B cells rejuvenates the peripheral B-cell compartment but is insufficient to restore immune competence in aging.

Aging is associated with increasing prevalence and severity of infections caused by a decline in bone marrow (BM) lymphopoiesis and reduced B-cell repertoire diversity. The current study proposes a strategy to enhance immune responsiveness in aged mice and humans, through rejuvenation of the B lineage upon B-cell depletion. We used hCD20Tg mice to deplete peripheral B cells in old and young mice, analyzing B-cell subsets, repertoire and cellular functions in vitro, and immune responsiveness in vivo. Additionally, elderly patients, previously treated with rituximab healthy elderly and young individuals, were vaccinated against hepatitis B (HBV) after undergoing a detailed analysis for B-cell compartments. B-cell depletion in old mice resulted in rejuvenated B-cell population that was derived from de novo synthesis in the bone marrow. The rejuvenated B cells exhibited a "young"-like repertoire and cellular responsiveness to immune stimuli in vitro. Yet, mice treated with B-cell depletion did not mount enhanced antibody responses to immunization in vivo, nor did they survive longer than control mice in "dirty" environment. Consistent with these results, peripheral B cells from elderly depleted patients showed a "young"-like repertoire, population dynamics, and cellular responsiveness to stimulus. Nevertheless, the response rate to HBV vaccination was similar between elderly depleted and nondepleted subjects, although antibody titers were higher in depleted patients. This study proposes a proof of principle to rejuvenate the peripheral B-cell compartment in aging, through B-cell depletion. Further studies are warranted in order to apply this approach for enhancing humoral immune responsiveness among the elderly population.

Heparanase level and procoagulant activity are reduced in severe sepsis.

BACKGROUND: During severe sepsis, levels and activity of all coagulation proteins are reduced. Heparanase is implicated in angiogenesis and tumor progression. We previously demonstrated that heparanase also affected the hemostatic system. It forms a complex and increases the activity of the blood coagulation initiator tissue factor. AIM: To evaluate heparanase levels and procoagulant activity as predictors of sepsis severity. MATERIALS AND METHODS: Twenty-one patients with non-trauma, non-surgical sepsis admitted to the intensive care unit and 35 controls were recruited. Plasma samples were drawn from the study participants on days 1 and 7 following admission. RESULTS: Heparanase levels and procoagulant activity on day 1 were significantly reduced in patients compared to controls (P < .0001, P < .0001, respectively). Day 1 heparanase procoagulant activity ≥350 ng/mL yielded a negative predictive value for severe sepsis of 89%. Additionally, heparanase procoagulant activity on day 7 correlated with the change in the APACHE score between days 1 and 7 (r = .66, P = .007). CONCLUSIONS: Heparanase procoagulant activity decreases during sepsis and returns to normal levels as soon as the patient recovers. Hence, it can be potentially used to predict the risk of severe sepsis. These findings need to be further explored in large-scale studies.

Hydrogel composition and laser micropatterning to regulate sciatic nerve regeneration.

Treatment of peripheral nerve injuries has evolved over the past several decades to include the use of sophisticated new materials endowed with trophic and topographical cues that are essential for in vivo nerve fibre regeneration. In this research, we explored the use of an advanced design strategy for peripheral nerve repair, using biological and semi-synthetic hydrogels that enable controlled environmental stimuli to regenerate neurons and glial cells in a rat sciatic nerve resection model. The provisional nerve growth conduits were composed of either natural fibrin or adducts of synthetic polyethylene glycol and fibrinogen or gelatin. A photo-patterning technique was further applied to these 3D hydrogel biomaterials, in the form of laser-ablated microchannels, to provide contact guidance for unidirectional growth following sciatic nerve injury. We tested the regeneration capacity of subcritical nerve gap injuries in rats treated with photo-patterned materials and compared these with injuries treated with unpatterned hydrogels, either stiff or compliant. Among the factors tested were shear modulus, biological composition, and micropatterning of the materials. The microchannel guidance patterns, combined with appropriately matched degradation and stiffness properties of the material, proved most essential for the uniform tissue propagation during the nerve regeneration process.

Alveolar Bone Fracture: Pathognomonic Sign for Clinical Diagnosis.

AIM: Dental injuries, especially luxation and avulsion, are common. Dental trauma can cause alveolar bone fracture that can lead to tooth loss and malocclusion. Single tooth alveolar bone fractures are difficult to identify unless it protrudes through the overlying mucosa and can be visualized. Pain, malocclusion, and tooth mobility provide signs of suspected alveolar bone fractures. Integrity of the proximate alveolar bone should be examined for fractures where avulsion, luxation, or other tooth trauma is detected. Any suggestion of alveolar fractures should be further investigated with an appropriate radiograph. SUMMARY: This case report shows a pathognomonic sign that detects and diagnosis single tooth alveolar bone fractures, i.e., a localized hematoma crossing the attached gingiva from the free gingival margin to the vestibular mucosa. This should serve as a warning for localized alveolar bone fracture. A visualized hematoma and gentle, careful palpation may help detect covered fractures when the overlying mucosa is not perforated.

Positive outcomes following gait therapy intervention for hip osteoarthritis: A longitudinal study.

Footwear-generated biomechanical manipulation of lower-limb joints was shown to beneficially impact gait and quality of life in knee osteoarthritis patients, but has not been tested in hip osteoarthritis patients. We examined a customized gait treatment program using a biomechanical device shown in previous investigations to be capable of manipulating hip biomechanics via foot center of pressure (COP) modulation. The objective of this study was to assess the treatment program for hip osteoarthritis patients, enrolled in a 1-year prospective investigation, by means of objective gait and spatiotemporal parameters, and subjective quality of life measures. Gait analysis and completion of questionnaires were performed at the start of the treatment (baseline), and after 3, 6, and 12 months. Outcome parameters were evaluated over time using linear mixed effects models, and association between improvement in quality of life measures and change in objective outcomes was tested using mixed effect linear regression models. Quality of life measures improved compared to baseline, accompanied by increased gait speed and cadence. Sagittal-plane hip joint kinetics, kinematics, and spatiotemporal parameters changed throughout the study compared to baseline, in a manner suggesting improvement of gait. The most substantial improvement occurred within 3 months after treatment initiation, after which improvement approximately plateaued, but was sustained at 12 months. Speed and cadence, as well as several sagittal-plane gait parameters, were significant predictors of improvement in quality of life. CLINICAL SIGNIFICANCE: Evidence suggests that a biomechanical gait therapy program improves subjective and objective outcomes measures and is a valid treatment option for hip osteoarthritis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2222-2232, 2017.

A novel self-care biomechanical treatment for obese patients with knee osteoarthritis.

AIM: To examine the effect of a novel biomechanical, home-based, gait training device on gait patterns of obese individuals with knee OA. METHODS: This was a retrospective analysis of 105 (32 males, 73 females) obese (body mass index > 30 kg/m2 ) subjects with knee OA who completed a 12-month program using a biomechanical gait training device and performing specified exercises. They underwent a computerized gait test to characterize spatiotemporal parameters, and completed the Western Ontario and McMaster Osteoarthritis Index (WOMAC) questionnaire and Short Form-36 (SF-36) Health Survey. They were then fitted with biomechanical gait training devices and began a home-based exercise program. Gait patterns and clinical symptoms were assessed after 3 and 12 months of therapy. RESULTS: Each gait parameter improved significantly at 3 months and more so at 12 months (P = 0.03 overall). Gait velocity increased by 11.8% and by 16.1%, respectively. Single limb support of the more symptomatic knee increased by 2.5% and by 3.6%, respectively. There was a significant reduction in pain, stiffness and functional limitation at 3 months (P < 0.001 for each) that further improved at 12 months. Pain decreased by 34.7% and by 45.7%, respectively. Functional limitation decreased by 35.0% and by 44.7%, respectively. Both the Physical and Mental Scales of the SF-36 increased significantly (P < 0.001) at 3 months and more so following 12 months. CONCLUSIONS: Obese subjects with knee OA who complied with a home-based exercise program using a biomechanical gait training device demonstrated a significant improvement in gait patterns and clinical symptoms after 3 months, followed by an additional improvement after 12 months.

Neuromuscular response of hip-spanning and low back muscles to medio-lateral foot center of pressure manipulation during gait.

BACKGROUND: Footwear-generated medio-lateral foot center of pressure manipulation has been shown to have potential positive effects on gait parameters of hip osteoarthritis patients, ultimately reducing maximum joint reaction forces. The objective of this study was to investigate effects of medio-lateral foot center of pressure manipulation on muscle activity of hip-spanning and back muscles during gait in bilateral hip osteoarthritis patients. METHODS: Foot center of pressure was shifted along the medio-lateral foot axis using a foot-worn biomechanical device allowing controlled center of pressure manipulation. Sixteen female bilateral hip osteoarthritis patients underwent electromyography analysis while walking in the device set to three parasagittal configurations: neutral (control), medial, and lateral. Seven hip-spanning muscles (Gluteus Medius, Gluteus Maximus, Tensor Fascia Latae, Rectus Femoris, Semitendinosis, Biceps Femoris, Adductor Magnus) and one back muscle (Erector Spinae) were analyzed. Magnitude and temporal parameters were calculated. RESULTS: The amplitude and temporal parameter varied significantly between foot center of pressure positions for 5 out of 8 muscles each for either the more or less symptomatic leg in at least one subphase of the gait cycle. CONCLUSION: Medio-lateral foot center of pressure manipulation significantly affects neuromuscular pattern of hip and back musculature during gait in female hip bilateral osteoarthritis patients.

Heparanase procoagulant activity as a predictor of wound necrosis following diabetic foot amputation.

BACKGROUND: Trans-metatarsal operation to diabetic foot necrosis is a common procedure although only half of the patients do not need a second amputation due to surgery wound ischemia. No current tools are available for early prediction of surgery success and the clinical decision for a second operation may take weeks. Heparanase protein is involved in inflammation, angiogenesis and coagulation activation. The aim of the study was to evaluate heparanase level and procoagulant activity as an early predictor for success or failure of diabetic foot trans-metatarsal surgery. METHODS: The study group included 40 patients with diabetic foot necrosis requiring trans-metatarsal surgical intervention. Eighteen patients designated as necrotic group, developed post-surgery necrosis at the surgery wound within the first month, requiring a second more proximal amputation. Skin biopsies from the proximal surgery edge were stained for heparanase, tissue factor (TF), TF pathway inhibitor (TFPI) and by hematoxylin and eosin. Plasma samples were drawn pre-surgery and at 1h, 1week and 1month post-surgery. Samples were tested for heparanase levels by ELISA and TF+heparanase activity, TF activity and heparanase procoagulant activity. RESULTS: Skin biopsy staining did not predict subsequent necrosis. In the non-necrotic group a significant rise in TF+heparanase activity, heparanase activity and heparanase levels were observed 1h and 1week post-surgery. The most significant increase was in heparanase procoagulant activity at the time point of 1h post-surgery (P<0.0001). Pre-surgery TF activity was significantly lower in the non-necrotic group compared to the necrotic group (P<0.05). CONCLUSIONS: Measuring heparanase procoagulant activity pre-surgery and 1h post-surgery could potentially serve as an early tool to predict the procedure success. The present results broaden our understanding regarding early involvement of heparanase in the wound healing process.

Reduction of hip joint reaction force via medio-lateral foot center of pressure manipulation in bilateral hip osteoarthritis patients.

Loading/excessive loading of the hip joint has been linked to onset and progression of hip osteoarthritis. Footwear-generated biomechanical manipulation in the frontal plane has been previously shown in a cohort of healthy subjects to cause a specific gait adaption when the foot center of pressure trajectory was shifted medially, which thereby significantly reduced hip joint reaction force. The objective of the present study was to validate these results in a cohort of female bilateral hip osteoarthritis patients. Sixteen patients underwent gait analysis while using a footworn biomechanical device, allowing controlled foot center of pressure manipulation, in three para-sagittal configurations: medial, lateral, and neutral. Hip osteoarthritis patients exhibited similar results to those observed in healthy subjects in that a medial center of pressure led to an increase in inter-maleolar distance while step width (i.e., distance between right and left foot center of pressure) remained constant. This adaptation, which we speculate subjects adopt to maintain base of support, was associated with significantly greater hip abduction, significantly decreased hip adduction moment, and significantly reduced joint reaction force compared to the neutral and lateral configurations. Recommendations for treatment of hip osteoarthritis emphasize reduction of loads on the pathological joint(s) during daily activities and especially in gait. Our results show that a medially deviated center of pressure causes a reduction in hip joint reaction force. The present study does not prove, but rather suggests, clinical significance, and further investigation is required to assess clinical implications. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1762-1771, 2016.

Recurrent episodes of micturition with expulsion of symphyseal plate screws following pelvic ring fixation: case report.

BACKGROUND: Based on a computer-assisted literature search, this case is the first description of repeated loosening of metallic internal fixation implants after pelvic ring stabilization, associated with intravesical metal migration and micturition with expulsion of two bone screws. CASE PRESENTATION: A 62-year old woman was seen after the urinary expulsion of a 6.5 mm diameter cancellous screw. About seven years earlier, she had been hit by a motorcyclist while crossing the street. On admission at the time of the initial injury, thoraco-abdominal computerized tomography with intravenous contrast material revealed a bladder injury and pelvic ring fractures. An anterior-posterior type injury to the pelvic ring was diagnosed with symphyseal pubis disruption, and widening of the left sacroiliac joint with an associated sacral fracture. Explorative laparotomy revealed two bladder lacerations of both the posterior and the anterior bladder wall, which were repaired primarily. Orthopedic surgeons reduced the pelvis and stabilized it with two plates and screws. Seven years after the original injury, the patient presented with recurrent abdominal pain after expelling a screw into the toilet while urinating. Planar radiographs showed only five of the original screws remaining in the two symphyseal plates, and all screws appeared to have loosened when compared to the original fixation radiograph. CONCLUSION: This clinical report emphasizes the importance of symphyseal plate positioning and the sequelae of imprecise positioning, especially postero-superiorly adjacent to the Retzius space. The presence of protruding metal prominences, even smooth ones like a plate corner or screw head, might endanger the bladder. When using superior plates, imprecise contouring may lead to plate edge protrusion which could damage the bladder even long after application.

Hyperbaric oxygen for stage I and II femoral head osteonecrosis.

Hyperbaric oxygen therapy is a suggested joint-preserving treatment for symptomatic early-stage osteonecrosis of the femoral head. Limited studies of this treatment have been published. The goal of this study was to evaluate the effectiveness of this treatment in a relatively large patient cohort. The authors reviewed the files of 68 patients with 78 symptomatic joints with Steinberg stage I and II osteonecrosis of the femoral head. All patients were treated with hyperbaric oxygen at the authors' medical health center. Pretreatment and immediate posttreatment magnetic resonance imaging (MRI) findings were compared. On follow-up, a telephone interview was conducted to determine the survival of the joint. Modified Harris Hip Score and Short Form 12 health survey (SF-12) questionnaires of the start of treatment and at follow-up were obtained and evaluated for statistically significant differences. Half of the joints were stage 1 and half were stage II. Seventy-four joints underwent both pre- and posttreatment MRI. Eighty-eight percent of joints showed improvement posttreatment. On follow-up at a mean of 11.1±5.1 years, 54 patients (58 joints) were located and answered the questionnaires. At the time of follow-up, 93% of the joints survived. Mean Harris Hip Score improved from 21 to 81 (P<.0001), the mean physical component of the SF-12 improved from 24 to 46 (P<.0001), and the mean mental component of the SF-12 improved from 54 to 59 (P<.0001). The authors concluded that hyperbaric oxygen treatment is effective in preserving the hip joint in stage I and II osteonecrosis of the femoral head.

Effect of seasonality, weather and holidays on the incidence of proximal hip fracture.

BACKGROUND: Proximal hip fractures in the elderly are common and place a heavy burden on health resources. Researching the timing of these fractures could contribute to diverting resources towards peaks in incidence and investing in prevention at certain times. OBJECTIVES: To examine the effect of seasonality, weather and Jewish holidays on hip fracture incidence in older adults. The study population comprised 2050 patients aged 65 years or more who sustained a proximal hip fracture. METHODS: The computerized files of the patients were reviewed for trends in incidence by season, precipitation, minimum and maximum temperatures, day of the week, and certain Jewish festivals. RESULTS: Hip fractures were more likely to occur in the winter than in the summer (P < 0.0001). Factors that significantly correlated with hip fracture were the maximum daily temperature (r = -0.746, P = 0.005) followed by the minimum daily temperature (r = -0.740, P = 0.006) and precipitation (r = 0.329, P = 0.02). There were fewer fractures on Saturdays (the Sabbath) as compared to other days of the week (P = 0.045). Researching the incidence on Jewish holidays, we found an elevated incidence on Passover (P < 0.0001) and a reduced incidence on the Day of Atonement (Yom Kippui) (P = 0.013). CONCLUSIONS: In older people there is an elevated incidence of proximal hip fractures during the winter and on the Jewish festivals. On weekends and on the Day of Atonement the incidence of proximal hip fractures was reduced.

Core decompression and alendronate treatment of the osteonecrotic rat femoral head: computer-assisted analysis.

Femoral head avascular necrosis is a process leading to femoral head deformity and osteoarthritic changes in the hip joint. Alendronate slows down bone resorption and remodelling in rats, while core decompression hastens the healing processes. We evaluated the influence of daily alendronate treatment on the rat femoral head shape after surgical osteonecrosis with core decompression, compared with controls. No differences were found in shape factor and femoral head height/length ratios. It was concluded that alendronate treatment slows down the process of replacing osteonecrotic bone by new bone and prevents early immature new bone collapse resulting from early revascularization because of core decompression.