Reprint of: Thoracolumbar burst fractures associated with incomplete neurological deficit in patients under the age of 40: Is the posterior approach enough? Surgical treatment and results in a case series of 10 patients with a minimum follow-up of 2 years.

INTRODUCTION: Surgical management of thoracolumbar burst fractures is controversial. While the goals of surgical treatment are well accepted (i.e., fracture reduction and stabilization, neural elements decompression, and segmental angular deformity correction), the choice of the best surgical approach (i.e., posterior vs. anterior vs. combined approach) remains controversial. Several studies have debated the advantages of each surgical approach but there is no definitive evidence available to date, particularly in young adult patients. The aim of this study was to assess whether posterior approach alone can be a valid surgical treatment for patient under the age of 40 affected by thoracolumbar burst fractures and incomplete neurological deficits. MATERIAL AND METHODS: A total of 10 consecutive patients affected by thoracolumbar burst fractures associated with incomplete neurological deficits treated at our institution from January 2015 to February 2017 were included in our study. All patients were under the age of 40 at the time of injury and underwent decompression and stabilization using the posterior surgical approach alone. Demographics, clinical, and radiographic parameters were recorded preoperatively, postoperatively and at the latest available follow-up. The minimum follow-up was set at 2 years post-operatively. RESULTS: The mean operative time was 303.6 min (range, 138-486). Average blood loss was 756 mL (range, 440-2100). Nine out of ten patients returned to a normal neurological status after surgery while 1 patient showed some improvement but did not recover completely. Segmental kyphotic deformity improved from a mean of 21.8° before surgery to 14.8° at the time of the last follow-up. The anterior and posterior wall height of the fractured vertebra was restored with an average of 4 mm. The Visual Analogue Scale score reported an improvement from the mean preoperative value of 7.92 to 1.24 at the last follow-up; 8 out of 10 patients resumed physical activity while all of them returned to work. CONCLUSIONS: A single posterior surgical approach is an acceptable option in terms of clinical, radiological and functional outcomes at 2 years follow-up in patients under the age of 40 presenting with a thoracolumbar burst fracture and neurological deficit.

Thoracolumbar burst fractures associated with incomplete neurological deficit in patients under the age of 40: Is the posterior approach enough? Surgical treatment and results in a case series of 10 patients with a minimum follow-up of 2 years.

INTRODUCTION: Surgical management of thoracolumbar burst fractures is controversial. While the goals of surgical treatment are well accepted (i.e., fracture reduction and stabilization, neural elements decompression, and segmental angular deformity correction), the choice of the best surgical approach (i.e., posterior vs. anterior vs. combined approach) remains controversial. Several studies have debated the advantages of each surgical approach but there is no definitive evidence available to date, particularly in young adult patients. The aim of this study was to assess whether posterior approach alone can be a valid surgical treatment for patient under the age of 40 affected by thoracolumbar burst fractures and incomplete neurological deficits. MATERIAL AND METHODS: A total of 10 consecutive patients affected by thoracolumbar burst fractures associated with incomplete neurological deficits treated at our institution from January 2015 to February 2017 were included in our study. All patients were under the age of 40 at the time of injury and underwent decompression and stabilization using the posterior surgical approach alone. Demographics, clinical, and radiographic parameters were recorded preoperatively, postoperatively and at the latest available follow-up. The minimum follow-up was set at 2 years post-operatively. RESULTS: The mean operative time was 303.6 min (range, 138-486). Average blood loss was 756 mL (range, 440-2100). Nine out of ten patients returned to a normal neurological status after surgery while 1 patient showed some improvement but did not recover completely. Segmental kyphotic deformity improved from a mean of 21.8° before surgery to 14.8° at the time of the last follow-up. The anterior and posterior wall height of the fractured vertebra was restored with an average of 4 mm. The Visual Analogue Scale score reported an improvement from the mean preoperative value of 7.92 to 1.24 at the last follow-up; 8 out of 10 patients resumed physical activity while all of them returned to work. CONCLUSIONS: A single posterior surgical approach is an acceptable option in terms of clinical, radiological and functional outcomes at 2 years follow-up in patients under the age of 40 presenting with a thoracolumbar burst fracture and neurological deficit.

Minimally invasive surgery for the treatment of thoraco lumbar pyogenic spondylodiscitis: indications and outcomes.

OBJECTIVE: Pyogenic spondylodiscitis (PS) is a non-specific infection affecting intervertebral disks and adjacent vertebral bodies. Once considered a rare condition in developed countries, the incidence of PS has been increasing alarmingly and still represents a challenge for clinicians and orthopedic surgeons. New minimally invasive techniques have been proposed but the proper indications for these different approaches remain controversial. The aim of this study was to describe the available minimally invasive surgical techniques and to evaluate their proper indications through a review of recent literature. MATERIALS AND METHODS: Over 30 articles of recent scientific literature have been reviewed and analyzed. Studies were searched through the PubMed database using the key words: spondylodiscitis, minimally invasive, and surgical treatment. The most interesting and valid techniques and results have been reported. Despite the exclusion of case reports, all the available studies have been conducted on small groups of patients. Indications for each technique have been reported according to a clinical-radiological classification of PS. RESULTS: Six of the most widely used minimally invasive surgical techniques have been described.  High success rates have been reported in terms of preventing the progression of spondylodiscitis into more destructive forms, reduction of time and operative hospitalization, faster pain relief, early mobilization, and achievement of microbiological diagnosis. CONCLUSIONS: The role of minimally invasive surgery in the treatment of PS is rapidly expanding. Reducing surgery-related morbidity in these frail patients is possible and often necessary. However, while more and more new techniques are being proposed, still few clinical data are available. Clinical comparison studies with open traditional surgery should be encouraged, and more attention should be paid to long-term outcomes. For the present, the indications for minimally invasive procedures should, therefore, be evaluated on a case by case basis and on clinical and radiological findings.

Medical management of acute non-specific low back pain: comparison of different medical treatments, one center's retrospective analysis.

Within the developed countries, low back pain and related ailments represent one of the most relevant conditions, affecting both health and socio-economic systems. Non-specific acute low back pain (nsALBP) could represent either an isolated event or the presenting symptom of an underlying condition. Its management is usually medical and radiological investigations should be avoided. However, a general agreement on the best pharmacological treatment is still missing. In the present study, we retrospectively collected patients' data from the institutional database. Two different medical treatments were recognized and groups consequently set. Outcomes were the clinical status, measured using the visual analogue scale (VAS) score for back pain, the use rate of rescue drugs, side effects related to medical treatment, compliance to the treatment, and global satisfaction. The pharma blending of Tramadol 75 mg and Dexketoprofen 25 mg (available blended in a single tablet), resulted effective in the nsALBP management, with less side effects and rescue-drug use along with a higher compliance. Furthermore, patient satisfaction in this treatment group was significatively higher. Many different medical treatments have been investigated and reported in nsALBP management during the last decades. Associations of different drugs are the most common protocols, even though there is no general agreement. Tramadol and Dexketoprofen provide a good clinical result, fewer side effects and a long-lasting and more effective painkiller action, reducing the use of rescue drugs. Moreover, our results suggest that a single tab may provide a higher compliance rate.

The effect of parathyroid hormone (1-84) treatment on serum bone morphogenetic protein 4 and vascular endothelial growth factor in postmenopausal women with established osteoporosis.

PURPOSE: To investigate the effect of 18 months' parathyroid hormone 1-84 (PTH 1-84) treatment on serum levels of bone morphogenetic protein 4 (BMP4) and vascular endothelial growth factor (VEGF), in postmenopausal women with established osteoporosis. METHODS: Thirty-seven postmenopausal women with osteoporosis (mean age 72.9 ± 8.1 years old) and 23 healthy controls (mean age 68.9 ± 9.9 years old) were enrolled. Patients were treated with daily subcutaneous injections of PTH (1-84) 100 mcg for 18 months, plus calcium 1 gr and vitamin D 800 IU per os daily. Blood samples were taken every 6 months during the study. RESULTS: At baseline, there were no differences considering anthropometric parameters, co-morbidities, current medications used between patients and controls. Mean serum VEGF levels were significantly higher in osteoporotic patients compared to controls (436.7 ± 259.7 vs. 260.3 ± 184.3 pg/ml, p = 0.006), while there were no differences in mean serum values of BMP4 (5.3 ± 1.7 vs. 5.7 ± 1.6 pg/ml, p = 0.40). Serum VEGF levels increased by approximately 20% after 12 months of PTH (1-84) treatment compared to baseline (p = 0.03) and by 22% after 18 months (p = 0.01). A significant increase of 10% in mean serum BMP4 levels was observed after 18 months of PTH (1-84) treatment compared to baseline (p = 0.02). In the control group we found no differences after 18 months compared to baseline in BMP4 (5.7 ± 1.6 vs. 6.0 ± 1.5 pg/ml, p = 0.53) and VEGF (260.3 ± 184.3 vs. 257.4 ± 107.1 pg/ml, p = 0.94). CONCLUSIONS: PTH (1-84) treatment increased serum levels of VEGF and BMP4 in postmenopausal women with severe osteoporosis.

Pregnancy-associated osteoporosis (PAO) with multiple vertebral fragility fractures: diagnosis and treatment in a young primigravid woman.

PAO is an uncommon condition affecting pregnant women during last trimester or early post-delivery period; it is often asymptomatic or presents with pain related to some acute fragility fractures. The diagnosis is often delayed or missed, the etiology remains unknown and no guidelines about treatment have been published. We present one case of PAO in a 33-year-old primigravid woman presenting acute worsening back pain. Our patient was treated with a TLSO brace, oral 25 (OH)-vitamin D supplementation and Teriparatide for 6 months. A short review of the literature has been included and useful advice about how to suspect and diagnose this uncommon disease were given in order to recognize and treat such a debilitating and severe condition for young mothers as best as possible, based on the available scientific evidences.

Kyphoplasty vs conservative treatment: a case-control study in 110 post-menopausal women population. Is kyphoplasty better than conservative treatment?

OBJECTIVE: Osteoporosis is a highly prevalent disease worldwide. Consequences of vertebral osteoporotic fractures include pain and progressive vertebral collapse resulting in spinal kyphosis, decreased quality of life, disability and mortality. Minimally invasive procedures represent an advance to the treatment of osteoporotic VCFs. Despite encouraging results reported by many authors, surgical intervention in an osteoporotic spine is fraught with difficulties. Advanced patients age and comorbidities are of great concern. PATIENTS AND METHODS: We designed a retrospective case-control study on 110 post-menopausal women consecutively visited at our institution. Study population was split in a surgical and a conservative cohort, according to the provided treatment. RESULTS: Kyphoplasty treated patients had lower back pain VAS scores at 1 month as compared with conservatively treated patients (p < 0.05). EQ5D validated questionnaire also showed a better quality of life at 1 month for surgically treated patients (p < 0.05). SF-12 scores showed greater improvements at 1 month and 3 months with statistically significant difference between the two groups just at 3 months (p < 0.05). At 12 months, scores from all scales were not statistically different between the two cohorts, although surgically treated patients showed better trends than conservatively treated patients in pain and quality of life. Kyphoplasty was able to restore more than 54.55% of the original segmental kyphosis, whereas patients in conservative cohort lost 6.67% of the original segmental kyphosis on average. CONCLUSIONS: Kyphoplasty is a modern minimal invasive surgery, allowing faster recovery than bracing treatment. It can avoid the deformity in kyphosis due to VCF. In fact, the risk to develop a new vertebral fracture after the first one is very high.

Paracetamol-codeine compared to ketorolac for pain control in the Emergency Department.

OBJECTIVE: Paracetamol /codeine has shown a strong analgesic activity in several studies conducted among different kind of subjects, including those with trauma. Nevertheless, its efficacy in patients accessing the Emergency Department (ED) for different kind of pain has never been tested. PATIENTS AND METHODS: This is a cross-sectional, observational, prospective, cohort study. Inclusion criteria were patients > 18 year old presenting to the ED for localized traumatic or inflammatory pain involving only extremities. Numeric scale (NRS) was recorded thirty minutes and two hours after the administration of the analgesic therapy, consisting of 15 mg of ketorolac or 1000 mg/60 mg of paracetamol/ codeine, both orally. RESULTS: Two-hundred patients were consecutively enrolled; 87 were treated with paracetamol/codeine and 113 with ketorolac. The combination paracetamol/codeine resulted to be not inferior to ketorolac in non-traumatic pain group and trauma group (p = 0.635 and p = 0.482, respectively). Compared to ketorolac, the combination paracetamol/codeine exerted a significantly higher analgesic activity in patients with fractures and muscular pain (p = 0.044) and was more effective in acute pain (p = 0.002), with a significant effect two hours after the administration (p = 0.029). CONCLUSIONS: Paracetamol/codeine is equivalent to ketorolac in non-traumatic pain and post-traumatic pain, but is superior in acute pain and in patients with fractures and muscular pain. Those results play in favor of the use of the combination paracetamol/codeine in patients accessing the ED for non-traumatic or traumatic pain of the extremities.

Clinical predictors of vertebral osteoporotic fractures in post-menopausal women: a cross-sectional analysis.

BACKGROUND: Osteoporosis is a very common bone disorder and accounts for 1.4 million vertebral compression fractures (VCFs) per year, mostly in post-menopausal women. AIM: The aim of this study was to develop a risk scoring system to identify and gauge the risk of osteoporotic VCFs in post-menopausal women. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study on 477 post-menopausal women consecutively visited at our institution. We studied 15 different clinical variables, i.e. age, body mass index (BMI), weight, L1-L4 lumbar T-Score, L1-L4 lumbar Z-Score, L1-L4 lumbar bone mineral density (BMD), femoral neck T-Score, femoral neck Z-Score, femoral neck BMD, smoking habit, alcohol consumption, 25-OH-vitamin D, total alkaline phosphatase, bone alkaline phosphatase, and L4 vertebral volume. Study population was split in a derivation and a validation cohort. A logistic regression model was used to develop a predictive score of osteoporotic VCFs in the derivation cohort, finally the performance of the score was tested in the validation cohort. RESULTS: Age, L1-L4 lumbar T-Score, femoral neck T-Score, L4 vertebral volume, and smoking habit were found to be predictors of VCFs. To each variable a score from 0 to +12 was assigned to the magnitude of regression coefficient. A score ≥ 22 identified VCFs with a sensitivity of 87%/89% and a specificity of 87%/90% in the derivation and validation cohorts, respectively. CONCLUSIONS: Our findings indicate that a simple score derived from clinical history and routine diagnostic workout can be usefully employed to gauge the risk of fragility VCFs in post-menopausal women.

Epidemiological and clinical features of pyogenic spondylodiscitis.

Pyogenic spondylodiscitis (PS) is an uncommon but important infection, that represents 3-5% of all cases of osteomyelitis. The annual incidence in Europe has been estimated to be from 0.4 to 2.4/100,000. A has been reported, with peaks at age less than 20 years and in the group aged 50-70 years. The incidence of PS seems to be increasing in the last years as a result of the higher life expectancy of older patients with chronic debilitating diseases, the rise in the prevalence of immunosuppressed patients, intravenous drug abuse, and the increase in spinal instrumentation and surgery. PS is in most cases a hematogenous infection. Staphylococcus aureus is the most frequent causative microorganism, accounting for about one half of the cases of PS. Gram-negative rods are causative agents in 7-33% of PS cases. Coagulase-negative staphylococci (CoNS) have been reported in 5-16% of cases. Staphylococcus epidermidis is often related to post-operative infections and intracardiac device-related bacteremia. Unremitting back pain, characteristically worsening during the night, is the most common presenting symptom, followed by fever that is present in about one half of the cases. The mortality of PS ranges from 0 to 11%. In a significant number of cases, recrudescence, residual neurological defects or persistent pain may occur.

Post-operative spondylodiscitis.

Postoperative spine infections (PSIs) are a frequent and dreaded complication of spine surgery. Although different studies have been published, the prevalence of PSIs is thought to be about 5% for most spine surgical procedures. Different risk factors have been identified for PSIs. Among the others, extensive soft tissue dissection, longer operative time, soft tissue devitalization, and use of surgical instrumentation have been associated with higher risks of infection. Direct inoculation during surgery is the common infection route for PSIs. Gram-positive cocci (such as Staphylococcus aureus, Staphylococcus epidermidis and beta-hemolytic streptococci) are the most common pathogens. Gram-negative bacteria also play a role in PSIs and may be associated with systemic illness and multisystem organ failure. A high level of suspicion is of paramount importance in early diagnosis of PSIs. Clinical symptoms of PSIs may be subtle and the infection may become apparent only in its late stages. Early diagnosis is the most important prognostic factor for PSIs. Although blood tests (i.e. ESR, CRP, and white blood cell count) and imaging studies (most commonly MRI) can be useful, it must be clear to the clinician that diagnostic modalities, either tissue biopsy or blood cultures, are of the utmost importance for diagnosing PSIs and devising a correct antibiotic therapy. Antibiotic therapy with early bracing (or bed rest) is the most commonly used treatment method for PSIs. Nevertheless, a more aggressive surgical treatment may be required in some patients. The goals of surgical treatment are to help the eradication of the infection, provide an adequate wound closure, and maintain spine column mechanical stability.

Medical and surgical treatment of pyogenic spondylodiscitis.

BACKGROUND: Pyogenic vertebral osteomyelitis (PVO) represents approximately 2-7% of all cases of osteomyelitis. The approach to the treatment of PVO may be conservative, which includes antibiotic therapy and orthopaedic treatment, or surgical. AIM: To overview conservative and surigical approaches to PVO. METHODS: A literature review was performed using the Pubmed database to identify studies published in the last 20 years, addressing the treatment of PVO. RESULTS: Empirical antibiotic treatment of PVO, while waiting for the results of cultures or in culture-negative cases, should include broad spectrum agents in association with agents active on Staphylococcus (S.) aureus. Based on local epidemiological data, antibiotics active on methicillin resistant S. aureus (MRSA) should be included. Once an organism has been identified, antibiotics should be initially administered intravenously but the optimal duration of antimicrobial therapy is unclear. Studies have reported that the incidence of treatment failure was higher when i.v. therapy was administered for less than 4 weeks. Rifampin is widely used in the combination therapy of PVO, but no controlled trials are available to define weather this approach is beneficial. Many PVO need a surgical treatment and can represent a real challenge for the orthopaedic surgeon. Anterior and posterior cervical, thoracic, lumbar approaches and the relatives surgical strategies are reported in this review. Moreover, recently the mininvasive posterior stabilization have been proposed as a efficient alternative to open surgery in elderly with severe comorbidities. Possible advantages and limitations of this technique are also reported. CONCLUSIONS: Further research is needed in order to define the optimal duration of antibiotic therapy, and the benefits and limitations of open or mini-invasive surgical techniques.

Surgical treatment of tuberculous spondylodiscitis.

BACKGROUND: Most patients affected by spinal tuberculosis can be successfully treated conservatively with chemotherapy, external bracing and prolonged rest. Nevertheless, kyphotic deformity, spinal instability and neurological deficit remain a common complication associated with conservative approach. AIM: To illustrate different indications and treatment modalities for tuberculous spondylodiscitis, focusing on the role of surgery as an adjuvant of effective chemotherapy in the management of selected patients. MATERIALS AND METHODS: Various early and late surgical procedures are recommended to treat spinal tuberculosis. The Authors analyzed surgical indications, approaches, complications and outcomes comparing their experience with available Literature. RESULTS: Conservative management is preferable in patients without vertebral instability and deformity; in presence of abscesses, invasive radiological techniques in combination with abscess drainage and chemotherapy are recommended. In patients with vertebral collapse, kyphotic deformity or abscess formation, vertebral instability or neurological deficits, anterior radical debridement, anterior strut grafting and anterior instrumentation is an optimal standardized procedure. In patients with involvement of more than two vertebral levels or lumbosacral junction and in those whose sagittal alignment is markedly deformed with segmental kyphosis, and in patients who have difficulty in undergoing anterior instrumentation, posterior instrumentation is recommended in combination with anterior radical debridement and anterior strut grafting in one or two staged procedures. CONCLUSIONS: Since surgery for spinal tuberculosis is demanding, it should be performed only after taking into account the risks and benefits in operable patients. Various surgical procedures are recommended to treat spinal tuberculosis but the common goals are to eradicate the infection and to prevent or to treat neurologic deficits or spinal deformity.

Bioplasty for vertebral fractures: preliminary results of a pre-clinical study on goats using autologous modified skin fibroblasts.

The debate is still ongoing about the long term effects of the mininvasive vertebral augmentation techniques and their usefulness in treating more complex cases where a bone inducing effect more than a merely bone substitution would be suitable, such as the vertebral fractures in young patients. We previously developed a clinically relevant gene therapy approach using modified dermal fibroblasts for inducing bone healing and bone formation in different animal models. The aim of this study is to show the feasibility of a minimally invasive percutaneous intrasomatic ex vivo gene therapy approach to treat thoracolumbar vertebral fractures and anterior column bone defects in a goat model.

A minimally invasive posterior lumbar interbody fusion for degenerative lumbar spine instabilities.

Percutaneous techniques may be helpful to reduce approach-related morbidity of conventional open surgery. The aim of the study was to evaluate the feasibility and safety of mini-open posterior lumbar interbody fusion for instabilities and degenerative disc diseases. From May 2005 until October 2008, 20 patients affected by monosegmental instability and disc herniation underwent mini-open lumbar interbody fusion combined with percutaneous pedicle screw fixation of the lumbar spine. Clinical outcome was assessed using the Visual Analog Scale, Oswestry Disability Index, and Short Form Health Survey-36. The mean follow-up was 24 months. The mean estimated blood loss was 126 ml; the mean length of stay was 5.3 days; the mean operative time was 171 min. At 24-month follow-up, the mean VAS score was 2.1, mean ODI was 27.1%, and mean SF-36 was 85.2%. 80 screws were implanted in 20 patients. 74 screws showed very good position, 5 screws acceptable, and 1 screw unacceptable. A solid fusion was achieved in 17 patients (85%). In our opinion, mini-open TLIF is a valid and safe treatment of lumbar instability and degenerative disc diseases in order to obtain faster return to daily activities.

A meta-analysis of interleukin-6 promoter polymorphisms on risk of hip and knee osteoarthritis.

OBJECTIVE: Interleukin-6 is a pro-inflammatory cytokine involved in the pathogenesis of osteoarthritis (OA). We investigated the role of two single nucleotide polymorphisms (SNPs) mapping to the promoter of the IL-6 gene on genetic susceptibility to hip and knee OA. METHODS: The -174G/C (rs1800795) and -597G/A (rs1800797) SNPs, implicated in the literature in risk of hip and hand OA, were genotyped in 2511 controls, 1101 hip OA cases and 1904 knee OA cases from four cohorts from the UK and Estonia. Data were analysed in conjuntion with published data on rs1800797 from the Genetics of OA and Lifestyle study (UK) on 791 controls, 1034 knee and 997 hip OA cases and rs1800795 data on 75 hip OA cases and 96 controls from Italy. Cases included both radiographic OA only and radiographic and symptomatic OA. Fixed and random-effects meta-analysis models were tested. RESULTS: No significant association was found with hip OA or knee OA with either SNP nor with the haplotypes formed by them. For individual SNPs the smallest P-value for hip OA was observed using a random-effects model for rs1800795 OR(Gallele)=1.066 (95% CI 0.89-1.28) P<0.49, and significant heterogeneity between cohorts (I(2)=65%, P<0.034) was detected. For knee OA the smallest P-value was seen for rs1800797 OR(Aallele)=1.055 (95%CI 0.98-1.12) P<0.18, no significant heterogeneity was observed (I(2)=0%, P<0.68). CONCLUSIONS: Our data do not support a role for the -174 and -597 IL-6 promoter polymorphisms in genetic susceptibility to knee or hip OA in Caucasian populations.

Cervical spondylotic myelopathy: proposal of a surveillance algorithm.

The review of the publications concerning cervical spondylotic myelopathy (CSM) suggests that it has not been achieved a clear consensus about the treatment of this pathology. In this paper an algorithm of surveillance, conceived as an assistant tool to decide the best indications of treatment is presented. The algorithm permits a clear separation of the symptomatic patients on the base of the presence or the absence of neurologic damage resulting at the evoked potentials examination. The negativity of the evoked potentials, that means neurologic integrity, excludes any type of surgical treatment. In case of proved neurologic damage, the algorithm permits a further differentiation in subgroups according to the degree of clinical disability. If evoked potentials are positive, a surgical decompression should be always performed in patients affected by a severe clinical disability. The group of patients affected by a mild degree of clinical disability but with positive evoked potentials represents the most challenging for the spinal surgeons. Actually, several studies support either surgical and non surgical treatment for these patients. Although the Authors think that a surgical decompression has to be always performed in case of proved neurologic damage, only further randomized studies based on accurate algorithms could elucidate the outcome of the CSM and could permit to choose the best treatment according to the degree of the disease.

Ex vivo-transduced autologous skin fibroblasts expressing human Lim mineralization protein-3 efficiently form new bone in animal models.

Local gene transfer of the human Lim mineralization protein (LMP), a novel intracellular positive regulator of the osteoblast differentiation program, can induce efficient bone formation in rodents. To develop a clinically relevant gene therapy approach to facilitate bone healing, we have used primary dermal fibroblasts transduced ex vivo with Ad.LMP-3 and seeded on a hydroxyapatite/collagen matrix prior to autologous implantation. Here, we demonstrate that genetically modified autologous dermal fibroblasts expressing Ad.LMP-3 are able to induce ectopic bone formation following implantation of the matrix into mouse triceps and paravertebral muscles. Moreover, implantation of the Ad.LMP-3-modified dermal fibroblasts into a rat mandibular bone critical size defect model results in efficient healing, as determined by X-rays, histology and three-dimensional microcomputed tomography (3DmuCT). These results demonstrate the effectiveness of the non-secreted intracellular osteogenic factor LMP-3 in inducing bone formation in vivo. Moreover, the utilization of autologous dermal fibroblasts implanted on a biomaterial represents a promising approach for possible future clinical applications aimed at inducing new bone formation.

Local infusion of norepinephrine reduces blood losses and need of transfusion in total knee arthroplasty.

Blood loss after total knee arthroplasty (TKA) is often associated with cardiovascular complications and a high transfusion rate of allogenic blood. In our study we focused our attention on developing a new intra-surgical procedure that appears safe, easy to perform and effective in the reduction of bleeding in TKA. We evaluated 84 patients who underwent TKA and met our inclusion criteria; they were assigned to two groups: 55 controls in which a saline solution was used to wash the surgical field before tourniquet release, and a second group of 29 patients, in which a saline solution containing a low dose of norepinephrine was locally applied before tourniquet release. The local administration of a low dose of norepinephrine has induced a significant reduction of perioperative blood loss and blood transfusion requirements; in addition, this method was characterised by the absence of complications or adverse effects. In conclusion, our data suggest that intraoperative local administration of a low dose of norepinephrine could represent an effective and safe method of reducing blood loss and preventing blood transfusions in patients with TKA.