Mid-Term Radiological and Functional Outcomes of Bicondylar Tibial Plateau Fractures Managed with Open Reduction and Internal Fixation Using Dual Plates.

Objectives: This study aimed to evaluate the mid-term radiological and functional outcome of tibial plateau fractures treated by plating. Methods: This study was conducted at the General Hospital of Thessaloniki 'Papageorgiou', Thessaloniki, Greece. Patients with Schatzker type V and VI tibial plateau fractures who were managed with open reduction and internal fixation using dual plates between January 2011 and December 2018 were included in this retrospective study. The functional evaluation of the patients was carried out with the visual analogue scale (VAS), the health-related quality of life status was measured using the Short Form-36 and the dimensions of pain, stiffness and function were assessed using the Western Ontario and McMaster Universities Arthritis Index. For the radiological outcome evaluation, the modified Rasmussen criteria were used. Results: Fifty-seven patients (30 male and 27 female) were included in the study with a mean follow-up of 50.88 months. There were 23 Schatzker type V and 34 type VI fractures. The majority of patients (86%) had a good to excellent radiological outcome. The mean VAS score was 1.65 for all the patients. The functional outcome was excellent in the majority of the patients. Among them, 5.3% (n = 3) suffered wound infection and all wounds healed after different treatments. All patients returned to their pre-injury activities of daily living and employment status, while 53% of the patients returned to sporting activities. Conclusion: The findings support previous literature which has demonstrated that bicondylar tibial plateau fractures can provide good-to-excellent radiological and functional outcomes if they are treated with open reduction and internal fixation with dual plating.

The inhibitory effect of tocilizumab on systemic bone loss and tendon inflammation in a juvenile Collagen-Induced arthritis rat model.

PURPOSE OF THE STUDY: Reduced Bone Mineral Density (BMD) is a prevalent comorbidity in Juvenile Idiopathic Arthritis (JIA). Enthesitis and other tendon abnormalities, such as tenosynovitis, tendinitis and tendon ruptures are, also, common extra-articular manifestations of the disease. The aim of the present study was to investigate the effect of tocilizumab, an antibody that binds the Interleukin-6 (IL-6) Receptor, on inflammation-related bone loss and tendon inflammation in an animal model of JIA. MATERIALS AND METHODS: The Collagen-Induced Arthritis (CIA) model was induced in male rats followed by intraperitoneal administration of tocilizumab for 8 weeks. Methotrexate, the most widely used Disease-Modifying Antirheumatic Drug in the management of JIA, was, also, administered, either as a monotherapy or as an add-on therapy to tocilizumab. BMD was evaluated with Micro-Computed Tomography (Micro-CT) and histopathological examination. Tendon damage was, also, assessed histologically. Finally, two pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNF-a) and Interleukin-23 (IL-23) were quantified in tendon tissues by ELISA analysis. RESULTS: Tocilizumab-treated animals exhibited a significantly improved trabecular microarchitecture on micro-CT analysis and histological examination. Tendon morphology was also improved. Anti-IL-6 treatment led to a significant decrease in TNF-a and IL-23 expression in tendon tissue. CONCLUSIONS: The results of the present study provide evidence that tocilizumab reduces inflammation-related bone loss and suppresses tendon inflammation in a juvenile CIA rat model. These findings offer perspectives for the management of osteoporosis and enthesitis in JIA.

Infliximab and Tocilizumab Reduce Anxiety-Like Behaviour and Improve Cognitive Performance in a Juvenile Collagen-Induced Arthritis Rat Model.

Anxiety disorders and cognitive decline are highly prevalent in rheumatic diseases, including Juvenile Idiopathic Arthritis (JIA). In this study, we investigated the effect of long-term treatment with infliximab and tocilizumab on anxiety-like behaviour and cognitive performance in a juvenile collagen-induced arthritis (CIA) rat model. Forty-nine rats with established moderate arthritis were randomly allocated into 7 equal groups: negative control, vehicle, methotrexate, infliximab, tocilizumab, methotrexate + infliximab and methotrexate + tocilizumab groups. Behavioural tests were performed to evaluate anxiety-like behaviour and cognitive function. Neuropathological changes were investigated by histological examination at the level of the hippocampus, the amygdala and the prefrontal cortex. Also, the expression of Brain-Derived Neurotrophic Factor (BDNF), a biomarker associated with neuronal survival and plasticity, was determined in the hippocampus and the amygdala by RT-qPCR. We found that both infliximab and tocilizumab reduced anxiety-like behaviour in the elevated-plus and elevated-zero maze tests. Tocilizumab, also, improved cognitive function in the olfactory social memory and passive avoidance tests. Anti-cytokine treatment reversed the histopathological changes in the brain induced by CIA. BDNF expression was higher in all treatment groups and especially those receiving monoclonal antibodies combined with methotrexate. Our data provide evidence that chronic infliximab and tocilizumab treatment reduces anxiety-like behaviour, improves cognitive function, reverses neuropathological changes and increases central BDNF expression in a juvenile arthritis rat model. These findings may be translated to humans to address behavioural comorbidities associated with JIA.

Efficacy and safety of anti-sclerostin antibodies in the treatment of osteoporosis: A meta-analysis and systematic review.

Osteoporosis is a chronic disease with an increasing prevalence. Anti-sclerostin antibodies are being investigated for the treatment of osteoporosis. The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of antis-sclerostin antibodies compared to placebo and conventional therapies (alendronate and teriparatide) in the treatment of osteoporosis. Randomized controlled trials were searched from PubMed, EMBASE and Cochrane Central Register of Controlled Trails (CENTRAL) from their inception up to June 2021 by using Medical Subject Headings terms "anti-sclerostin antibody", "romosozumab", "blosozumab", "AMG 785″, "LY2541546", and "osteoporosis". Two investigators independently screened eligible studies, assessed the risk of bias and extracted the data from each study. The I2 index was used to assess heterogeneity. Meta-analysis was conducted using the Review Manager Software (RevMan, Version 5.4). The GRADE approach was used to rate the quality of evidence for all the pooled outcomes. 8 RCTs with 12,416 patients met the inclusion criteria. Anti-sclerostin antibodies significantly increased lumbar spine, total hip and femoral neck bone mineral density compared to placebo, alendronate and teriparatide at both 6 and 12 mo. Adverse events were comparable between anti-sclerostin antibodies and other treatments, except for the incidence of injection-site reactions that was higher in the anti-sclerostin antibody groups. Anti-sclerostin antibodies represent a valid theurapeutic option in the treatment of osteoporosis. Further studies with longer duration and follow-up are needed to confirm the results of this meta-analysis.

Effects of long-term infliximab and tocilizumab treatment on anxiety-like behavior and cognitive function in naive rats.

BACKGROUND: Circulating cytokines have been proposed to be implicated in the development of mood disorders and cognitive impairment. This study aims to examine the effect of chronic treatment with infliximab, a tumor necrosis factor-alpha (TNF-alpha) inhibitor, and tocilizumab, an antibody against interleukin-6 (IL-6) receptor on anxiety-like behavior and cognitive function. METHODS: Twenty-eight male, Wistar rats were randomly allocated into negative control, vehicle, infliximab and tocilizumab groups. After 8 weeks of intraperitoneal drug administration, rats performed the elevated-plus maze, the elevated-zero maze, the olfactory social memory and the passive avoidance tests. Brain sections at the level of the hippocampus, the amygdala and the prefrontal cortex were histologically examined. Finally, hippocampal and amygdaloid brain-derived neurotrophic factor (BDNF) expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Infliximab group exhibited a significantly higher number of entries and time spent into the open arms of the mazes, showing a lower level of anxiety. In the olfactory social memory test, tocilizumab significantly increased the ratio of interaction. Both infliximab- and tocilizumab-treated animals had a significantly lower latency time in the passive avoidance test that suggests an improved memory. Histological examination revealed similar morphology and neuronal density between groups. BDNF expression levels were significantly increased in the groups receiving anti-cytokine treatment. CONCLUSIONS: Our findings suggest that long-term peripheral TNF-alpha and IL-6 inhibition improves anxiety and cognitive function in rats and leads to an increased BDNF expression in the brain.

Adenoviral Infections in Bone Marrow Transplanted Adult Patients: A Review of the 44 Cases Reported in the Last 25 Years.

Adenoviral infections in immunocompromised individuals may be life-threatening conditions. The aim of this review is to document all the reported cases of adenoviral infection is patients having undergone bone marrow transplantation (BMT). A comprehensive literature search of the databases Pubmed, Science Direct, and Google Scholar was conducted to identify all the case reports of adenoviral infections in BMT patients. A total of 30 articles with 44 patients were included. The most common underlying condition was acute lymphocytic leukemia (23%) followed by acute myeloid leukemia (18%). The most common site of infection was disseminated (50%), followed by liver infection (8%) and hemorrhagic cystitis (8%). Cidofovir was administered in 40.9% of the cases, and death was reported in 34.4% of them. Ribavirin was administered as monotherapy in 15.9% of patients, with a mortality rate of 57.1%. We found that the antiviral drug option had no statistically significant effect on the mortality rate (p=0.242). Also, the absence of graft-versus-host disease (GVHD) was not associated with an improved outcome (p=0.523). There was, however, a statistically significant difference in the outcome based on the site of infection (p=0.005), with a higher rate of mortality in the disseminated and gastrointestinal cases. To the best of our knowledge, this is the first review documenting all the cases of adenoviral infections in BMT patients. Future randomized studies are needed to validate the results of the present study.

Propafenone Poisoning of a Female Adolescent After a Suicide Attempt.

Propafenone is an antiarrhythmic agent for the management of ventricular and supraventricular tachycardia and atrial fibrillation. Propafenone poisoning is rare but may be life-threatening due to drug-induced arrhythmias. Electrocardiographic changes in PR, QRS, and QT intervals have been recorded. We present a case of a 15-year-old female adolescent who developed arrhythmias and convulsions due to propafenone intoxication, in an attempt to commit suicide. The outcome of the case was a full recovery from the arrhythmias and the seizures. The aim of this article is to highlight the possibility of a lethal intoxication by a common antiarrhythmic drug. Our case aims to present our therapeutic strategy that relies mainly on close monitoring of patients and cardiac output support.

Ibuprofen and COVID-19 disease: separating the myths from facts.

Introduction: The Coronavirus disease 2019 (COVID-19) poses novel challenges in the healthcare systems around the world. Concern about the role of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and, in particular, ibuprofen has led to significant speculation.Areas covered: A literature search was conducted to evaluate ibuprofen's potential benefits and harms in the COVID-19 disease. Angiotensin-Converting Enzyme 2 (ACE-2) is crucial entry receptor for Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) in host cells. We found no scientific evidence linking ibuprofen use and an ACE-2 overexpression. Ibuprofen suppresses the production of various pro-inflammatory cytokines that are implicated in the 'cytokine storm' and subsequent ARDS in COVID-19 disease. Nevertheless, the exact role of ibuprofen in the immune response in COVID-19 disease is still unknown. There are no double-blind, placebo-controlled studies assessing the effect of ibuprofen on COVID-19 disease progression.Expert opinion: The studies that have been performed so far demonstrate no association between ibuprofen use and increased mortality rates or an increased risk for respiratory support. Accordingly, we recommend ibuprofen to be used for managing COVID-19 symptoms.

Infliximab and tocilizumab reduce anxiety-like behavior, improve cognitive performance and reverse neuropathological alterations in juvenile rats with severe autoimmune arthritis.

Several studies have demonstrated that rheumatic diseases, including Juvenile Idiopathic Arthritis (JIA), are associated with anxiety-like behavior and a cognitive decline. Infliximab, a Tumor Necrosis Factor-alpha (TNF-a) inhibitor, and tocilizumab, an antibody against Interleukin-6 (IL-6) receptor, are commonly used in the treatment of JIA. Here, we aimed to evaluate the effects of infliximab and tocilizumab on anxiety symptoms and cognitive function in a juvenile model of severe autoimmune arthritis. We found that both infliximab and tocilizumab improved anxiety-like behavior in the elevated-plus and elevated-zero maze tests. Tocilizumab, also, improved cognitive performance in the passive avoidance and olfactory social memory tests. Histological examination showed that anti-cytokine treatment reversed the histopathological alterations in the brain induced by arthritis. Further, infliximab and tocilizumab treatment increased Brain-Derived Neurotrophic Factor (BDNF) expression in the hippocampal and amygdaloid area of rat brain. In summary, our findings provide evidence that infliximab and tocilizumab have a beneficial effect on anxiety-like behavior and cognitive function and alleviate neuropathological alterations in a juvenile rat model of severe arthritis, suggesting that inhibition of TNF-a and IL-6 in the periphery, may be associated with a mood and memory enhancement in JIA patients.

Operative Treatment of Adult Pyogenic Spondylodiscitis: A Retrospective Study of 32 Cases.

Background Spondylodiscitis is a potentially life-threatening infection that imposes a significant financial burden on healthcare systems. Current reports suggest an increase in the incidence of spondylodiscitis, which could be attributed to the aging population and the growing rates of drug abuse. This study aims to evaluate the safety and effectiveness of surgical treatment of spondylodiscitis. Materials and methods Thirty-two cases diagnosed with spondylodiscitis and treated operatively between 2010 and 2015 were enrolled in this study. Indications for surgery were progressive neurologic involvement, progressive spinal deformity or instability, impending fracture, epidural abscess, and poor response to antibiotics. Patients underwent a single-stage procedure. A combined anterior and posterior approach was used in 28 of the patients. In 20 patients, a titanium mesh cage was used for reconstruction. The mean follow-up was 5.6 years. Results There were 18 males and 14 females. The mean age of the patients was 68.4 years (range 56-78). The cervical spine was affected in two cases (6.3%), the thoracic spine in 12 cases (37.5%), and the lumbar spine in 18 cases (56.3%). The most commonly isolated microorganisms were Staphylococcus aureus and Escherichia coli. There was neither mortality nor severe complications. Fusion was achieved in all the patients. There was complete resolution of the neurologic deficits that were recorded preoperatively. No signs of recurrent or residual infection were recorded until the last follow-up. Conclusions Our data suggest that early detection and surgical intervention of spondylodiskitis is associated with favorable outcomes.

Effects of Long-Term Methotrexate, Infliximab, and Tocilizumab Administration on Bone Microarchitecture and Tendon Morphology in Healthy Wistar Rats.

Objective Rheumatic diseases are associated with bone loss, both systemic and periarticular, and tendon abnormalities. The aim of this study is to examine the effect of three antiarthritic drugs, methotrexate, an anti-folate metabolite; infliximab, a Tumor Necrosis Factor-alpha (TNF-α) inhibitor; and tocilizumab, an antibody against Interleukin-6 (IL-6) receptor, on bone microarchitecture and tendon morphology in the absence of an inflammatory state. Materials and methods Thirty-five, 8- to 9-week-old, male, Wistar rats were randomly allocated into five groups: negative control (CTRL), vehicle (VEH), methotrexate (MTX), infliximab (INFX), and tocilizumab (TCZ). After 8 weeks of antiarthritic drug intraperitoneal administration, animals were euthanized and rat tibiae and patellar tendons were histologically examined. Results All sections exhibited normal bone microarchitecture. Histological scores in all groups corresponded to normal bone mineral density. No no apparent differences in tenocyte morphology and architecture of collagen fibers were observed. Conclusions The results of this study indicate that long-term administration of methotrexate, infliximab, and tocilizumab had no effect on bone microarchitecture and tendon morphology in rats in the absence of an inflammatory condition.

Infliximab prevents systemic bone loss and suppresses tendon inflammation in a collagen-induced arthritis rat model.

Reduced Bone Mineral Density (BMD) and tendon abnormalities, such as tenosynovitis and enthesitis, are prevalent comorbidities in patients with rheumatoid arthritis (RA). The aim of the present study was to investigate the effect of chronic treatment with infliximab on BMD and tendon inflammation in an animal model of inflammatory arthritis. Collagen-Induced Arthritis (CIA) was induced in rats, followed by long-term intraperitoneal administration of infliximab. Two additional groups of animals received methotrexate either as a monotherapy or as a co-treatment to infliximab. BMD was evaluated by Micro-Computed Tomography (Micro-CT) and bone histological examination. Tendon inflammation was assessed histologically and by quantitative ELISA analysis of pro-inflammatory cytokines in tendon tissues. Both methotrexate and infliximab treatment alleviated joint inflammation and reduced paw edema. Infliximab-treated animals exhibited an improved trabecular microarchitecture on micro-CT and histological analysis compared to both non-treated and methotrexate-treated animals. Infliximab almost reversed the pathological changes in tendons induced by CIA. Finally, we observed statistically significant declines in tendon TNF-a and IL-23 levels after infliximab treatment. Our study provides evidence that infliximab prevents arthritis-related osteoporosis and suppresses tendon inflammation in an animal model of inflammatory arthritis, in addition to controlling disease activity. These findings offer perspectives for the management of osteoporosis and enthesitis in RA.

An Improved Method for Isolating High-Quality RNA From Rat Bone at Room Temperature Without the Need for Specialized Equipment.

Research on bone diseases often requires investigation of bone gene expression. Isolating high-quality RNA is essential to obtain reliable and accurate gene expression data. In an effort to analyze the expression of genes related to osteoporosis in rat bones, we developed an improved method for extraction of high-quality RNA without the need for liquid nitrogen or specialized equipment. This method involved transitioning frozen bone tissues to a more pliable state with RNAlater ice and pulverization of the samples with a simple homogenizer, followed by a phenol-chloroform-based RNA extraction. Spectrophotometric analysis indicated high purity of the isolated RNA. Electrophoresis on agarose gel revealed two well-defined ribosomal RNA bands. Herein, we present a method that consistently yields RNA of high purity and integrity from rat bone.

Conventional Microscopic Stapedotomy: An Obsolete Technique or Still the Gold Standard for the Management of Otosclerosis?

Background and objectives Clinical otosclerosis is a relatively common entity, accounting for 0.5%-2% of the general population. Otosclerosis is characterized by an abnormal bone formation in the temporal bone that eventually causes conductive hearing loss. Bilateral involvement is fairly common. Treatment can be either conservative with medications and a hearing aid, or surgical. Stapedotomy is considered, nowadays, the most effective surgical technique for the management of otosclerosis. The purpose of the present study is to present our long-term results with stapedectomy, the audiological outcome, as well as the complications encountered. Subjects and methods This is a retrospective single-centre study. All patients diagnosed with otosclerosis and treated operatively with a stapedotomy from January 2010 to December 2019 were included in the study. Demographic data, air and bone conduction thresholds, complications and length of the prosthesis were recorded.  Results The study included a total of 72 patients. The audiological results showed a statistically significant improvement in the air conduction thresholds in all the affected frequencies (p<0.001). Post-operative complications included deterioration or severe hearing loss up to 100 dB (n=1, 1.39%), loss or distortion of taste (n=4, 5.6%) and tinnitus (n=2, 2.8%). Conclusions Our results demonstrate that stapedotomy is an effective technique for the management of otosclerosis. Stapedotomy, when performed by an experienced surgeon, provides excellent outcomes, with limited complications.

Acute Periprosthetic Hip Joint Infection Caused by Multidrug-Resistant Acinetobacter Baumannii: Is Debridement, Antibiotics, Irrigation, and Implant Retention a Viable Treatment Option?

In this study, we aimed to investigate the effectiveness of debridement, antibiotics, irrigation, and implant retention (DAIR) in periprosthetic hip joint infection caused by multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii). From July 2019 to June 2020, we retrospectively reviewed all patients treated for periprosthetic hip joint infections caused by MDR A. baumannii at our institution. The diagnosis of periprosthetic joint infection (PJI) was established based on the Musculoskeletal Infection Society (MSIS) 2018 criteria. The Charlson Comorbidity Index (CCI) was used to estimate the risk of mortality. The patients were followed up for over a year, until their death, or loss to follow-up. Four patients (three females and one male), with a mean age of 68 years, were included in the study. A. baumannii exhibited resistance to fluoroquinolones in all cases. All patients were treated with the DAIR procedure followed by intravenous tigecycline and colistin combination treatment. Prosthesis retention with good functional results was achieved in two patients. One patient required resection arthroplasty and one patient died two months after the initial surgical treatment, yielding a success rate of 50% for the DAIR procedure. Periprosthetic hip joint infection caused by MDR A. baumannii is one of the most demanding and challenging complications in orthopaedic practice. This case series suggests that the outcome of the DAIR is affected by a number of factors that are in a complex interplay. Our results indicate a limited success rate for the DAIR procedure in the treatment of a periprosthetic hip joint infection caused by MDR A. baumannii.

Caudal Epidural Injections in Lumbar Spinal Stenosis: Comparison of Nonimage, Ultrasonography-, and Fluoroscopy-Guided Techniques. A Randomized Clinical Trial.

INTRODUCTION: Caudal epidural injections (CEIs) are widely used in the treatment of lumbar spinal stenosis (LSS). Imaging modalities, such as fluoroscopy and ultrasonography, are frequently employed to confirm proper needle placement and to prevent possible complications. This is a prospective, randomized, study aiming to compare the efficacy of nonimage, ultrasonography-, and fluoroscopy-guided CEIs for the management of LSS. METHODS: A total of 45 patients were included based on their clinical symptoms and their magnetic resonance images indicative of LSS. Patients were randomized and allocated into 3 equal groups, the nonimage, the ultrasonography-guided, and the fluoroscopy-guided group. All patients received 12 mg betamethasone and 4 mg ropivacaine dissolved in 20 mL normal saline. The injections were administered twice, with a 30-day interval. Visual Analogue Scale (VAS) and Oswestry Disability Index were recorded before the injections and 1 month after the second injection. The procedure times for each group were also compared. RESULTS: Visual Analogue Scale scores and Oswestry Disability Index values were improved in all the groups compared to the baseline values (p < 0.001). The intergroup difference in Visual Analogue Scale scores and Oswestry Disability Index values before and after CEIs was not statistically significant (p = 0.836 and p = 0.438, respectively). The mean procedure time was higher for the fluoroscopy-guided group, followed by ultrasonography-guided, but the differences were not statistically significant (p = 0.067). CONCLUSION: CEIs are an effective analgesic method for patients suffering from LSS. Nonimage, ultrasonography-, and fluoroscopy-guided CEIs are similarly effective in terms of pain relief and functional improvement.

Sciatic Nerve Variants and the Piriformis Muscle: A Systematic Review and Meta-Analysis.

The present systematic review and meta-analysis provides a comprehensive assessment of the sciatic nerve (SN) variants relative to the piriformis muscle (PM) and compares those variants' prevalence among different geographical populations with respect to gender and laterality. A database search was conducted to identify cadaveric studies pertinent to SN variants relative to the PM. A total of 44 articles were included. The typical morphological pattern (type A, with the SN passing undivided below the PM) was found to be the most common variant, with 90% pooled prevalence. SN variants were more common among East Asians, with a 31% pooled prevalence of total variants. No significant differences were established with respect to gender and laterality. In greater than 10% of the population, the SN coursed through or above piriformis. Patients' epidemiological characteristics may predispose them to certain variants. The common peroneal nerve (CPN) is more susceptible to injury during a total hip arthroplasty or a hip arthroscopy where anomalies are encountered. As anatomical variants are commonly associated with piriformis syndrome, they should always be considered during diagnosis and treatment.

The Combination of rTMS and Pharmacotherapy on In Vitro Models: A Mini-Review.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive brain stimulation technique that is being actively explored as a potential therapeutic modality in various neuropsychiatric disorders, such as depression, neuropathic pain, epilepsy, multiple sclerosis, and neurodegenerative disorders, including the Parkinson's and Alzheimer's disease. The Food and Drug Administration (FDA) approved rTMS for the treatment of major depression, migraine-associated headaches, and Obsessive Compulsive Disorder (OCD). The fact that a significant proportion of patients suffering from these disorders fail to respond to current pharmacological interventions indicates the need for alternative therapies like rTMS. OBJECTIVE: The objective was to find and summarize all studies combining the use of rTMS and pharmacological interference in vitro, in order to facilitate future studies. METHODS: The results of studies combining the use of rTMS with pharmacological interference in vitro were focused on. The PubMed database was searched using the terms "rTMS", "repetitive", "transcranial", "magnetic", "stimulation", "in vitro", "in vivo", "cell cultures" untilMarch 2019 and 7 eligible studies were found. RESULTS: Overall results show a synergistic effect of rTMS and pharmacotherapy in vitro with additive effectiveness, better prognosis, and superior potential management. CONCLUSION: The limited amount of knowledge denotes the need for additional in vitro studies on the combination of rTMS and pharmacotherapy, which could be extended to in vivo studies and ultimately help design clinical trials so as to improve the therapeutic management of patients with a wide array of neuropsychiatric disorders.

The Use of Collagen-Induced Arthritis Animal Model on Studying Bone Metabolism.

CIA is a well-studied animal model of autoimmune arthritis. It resembles rheumatoid arthritis as far as histopathological changes and molecular pathogenesis are concerned. CIA is induced by immunization with collagen type II in susceptible strains. The purpose of this review is to assess the use of CIA animal model on bone metabolism and the potential therapeutic agents that could reverse this effect. A database search from their inception to 2019 was conducted to identify experimental animal studies pertinent to CIA model and bone examination. Studies including ovariectomy or without a direct comparison between control and CIA groups were excluded. Forty-eight articles were considered suitable for inclusion. Imaging techniques, biomechanical analysis, histopathological studies, and molecular biology techniques were employed. A decrease in bone mineral density in CII arthritic animals was established. Bone loss was either periarticular, generalized or both. Although trabecular bone loss was clear, the effect on cortical bone is yet to be determined. The proposed mechanism is an imbalance between bone formation and resorption as a result of osteoclast activation. The signal pathways implicated appear to be the RANKL/RANK/OPG and the Wnt pathway. Many therapeutic targets were investigated with promising results.

Flexible intramedullary nailing in the treatment of forearm fractures in children and adolescents, a systematic review.

BACKGROUND: Forearm fractures are common injuries among children and adolescents. Traditionally, they were managed conservatively with closed reduction and cast immobilization. The last decade there is an increasing trend towards operative treatment. The treatment modalities available include plate and screws, flexible intramedullary nailing and external fixation devices - rarely used nowadays. The aim of this systematic review is to investigate the indications of flexible intramedullary nailing in the childhood population, to compare its results with plating and to provide detailed information considering technical pitfalls and complications that may be encountered. MATERIALS AND METHODS: An extensive search was performed in the electronic databases (PubMed, EMBASE) from their inception up to June 2019 in order articles relevant to this review to be retrieved. The search terms used were the following: forearm fracture, both-bone fracture, pediatric, nailing, fixation. 56 articles were considered suitable for inclusion. RESULTS: The indications for surgery are unstable and irreducible fractures, open and fractures with neurovascular compromise. As far as the fracture site is concerned, radius and ulna shaft fractures, radial head and Monteggia fractures are suitable for nailing.Although plates and nailing have comparable clinical outcomes and complication rates, flexible intramedullary nailing has the advantage of smaller incisions, less tissue disruption, shorter operative and hospital times and an ease in hardware removal.Controversy exists over the need of single or double nailing in both-bone fractures of the forearm. In addition, there is no consensus as to which is the preferred nail diameter. Yet, all the authors agree that open reduction must be considered after certain failed closed reductions in order compartment syndrome to be avoided.Flexible intramedullary nailing is not complication-free. Skin irritation, Extensor Pollicis Longus rupture, superficial radial nerve injury, delayed union or even nonunion, malunion and refractures are some of the complications that may be encountered. DISCUSSION: Flexible nails are excellent implants combining stability and elasticity. The procedure of passing the nails across radius and ulna is relatively simple, requiring a small learning curve. Flexible intramedullary nailing is an excellent treatment modality for the treatment of forearm fractures in children and adolescents.