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OBJECTIVE: The aim of the study is to identify and validate, through the recording of clinical and radiological data, the different surgical approaches and treatments valid for most subaxial cervical dislocation fractures and whether there is an advantage from using an anterior approach rather than a posterior approach and conversely.. MATERIAL AND METHODS: A retrospective study was carried out analyzing the case history of the last 10 years of vertebromedullary traumas treated at the spine surgery unit of the Policlinico Gemelli in Rome. Data on surgical timing, American Spinal Injury Association (ASIA) scores for neurological damage, and subsequent assessments on recovery, survival, and mortality were also examined. RESULTS: A total of 80 patients were treated: 50 by the posterior approach, 24 by the anterior approach, and six by the double approach. Our average follow-up time was 4.2 years. A prevalence of surgery with the posterior approach was noted. We observed the worsening of cervical kyphosis about 15 months after the trauma in two cases treated with the posterior approach alone. A second surgical treatment was performed in these patients. One of these patients underwent an anterior fusion; the other case underwent a posterior revision because the patient had ankylosing spondylitis. Although we found no statistically significant difference in outcomes between the various surgical treatments, in this retrospective study, we analyzed the characteristics and outcomes of cervical spine injuries that required surgical treatment. CONCLUSION: The aim of surgery in unstable cervical spine injuries should be to reduce and stabilize the damaged segment, maintain lordosis, and decompress when indicated. The optimal choice of surgical approach and treatment, or its superiority in terms of outcomes, remains a debated issue.
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Tratamiento de Urgencia , Luxaciones Articulares , Animales , Humanos , Estudios Retrospectivos , Cuello , Evaluación de Resultado en la Atención de SaludRESUMEN
Introduction: The "postural control system" acts through biomechanical strategies and functional neuromuscular adaptations to maintain body balance under static and dynamic conditions. Postural stability and body weight distribution can be affected by external sensory inputs, such as different visual stimuli. Little information is available about the influence of visual receptors on stabilometric and plantar pressure parameters. The aim of this study was to analyze variability, correlations, and changes in these parameters under open- (OE) and closed-eye (CE) conditions. Methods: A total of 31 stabilometric and plantar pressure parameters were acquired in 20 young and healthy adults during baropodometric examination performed in bipedal standing under both visual conditions. Variability of parameters was evaluated via the coefficient of variation, correlation analysis via Pearson's R2, and statistical differences via the Wilcoxon test. Results: High intra-subject repeatability was found for all plantar pressure parameters and CoP-speed (CV < 40%) under OE and CE conditions, while CoP-sway area (CoPsa) and length surface function (LSF) showed larger variability (CV > 50%). Mean and peak pressures at midfoot and total foot loads showed the least number of significant correlations with other parameters under both visual conditions, whereas the arch-index and rearfoot loads showed the largest number of significant correlations. The limb side significantly affected most plantar pressure parameters. A trend of larger LSF and lower CoPsa and mean and peak pressures at the right forefoot was found under the CE condition. Discussion: The present study provides a deeper insight into the associations between postural stability and foot load. Interesting postural adaptations, particularly with respect to different visual stimuli, the effect of the dominant side, and the specific role of the midfoot in balance control were highlighted.
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The aim of this study was to evaluate the effect of added Cd and Pb to milk on its stability by determining antioxidant enzymatic activities, lysozyme content, and protein degradation. Antioxidant enzymatic activities were spectrophotometrically determined by superoxide dismutase, catalase, xanthine oxidase, and glutathione peroxidase assays; lysozyme was identified and quantified by HPLC-UV analysis, and protein degradation was investigated by spectrophotometric analysis of advanced oxidation protein products (AOPP) and dityrosine content. In this study, contaminated milk samples showed a significant reduction in activity of all studied enzymes compared with control milk. The contamination of milk also led to a significant reduction in the lysozyme content; lysozyme content was decreased about 22% and 18% in Pb milk and Cd milk, respectively, compared with control milk. The presence of the contaminants in the milk resulted in a significant increase of both dityrosine concentration and AOPP compared with the control milk. Moreover, between types of contaminated milk, dityrosine and AOPP values were significantly higher in the Pb milk than in the Cd milk. Therefore, it is important to monitor the presence of these toxic elements in milk for the damage they cause to consumer health both directly due to their ingestion and indirectly due to loss of milk stability.
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Distal Radius Fractures (DRFs) represent one of the most common elderly patient's fractures. Often DRFs required surgical treatment based on instability of the fragments and due to the high functional demand from patients. A general agreement on the best pharmacological treatment in the post-operative is still missing. The present study describes the clinical outcome in patients who underwent surgery for Colles fracture using ES fixation osteosynthesis. ; The present investigation represents a one center retrospective analysis. In this study, two different medical treatments were recognized, and groups consequently set (Group A: Ketoprofene 100 mg twice a day for 5 days, 59 patients; Group B: Tramadol 75 mg and Dexketoprofen 25 mg, 62 patients). Outcomes were the functionality of the affected wrist through AROM assessment and the evaluation of painkillers intake, pain itself and Quick-DASH.; 121 patients were included in the present study. The pharma blending of Tramadol 75 mg and Dexketoprofen 25 mg resulted effective for the rapid recovery of the treated wrist motion. In fact, in the group B motion was better compared to group A (p<0.05) for any movement examined (flexion, extension, pronation, supination) until the last follow-up (70 days).; Associations of different painkillers are common, even if a general agreement on the most effective combination is still missing. Tramadol and Dexketoprofen provide a good clinical result, less side effects and a better functional recovery of the wrist motion. This guarantees a fewer social cost and a best management of post-operative physiotherapy.
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Fractura de Colles , Fracturas del Radio , Tramadol , Humanos , Anciano , Fractura de Colles/cirugía , Fracturas del Radio/cirugía , Tramadol/uso terapéutico , Estudios Retrospectivos , Dolor Postoperatorio/tratamiento farmacológicoRESUMEN
OBJECTIVE: The C2 odontoid fractures represent one of the most common cervical spine injuries. Stabilization and immobility are required for a correct treatment. However, in some cases surgical treatment is recommended. There are still no guidelines for Type II odontoid fractures management. The present study aims at determining how non-union could impact on mortality, functional and clinical outcomes in octogenarian patients conservatively treated. MATERIALS AND METHODS: The present investigation is a retrospective case series. All patients with diagnosis of Type II odontoid fractures, over 80 years and conservatively treated in our institution between January 2016 to April 2020 were potentially eligible for the study. The primary outcome was the bony fusion of the fracture after 3 months of conservative treatment. The secondary outcomes were clinical, functional outcomes and mortality. RESULTS: Sixty-four patients were eligible for the study according to inclusion and exclusion criteria. Computer Tomography (CT) evaluation performed 3 months after trauma showed complete fracture healing in 31 patients (48.4%, Fused), while 33 patients (51.6%) were evaluated as non-fused. Among these, 6 months after the CT evaluation, 14 patients were classified as stable, while 19 were classified as unstable. There were no statistically significant changes in clinical and functional outcomes reported in our patient series between patients with complete radiological healing and patients who reported stable fibrous non-union. CONCLUSIONS: In a selected group of elderly patients with a high risk for surgery, the conservative treatment of odontoid Type II fractures can be considered a viable management strategy. The achievement of a stable non-union allows for clinical and functional results comparable to complete fracture healing.
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Fracturas Óseas , Apófisis Odontoides , Anciano , Anciano de 80 o más Años , Humanos , Tratamiento Conservador , Octogenarios , Apófisis Odontoides/diagnóstico por imagen , Estudios Retrospectivos , Curación de FracturaRESUMEN
OBJECTIVE: Spinal infections, represent quite rare but often severe conditions. However, due to symptoms' non-specificity and the lack of specific laboratory tests, diagnosis is often delayed with serious consequences for the patient's outcomes. The present investigation aimed at evaluating the role of procalcitonin (PCT) and other clinical features on the risk stratification and the clinical outcomes in spondylodiscitis patients treated in our Emergency Department. PATIENTS AND METHODS: The present investigation represents a single-center retrospective study. Clinical records of consecutive patients admitted to our Emergency Department from 1 January 2015 to 31 March 2021 were evaluated and patients with spondylodiscitis diagnosis in this period were recruited. Our primary outcome was the degree of autonomy of patients following the acute event. Our secondary outcome was the resolution of the infection. RESULTS: In the study period, a total of 345 patients were evaluated. Among these, 165 met the inclusion criteria, and constituted the study cohort. Concerning the primary outcome, we observed that the most significant predictive factors for being non-autonomous were elevated serum creatinine (> 1.05 mg/dl), Blood Urea Nitrogen (BUN) > 23 mg/dl, Lactate dehydrogenase > 228 U/L, PCT > 0.11 ng/mL. Patients with higher PCT (PCT > 0.11 ng/mL) and higher BUN (BUN > 23 mg/dl) had higher odds of infection persistence (the Odd Ratio, OR, were respectively 3.78 for PCT and 3.14 for BUN). CONCLUSIONS: PCT assay may play a role in diagnosing spondylodiscitis in an emergency setting. A PCT value > 0.11 ng/mL should be considered as a red flag, a predictor of worse clinical outcomes and persistence of infection.
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Discitis , Polipéptido alfa Relacionado con Calcitonina , Humanos , Discitis/diagnóstico , Estudios Retrospectivos , Nitrógeno de la Urea Sanguínea , BioensayoRESUMEN
OBJECTIVE: The use of megaprosthetic implants could provide substantial advantages in elderly population affected by complex fractures. The aim of the study was to identify the patients suitable to megaprosthetic implants in the treatment of lower limbs fractures, as well as periprosthetic fractures. PATIENTS AND METHODS: From January 1st, 2015, to December 31st, 2021, all patients affected by femoral fractures with severe bone loss or previous surgery failure were retrospectively reviewed. ADL, IADL, SF-12 values pre- and post-operative were recorded. Hemoglobin value, NLR, PLR were recorded pre- and peri-operatively for all patients. Complications were recorded. All patients underwent a radiological follow-up. Significance was set at p ≤ 0.05. RESULTS: 23 patients were considered eligible, 10 males and 13 females; the mean age was 72.87 years old (± 12.33), while the mean BMI was 27.2 points (± 5.2). The mean follow-up was 2 years (± 1.4). The mean preoperative ADL and IADL scores were correlated with a positive independence of the patient, while the mean postoperative scores corresponded to a moderate-low independence. Also the mean Mental and Physical SF12 scores saw a decrease in values. NLR values were higher in the first group of patients with complications. CONCLUSIONS: A careful multiparametric and multidisciplinary patient selection is required to identify the suitable patient to this treatment.
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Fracturas del Fémur , Extremidad Inferior , Femenino , Masculino , Humanos , Anciano , Estudios Retrospectivos , Extremidad Inferior/cirugía , Algoritmos , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/cirugía , Periodo PosoperatorioRESUMEN
OBJECTIVE: Proximal femur fractures are among the most common type of trauma in elderly patients, and Euthyroid sick syndrome has already been related to fractures and trauma. The evidence of a consistent inflammatory state occurring during hip fracture, made us consider as a potential marker also the neutrophil-to-lymphocyte ratio (NLR), which is already in use to measure the prognosis and guide the therapeutic management in various conditions. PATIENTS AND METHODS: A retrospective observational analysis on patients affected by proximal femur fractures was conducted. Patients were divided between affected and non-affected by Euthyroid Sick Syndrome (ESS). Standard follow up was conducted at 1, 3, 6 and 12 months. RESULTS: 79 patients were enrolled in this study. There were 19 males and 60 females, the mean age was 83.8 ± 6.5 y.o., and 44 patients were affected by ESS. Affected patients showed higher NLR values (10.2 ± 9.4 vs. 6.9 ± 3.9; p= 0.001) and higher decrease in fT3 values in the 1st post-operative day (1.8 ± 0.4 vs. 2.2 ± 0.3; p= 0.001), higher values of PTH (97.9 ± 46.2 vs. 70.1 ± 36.2; p=0.004) and lower levels of Vitamin D (18.8 ± 7.8 vs. 23.5 ± 12.9; p= 0.04). As regards complications, we found them in 27% of patients in group A, while only in 8% in Group B, with a statistically significant difference (p= 0.03). CONCLUSIONS: ESS and NLR are promising prognostic markers in PFF in the elderly patients. If used together, they could help in the pre- and post-operative management of the patients.
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Síndromes del Eutiroideo Enfermo , Fracturas del Fémur , Anciano , Femenino , Masculino , Humanos , Anciano de 80 o más Años , Neutrófilos , Síndromes del Eutiroideo Enfermo/diagnóstico , Estudios Retrospectivos , Linfocitos , FémurRESUMEN
OBJECTIVE: Sub-trochanteric fractures are among the most challenging for trauma surgeons. The purpose of this study was to analyze our own experience about subtrochanteric fractures. We focused on functional and radiographic outcomes after intramedullary locked nail fixation with or without cerclage assist. PATIENTS AND METHODS: A retrospective analysis on subtrochanteric fractures managed from January 2016 to April 2021 was conducted. Patients treated by closed reduction and intramedullary nail fixation were enrolled in Group A, while Group B included those patients who underwent wire-assisted intramedullary nail fixation. All patients performed clinical and radiological follow-up and complications were analyzed. The significance was established for a value of p < 0.05. RESULTS: 80 patients were included in the present study. The mean age was 74.2 (+/-19.2) years. The mean surgical time was 84.7 (+/-24.6) and 254.7 (+/-80.2) minutes in Group A and Group B, respectively. The mean blood loss was 87.3 (+/-18.3) ml in Group A and 224.4 (+/-37.8) ml in Group B. Quality of reduction was mainly superior in Group B. The mean time of union was 4.2 (+/-1.4) months in Group A and 3.4 (+/-2.1) months in Group B. Statistical differences were observed in Visual Analogue Scale (VAS) and in the Short Form 12 (SF-12) after 6 and 12 months of follow-up with better results in Group B. The complication rate was 18.2% in Group A and 12.2% in Group B. CONCLUSIONS: We recommend the use of wires when acceptable closed reduction cannot be obtained because its use may be useful for medial wall stability. For elderly patients, closed reduction may be more appropriate as the quality of life and functional recovery between the two methods is almost overlapped.
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Fracturas de Cadera , Procedimientos de Cirugía Plástica , Cirujanos , Anciano , Humanos , Calidad de Vida , Estudios Retrospectivos , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugíaRESUMEN
Recent studies have identified NOTCH signaling as a contributor of neurodegeneration including Alzheimer's disease' (AD) pathophysiology. As part of the efforts to understand molecular mechanisms and players involved in neurodegenerative dementia, we employed transgenic mouse models with Notch1 and Rbpjk loss of function (LOF) mutation in pyramidal neurons of the CA fields. Using RNA-seq, we have investigated the differential expression of NOTCH-dependent genes either upon environmental enrichment (EE) or upon kainic acid (KA) injury. We found a substantial genetic diversity in absence of both NOTCH1 receptor or RBPJK transcriptional activator. Among differentially expressed genes, we observed a significant upregulation of Gabra2a in both knockout models, suggesting a role for NOTCH signaling in the modulation of E/I balance. Upon excitotoxic stimulation, loss of RBPJK results in decreased expression of synaptic proteins with neuroprotective effects. We confirmed Nptx2, Npy, Pdch8, TncC as direct NOTCH1/RBPJK targets and Bdnf and Scg2 as indirect targets. Finally, we translate these findings into human entorhinal cortex containing the hippocampal region from AD patients performing targeted transcripts analysis. We observe an increased trend for RBPJK and the ligand DNER starting in the mild-moderate stage of the disease with no change of NOTCH1 expression. Alongside, expression of the Notch targets Hes5 and Hey1 tend to rise in the intermediate stage of the disease and drop in severe AD. Similarly the newly discovered NOTCH targets, NPTX2, NPY, BDNF show an up-warding tendency during the mild-moderate stage, and decline in the severe phase of the disease. This study identifies NOTCH as a central signaling cascade capable of modulating synaptic transmission in response to excitatory insult through the activation of neuroprotective genes that have been associated to AD.
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Enfermedad de Alzheimer , Fármacos Neuroprotectores , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Animales , Hipocampo/metabolismo , Humanos , Ácido Kaínico , Ratones , Proteínas del Tejido Nervioso , Fármacos Neuroprotectores/uso terapéutico , Receptor Notch1/metabolismo , Receptores de Superficie CelularRESUMEN
We present the clinical case of a young woman with pilomatricoma of the finger, a very rare location. The patient got infected after receiving radioiodine therapy to treat a thyroid carcinoma. Given the patient's high functional requirements we choose a minimal treatment which allowed her to maintain a sufficient functionality.
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Enfermedades del Cabello , Pilomatrixoma , Neoplasias Cutáneas , Neoplasias de la Tiroides , Femenino , Humanos , Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Tiroides/radioterapiaRESUMEN
We present a simple three-dimensional model to describe the autonomous expansion of a substrate whose growth is driven by the local mean curvature of its surface. The model aims to reproduce the nest construction process in arboreal Nasutitermes termites, whose cooperation may similarly be mediated by the shape of the structure they are walking on, for example focusing the building activity of termites where local mean curvature is high. We adopt a phase-field model where the nest is described by one continuous scalar field and its growth is governed by a single nonlinear equation with one adjustable parameter d. When d is large enough the equation is linearly unstable and fairly reproduces a growth process in which the initial walls expand, branch and merge, while progressively invading all the available space, which is consistent with the intricate structures of real nests. Interestingly, the linear problem associated with our growth equation is analogous to the buckling of a thin elastic plate under symmetric in-plane compression, which is also known to produce rich patterns through nonlinear and secondary instabilities. We validated our model by collecting nests of two species of arboreal Nasutitermes from the field and imaging their structure with a micro-computed tomography scanner. We found a strong resemblance between real and simulated nests, characterized by the emergence of a characteristic length scale and by the abundance of saddle-shaped surfaces with zero-mean curvature, which validates the choice of the driving mechanism of our growth model.
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Isópteros , Animales , Árboles , Microtomografía por Rayos XRESUMEN
OBJECTIVE: To verify the main advantages and drawbacks of mechanical suturing for pharyngeal closure after total laryngectomy versus a manual suturing technique. METHODS: A retrospective review was carried out of 126 total laryngectomies performed between 2008 and 2018. Manual closure was performed in 80 cases (63.5 per cent) and mechanical suturing was performed in 46 cases (36.5 per cent). RESULTS: Mechanical suturing was used significantly more frequently in patients with: glottic tumours (p = 0.008), less local tumour extension (p = 0.017) and less pre-operative morbidity (p = 0.014). There were no significant differences in the incidence of pharyngocutaneous fistula between the manual suture group (16.3 per cent) and the mechanical suture group (13.0 per cent) (p = 0.628). None of the patients treated with mechanical suturing had positive surgical margins. Cancer-specific survival for the mechanical suture group was higher than that for the manual suture group (p = 0.009). CONCLUSION: Mechanical suturing of the pharynx after total laryngectomy is an oncologically safe technique if used in suitable cases.
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Laringectomía/métodos , Faringe/cirugía , Técnicas de Sutura , Anciano , Femenino , Humanos , Neoplasias Laríngeas/cirugía , Masculino , Persona de Mediana Edad , Estudios RetrospectivosAsunto(s)
Ataxias Espinocerebelosas , Temblor , Adulto , Humanos , Mutación/genética , Proteína Quinasa C/genética , Temblor/genéticaRESUMEN
INTRODUCTION: Carpal tunnel syndrome is one of the most common peripheral neuropathies. Only a few studies evaluate the efficacy of "nutraceuticals" on peripheral nerves and neuropathic pain. The aim of the present investigation is to evaluate the role of Alfa-Lipoic Acid-R (ALA-R) on clinical and functional outcomes in patients affected by mild to moderate carpal tunnel syndrome. MATERIAL AND METHODS: The present investigation is a prospective randomised controlled open label study, performed at our Hand Surgery Department (Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome) from October 2018 to March 2019. The enrolled patients were divided in two groups: Group A (ALA-R 600mg once day for 60 days) and Group B (control Group, no drug administration). RESULTS: 134 patients (74 F, 60 M) met the inclusion and exclusion criteria. In Group A, there was a statistically significant pain reduction compared to the control Group. Using the Boston Carpal Tunnel Questionnaire, there were no significant improvements in the other symptoms and function. CONCLUSION: ALA-R full dose administration for two months leads to positive short term results in terms of symptoms and function improvement, even if the surgical carpal tunnel release remains the treatment of choice.
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Betacoronavirus , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Infección Hospitalaria/prevención & control , Higiene de las Manos/normas , Personal de Salud/educación , Exposición Profesional/prevención & control , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , Adulto , COVID-19 , Femenino , Personal de Salud/estadística & datos numéricos , Humanos , Italia , Masculino , Persona de Mediana Edad , Exposición Profesional/estadística & datos numéricos , Guías de Práctica Clínica como Asunto , Factores de Riesgo , SARS-CoV-2 , Heridas y LesionesAsunto(s)
Síndrome de Gitelman , Guanina/análogos & derivados , Humanos , Hipopotasemia , Masculino , Persona de Mediana EdadRESUMEN
@#Introduction:Carpal tunnel syndrome is one of the most common peripheral neuropathies. Only a few studies evaluate the efficacy of “nutraceuticals” on peripheral nerves and neuropathic pain. The aim of the present investigation is to evaluate the role of Alfa-Lipoic Acid-R (ALA-R) on clinical and functional outcomes in patients affected by mild to moderate carpal tunnel syndrome. Material and Methods: The present investigation is a prospective randomised controlled open label study, performed at our Hand Surgery Department (Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome) from October 2018 to March 2019. The enrolled patients were divided in two groups: Group A (ALA-R 600mg once day for 60 days) and Group B (control Group, no drug administration). Results: 134 patients (74 F, 60 M) met the inclusion and exclusion criteria. In Group A, there was a statistically significant pain reduction compared to the control Group. Using the Boston Carpal Tunnel Questionnaire, there were no significant improvements in the other symptoms and function. Conclusion: ALA-R full dose administration for two months leads to positive short term results in terms of symptoms and function improvement, even if the surgical carpal tunnel release remains the treatment of choice.
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Percutaneous techniques for treatment of thoraco-lumbar fractures type A2 and A3 are widely used. These techniques are considered temporary fixations and instrumentation must be removed with fracture healing. The aim of the study is to analyze clinical results, motility of treated segments and any loss of correction after the removal of instrumentation. We evaluated 36 patients who underwent surgery for removal of the instrumentation. Standard and dynamics x-ray before surgery and at 1 and 12 months after surgery were obtained. Radiographic evaluation was performed by comparing loss of correction after removal of the instrumentation, residual mobility of fractured vertebra, upper and lower level with values defined by Dvorak. For clinical assessment were used SF-12, Oswestry Disability Index (ODI) and Visual Analog Scale (VAS), administered before surgery and at 1 and 12 months after the removal. We analyzed a total of 108 levels in 36 patients. After removal of the instrumentation a normal range of motion was restored in the proximal and distal segment of the fracture, while at level of fractured segment we noticed a decrease in motility. Clinically, patients had a significant decrease in VAS and ODI at 1 month after removal. Our study shows that percutaneous fixation for treatment of thoraco-lumbar fractures type A2 and A3, allows to preserve motility of the treated segments after the removal of the instrumentation until 12 months. The removal of instrumentation is associated with good clinical results without of loss of correction in treated segment.
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Fijación Interna de Fracturas , Tornillos Pediculares , Rango del Movimiento Articular , Fracturas de la Columna Vertebral/cirugía , Humanos , Vértebras Lumbares/cirugía , Vértebras Torácicas/cirugía , Resultado del TratamientoRESUMEN
Osteoid Osteoma (OO) is a benign tumor that can affect any age, but it occurs mostly in adolescents. Only few cases are reported in early infancy but very rare in advanced age. From our series of OO of the spine, we selected a rare case that combines many unusual features that makes diagnosis very difficult. A case of a painful thoracic syndrome in an old female patient due to an OO localized in the inferior edge of the left pedicle of T11 with engagement of the foramen was reported. The age of the patient, the absence of any typical clinical and diagnostic signs, such as nocturnal pain or side effects to NSAIDs administration, are unusual at presentation of OO. She presented instead, a type of pain to the chest that was stabbing, fulminating and radiating. The interest of the case is due to the association of a variety of clinical aspects that stimulate discussion as well as to the role of the modern investigative diagnostic process.