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Background: One of the main challenges of orthopedic surgery is adequate pain management after total knee arthroplasty. This work aimed to determine the anatomical safety area for infiltration through the posterior capsule of the knee in prosthetic surgery using Magnetic Resonance Imaging (MRI). Methods: A descriptive, observational, cross-sectional study was performed on 126 knee MRIs. The variables studied were age, sex, and distance between different neurovascular structures of the popliteal fossa (tibial nerve, common peroneal nerve, and vascular bundle). Data were analyzed for normality (Kolmogorov-Smirnov) and variance homogeneity (Levène). A value of p < 0.05 and a confidence interval of 9% were considered statistically significant for all comparisons. Student's t-test was used to compare the means between independent samples. Results: We observed statistically significant differences between the sexes regarding EP-EPS (external plateau-external popliteal sciatic nerve (common peroneal)), EP-IPS (external plateau-internal popliteal sciatic nerve (tibial)), and IP-PA (internal plateau-popliteal artery) measurements. The average distance between both nerves, EPS-IPS (external popliteal sciatic nerve and internal popliteal sciatic nerve), was 25.96 mm in females, while the value obtained in males was 29.93 mm, but this difference was not statistically significant. Conclusions: The average distance from the posterior capsule to the EPS and IPS nerves is greater in males than in females, despite no statistical differences. The presence of a lateralized arteriovenous bundle reduces the infiltration area of the external compartment. Regarding the safety area, infiltration of the internal compartment is safe since the volume diffuses into the muscle mass of the internal gastrocnemius upon injection. To infiltrate the external compartment, the needle must move at least 2 cm from the midline toward the external side (to exceed the maximum displacement of the neurovascular bundle established at 1.82 cm), and not advance beyond 0.76 cm (minimum distance at which we located the common peroneal nerve in the external compartment).
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(1) Background: Fibromyalgia syndrome (FMS) is a chronic pain condition with widespread pain and multiple comorbidities, for which conventional therapies offer limited benefits. The reserpine-induced myalgia (RIM) model is an efficient animal model of FMS in rodents. This study aimed to develop a pharmacokinetic-pharmacodynamic (PK-PD) model of reserpine in rats, linking to its impact on monoamines (MAs). (2) Methods: Reserpine was administered daily for three consecutive days at dose levels of 0.1, 0.5, and 1 mg/kg. A total of 120 rats were included, and 120 PK and 828 PD observations were collected from 48 to 96 h after the first dose of reserpine. Non-linear mixed-effect data analysis was applied for structural PK-PD model definition, variability characterization, and covariate analysis. (3) Results: A one-compartment model best described reserpine in rats (V = 1.3 mL/kg and CL = 4.5 × 10-1 mL/h/kg). A precursor-pool PK-PD model (kin = 6.1 × 10-3 mg/h, kp = 8.6 × 10-4 h-1 and kout = 2.7 × 10-2 h-1) with a parallel transit chain (k0 = 1.9 × 10-1 h-1) characterized the longitudinal levels of MA in the prefrontal cortex, spinal cord, and amygdala in rats. Reserpine stimulates the degradation of MA from the pool compartment (Slope1 = 1.1 × 10-1 h) and the elimination of MA (Slope2 = 1.25 h) through the transit chain. Regarding the reference dose (1 mg/kg) of the RIM model, the administration of 4 mg/kg would lead to a mean reduction of 65% (Cmax), 80% (Cmin), and 70% (AUC) of MA across the brain regions tested. (4) Conclusions: Regional brain variations in neurotransmitter depletion were identified, particularly in the amygdala, offering insights for therapeutic strategies and biomarker identification in FMS research.
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BACKGROUND: Previous evidence indicated that atrial fibrillation (AF) patients with polypharmacy presented increased probability of adverse events. We investigated the prevalence of polypharmacy, risk factors for polypharmacy, and the impact of polypharmacy in clinical outcomes in a 'real-world' cohort of AF patients starting vitamin K antagonists (VKAs). METHODS: Prospective study including AF outpatients starting VKA therapy from July, 2016 to June, 2018. At inclusion, all concomitant drugs were carefully collected and recorded. Polypharmacy was defined as the intake of ≥ 5 concomitant drugs. During 2-years of follow-up, ischemic strokes/transient ischemic attacks (TIAs), fatal/nonfatal myocardial infarctions (MIs), bleeding events, venous thromboembolisms, and all-cause deaths were recorded. RESULTS: 1050 patients (51.5 % females, median age 77 [69-83] years) were included, and the prevalence of polypharmacy was 32.9 % (345). Female sex (OR 1.5; 95 % CI 1.11-2.03), hypertension (OR 2.53; 95 % CI 1.51-4.22), diabetes (OR 3.11; 95 % CI 2.31-4.17), vascular disease (OR 3.08; 95 % CI 2.19-4.33), heart failure (OR 1.86; 95 % CI 1.35-2.58) and dyslipidemia (OR 2.61; 95 % CI 1.9-3.58) were independently associated to the polypharmacy. Patients with polypharmacy showed significantly higher incidence of major bleeding, net clinical outcomes (composite of major bleeding, ischemic stroke/TIA, and mortality), MACE (composite of ischemic stroke/TIA, MI, and cardiovascular death), and composite thrombotic/thromboembolic events; being an independent risk factor for major bleeding (HR 1.77, 95 % CI 1.07-2.92), and composite thrombotic/thromboembolic events (HR 1.55, 95 % CI 1.05-2.31). CONCLUSION: In this "real world" AF cohort, polypharmacy was highly prevalent and conditioned worse prognosis due to its association with bleeding and thromboembolic events.
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Fibrilación Atrial , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Femenino , Anciano , Masculino , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Accidente Cerebrovascular/tratamiento farmacológico , Ataque Isquémico Transitorio/complicaciones , Estudios Prospectivos , Multimorbilidad , Polifarmacia , Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Hemorragia/tratamiento farmacológico , Factores de Riesgo , Accidente Cerebrovascular Isquémico/tratamiento farmacológicoRESUMEN
PURPOSE: The purpose of this article is to highlight the risk of pseudoaneurysms formation after orthognathic surgery, their clinical features and management. METHODS: A case report of a 24-year-old man who suffered a pseudoaneurysm of the internal maxillary artery after sagittal osteotomy during orthognathic is reported. After three bleeding episodes, a pseudoaneurysm was diagnosed with a computed tomography angiogram (CTA) and treated with an embolization of the internal maxillary artery with polyvinyl alcohol (PVA) successfully. RESULTS: Pseudoaneurysms derived from the external carotid artery are an uncommon complication of orthognathic surgery, especially related to sagittal osteotomy instead of LeFort I osteotomy. CONCLUSION: Pseudoaneurysms derived from external carotid artery branches must be suspected when patients show multiple episodes of bleeding (epistaxis or through the surgical approach) within the first two weeks after orthognathic surgery. If so, vascular CT or angiography should be performed to rule out the presence of vascular injuries. In case a pseudoaneurysm is identified, vascular embolization with N-butyl-cyanoacrylate seems to be the best treatment if available. If this treatment is not available or bleeding cannot be controlled, surgical ligature of the injured vessel is a valid treatment.
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AIMS: The main objective of this study is to analyze the penetration of bone cement in four different full cementation techniques of the tibial tray. METHODS: In order to determine the best tibial tray cementation technique, we applied cement to 40 cryopreserved donor tibiae by four different techniques: 1) double-layer cementation of the tibial component and tibial bone with bone restrictor; 2) metallic cementation of the tibial component without bone restrictor; 3) bone cementation of the tibia with bone restrictor; and 4) superficial bone cementation of the tibia and metallic keel cementation of the tibial component without bone restrictor. We performed CT exams of all 40 subjects, and measured cement layer thickness at both levels of the resected surface of the epiphysis and the endomedular metaphyseal level. RESULTS: At the epiphyseal level, Technique 2 gave the greatest depth compared to the other investigated techniques. At the endomedular metaphyseal level, Technique 1 showed greater cement penetration than the other techniques. CONCLUSION: The best metaphyseal cementation technique of the tibial component is bone cementation with cement restrictor. Additionally, if full tibial component cementation is to be done, the cement volume used should be about 40 g of cement, and not the usual 20 g. Cite this article: Bone Joint Res 2021;10(8):467-473.
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The pathogenesis of fibromyalgia is still unknown. Core symptoms include pain, depression, and sleep disturbances with high comorbidity, suggesting alterations in the monoaminergic system as a common origin of this disease. The reserpine-induced myalgia (RIM) model lowers pain thresholds and produces depressive-like symptoms. The present work aims to evaluate temporal dynamics in the oscillatory profiles and motor activity during sleep in this model and to evaluate if the model mimics the sleep disorders that occur in fibromyalgia patients. Hippocampal and electromyogram activity were recorded in chronically implanted rats. Following 3 days of basal recordings, reserpine was administered on three consecutive days to achieve the RIM. Postreserpine recordings were taken on alternate days for 21 days. Reserpine induced changes in the sleep architecture with more transitions between states, and a different pattern between the administration period and postreserpine weeks. Administration days were characterized by a larger amount of rapid eyes movement sleep with dominant theta waves without atonia. Following the reserpinization, theta oscillations were always more fragmented and with lower frequency. On the postreserpine days, sleep was dominated by slow-wave sleep with fast intrusions and reduced hierarchical coupling with spindles and ripples. Simultaneous electromyography recordings also showed muscle twitches during sleep and the dissociation of theta activity and muscle atonia. Abnormally high slow waves, alpha/delta intrusions, frequent transitions, and muscle twitches are common traits in fibromyalgia. Therefore, our analyses support the validity of the RIM model to study sleep disorders in fibromyalgia, and provide new insights into the research of oscillographic biomarkers.
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Ondas Encefálicas/fisiología , Fibromialgia/fisiopatología , Hipocampo/fisiopatología , Reserpina/toxicidad , Trastornos del Sueño-Vigilia/fisiopatología , Animales , Antipsicóticos/toxicidad , Ondas Encefálicas/efectos de los fármacos , Electroencefalografía/efectos de los fármacos , Electroencefalografía/métodos , Fibromialgia/inducido químicamente , Hipocampo/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Sueño/efectos de los fármacos , Sueño/fisiología , Trastornos del Sueño-Vigilia/inducido químicamenteRESUMEN
BACKGROUND: Anticonvulsants are often prescribed as coanalgesics for pathologies presenting chronic pain, such as chronic neuropathic pain and fibromyalgia. These pathologies are associated with a wide range of comorbidities: chronic fatigue, cognitive impairment, sleep disturbances, and mood disorders. Pregabalin, an anticonvulsant used to treat fibromyalgia syndrome, has been proven to improve pain and fatigue symptoms. However, most studies have not considered the analytic effect of this drug on comorbid depressive-like symptoms in this syndrome. OBJECTIVES: The main study objective was to examine the role of pregabalin in depressive symptomatology comorbid to chronic widespread pain using a reserpine-induced myalgia model. STUDY DESIGN: A randomized, controlled, animal study. SETTING: Research and data analyses were performed at the GESADA laboratory, Department of Human Anatomy and Embryology, University of Valencia, Spain. METHODS: Forty-six Sprague-Dawley male rats were used. Acute chronic pregabalin administration was tested for depressive-like behaviors (Forced Swimming and Novelty-Suppressed Feeding Tests) and for alteration of pain thresholds (tactile allodynia, Electronic Von Frey test; and mechanical hyperalgesia, Randall and Selitto test). The same procedures were followed with duloxetine as a positive control. RESULTS: Pregabalin significantly improved depressive-like behaviors in acute, but not chronic treatment, and significantly ameliorated pain thresholds. LIMITATIONS: Lack of histological and electrophysiological tests. CONCLUSIONS: Pregabalin is not effective in depressive-like symptoms associated with chronic pain but might play an acute antidepressive-like role given its antinociceptive effect.
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Anticonvulsivantes/administración & dosificación , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Mialgia/tratamiento farmacológico , Pregabalina/administración & dosificación , Reserpina/toxicidad , Animales , Antihipertensivos/toxicidad , Dolor Crónico/tratamiento farmacológico , Depresión/psicología , Esquema de Medicación , Masculino , Mialgia/inducido químicamente , Mialgia/psicología , Umbral del Dolor/efectos de los fármacos , Umbral del Dolor/fisiología , Umbral del Dolor/psicología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Resultado del TratamientoRESUMEN
Tests based on hyponeophagia phenomena are the most widely used to check the efficacy and efficiency of new-generation chronic antidepressant treatments. Even so, these tests lack strict consensus about their methodology, which reduces their validity, reproducibility and makes translatability difficult. Therefore, after an extensive literature review on this subject, we propose a methodological protocol for the Novelty-Suppressed Feeding Test to normalize this situation. Animals were induced to a reserpine-induced depression model and were then chronically treated with duloxetine, desvenlafaxine or vehicle. After a 14-day treatment, a standardized Novelty-Suppressed Feeding Test was performed. Standardization included three-phase deprivation and the introduction of standard highly palatable food. The duloxetine-treated and desvenlafaxine-treated animals exhibited behavioral improvement of depressive-like symptoms. They took less time to eat from the center of the open-field, and approached food more times per minute than the vehicle-treated animals. This normalization proposal proves effective in measuring the antidepressant effect on chronic treatment. Thus introducing this normalization proposal would reduce inter-laboratory variability and increase the validity and robustness of this behavioral test.
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Antidepresivos/farmacología , Clorhidrato de Duloxetina/farmacología , Conducta Exploratoria/efectos de los fármacos , Reserpina/farmacología , Animales , Depresión/tratamiento farmacológico , Trastorno Depresivo/tratamiento farmacológico , Modelos Animales de Enfermedad , Masculino , Ratas Sprague-Dawley , Reproducibilidad de los ResultadosRESUMEN
Since the pathogenesis of fibromyalgia is unknown, treatment options are limited, ineffective and in fact based on symptom relief. A recently proposed rat model of fibromyalgia is based on central depletion of monamines caused by reserpine administration. This model showed widespread musculoskeletal pain and depressive-like symptoms, but the methodology used to measure such symptoms has been criticized. Evidence relates the high prevalence of pain and depression in fibromyalgia to common pathogenic pathways, most probably focused on the monoaminergic system. The present study aims at a validation of the reserpine model of fibromyalgia. For this purpose, rats undergoing this model have been tested for depressive-like symptoms with a Novelty-Suppressed Feeding Test adaptation. Animals administered with reserpine and subjected to forced food deprivation performed a smaller number of incursions to the center of the open field, evidenced by a decrease in the per-minute rate of the rats' approaching, smelling or touching the food. They also took more time to eat from the central food than control rats. These NSFT findings suggest the presence of depressive-like disorders in this animal model of fibromyalgia.