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Introduction: Brain death (BD) is known to compromise graft quality by causing hemodynamic, metabolic, and hormonal changes. The abrupt reduction of female sex hormones after BD was associated with increased lung inflammation. The use of both corticoids and estradiol independently has presented positive results in modulating BD-induced inflammatory response. However, studies have shown that for females the presence of both estrogen and corticoids is necessary to ensure adequate immune response. In that sense, this study aims to investigate how the association of methylprednisolone (MP) and estradiol (E2) could modulate the lung inflammation triggered by BD in female rats. Methods: Female Wistar rats (8 weeks) were divided into four groups: sham (animals submitted to the surgical process, without induction of BD), BD (animals submitted to BD), MP/E2 (animals submitted to BD that received MP and E2 treatment 3h after BD induction) and MP (animals submitted to BD that received MP treatment 3h after BD induction). Results: Hemodynamics, systemic and local quantification of IL-6, IL-1ß, VEGF, and TNF-α, leukocyte infiltration to the lung parenchyma and airways, and adhesion molecule expression were analyzed. After treatment, MP/E2 association was able to reinstate mean arterial pressure to levels close to Sham animals (p<0.05). BD increased leukocyte infiltration to the airways and MP/E2 was able to reduce the number of cells (p=0.0139). Also, the associated treatment modulated the vasculature by reducing the expression of VEGF (p=0.0616) and maintaining eNOS levels (p=0.004) in lung tissue. Discussion: Data presented in this study show that the association between corticoids and estradiol could represent a better treatment strategy for lung inflammation in the female BD donor by presenting a positive effect in the hemodynamic management of the donor, as well as by reducing infiltrated leukocyte to the airways and release of inflammatory markers in the short and long term.
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Morte Encefálica , Estradiol , Metilprednisolona , Pneumonia , Ratos Wistar , Animais , Feminino , Estradiol/farmacologia , Metilprednisolona/farmacologia , Ratos , Pneumonia/tratamento farmacológico , Pneumonia/metabolismo , Citocinas/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Pulmão/imunologia , Modelos Animais de Doenças , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêuticoRESUMO
Introducción: La oftalmopatía tiroidea (OT) es un trastorno debilitante en pacientes con enfermedad tiroidea autoinmune, principalmente enfermedad de Graves, que se desarrolla entre el 30 a 50% de los casos. Objetivos: Describir las características clínico-oftalmológicas y la evolución de los pacientes con oftalmopatía tiroidea activa moderada severa tratados con bolos de metilprednisolona que acuden al Hospital Central del Instituto de Previsión Social en el tiempo comprendido entre enero de 2018 y setiembre de 2021. Materiales y métodos: Investigación de diseño observacional, con estudio descriptivo, retrospectivo. Resultados: Se revisaron fichas de 34 pacientes con OT activa moderada severa que recibieron bolos de metilprednisolona basado en las guías EUGOGO 2016, de los cuáles se excluyeron 3 pacientes por tener fichas incompletas y otros 3 pacientes ya que requirieron tratamiento de segunda línea previo al término del esquema de 12 sesiones. De los 28 pacientes estudiados, la edad promedio fue de 43,6 ±13,1 años, el 89% de sexo femenino y el 28,5%, fumadores. En cuanto a la función tiroidea de la población previo al tratamiento, se constató hipertiroidismo en el 82%, hipotiroidismo en el 11% y eutiroidismo en el 7%; y posterior al tratamiento, se constató hipertiroidismo en el 78,6% (subclínico), eutiroidismo en el 17,9% e hipotiroidismo en el 3,5%. La mayoría (92.6%) contaba con anticuerpos contra el receptor de TSH positivo, con un promedio de 18 ± 9,9 mIU/Ml. Respecto a la actividad de la oftalmopatía según la escala CAS, se constató un promedio de 4,1 ±1,0 previo al tratamiento y posterior 1,2 ±1,4; de ellos el 46,4% presentó un estado leve según escala de gravedad, 39% sin criterios de gravedad y 14 % persistió en moderada -severa. Se constató mejoría de la agudeza visual tras el tratamiento (57,1%), el promedio de exoftalmía previo al tratamiento fue 22,2 mm y posterior 21,1 mm; se presentó diplopía en el 7,1% previo al tratamiento y en el 3,6% posterior al tratamiento. Conclusión: El tratamiento con glucocorticoides endovenosos en la oftalmopatía de Graves moderada-severa (esquema EUGOGO 2016) fue muy efectivo, revirtiendo la actividad y consecuentemente ayudando a disminuir la gravedad, en la gran mayoría de nuestros pacientes. Esto podría explicarse porque la oftalmopatía era incipiente y por el alto grado de adherencia de los pacientes en el contexto de un manejo multidisciplinar bien protocolizado.
Introduction: Graves' orbitopathy (GO) is a debilitating disorder in patients with autoimmune thyroid disease, mainly Graves' disease, which develops in 30 to 50% of cases. Objectives: To describe the clinical-ophthalmological characteristics and evolution of patients with moderate-to- severe active GO treated with methylprednisolone boluses who attended the Central Hospital of the Institute of Social Security between January 2018 and September 2021. Materials and methods: Observational design research, descriptive, retrospective study. Results: Records of 34 patients with active moderate-to-severe GO who received boluses of methylprednisolone based on the EUGOGO 2016 guidelines, were reviewed, of which 3 patients were excluded due to having incomplete records and another 3 patients since they required second-line treatment prior to end the 12-session scheme. Of the 28 patients studied, the average age was 43.6 ±13.1 years, 89% were female and 28.5% were smokers. Regarding the thyroid function of the population prior to treatment, hyperthyroidism was found in 82%, hypothyroidism in 11% and euthyroidism in 7%; and after treatment, hyperthyroidism was found in 78.6% (subclinical), euthyroidism in 17.9% and hypothyroidism in 3.5%. The majority (92.6%) had positive thyrotropin receptor antibodies, with an average of 18 ± 9.9 mIU/Ml. Regarding the activity of orbitopathy according to the CAS scale, an average of 4.1 ±1.0 was found before treatment and 1.2 ±1.4 after; Of them, 46.4% presented a mild condition according to the severity scale, 39% without severity criteria and 14% persisted in moderate-severe. Improvement in visual acuity was noted after treatment (57.1%), the average exophthalmia before treatment was 22.2 mm and after 21.1 mm; Diplopia occurred in 7.1% before treatment and in 3.6% after treatment. Conclusion: Treatment with intravenous glucocorticoids in moderate-severe Graves' orbitopathy (EUGOGO 2016 scheme) was very effective, reversing the activity and consequently helping to reduce the severity, in the vast majority of our patients. This could be explained because the orbitopathy was incipient and by the high degree of patient adherence in the context of well-protocolized multidisciplinary management.
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Oftalmologia/classificaçãoRESUMO
IMPORTANCE: The SARS-CoV-2 virus infection in humans induces significant inflammatory and systemic reactions and complications of which corticosteroids like methylprednisolone have been recommended as treatment. Our understanding of the metabolic and metabolomic pathway dysregulations while using intravenous corticosteroids in COVID-19 is limited. This study will help enlighten the metabolic and metabolomic pathway dysregulations underlying high daily doses of intravenous methylprednisolone in COVID-19 patients compared to those receiving placebo. The information on key metabolites and pathways identified in this study together with the crosstalk with the inflammation and biochemistry components may be used, in the future, to leverage the use of methylprednisolone in any future pandemics from the coronavirus family.
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COVID-19 , Humanos , Metilprednisolona/efeitos adversos , SARS-CoV-2 , Administração Intravenosa , Corticosteroides/efeitos adversosRESUMO
Background: The novel coronavirus disease 2019 (COVID-19) presents with complex pathophysiological effects in various organ systems. Following the COVID-19, there are shifts in biomarker and cytokine equilibrium associated with altered physiological processes arising from viral damage or aggressive immunological response. We hypothesized that high daily dose methylprednisolone improved the injury biomarkers and serum cytokine profiles in COVID-19 patients. Methods: Injury biomarker and cytokine analysis was performed on 50 SARS-Cov-2 negative controls and 101 hospitalized severe COVID-19 patients: 49 methylprednisolone-treated (MP group) and 52 placebo-treated serum samples. Samples from the treated groups collected on days D1 (pre-treatment) all the groups, D7 (2 days after ending therapy) and D14 were analyzed. Luminex assay quantified the biomarkers HMGB1, FABP3, myoglobin, troponin I and NTproBNP. Immune mediators (CXCL8, CCL2, CXCL9, CXCL10, TNF, IFN-γ, IL-17A, IL-12p70, IL-10, IL-6, IL-4, IL-2, and IL-1ß) were quantified using cytometric bead array. Results: At pretreatment, the two treatment groups were comparable demographically. At pre-treatment (D1), injury biomarkers (HMGB1, TnI, myoglobin and FABP3) were distinctly elevated. At D7, HMGB1 was significantly higher in the MP group (p=0.0448) compared to the placebo group, while HMGB1 in the placebo group diminished significantly by D14 (p=0.0115). Compared to healthy control samples, several immune mediators (IL-17A, IL-6, IL-10, MIG, MCP-1, and IP-10) were considerably elevated at baseline (all p≤0.05). At D7, MIG and IP-10 of the MP-group were significantly lower than in the placebo-group (p=0.0431, p=0.0069, respectively). Longitudinally, IL-2 (MP-group) and IL-17A (placebo-group) had increased significantly by D14. In placebo group, IL-2 and IL-17A continuously increased, as IL-12p70, IL-10 and IP-10 steadily decreased during follow-up. The MP treated group had IL-2, IFN-γ, IL-17A and IL-12p70 progressively increase while IL-1ß and IL-10 gradually decreased towards D14. Moderate to strong positive correlations between chemokines and cytokines were observed on D7 and D14. Conclusion: These findings suggest MP treatment could ameliorate levels of myoglobin and FABP3, but appeared to have no impact on HMGB1, TnI and NTproBNP. In addition, methylprednisolone relieves the COVID-19 induced inflammatory response by diminishing MIG and IP-10 levels. Overall, corticosteroid (methylprednisolone) use in COVID-19 management influences the immunological molecule and injury biomarker profile in COVID-19 patients.
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COVID-19 , Proteína HMGB1 , Humanos , Citocinas , Interleucina-10 , Interleucina-17 , Metilprednisolona/uso terapêutico , Quimiocina CXCL10 , Interleucina-2 , Interleucina-6 , Mioglobina , SARS-CoV-2 , Interleucina-12RESUMO
BACKGROUND: A short course of corticosteroids is among the management strategies considered by specialists for the treatment of vestibular neuritis (VN). We conducted an umbrella review (systematic review of systematic reviews) to summarize the evidence of corticosteroids use for the treatment of VN. METHODS: We included systematic reviews of randomized controlled trials (RCTs) and observational studies that evaluated the effects of corticosteroids compared to placebo or usual care in adult patients with acute VN. Titles, abstracts, and full texts were screened in duplicate. The quality of reviews was assessed with the A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) tool. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) assessment was used to rate certainty of evidence. No meta-analysis was performed. RESULTS: From 149 titles, five systematic reviews were selected for quality assessment, and two reviews were of higher methodological quality and were included. These two reviews included 12 individual studies and 660 patients with VN. In a meta-analysis of two RCTs including a total of 50 patients, the use of corticosteroids (compared to placebo) was associated with higher complete caloric recovery (risk ratio 2.81, 95% confidence interval [CI] 1.32 to 6.00, low certainty). It is very uncertain whether this translates into clinical improvement as shown by the imprecise effect estimates for outcomes such as patient-reported vertigo or patient-reported dizziness disability. There was a wide CI for the outcome of dizziness handicap score (one study, 30 patients, 20.9 points in corticosteroids group vs. 15.8 points in placebo, mean difference +5.1, 95% CI -8.09 to +18.29, very low certainty). Higher rates of minor adverse effects for those receiving corticosteroids were reported, but the certainty in this evidence was very low. CONCLUSIONS: There is limited evidence to support the use of corticosteroids for the treatment of VN in the emergency department.
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Neuronite Vestibular , Adulto , Humanos , Corticosteroides/uso terapêutico , Tontura , Serviço Hospitalar de Emergência , Revisões Sistemáticas como Assunto , Vertigem , Neuronite Vestibular/diagnóstico , Neuronite Vestibular/tratamento farmacológicoRESUMO
RESUMEN Introducción: la dexametasona es un medicamento que demostró una disminución de la mortalidad en la neumonía por SARS-CoV-2. Se desconoce la utilidad de otros corticoides, dosis y su duración para mejorar este resultado clínico. Objetivo: comparar la mortalidad de los pacientes adultos con neumonía por SARS-CoV-2 tratados con dexametasona versus metilprednisolona en el Hospital Nacional, Itauguá, Paraguay. Materiales y métodos: estudio ambispectivo. Se incluyeron 97 pacientes, 52 recibieron dexametasona y 45 metilprednisolona. Se utilizó un muestreo no probabilístico de casos consecutivos. Las variables fueron sometidas a estadística descriptiva y analítica. El protocolo fue aprobado por el Comité de Ética del Hospital Nacional. Los autores no presentan conflictos de interés. Resultados: todos los pacientes ingresaron con neumonía con valoración de 4 (OMS). No se encontraron diferencias significativas en la mortalidad entre ambos grupos. Al aplicar un análisis estratificado por edad, en los pacientes <65 años la mortalidad en los que recibieron dexametasona fue 15,8% mientras que los que recibieron metilprednisolona no fallecieron (p 0,03). En el grupo de ≥65 años la mortalidad n los recibieron dexametasona fue 29,4% vs. 21,4% en los que recibieron metilprednisolona (p 0,7). Conclusiones: en los pacientes <65 años tratados con dexametasona la mortalidad fue mucho más alta que en los que recibieron metilprednisolona, ya que en este último grupo no se registraron fallecimientos.
ABSTRACT Introduction: Dexamethasone is a medication that demonstrated a decrease in mortality in SARS-CoV-2 pneumonia. The usefulness of other corticosteroids, dose and their duration to improve this clinical result is unknown. Objective: To compare the mortality of adult patients with SARS-CoV-2 pneumonia treated with dexamethasone versus methylprednisolone at the Hospital Nacional of Itauguá, Paraguay. Materials and Methods: Ambispective study. Ninety seven patients were included, 52 received dexamethasone and 45 methylprednisolone. A non-probabilistic sampling of consecutive cases was used. The variables were subjected to descriptive and analytical statistics. The protocol was approved by the Ethics Committee of the Hospital Nacional. The authors do not present conflicts of interest. Results: All patients entered with 4 (WHO) vaulting pneumonia. No significant differences were found in mortality between both groups. When applying an age stratified analysis, in patients <65 years who received dexamethasone the mortality was 15.8% while those who received methylprednisolone did not die (p 0.03). In the ≥65 years group, mortality in those who received dexamethasone was 29.4% vs. 21.4% in those who received methylprednisolone (p 0.7). Conclusions: In patients <65 years treated with dexamethasone, mortality was much higher than in those who received methylprednisolone, since in the latter group no deaths were recorded.
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Inhalants are chemical substances that induce intoxication, and toluene is the main component of them. Increasing evidence indicates that a dependence on inhalants involves a state of chronic stress associated to the activation of immune cells in the central nervous system and release of proinflammatory mediators, especially in some brain areas such as the nucleus accumbens and frontal cortex, where the circuits of pleasure and reward are. In this study, anti-neuroinflammatory treatment based on a single dose of intranasal methylprednisolone was assessed in a murine model of chronic toluene exposure. The levels of proinflammatory mediators, expression levels of Iba-1 and GFAP, and histological changes in the frontal cortex and nucleus accumbens were evaluated after the treatment. The chronic exposure to toluene significantly increased the levels of TNF-α, IL-6, and NO, the expression of GFAP, and induced histological alterations in mouse brains. The treatment with intranasally administered MP significantly reduced the expression of TNF-α and NO and the expression of GFAP (p < 0.05); additionally, it reversed the central histological damage. These results indicate that intranasally administered methylprednisolone could be considered as a treatment to reverse neuroinflammation and histological damages associated with the use of inhalants.
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The purpose of this systematic review and meta-analysis was to assess the efficacy of methylprednisolone compared to other drugs to control postoperative complications following third molar surgery. PubMed and Google Scholar were used for article searching. Thereafter, the trials meeting the selection criteria and with high methodological quality, according to the Cochrane Collaboration's risk of bias tool, were included in this study. The inverse variance test and mean difference using the Review Manager Software 5.3 for Windows were used to carry out data analysis. Qualitative analysis shows that methylprednisolone is more effective than NSAIDs, but inferior to dexamethasone, for controlling postoperative complications after third molar removal. The quantitative analysis showed no statistical difference for pain control, while trismus evaluation showed a statistical difference after 7 postoperative days in favor of methylprednisolone, when compared to other drugs. In conclusion, methylprednisolone was more effective for trismus control compared to other drugs after lower third molar surgery.
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Dexamethasone (DXM) and methylprednisolone (MEP) are potent glucocorticoids used to control several inflammatory conditions. Evidence of delayed DXM reaching the central nervous system (CNS) as well as tachyphylaxis and systemic, undesirable side effects are the main limitations of peripheral delivery. Intranasal administration offers direct access to the brain as it bypasses the blood-brain barrier. The Mucosal Atomization Device is an optimal tool that can achieve rapid absorption into the CNS and the bloodstream across mucosal membranes. This study was designed to evaluate and compare the bioavailability of DXM and MEP after intranasal versus intravenous administration. Two open-label, balanced, randomized, two-treatment, two-period, two-sequence, single-dose, crossover studies were conducted, which involved healthy male and female adult volunteers. After intranasal administration, DXM and MEP were detected in plasma after the first sampling time. Mean peak concentrations of DXM and MEP were 86.61 ng/mL at 60 min and 843.2 ng/mL at 1.5 h post-administration, respectively. DXM and MEP showed high absolute bioavailability, with values of 80% and 95%, respectively. No adverse effects were observed. DXM and MEP systemic bioavailability by intranasal administration was comparable with the intravenous one, suggesting that the intranasal route can be used as a non-invasive and appropriate alternative for systemic drug delivery.
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OBJECTIVE: To estimate the effect of tocilizumab or glucocorticoids in preventing death and intubation in patients hospitalized with SARS-CoV-2 pneumonia. METHODS: This was a retrospective cohort study enrolling all consecutive patients hospitalized at Reggio Emilia AUSL between February the 11th and April 14th 2020 for severe COVID-19 and treated with tocilizumab or glucocorticoids (at least 80 mg/day of methylprednisolone or equivalent for at least 3 days). The primary outcome was death within 30 days from the start of the considered therapies. The secondary outcome was a composite outcome of death and/or intubation. All patients have been followed-up until May 19th 2020, with a follow-up of at least 30 days for every patient. To reduce confounding due to potential non-comparability of the two groups, those receiving tocilizumab and those receiving glucocorticoids, a propensity score was calculated as the inverse probability weighting of receiving treatment conditional on the baseline covariates. RESULTS AND CONCLUSION: Therapy with tocilizumab alone was associated with a reduction of deaths (OR 0.49, 95% CI 0.21-1.17) and of the composite outcome death/intubation (OR 0.35, 95% CI 0.13-0.90) compared to glucocorticoids alone. Nevertheless, this result should be cautiously interpreted due to a potential prescription bias.
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Tratamento Farmacológico da COVID-19 , Glucocorticoides , Anticorpos Monoclonais Humanizados , Glucocorticoides/uso terapêutico , Humanos , Estudos Retrospectivos , SARS-CoV-2 , Resultado do TratamentoRESUMO
Abstract Objective To estimate the effect of tocilizumab or glucocorticoids in preventing death and intubation in patients hospitalized with SARS-CoV-2 pneumonia. Methods This was a retrospective cohort study enrolling all consecutive patients hospitalized at Reggio Emilia AUSL between February the 11th and April 14th 2020 for severe COVID-19 and treated with tocilizumab or glucocorticoids (at least 80 mg/day of methylprednisolone or equivalent for at least 3 days). The primary outcome was death within 30 days from the start of the considered therapies. The secondary outcome was a composite outcome of death and/or intubation. All patients have been followed-up until May 19th 2020, with a follow-up of at least 30 days for every patient. To reduce confounding due to potential non-comparability of the two groups, those receiving tocilizumab and those receiving glucocorticoids, a propensity score was calculated as the inverse probability weighting of receiving treatment conditional on the baseline covariates. Results and conclusion Therapy with tocilizumab alone was associated with a reduction of deaths (OR 0.49, 95% CI 0.21-1.17) and of the composite outcome death/intubation (OR 0.35, 95% CI 0.13-0.90) compared to glucocorticoids alone. Nevertheless, this result should be cautiously interpreted due to a potential prescription bias.
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Cryptococcus neoformans is a fungal pathogen that causes life-threatening infections in immunocompromised individuals, who often have some inflammatory condition and, therefore, end up using glucocorticoids, such as dexamethasone and methylprednisolone. Although the effects of this class of molecules during cryptococcosis have been investigated, their consequences for the biology of C. neoformans is less explored. Here, we studied the effects of dexamethasone and methylprednisolone on the metabolism and on the induction of virulence factors in C. neoformans. Our results showed that both glucocorticoids increased fungal cell proliferation and surface electronegativity but reduced capsule and secreted polysaccharide sizes, as well as capsule compaction, by decreasing the density of polysaccharide fibers. We also tested whether glucocorticoids could affect the fungal virulence in Galleria mellonella and mice. Although the survival rate of Galleria larvae increased, those from mice showed a tendency to decrease, with infected animals dying earlier after glucocorticoid treatments. The pathogenesis of spread of cryptococcosis and the interleukin secretion pattern were also assessed for lungs and brains of infected mice. While increases in the spread of the fungus to lungs were observed after treatment with glucocorticoids, a significant difference in brain was observed only for methylprednisolone, although a trend toward increasing was also observed for dexamethasone. Moreover, increases in both pulmonary and cerebral IL-10 production, reduction of IL-6 production but no changes in IL-4, IL-17, and INF-γ were also observed after glucocorticoid treatments. Finally, histopathological analysis confirmed the increase in number of fungal cells in lung and brain tissues of mice previously subjected to dexamethasone or methylprednisolone treatments. Together, our results provide compelling evidence for the effects of dexamethasone and methylprednisolone on the biology of C. neoformans and may have important implications for future clinical treatments, calling attention to the risks of using these glucocorticoids against cryptococcosis or in immunocompromised individuals.
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We present two cases of severe COVID-19 that were rejected by medical institutions. The management of the disease was done at home with methylprednisolone (MP) pulse therapy for three days. This resulted in a favorable evolution and resolution of most symptoms. COVID-19 infection presents as asymptomatic disease, non-severe symptomatic disease, and severe respiratory inflammatory disease. The first two forms are dependent on viral response and a "cytokine storm" is responsible for the progression into severe disease. Glucocorticoids (GC) reduce inflammation by different mechanism depending of their concentration. Pulses lead to overall apoptosis of immune cells. Studies using pulse MP as treatment for SARS-CoV-1 showed clinical improvement and decreased incidence of ARDS compared with patients who received low dose steroid treatment. Inhibition of excessive inflammation through timely administration of GC in the early stage of inflammatory cytokine storm effectively prevents the occurrence of ARDS.
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STUDY DESIGN: Retrospective study. OBJECTIVE: The aim of this study was to evaluate the clinical presentation, treatments, outcome, complications, and recurrence rate in the surgical and nonsurgical management of spinal aneurysmal bone cyst (ABC) in a series of 18 pediatric patients. METHODS: Between 1988 and 2014, we evaluated 18 pediatric patients diagnosed with ABC confirmed by pathology studies. We analyzed clinical and radiological features, non-surgical and surgical treatment, outcome, and complications. RESULTS: The series included 12 male and 6 female patients with a mean age of 10 years and 4 months, with a mean follow-up of 5 years. Location of the ABC was lumbar in 8, cervical in 7, thoracic in 2, and sacral in 1 case. Axial pain was the most common symptom followed by radicular involvement. Surgery was performed in the presence of spine instability or neurological involvement (tumor resection) and in the remaining, nonsurgical treatment (percutaneous intralesional injection of methylprednisolone and calcitonin). Recurrence was observed in 4 patients requiring reintervention. There were no procedure-related complications. CONCLUSION: In patients without neurological involvement or spinal instability, nonsurgical treatment is the treatment of choice. Total or subtotal removal combined with posterior instrumented spinal fusion is recommended in cases with a neurological deficit. Both procedures have shown good long-term results.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread throughout the world causing significant mortality in high risk patients with severe manifestations. To date, Remdesivir has been the only antiviral authorized by FDA as therapy for emergency use. One of the potential complications of this infection is cytokine storm, which optimal treatment remains unknown. We present the case of a 48-year-old man with no past medical history who presented to the hospital with dyspnea, cough, subjective fever, and diarrhea for 10 days. Nasopharyngeal PCR was positive for SARS-CoV-2. His respiratory status rapidly worsened to the point of requiring supplemental oxygen by high flow nasal cannula with FiO2 of 80%. Chest computed tomography showed confluent ground glass opacities in upper lobes accompanied by patchy airspace opacities in lower lobes bilaterally. He was started on hydroxychloroquine, which was switched to Remdesivir when it became available. Then, methylprednisolone was initiated for suspected cytokine storm. The patients oxygenation improved significantly over the following days and he was discharged home with no oxygen supplementation and saturating 96% on room air. Our case illustrates the role of Remdesivir for the treatment of severe COVID-19 pneumonia. We also observed a possible clinical benefit of corticosteroids in the context of suspected cytokine storm. Further studies are needed to evaluate this therapeutic strategy.
El síndrome respiratorio agudo grave coronavirus 2 (SARS-CoV-2) se ha diseminado rápidamente a lo largo del mundo causando una mortalidad significativa en pacientes de alto riesgo con manifestaciones severas. A la fecha, Remdesivir ha sido el único antiviral autorizado por la FDA para uso de emergencia. Una de las posibles complicaciones de esta infección es el desarrollo de tormenta de citoquinas, para la cual no existe un tratamiento óptimo. Presentamos el caso de un varón de 48 años sin antecedentes médicos que acudió al hospital con disnea, tos, fiebre subjetiva y diarrea durante 10 días. La reacción de cadena polimerasa nasofaríngea fue positiva para SARS-CoV-2. Su estado respiratorio empeoró rápidamente hasta el punto de requerir oxígeno suplementario a través cánula nasal de alto flujo con 80% de FiO2. La tomografía computarizada de tórax mostró opacidades confluyentes en vidrio esmerilado en los lóbulos superiores, acompañadas de opacidades irregulares alveolares en los lóbulos inferiores bilateralmente. Se inició terapia con hidroxicloroquina, la cual se cambió a Remdesivir cuando estuvo disponible. Luego se inició metilprednisolona como tratamiento de una posible tormenta de citoquinas. La oxigenación del paciente mejoró significativamente en los días posteriores y fue dado de alta sin requerir oxigeno adicional y saturando 96% en medio ambiente. Nuestro caso ilustra el papel de Remdesivir en el tratamiento de la neumonía grave por COVID-19. También observamos un posible beneficio clínico de los corticoides en tormenta de citoquinas. Se necesitan más estudios para evaluar la eficacia de esta estrategia terapéutica.
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Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/etiologia , Glucocorticoides/uso terapêutico , Humanos , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , SARS-CoV-2 , Tratamento Farmacológico da COVID-19RESUMO
Since the discovery of glucocorticoids (GCs), their important anti-inflammatory effect, rapid mechanism of action, low cost, and accessibility have made them one of the mainstays of treatment for Systemic lupus erythematosus (SLE). Although their use has allowed controlling the disease and reducing acute mortality in severe conditions, the implementation of a scheme based on high doses for long periods has inevitably been accompanied by an increase in adverse effects and infections, including long-term damage. The objective of this review is to answer some important questions that may arise from its use in daily clinical practice, and to propose a paradigm based on the use of methylprednisolone pulses followed by medium-low doses and a rapid decrease of prednisone.
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BACKGROUND AND OBJECTIVES: Sugammadex is a modified gamma-cyclodextrin that reverses the effects of aminosteroidal neuromuscular blocking agents. Likewise, some steroid molecules, such as toremifene, fusidic acid, and flucloxacillin, can also be encapsulated by sugammadex. Methylprednisolone, which is a synthetic steroid used commonly for airway oedema prophylaxis, can also be encapsulated by sugammadex. The objective of this study was to compare the recovery times of sugammadex for reversing rocuronium-induced moderate neuromuscular blockade in those who received intraoperative 1 mg.kg-1 methylprednisolone or saline. METHOD: This single-centered, randomized, controlled, prospective study included 162 adult patients undergoing elective ear-nose-throat procedures (aged from 18-65, an ASA physical status I-II, a BMI less than 30 kg.m-2, and not taking steroid drug medication) with propofol, remifentanyl, rocuronium and sevoflurane. Neuromuscular monitoring was performed using calibrated acceleromyography. The Control Group (Group C) received 5 mL of saline, while the Methylprednisolone Group (Group M) received 1 mg.kg-1 of methylprednisolone in 5mL of saline just after induction. After the completion of surgery, regarding the TOF count, two reappeared spontaneously and 2 mg.kg-1 sugammadex was administered to all patients. Recovery of the TOF ratio to 0.9 was recorded for both groups, and the estimated recovery time to reach a TOF ratio (TOFr) of 0.9 was the primary outcome of the study. RESULTS: Median time to TOFr = 0.9 was for 130.00 s (range of 29-330) for Group C and 181.00 s (100-420) for Group M (p < 0.001). The differences between the two groups were statistically significant. CONCLUSION: When using 2 mg.kg-1 of sugammadex to reverse rocuronium-induced neuromuscular blockade in patients who received 1 mg.kg-1 of intraoperative methylprednisolone, demonstrated delayed recovery times.
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Glucocorticoides/farmacologia , Metilprednisolona/farmacologia , Bloqueio Neuromuscular , Sugammadex/farmacologia , Adolescente , Adulto , Idoso , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Neuromusculares não Despolarizantes/uso terapêutico , Estudos Prospectivos , Rocurônio/uso terapêutico , Método Simples-Cego , Sugammadex/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Abstract Background and objectives: Sugammadex is a modified gamma-cyclodextrin that reverses the effects of aminosteroidal neuromuscular blocking agents. Likewise, some steroid molecules, such as toremifene, fusidic acid, and flucloxacillin, can also be encapsulated by sugammadex. Methylprednisolone, which is a synthetic steroid used commonly for airway edema prophylaxis, can also be encapsulated by sugammadex. The objective of this study was to compare the recovery times of sugammadex for reversing rocuronium-induced moderate neuromuscular blockade in those who received intraoperative 1 mg kg-1 methylprednisolone or saline. Method: This single-centered, randomized, controlled, prospective study included 162 adult patients undergoing elective ear-nose-throat procedures (aged from 18 to 65, an ASA physical status I-II, a BMI less than 30 kg m-2, and not taking steroid drug medication) with propofol, remifentanyl, rocuronium and sevoflurane. Neuromuscular monitoring was performed using calibrated acceleromyography. The Control Group (Group C) received 5 mL of saline, while the Methylprednisolone Group (Group M) received 1 mg kg-1 of methylprednisolone in 5 mL of saline just after induction. After the completion of surgery, regarding the TOF count, two reappeared spontaneously and 2 mg kg-1 sugammadex was administered to all patients. Recovery of the TOF ratio to 0.9 was recorded for both groups, and the estimated recovery time to reach a TOF ratio (TOFr) of 0.9 was the primary outcome of the study. Results: Median time to TOFr = 0.9 was for 130.00 s (range of 29-330) for Group C and 181.00 s (100-420) for Group M (p < 0.001). The differences between the two groups were statistically significant. Conclusion: When using 2 mg kg-1 of sugammadex to reverse rocuronium-induced neuromuscular blockade in patients who received 1 mg kg-1 of intraoperative methylprednisolone, demonstrated delayed recovery times.
Resumo Justificativa e objetivos: Sugammadex é uma gama-ciclodextrina modificada que reverte os efeitos de agentes de bloqueio neuromuscular aminoesteroides. Da mesma forma, algumas moléculas esteroides, como toremifene, ácido fusídico e flucloxacilina, podem ser encapsulados pelo sugammadex. A metilprednisolona, esteroide sintético usado geralmente para a profilaxia de edema de vias aéreas, também pode ser encapsulada pelo sugammadex. O objetivo do estudo foi comparar os tempos de recuperação do sugammadex na reversão de bloqueio neuromuscular moderado induzido pelo rocurônio em pacientes em que foi administrado 1 mg.kg-1 de metilprednisolona ou solução salina no período intraoperatório. Método: Este estudo prospectivo, randomizado, controlado, unicêntrico incluiu 162 pacientes adultos (idades de 18-65, ASA I-II, IMC abaixo de 30 kg.m-2, e não usando medicação esteroide) submetidos à anestesia geral para procedimento eletivo de otorrinolaringologia com propofol, remifentanil, rocurônio e sevoflurano. A monitorização neuromuscular foi realizada usando aceleromiógrafo calibrado. O grupo controle (Grupo C) recebeu 5 mL de solução salina, enquanto o grupo metilprednisolona (Grupo M) recebeu 1 mg.kg-1 de metilprednisolona em 5 mL de solução salina logo após a indução. Ao término da cirurgia, em relação à contagem do número de respostas à sequência de quatro estímulos (TOFc), dois pacientes mostraram recuperação espontânea e todos os pacientes receberam 2 mg.kg-1 de sugammadex. A recuperação da razão T4/T1 (TOFr) para 0,9 foi registrada nos dois grupos, e o desfecho primário do estudo foi o tempo estimado de recuperação, momento em que a razão TOFr alcançou o valor de 0,9 (TOFr = 0.9). Resultados: O tempo mediano para TOFr = 0,9 foi 130 s (29-330) para o Grupo C e 181s (100-420) para o Grupo M (p < 0,001). As diferenças entre os dois grupos foi estatisticamente significante. Conclusões: Pacientes que receberam 1 mg.kg-1 de metilprednisolona no intraoperatório apresentaram tempo de recuperação mais prolongado após o uso de 2 mg.kg-1 de sugammadex para reverter o bloqueio neuromuscular induzido pelo rocurônio.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Idoso , Adulto Jovem , Metilprednisolona/farmacologia , Glucocorticoides/farmacologia , Interações MedicamentosasRESUMO
El síndrome respiratorio agudo grave coronavirus 2 (SARS-CoV-2) se ha diseminado rápidamente a lo largo del mundo causando una mortalidad significativa en pacientes de alto riesgo con manifestaciones severas. A la fecha, Remdesivir ha sido el único antiviral autorizado por la FDA para uso de emergencia. Una de las posibles complicaciones de esta infección es el desarrollo de tormenta de citoquinas, para la cual no existe un tratamiento óptimo. Presentamos el caso de un varón de 48 años sin antecedentes médicos que acudió al hospital con disnea, tos, fiebre subjetiva y diarrea durante 10 días. La reacción de cadena polimerasa nasofaríngea fue positiva para SARS-CoV-2. Su estado respiratorio empeoró rápidamente hasta el punto de requerir oxígeno suplementario a través cánula nasal de alto flujo con 80% de FiO2. La tomografía computarizada de tórax mostró opacidades confluyentes en vidrio esmerilado en los lóbulos superiores, acompañadas de opacidades irregulares alveolares en los lóbulos inferiores bilateralmente. Se inició terapia con hidroxicloroquina, la cual se cambió a Remdesivir cuando estuvo disponible. Luego se inició metilprednisolona como tratamiento de una posible tormenta de citoquinas. La oxigenación del paciente mejoró significativamente en los días posteriores y fue dado de alta sin requerir oxigeno adicional y saturando 96% en medio ambiente. Nuestro caso ilustra el papel de Remdesivir en el tratamiento de la neumonía grave por COVID-19. También observamos un posible beneficio clínico de los corticoides en tormenta de citoquinas. Se necesitan más estudios para evaluar la eficacia de esta estrategia terapéutica.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread throughout the world causing significant mortality in high risk patients with severe manifestations. To date, Remdesivir has been the only antiviral authorized by FDA as therapy for emergency use. One of the potential complications of this infection is cytokine storm, which optimal treatment remains unknown. We present the case of a 48-year-old man with no past medical history who presented to the hospital with dyspnea, cough, subjective fever, and diarrhea for 10 days. Nasopharyngeal PCR was positive for SARS-CoV-2. His respiratory status rapidly worsened to the point of requiring supplemental oxygen by high flow nasal cannula with FiO2 of 80%. Chest computed tomography showed confluent ground glass opacities in upper lobes accompanied by patchy airspace opacities in lower lobes bilaterally. He was started on hydroxychloroquine, which was switched to Remdesivir when it became available. Then, methylprednisolone was initiated for suspected cytokine storm. The patient's oxygenation improved significantly over the following days and he was discharged home with no oxygen supplementation and saturating 96% on room air. Our case illustrates the role of Remdesivir for the treatment of severe COVID-19 pneumonia. We also observed a possible clinical benefit of corticosteroids in the context of suspected cytokine storm. Further studies are needed to evaluate this therapeutic strategy.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , COVID-19/tratamento farmacológico , Metilprednisolona/uso terapêutico , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , Pandemias , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/tratamento farmacológico , COVID-19/complicações , COVID-19/diagnóstico , Glucocorticoides/uso terapêuticoRESUMO
ABSTRACT Introduction: Neuromyelitis optica is an inflammatory disorder of the central nervous system that accounts for 5% of demyelinating diseases in pediatrics. Its clinical presentation is variable and associated to the involved area of the central nervous system. Case presentation: This is the case of a 15-year-old patient who consulted several times for nonspecific neurological symptoms. During his last visit to the Clínica Universitaria Colombia in Bogotá, he presented with bilateral optic neuritis, associated with frontal and parietal headache. Immunophenotyping studies were carried out, reporting positive IgG anti-aquaporin 4 antibodies (anti-AQP4 antibody), thus leading to a diagnosis of seropositive neuromyelitis optica spectrum disorder (NMOSD). Management with methylprednisolone pulses was initiated with subsequent outpatient management with rituximab that allowed stabilizing the disease. Discussion: This is an interesting case due to its insidious and uncertain onset in a pediatric patient. It was possible to evaluate clinical and diagnostic differences in relation to its presentation in adults. NMOSD mediated by anti-AQP4 is rare; brain and bone marrow MRI are essential for diagnosis. The treatment of choice for acute conditions consists of high doses of methylprednisolone. Conclusion: This disorder may result in irreversible neurological damage; for this reason, high suspicion is required for early diagnosis and timely treatment.
RESUMEN Introducción. La neuromielitis óptica es un trastorno inflamatorio del sistema nervioso central que representa el 5% de las enfermedades desmielinizantes en pediatría. Su presentación clínica es variable y está ligada al área del sistema nervioso central comprometida. Presentación de caso. Paciente masculino de 15 años quien consulta en varias oportunidades por síntomas neurológicos inespecíficos y que en su última visita a la Clínica Universitaria Colombia, en Bogotá, presenta un cuadro de neuritis óptica bilateral, asociado a cefalea frontal y parietal. Se realizan estudios de in-munotipificación que documentan positividad para anticuerpos IgG y anti acuaporina 4 (ACS anti-AQP4), permitiendo así el diagnóstico de desorden del espectro de neuromielitis óptica (NMOSD, por su sigla en inglés) seropositivo; se inicia manejo con pulsos de metilprednisolona a dosis de 1g intravenoso cada 24 horas, con posterior manejo ambulatorio con Rituximab, que permiten estabilización de la enfermedad. Discusión. Se presenta un caso interesante por su inicio insidioso e incierto en un paciente pediátrico. Este caso permite evaluar las diferencias clínicas y diagnósticas en relación a su presentación en adultos. El NMOSD mediado por ACS anti-AQP4 es poco común; para su diagnóstico es esencial la resonancia magnética cerebral y de médula ósea. El tratamiento de elección para cuadros agudos consiste en altas dosis de metilprednisolona. Conclusión. El NMOSD puede producir daño neurológico irreversible, por esto requiere un alto índice de sospecha para su diagnóstico temprano y tratamiento oportuno.