RESUMO
BACKGROUND: There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly. RESULTS: The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids (n = 78; MTX group) or corticosteroids alone (n = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group (p = .005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group (p = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group (p = .002). There were no differences in treatment-related adverse events between the two groups. CONCLUSIONS: In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX. TRIAL REGISTRATION: The trial was registered with clinicaltrials.gov (NCT04960644).
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Metotrexato , Metilprednisolona , Humanos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Feminino , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Adulto , Metilprednisolona/uso terapêutico , Metilprednisolona/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adulto Jovem , Resultado do Tratamento , Quimioterapia Combinada , Idoso , Adolescente , Doença AgudaRESUMO
The pharmacokinetics (PK) of methylprednisolone (MPL) exhibited tissue-specific saturable binding and reversible conversion with its metabolite, methylprednisone (MPN). Blood and 11 tissues were collected in male rats after intravenous (i.v.) bolus doses of 50 mg/kg MPL and 20 mg/kg MPN and upon i.v. infusion of MPL and MPN at 0.3, 3, and 10 mg/h per kg. The concentrations of MPL and MPN were simultaneously measured. A comprehensive physiologically based pharmacokinetic (PBPK) model was applied to describe the plasma and tissue profiles and estimate PK parameters of the MPL/MPN interconversion system. Both dosed and formed MPL and MPN were in rapid equilibrium or achieved steady-state rapidly in plasma and tissues. MPL tissue partitioning was nonlinear, with highest capacity in liver (322.9 ng/ml) followed by kidney, heart, intestine, skin, spleen, bone, brain, muscle, and lowest in adipose (2.74 ng/ml) and displaying high penetration in lung. The tissue partition coefficient of MPN was linear but widely variable (0.15â¼5.38) across most tissues, with nonlinear binding in liver and kidney. The conversion of MPL to MPN occurred in kidney, lung, and intestine with total clearance of 429 ml/h, and the back conversion occurred in liver and kidney at 1342 ml/h. The irreversible elimination clearance of MPL was 789 ml/h from liver and that of MPN was 2758 ml/h with liver accounting for 44%, lung 35%, and kidney 21%. The reversible metabolism elevated MPL exposure in rats by 13%. This highly complex PBPK model provided unique and comprehensive insights into the disposition of a major corticosteroid. SIGNIFICANCE STATEMENT: Our dual physiologically based pharmacokinetic (PBPK) study and model of methylprednisolone/methylprednisone (MPL/MPN) with multiple complexities reasonably characterized and parameterized their disposition, and provided greater insights into the interpretation of their pharmacodynamics in rats. Drug knowledge gained in this study may be translatable to higher-order species to appreciate the clinical utility of MPL. The complex model itself is instructive for advanced PBPK analysis of drugs with reversible metabolism and/or nonlinear tissue partitioning features.
Assuntos
Metilprednisolona , Modelos Biológicos , Ratos Sprague-Dawley , Animais , Metilprednisolona/farmacocinética , Metilprednisolona/administração & dosagem , Metilprednisolona/metabolismo , Masculino , Ratos , Distribuição Tecidual , Fígado/metabolismoRESUMO
BACKGROUND: This study explored the relationship between inflammatory markers and glucocorticoid dosage upon admission. METHODS: We conducted a retrospective analysis of 206 patients with refractory Mycoplasma pneumoniae pneumonia (RMPP) admitted to a Children's Hospital from November 2017 to January 2022. Patients were categorized into three groups based on their methylprednisolone dosage: low-dose (≤ 2 mg/kg/d), medium-dose (2-10 mg/kg/d), and high-dose (≥ 10 mg/kg/d). We compared demographic data, clinical manifestations, laboratory findings, and radiological outcomes. Spearman's rank correlation coefficient was used to assess relationships between variables. RESULTS: The median age was highest in the low-dose group at 7 years, compared to 5.5 years in the medium-dose group and 6 years in the high-dose group (P < 0.001). The body mass index (BMI) was also highest in the low-dose group at 16.12, followed by 14.86 in the medium-dose group and 14.58 in the high-dose group (P < 0.001). More severe radiographic findings, longer hospital stays, and greater incidence of hypoxia were noted in the high-dose group (P < 0.05). Additionally, significant increases in white blood cells, C-reactive protein, procalcitonin, lactate dehydrogenase (LDH), alanine transaminase, aspartate transaminase, ferritin, erythrocyte sedimentation rate, and D-dimer levels were observed in the high-dose group (P < 0.05). Specifically, LDH and ferritin were markedly higher in the high-dose group, with levels at 660.5 U/L and 475.05 ng/mL, respectively, compared to 450 U/L and 151.4 ng/mL in the medium-dose group, and 316.5 U/L and 120.5 ng/mL in the low-dose group. Correlation analysis indicated that LDH and ferritin levels were significantly and positively correlated with glucocorticoid dose (Spearman ρ = 0.672 and ρ = 0.654, respectively; P < 0.001). CONCLUSIONS: Serum LDH and ferritin levels may be useful biomarkers for determining the appropriate corticosteroid dosage in treating children with RMPP.
Assuntos
Biomarcadores , Ferritinas , L-Lactato Desidrogenase , Pneumonia por Mycoplasma , Humanos , Feminino , Masculino , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/sangue , Pneumonia por Mycoplasma/diagnóstico , Criança , Ferritinas/sangue , Estudos Retrospectivos , Pré-Escolar , Biomarcadores/sangue , L-Lactato Desidrogenase/sangue , Relação Dose-Resposta a Droga , Adolescente , Mycoplasma pneumoniae/efeitos dos fármacos , Metilprednisolona/administração & dosagem , Glucocorticoides/administração & dosagemRESUMO
INTRODUCTION: Hepatic veno-occlusive disease (VOD) is a critical medical emergency with a high mortality rate of up to 90% if not promptly treated. Defibrotide is the only approved medication for VOD treatment, exhibiting anti-inflammatory, antithrombotic, and anti-ischemic properties. This report presents a case of severe VOD in a patient undergoing acute lymphoblastic leukemia (ALL) treatment. CASE PRESENTATION: We describe the successful and rapid treatment of severe VOD in an ALL patient using therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and methylprednisolone (MPZ). The patient showed significant clinical and laboratory improvement after this combined therapeutic approach. CONCLUSION: This case highlights the effectiveness of TPE, IVIG, and MPZ in the treatment of severe VOD in ALL patients, providing insights into alternative therapeutic strategies in the absence of Defibrotide.
Assuntos
Hepatopatia Veno-Oclusiva , Imunoglobulinas Intravenosas , Metilprednisolona , Troca Plasmática , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Hepatopatia Veno-Oclusiva/terapia , Troca Plasmática/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/administração & dosagem , Metilprednisolona/uso terapêutico , Metilprednisolona/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Masculino , Polidesoxirribonucleotídeos/uso terapêutico , Terapia Combinada , FemininoRESUMO
PURPOSE: We aimed to assess adrenal function following treatment of moderate-to-severe and active Graves' orbitopathy (GO) with intravenous methylprednisolone (IVMP) in weekly pulses in a cumulative dose of 4.5 or 7.5 g. We evaluated the impact of IVMP pulses on adrenal reserve using a low-dose (1 µg) ACTH stimulation test (LDT) for the first time. METHODS: In this prospective study we evaluated adrenal function in 21 patients with moderate-to-severe and active GO treated with 12 weekly IVMP pulses according to the European Group on Graves' Orbitopathy (EUGOGO) recommendations. We assessed serum cortisol, plasma adrenocorticotropic hormone (ACTH), and dehydroepiandrosterone sulfate (DHEA-S) levels before the 1st and 12th IVMP pulse. We performed dynamic testing using LDT before the 12th IVMP pulse in all patients. In those who failed LDT, adrenal function was reassessed with LDT and the overnight metyrapone test after 4-7 weeks. RESULTS: Two patients failed to achieve serum cortisol levels ≥ 18.1 µg/dL at 30 and 60 min in LDT and were diagnosed with glucocorticoid-induced adrenal insufficiency (GC-induced AI). They were recommended to take hydrocortisone in situations of acute stress. Both patients were reassessed within 4-7 weeks after treatment cessation and showed an adequate response in LDT and overnight metyrapone test. We observed a statistically significant decrease in DHEA-S levels (p = 0.004) before the 12th IVMP pulse compared to baseline in all patients. CONCLUSION: For the first time, our research shows that administering IVMP in 12 weekly pulses can result in GC-induced AI. We suggest that patients should undergo careful evaluation for GC-induced AI, including LDT, after therapy with IVMP according to EUGOGO guidelines. Screening for altered adrenal reserve could prevent life-threatening complications, particularly during acute stress situations.
Assuntos
Insuficiência Adrenal , Hormônio Adrenocorticotrópico , Glucocorticoides , Oftalmopatia de Graves , Metilprednisolona , Humanos , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Oftalmopatia de Graves/tratamento farmacológico , Oftalmopatia de Graves/sangue , Oftalmopatia de Graves/diagnóstico , Feminino , Masculino , Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/sangue , Insuficiência Adrenal/diagnóstico , Pessoa de Meia-Idade , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Estudos Prospectivos , Adulto , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/administração & dosagem , Idoso , Hidrocortisona/sangue , Administração Intravenosa , Índice de Gravidade de Doença , SeguimentosRESUMO
To date, no therapy has been proven to be efficacious in fully restoring neurological functions after spinal cord injury (SCI). Systemic high-dose methylprednisolone (MP) improves neurological recovery after acute SCI in both animal and human. MP therapy remains controversial due to its modest effect on functional recovery and significant adverse effects. To overcome the limitation of MP therapy, we have developed a N-(2-hydroxypropyl) methacrylamide copolymer-based MP prodrug nanomedicine (Nano-MP) that can selectively deliver MP to the SCI lesion when administered systemically in a rat model of acute SCI. Our in vivo data reveal that Nano-MP is significantly more effective than free MP in attenuating secondary injuries and neuronal apoptosis. Nano-MP is superior to free MP in improving functional recovery after acute SCI in rats. These data support Nano-MP as a promising neurotherapeutic candidate, which may provide potent neuroprotection and accelerate functional recovery with improved safety for patients with acute SCI.
Assuntos
Metilprednisolona , Nanomedicina , Fármacos Neuroprotetores , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Metilprednisolona/farmacologia , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Ratos , Recuperação de Função Fisiológica/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Sistemas de Liberação de Medicamentos , Neuroproteção/efeitos dos fármacosRESUMO
OBJECTIVES: This study aimed to compare the side effects of different steroids used in the intratympanic injections (IT). METHODS: One hundred and sixty patients diagnosed with sudden sensorineural hearing loss and undergoing IT were assigned to four groups based on the type or concentration of steroids administered (Group DM5: 5 mg/ml Dexamethasone sodium phosphate; Group DM10: 10 mg/ml Dexamethasone sodium phosphate; Group MP: 40 mg/ml Methylprednisolone sodium succinate; Group BM: 4 mg/ml Betamethasone sodium phosphate). Each group comprised 40 patients, and all participants received IT six times. The study assessed and compared the degrees and duration of pain, dizziness, and tympanic membrane damage following IT. Patients were asked to report the pain they felt using the numeric rating scale (NRS). RESULTS: NRS scores for pain after IT showed significant differences among the four groups (p < 0.001). The average NRS scores for pain in each group were as follows: Group DM5: 1.53 ± 1.04; Group DM10: 1.45 ± 1.30; Group MP: 4.33 ± 2.22; Group BM: 6.03 ± 1.46. The durations of pain after IT also exhibited significant differences among the four groups (p < 0.001), with the longest duration observed in Group MP at 31.93 ± 15.20 min. CONCLUSION: Different types of steroids could lead to varying degrees of pain when used in IT. Betamethasone could cause the most severe pain, and methylprednisolone could result in the longest duration of pain.
Assuntos
Betametasona , Betametasona/análogos & derivados , Dexametasona , Dexametasona/análogos & derivados , Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Injeção Intratimpânica , Metilprednisolona , Humanos , Masculino , Feminino , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Betametasona/administração & dosagem , Betametasona/efeitos adversos , Pessoa de Meia-Idade , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Adulto , Perda Auditiva Súbita/tratamento farmacológico , Perda Auditiva Súbita/induzido quimicamente , Perda Auditiva Neurossensorial/induzido quimicamente , Membrana Timpânica , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Hemissuccinato de Metilprednisolona/administração & dosagem , Hemissuccinato de Metilprednisolona/efeitos adversos , Tontura/induzido quimicamente , Idoso , Dor/tratamento farmacológico , Dor/etiologia , Medição da DorRESUMO
Hyperinflammatory Coronavirus disease 2019 (COVID-19) and rapidly-progressive interstitial lung diseases (RP-ILD) secondary to inflammatory myopathies (IIM) present important similarities. These data support the use of anti-rheumatic drugs for the treatment of COVID-19. The aim of this study was to compare the efficacy of combining baricitinib and pulse steroids with the Standard of Care (SoC) for the treatment of critically ill COVID-19 patients. We retrospectively enrolled consecutive patients admitted to the Intensive Care Unit (ICU) with COVID-19-pneumonia. Patients treated with SoC (dexamethasone plus remdesivir) were compared to patients treated with baricitinib plus 6-methylprednisolone pulses (Rheuma-group). We enrolled 246 patients: 104/246 in the SoC and 142/246 in the Rheuma-group. All patients presented laboratory findings suggestive of hyperinflammatory response. Sixty-four patients (26.1%) died during ICU hospitalization. The mortality rate in the Rheuma-group was significantly lower than in the SoC-group (15.5 vs. 40.4%, p < 0.001). Compared to the SoC-group, patients in the Rheuma-group presented significantly lower inflammatory biomarker levels after one week of treatment. Higher ferritin levels after one week of treatment were strongly associated with mortality (p < 0.001). In this large real-life COVID-19 cohort, baricitinib and pulse steroids led to a significant reduction in mortality, paralleled by a prompt reduction in inflammatory biomarkers. Our experience supports the similarities between hyperinflammatory COVID-19 and the IIM-associated RP-ILD.
Assuntos
Azetidinas , Tratamento Farmacológico da COVID-19 , COVID-19 , Quimioterapia Combinada , Unidades de Terapia Intensiva , Metilprednisolona , Purinas , Pirazóis , SARS-CoV-2 , Sulfonamidas , Humanos , Purinas/uso terapêutico , Purinas/administração & dosagem , Masculino , Feminino , Azetidinas/uso terapêutico , Azetidinas/administração & dosagem , Sulfonamidas/uso terapêutico , Sulfonamidas/administração & dosagem , Pirazóis/uso terapêutico , Pirazóis/administração & dosagem , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Metilprednisolona/uso terapêutico , Metilprednisolona/administração & dosagem , COVID-19/mortalidade , COVID-19/complicações , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Monofosfato de Adenosina/administração & dosagem , Resultado do Tratamento , Alanina/análogos & derivados , Alanina/uso terapêutico , Alanina/administração & dosagemRESUMO
BACKGROUND: Haemoperfusion (HP) is an innovative extracorporeal therapy that utilizes special cartridges to filter the blood, effectively removing pro-inflammatory cytokines, toxins, and pathogens in COVID-19 patients. This retrospective cohort study aimed to assess the clinical benefits of HP for severe COVID-19 cases using Shapley values for machine learning models. METHODS: The research involved 578 inpatients (≥ 20 years old) admitted to Baqiyatallah hospital (Tehran, Iran). The control group (359 patients) received standard treatment, including high doses of corticosteroids (a single 500 mg methylprednisolone pulse, followed by 250 mg for 2 days), categorized as regimen (I). On the other hand, the HP group (219 patients) received regimen II, consisting of the same corticosteroid treatment (regimen I) along with haemoperfusion using Cytosorb H300. The frequency of haemoperfusion sessions varied based on the type of lung involvement determined by chest CT scans. In addition, the value function v defines the Shapley value of the i th feature for the query point x , where the input matrix features represent individual characteristics, drugs, and history and clinical conditions of the patient. RESULTS: Our data showed a favorable clinical response in the HP group compared to the control group. Notably, one-to-three sessions of HP using the CytoSorb® 300 cartridge led to reduced ventilation requirements and mortality rates in severe COVID-19 patients. Shapley values were calculated to evaluate the contribution of haemoperfusion among other factors, such as side effects, medications, and individual characteristics, to COVID-19 patient outcomes. In addition, there is a significant difference between the two groups among the treatments and medications used remdesivir, adalimumab, tocilizumab, favipiravir, Interferon beta-1a, enoxaparin prophylaxis, enoxaparin full dose, heparin prophylaxis, and heparin full dose (P < 0.05). It seems that haemoperfusion has a positive impact on the reduction of inflammation markers and renal functional such as ferritin and creatinine, respectively, as well as D-dimer and WBC levels in the HP group were significantly lower than the control group. CONCLUSION: The findings indicated that haemoperfusion played a crucial role in predicting patient survival, making it a significant feature in classifying patients' prognoses.
Assuntos
COVID-19 , Hemoperfusão , Aprendizado de Máquina , Humanos , Hemoperfusão/métodos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Irã (Geográfico) , Adulto , Idoso , Resultado do Tratamento , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Tratamento Farmacológico da COVID-19 , Corticosteroides/uso terapêutico , Corticosteroides/administração & dosagemRESUMO
BACKGROUND: The modified Ponticelli regimen (mPR) is a first-line therapy in patients with idiopathic membranous nephropathy (IMN); however, it has a less favorable safety profile. Though mycophenolate mofetil (MMF) + steroid (S) is not recommended by Kidney Disease Improving Global Outcomes guidelines, it can be used as an alternative to mPR due to higher tolerability and steroid-sparing effect. Thus, we compared the safety and effectiveness of MMF + S and mPR regimens in patients with IMN. METHODS: This randomized, open-label study enrolled patients with adult-onset nephrotic syndrome (NS) and biopsy-proven IMN. Forty-two patients were allocated to MMF + S group (MMF 1 gm twice daily + oral prednisolone 0.5 mg/kg/day; n = 21) and mPR group [methylprednisolone (1 gm intravenous) for 3 days followed by alternating monthly cycles of oral prednisolone (0.5 mg/kg/day) for the next 27 days and cyclophosphamide (2 mg/kg/day) for 6 months; n = 21]. The primary outcome measure was change in urinary protein creatinine ratio (UPCR). RESULTS: At 6 months, both groups demonstrated a significant increase in serum albumin levels and estimated glomerular filtration rate (eGFR) (both p-values <0.0001) as well as a decrease in 24-hour proteinuria (MMF + S group: p-value = 0.003, and mPR group: p-value <0.0001) and UPCR (both p-values <0.0001). However, the groups did not differ in any of these parameters at any of the monthly follow-up visits. Moreover, the groups did not differ significantly in terms of the composite remission rates (61.91% for MMF + S group and 71.43% for mPR group). CONCLUSION: MMF + S and mPR had comparable tolerability and effectiveness, with MMF-associated advantage of reduced steroid exposure.
Assuntos
Quimioterapia Combinada , Glomerulonefrite Membranosa , Imunossupressores , Ácido Micofenólico , Prednisolona , Humanos , Glomerulonefrite Membranosa/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Ácido Micofenólico/administração & dosagem , Masculino , Feminino , Adulto , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Pessoa de Meia-Idade , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Resultado do TratamentoRESUMO
Objective: To determine the complications, outcomes, and patency of a permanent epidural catheter and subcutaneous access port system (ECAPS) as part of conservative management of degenerative lumbosacral stenosis in dogs. Animals and procedure: Medical records of 11 client-owned dogs that underwent an ECAPS insertion were evaluated retrospectively. Clinical signs, complications related to the procedure, and system patency are reported. Results: All dogs had lumbosacral pain at their initial neurological assessment, with comfort levels adequately controlled following epidural infiltrations. None suffered from complications related to the ECAPS procedure. In 10 dogs, there were no malfunctions for the duration of the study. However, in 1 dog, there was a suspected leak at Day 814. The longest duration of patency reported in this study was 870 d (at the time of writing). Conclusion: Placement of an ECAPS is a feasible technique and a viable option to permit repeated epidural injections of steroids in dogs with degenerative lumbosacral stenosis that is managed conservatively. Further studies are required to evaluate complication rates.
Évaluation préliminaire d'un cathéter épidural permanent (à demeure) pour l'administration répétée de méthylprednisolone lors de sténose lombosacrée dégénérative chez le chien. Objectif: Décrire la technique, les complications, les résultats et la perméabilité d'un système composé d'un cathéter épidural et d'un port d'injection sous-cutanée (ECAPS) pour le traitement médical de la sténose lombosacrée dégénérative chez le chien. Animaux et protocole: Les dossiers médicaux de 11 chiens appartenant à des clients ayant subi l'implantation d'un ECAPS ont été évalués de façon rétrospective. Cette étude décrit les signes cliniques, les complications reliées à la procédure et la perméabilité du système. Résultats: Tous les patients inclus présentaient de la douleur lombosacrée à l'examen initial. Le niveau de confort de tous les patients suite aux injections épidurales fut maitrisé de façon adéquate. Aucun des patients n'a subi de complications reliées à l'implantation du système. Le système n'a pas démontré de dysfonctionnement dans le cas de dix patients. Chez un des patients, une fuite fut suspectée au jour 814. La durée maximale de perméabilité enregistrée dans cette étude est de 870 jours (au moment de la rédaction). Conclusion: L'implantation d'un système ECAPS représente une option faisable et viable pour l'administration additionnelle de stéroïdes pour une gestion conservatrice de sténose lombosacrée dégénérative chez les chiens atteints. Des recherches supplémentaires sont requises pour l'évaluation des taux de complications.(Traduit par les auteurs).
Assuntos
Cateteres de Demora , Doenças do Cão , Metilprednisolona , Estenose Espinal , Animais , Cães , Doenças do Cão/tratamento farmacológico , Injeções Epidurais/veterinária , Estudos Retrospectivos , Masculino , Feminino , Estenose Espinal/veterinária , Estenose Espinal/tratamento farmacológico , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Cateteres de Demora/veterinária , Cateteres de Demora/efeitos adversos , Região LombossacralRESUMO
A case report of Jarisch-Herxheimer (JHR) reaction on a 10th day of Leptospirosis caused by Leptospira Pomona. JHR occurs as a complication of an antibiotic treatment of various spirochetes and may lead to respiratory distress syndrome, renal failure, hepatic insufficiency, and multiple organ failure. This case represents a skin and cardio-vascular form of JHR with no lung involvement. The patient was treated with benzylpenicillin and low dexamethasone doses for 5th day of the disease with a shift to ceftriaxone and high doses of methylprednisolone. The fastest diagnosis of a sporadic zoonotic disease, early start of antibiotic therapy, and adequate doses of corticosteroids are key to the successful treatment of leptospirosis.
Assuntos
Antibacterianos , Leptospirose , Humanos , Masculino , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Ceftriaxona/uso terapêutico , Ceftriaxona/efeitos adversos , Dexametasona/uso terapêutico , Dexametasona/efeitos adversos , Leptospira/isolamento & purificação , Leptospirose/tratamento farmacológico , Leptospirose/complicações , Metilprednisolona/uso terapêutico , Metilprednisolona/administração & dosagem , IdosoRESUMO
BACKGROUND: Because lateral epicondylitis is a common musculoskeletal disorder that affects the forearm's extensor tendons, an effective therapeutic approach should reverse the degeneration and promote regeneration. This study aimed to compare the efficacies of autologous blood (AB) injection, corticosteroid (CS) injection, and a combined injection of both in treating lateral epicondylitis (LE), hypothesizing that the combined approach might offer immediate symptom resolution and a lower recurrence. MATERIALS AND METHODS: A total of 120 patients diagnosed with lateral epicondylitis were systematically distributed among three distinct therapeutic injection groups. Those in the AB group were administered 1 ml of autologous venous blood mixed with 2 ml of 2% prilocaine HCl. Participants in the CS category were given 1 ml of 40 mg methylprednisolone acetate mixed with 2 ml of 2% prilocaine HCl. Meanwhile, patients in the combined group received a mixture containing 1 ml each of autologous venous blood and 40 mg methylprednisolone acetate along with 1 ml of 2% prilocaine HCl. Prior to receiving their respective injections, a comprehensive assessment of all participants was carried out. Follow-up assessments were subsequently conducted on days 15, 30, and 90 utilizing metrics of the patient-rated tennis elbow evaluation (PRTEE) and measurements of hand grip strength (HGS). RESULTS: One patient dropped out from the combined group, and 119 patients completed the trial. No complications were recorded during the course of follow-up. By day 15, all groups had demonstrated significant PRTEE improvement, with CS showing the most pronounced reduction (p = 0.001). However, the benefits of CS had deteriorated by day 30 and had deteriorated further by day 90. The AB and AB + CS groups demonstrated sustained improvement, with AB + CS revealing the most effective treatment, achieving a clinically significant improvement in 97.4% of the patients. The improved HGS parallelled the functional enhancements, as it was more substantial in the AB and AB + CS groups (p = 0.001), corroborating the sustained benefits of these treatments. CONCLUSIONS: The study concluded that while AB and CS individually offer distinct benefits, a combined AB + CS approach optimizes therapeutic outcomes, providing swift and sustained functional improvement with a lower recurrence rate. These findings have substantial clinical implications, suggesting a balanced, multimodal treatment strategy for enhanced patient recovery in LE. LEVEL OF EVIDENCE: Randomized clinical trial, level 1 evidence. TRIAL REGISTRATION: NCT06236178.
Assuntos
Transfusão de Sangue Autóloga , Acetato de Metilprednisolona , Metilprednisolona , Prilocaína , Cotovelo de Tenista , Humanos , Cotovelo de Tenista/terapia , Cotovelo de Tenista/tratamento farmacológico , Masculino , Feminino , Transfusão de Sangue Autóloga/métodos , Pessoa de Meia-Idade , Adulto , Metilprednisolona/administração & dosagem , Resultado do Tratamento , Prilocaína/administração & dosagem , Acetato de Metilprednisolona/administração & dosagem , Anestésicos Locais/administração & dosagem , Glucocorticoides/administração & dosagem , Medição da DorRESUMO
BACKGROUND AND AIMS: Consensus guidelines recommend high-dose corticosteroids (1-2 mg/kg/day methylprednisolone equivalents) for treating grade ≥3 immune checkpoint inhibitor (ICI) hepatitis. We examined the effect of corticosteroid dosing on time to alanine aminotransferase (ALT) normalization, need for additional immunosuppression, and steroid-related complications. APPROACH AND RESULTS: We conducted a retrospective cohort study of 215 ICI-treated patients from 2010 to 2020 who developed grade ≥3 (ALT > 200 U/L) ICI hepatitis. Patients were grouped by initial corticosteroid dose (≥1.5 mg/kg or <1.5 mg/kg methylprednisolone equivalents). Propensity scores were calculated predicting the risk of receiving the higher steroid dose and used in inverse probability of treatment weighted (IPTW) logistic or Cox regression. The 87 patients in the ≥1.5 mg/kg group received higher initial (2.0 vs. 0.8 mg/kg/day, p < 0.001) and maximum (2.0 vs. 1.0 mg/kg/day, p < 0.001) steroid doses than the 128 patients in the <1.5 mg/kg group. There was no difference between the higher versus lower-dose groups in development of steroid-refractory hepatitis (OR 1.22, 95% CI 0.79-1.89, p = 0.365) on IPTW-logistic regression. In patients with steroid-responsive disease, there was no difference between the two groups in time to ALT normalization using either standard Cox regression (HR 1.02, 95% CI 0.72-1.45, p = 0.903) or IPTW-Cox regression (HR 1.09, 95% CI 0.78-1.51, p = 0.610). The ≥1.5 mg/kg group had longer exposure to corticosteroids (median 60 vs. 44 days, p = 0.005) and higher incidences of infection (18.4% vs. 7.0%, relative risk [RR] 2.6, 95% CI 1.2-5.6, p = 0.011) and hyperglycemia requiring treatment (23.3% vs. 7.8%, RR 3.0, 95% CI 1.5-6.0, p = 0.001). CONCLUSIONS: In patients with high-grade ICI hepatitis, initial treatment with 1 mg/kg/day methylprednisolone equivalents provides similar hepatitis outcomes with reduced risk of steroid-related complications when compared with higher-dose regimens.
Assuntos
Alanina Transaminase/sangue , Doença Hepática Induzida por Substâncias e Drogas , Relação Dose-Resposta a Droga , Relação Dose-Resposta Imunológica , Inibidores de Checkpoint Imunológico/efeitos adversos , Metilprednisolona , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Resistência a Medicamentos , Feminino , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Terapia de Imunossupressão/métodos , Testes de Função Hepática/métodos , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Avaliação de Processos e Resultados em Cuidados de Saúde , Estudos Retrospectivos , Medição de RiscoRESUMO
Objective: To study the efficacy of pulse methylprednisolone (MPS) therapy in patients with malaria-associated acute respiratory distress syndrome (ARDS). Materials and methods: The study was a randomized, single-blind, placebo-controlled trial with a total sample size of 44 patients. The total random number table was used on a computer for randomization. The sample size was divided into either the study group that received pulse MPS therapy along with the standard therapy to manage acute lung injury (ALI)/ARDS or the control group that received a placebo in the form of 100 mL of normal saline with the standard therapy to manage ALI/ARDS. The primary outcome was defined as either death of the patient or discharge from the hospital. The sequential organ failure assessment (SOFA) score, the lung injury score (LIS), duration of stay in the medical intensive care unit (MICU), number of days for which mechanical ventilation was required, and the rate of secondary infections between the study and the control groups were also calculated. Statistically significant differences among continuous variables were analyzed by t-test, and differences between categorical variables were assessed by Chi-squared test. Results: A total of 30 patients passed initial screening, out of which 60% were males and 40% were females. About 73.3% of the patients fell between the age groups of 36-45 years. A total of 20 patients (66.7%) were discharged from the hospital, while the remaining 10 patients succumbed to death in the intensive care unit (ICU) (33.3%). The outcome of death or discharge was found to be independent of the use of pulse MPS therapy (p = 0.44). No statistically significant difference was found between the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, SOFA score, and LIS between the two groups. Furthermore, the differences between the mean duration of stay in the MICU, the mean duration for the provision of mechanical ventilation (p = 0.41), and the rate of secondary infections (p = 0.46) remained unaffected with the use of pulse MPS therapy. Conclusion: Pulse MPS therapy has not shown any clear-cut benefit in the management of malaria-associated ARDS, and in fact, the continuous use of this treatment in hospitals may lead to worsened outcomes. A novel, effective therapy for this grave complication needs to be developed to reduce the morbidity and mortality in such patients, which is frequently encountered. The development of a robust surveillance system is required for adequate monitoring and early diagnosis of this complication, along with larger multicentric randomized clinical trials. Disclosures: Approval was granted by the Institutional Ethics Committee (IEC). All participants were only selected after taking their written informed consent. The authors have no conflicts of interest or acknowledgments to report. How to cite this article: Tiwari S, Kursange S, Goyal A, et al. Efficacy of Pulse Methylprednisolone in Treatment of Acute Respiratory Distress Syndrome due to Malaria: A Randomized Controlled Clinical Trial. J Assoc Physicians India 2023;71(11):36-39.
Assuntos
Malária , Metilprednisolona , Síndrome do Desconforto Respiratório , Humanos , Metilprednisolona/administração & dosagem , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/etiologia , Feminino , Masculino , Adulto , Método Simples-Cego , Malária/complicações , Malária/tratamento farmacológico , Pessoa de Meia-Idade , Respiração Artificial/estatística & dados numéricos , Resultado do Tratamento , Pulsoterapia , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Tempo de Internação/estatística & dados numéricos , Adulto JovemRESUMO
OBJECTIVE: The primary aim of this study was to evaluate the efficacy of a single preoperative dose of methylprednisolone for preventing postoperative complications after major liver resections. SUMMARY BACKGROUND DATA: Hepatic resections are associated with a significant acute systemic inflammatory response. This effect subsequently correlates with postoperative morbidity, mortality, and length of recovery. Multiple small trials have proposed that the administration of glucocorticoids may modulate this effect. METHODS: This study was a parallel, dual-arm, double-blind randomized controlled trial. Adult patients undergoing elective major hepatic resection (≥3 segments) at a quaternary care institution were included (2013-2019). Patients were randomly assigned to receive a single preoperative 500âmg dose of methylprednisolone versus placebo. The main outcome measure was postoperative complications after liver resection, within 90âdays of the index operation. Standard statistical methodology was employed (P < 0.05 = significant). RESULTS: A total of 151 patients who underwent a major hepatic resection were randomized (mean age = 62.8âyears; 57% male; body-mass-index = 27.9). No significant differences were identified between the intervention and control groups (age, sex, body-mass-index, preoperative comorbidities, hepatic function, ASA class, portal vein embolization rate) (P > 0.05). Underlying hepatic diagnoses included colorectal liver metastases (69%), hepatocellular carcinoma (18%), noncolorectal liver metastases (7%), and intrahepatic cholangiocarcinoma (6%). There was a significant reduction in the overall incidence of postoperative complications in the methylprednisolone group (31.2% vs 47.3%; P = 0.042). Patients in the glucocorticoid group also displayed less frequent organ space surgical site infections (6.5% vs 17.6%; P = 0.036), as well as a shorter length of hospital stay (8.9 vs 12.5âdays; P = 0.015). Postoperative serum bilirubin and prothrombin timeinternational normalized ratio (PT-INR) levels were also lower in the steroid group (P = 0.03 and 0.04, respectively). Multivariate analysis did not identify any additional significant modifying factor relationships (estimated blood loss, duration of surgery, hepatic vascular occlusion (rate or duration), portal vein embolization, drain use, etc) (P > 0.05). CONCLUSIONS: A single preoperative dose of methylprednisolone significantly reduces the length of hospital stay, postoperative serum bilirubin, and PT-INR, as well as infectious and overall complications following major hepatectomy.
Assuntos
Glucocorticoides/administração & dosagem , Hepatectomia , Metilprednisolona/administração & dosagem , Infecção da Ferida Cirúrgica/prevenção & controle , Método Duplo-Cego , Feminino , Hepatectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos ProspectivosRESUMO
Coronavirus disease 2019 (COVID-19) is characterized by dysregulated hyperimmune response and steroids have been shown to decrease mortality. However, whether higher dosing of steroids results in better outcomes has been debated. This was a retrospective observation of COVID-19 admissions between March 1, 2020, and March 10, 2021. Adult patients (≥18 years) who received more than 10 mg daily methylprednisolone equivalent dosing (MED) within the first 14 days were included. We excluded patients who were discharged or died within 7 days of admission. We compared the standard dose of steroids (<40 mg MED) versus the high dose of steroids (>40 mg MED). Inverse probability weighted regression adjustment (IPWRA) was used to examine whether higher dose steroids resulted in improved outcomes. The outcomes studied were in-hospital mortality, rate of acute kidney injury (AKI) requiring hemodialysis, invasive mechanical ventilation (IMV), hospital-associated infections (HAI), and readmissions. Of the 1379 patients meeting study criteria, 506 received less than 40 mg of MED (median dose 30 mg MED) and 873 received more than or equal to 40 mg of MED (median dose 78 mg MED). Unadjusted in-hospital mortality was higher in patients who received high-dose corticosteroids (40.7% vs. 18.6%, p < 0.001). On IPWRA, the use of high-dose corticosteroids was associated with higher odds of death (odds ratio [OR] 2.14; 95% confidence interval [CI] 1.45-3.14, p < 0.001) but not with the development of HAI, readmissions, or requirement of IMV. High-dose corticosteroids were associated with lower rates of AKI requiring hemodialysis (OR 0.33; 95% CI 0.18-0.63). In COVID-19, corticosteroids more than or equal to 40 mg MED were associated with higher in-hospital mortality.
Assuntos
Injúria Renal Aguda/epidemiologia , Corticosteroides/uso terapêutico , Tratamento Farmacológico da COVID-19 , COVID-19/mortalidade , Metilprednisolona/uso terapêutico , Corticosteroides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Infecção Hospitalar/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , SARS-CoV-2/efeitos dos fármacosRESUMO
Corticosteroid dosing in the range of 0.5-2 mg/kg/day of methylprednisolone equivalents has become a standard part of the management of intensive care unit (ICU) patients with COVID-19 pneumonia based on positive results of randomized trials and a meta-analysis. Alongside such conventional dosing, administration of 1 gm of methylprednisolone daily (pulse dosing) has also been reported in the literature with claims of favorable outcomes. Comparisons between such disparate approaches to corticosteroids for Coronavirus disease 2019 (COVID-19) pneumonia are lacking. In this retrospective study of patients admitted to the ICU with COVID-19 pneumonia, we compared patients treated with 0.5-2 mg/kg/day in methylprednisolone equivalents (high-dose corticosteroids) and patients treated with 1 gm of methylprednisolone (pulse-dose corticosteroids) to those who did not receive any corticosteroids. The endpoints of interest were hospital mortality, ICU-free days at Day 28, and complications potentially attributable to corticosteroids. Pulse-dose corticosteroid therapy was associated with a significant increase in ICU-free days at Day 28 compared to no receipt: adjusted relative risk (aRR): 1.45 (95% confidence interval [CI]: 1.05-2.02; p = 0.03) and compared with high-dose corticosteroid administration (p = 0.003). Nonetheless, receipt of high-dose corticosteroids-but not of pulse-dose corticosteroids-significantly reduced the odds of hospital mortality compared to no receipt: adjusted Odds ratio (aOR) 0.31 (95% CI: 0.12-0.77; p = 0.01). High-dose corticosteroids reduced mortality compared to pulse-dose corticosteroids (p = 0.04). Pulse-dose corticosteroids-but not high-dose corticosteroids-significantly increased the odds of acute kidney injury requiring renal replacement therapy compared to no receipt: aOR 3.53 (95% CI: 1.27-9.82; p = 0.02). The odds of this complication were also significantly higher in the pulse-dose group when compared to the high-dose group (p = 0.05 for the comparison). In this single-center study, pulse-dose corticosteroid therapy for COVID-19 pneumonia in the ICU was associated with an increase in ICU-free days but failed to impact hospital mortality, perhaps because of its association with development of severe renal failure. In line with existing trial data, the effect of high-dose corticosteroids on mortality was favorable.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Corticosteroides/uso terapêutico , Tratamento Farmacológico da COVID-19 , COVID-19/mortalidade , Metilprednisolona/uso terapêutico , Pulsoterapia/efeitos adversos , Injúria Renal Aguda/epidemiologia , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Cuidados Críticos/métodos , Mortalidade Hospitalar , Humanos , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pulsoterapia/métodos , Estudos Retrospectivos , SARS-CoV-2/efeitos dos fármacosRESUMO
BACKGROUND: Multisystem inflammatory syndrome (MIS), which develops after a past covid-19 infection. MIS can be described in different tissue inflammation, including the heart, lung, kidney, brain, skin, eye, and or gastrointestinal organs at the presence of COVID-19. Initially, MIS was described in Europe in children infected with SARS-CoV-2, then it was recently seen in the USA in 2020. MIS is a rare but serious disease condition associated with COVID-19 that can affect children (MIS-C) and adults (MIS-A). CASE PRESENTATION: A 44-year-old male who showed MIS-A in 59-day after his first covid-19 contact history. The patient presented to our emergency department with complaints of high fever, nausea, weakness, redness of the eyes, headache, and joint pain. On the second day of his hospitalization, a maculopapular skin lesion was seen in most of the skin. His fever could not be controlled even given paracetamol and broad effective antibiotics. His clinical, radiological, and laboratory findings showed that he had MIS-A. The patient was given intravenous pulse methylprednisolone and intravenous immunoglobulin (IVIG). These treatments, then, resulted in improvement of his clinical conditions, including fever and skin lesions, on the second day of the treatment. The patient was discharged in 14 days after the treatment. CONCLUSION: This report indicated that diagnosis and treatment of MIS-A could result in reducing patient morbidity and mortality.
Assuntos
COVID-19/complicações , Glucocorticoides/uso terapêutico , Metilprednisolona/uso terapêutico , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Adulto , COVID-19/diagnóstico , Glucocorticoides/administração & dosagem , Humanos , Imunoglobulinas Intravenosas , Injeções Intraventriculares , Masculino , Metilprednisolona/administração & dosagem , SARS-CoV-2 , Dermatopatias , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND: Critical coronavirus disease 2019 (COVID-19) has a high fatality rate, especially in hemodialysis (HD) patients, with this poor prognosis being caused by systemic hyperinflammation; cytokine storms. Steroid pulse therapy or tocilizumab (TCZ) have insufficient inhibitory effects against cytokine storms in critical cases. This study evaluated the clinical effects and safety of combining steroid pulse therapy and TCZ. METHODS: From September 2020 to May 2021, 201 patients with COVID-19 were admitted to our hospital. Before February 2021, patients with an oxygen demand exceeding 8 L/min were intubated and treated with standard therapy (dexamethasone and antiviral therapy). After February 2021, patients underwent high-flow nasal cannula oxygen therapy and were treated with TCZ (8 mg/kg) and methylprednisolone (mPSL) (500 mg/day [≤ 75 kg], 1000 mg/day [> 75 kg]) for 3 days. We compared background characteristics, laboratory findings, and prognosis between non-HD and HD patients and between patients who received and did not receive TCZ and mPSL pulse therapy. RESULTS: Among non-HD patients, the TCZ + mPSL pulse group had significantly higher survival rates and lower secondary infection rates (p < 0.05), than the standard therapy group. All HD patients in the standard therapy group with oxygen demand exceeding 8 L/min died. Contrastingly, all patients in the TCZ + mPSL pulse group survived, with their oxygen demand decreasing to 0-1 L/min within 3 weeks post-administration. CONCLUSION: TCZ combined with mPSL pulse therapy improved the survival rate without significant adverse events in critical HD and non-HD patients with COVID-19 by strongly suppressing systemic hyperinflammation.