RESUMO
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
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: IgA nephropathy is a typical chronic glomerulonephritis that tends to occur in childhood. METHOD: We reviewed the report on pathogenesis, treatment strategy with multidrug therapy and tonsillectomy pulse therapy for childhood-onset severe IgA nephropathy to clarify the pathophysiology and treatment of IgA nephropathy in childhood. RESULTS: In recent years, it has been found that the pathogenesis at onset is associated with aberrant glycosylation at the IgA1 hinge. Given this genetic background, the aberrantly glycosylated IgA1immune complex produced by antigen-stimulated T cells and B cells is deposited in the glomeruli. Inflammation is induced via activation of the complement, macrophages and mesangial cells, and glomerular damage progresses thereafter. Treatment is selected according to the severity of IgA nephropathy. In order to prevent the development of renal damage, it is important to control the associated immune responses. For severe IgA nephropathy, in particular, multidrug therapy with prednisolone, immunosuppressants, and angiotensin enzyme synthesis inhibitors and tonsillectomy methylprednisolone pulse therapy are now performed- and, as a result, the number of renal deaths has decreased and the long-term prognosis has improved. CONCLUSION: The prognosis of IgA nephropathy is improving. In the future, it will be important to develop a treatment method that takes into consideration the fact that children are in their growth and development stage and, therefore, seeks to minimizes side effects.
Assuntos
Glomerulonefrite por IGA , Tonsilectomia , Criança , Quimioterapia Combinada , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/patologia , Humanos , Imunoglobulina A , Hansenostáticos/uso terapêutico , PulsoterapiaRESUMO
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.
Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Tratamento Farmacológico da COVID-19 , Síndrome da Liberação de Citocina/prevenção & controle , Glucocorticoides/administração & dosagem , Nefropatias/terapia , Metilprednisolona/administração & dosagem , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/mortalidade , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/mortalidade , Quimioterapia Combinada , Feminino , Glucocorticoides/efeitos adversos , Humanos , Nefropatias/diagnóstico , Nefropatias/imunologia , Nefropatias/mortalidade , Masculino , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Pulsoterapia , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Vincristine plus dexamethasone pulses are generally used throughout maintenance treatment for childhood acute lymphoblastic leukaemia. However, previous studies remain inconclusive about the benefit of this maintenance therapy and the absence of randomised, controlled trials in patients with low-risk or high-risk acute lymphoblastic leukaemia provides uncertainty. We therefore aimed to determine if this therapy could be safely omitted beyond 1 year of treatment without leading to an inferior outcome in any risk subgroup of childhood acute lymphoblastic leukaemia. METHODS: This open-label, multicentre, randomised, phase 3, non-inferiority trial involved 20 major medical centres across China. We enrolled patients who were aged 0-18 years with newly diagnosed acute lymphoblastic leukaemia that was subsequently in continuous remission for 1 year after initial treatment. Patients with secondary malignancy or primary immunodeficiency were excluded. Eligible patients were classified as having low-risk, intermediate-risk, or high-risk acute lymphoblastic leukaemia based on minimal residual disease and immunophenotypic and genetic features of leukaemic cells. Randomisation and analyses were done separately for the low-risk and intermediate-to-high-risk cohorts. Randomisation was generated by the study biostatistician with a block size of six. Stratification factors included participating centre, sex, and age at diagnosis; the low-risk cohort was additionally stratified for ETV6-RUNX1 status, and the intermediate-to-high-risk cohort for cell lineage. Patients in each risk cohort were randomly assigned (1:1) to either receive (ie, the control group) or not receive (ie, the experimental group) seven pulses of intravenous vincristine (1·5 mg/m2) plus oral dexamethasone (6 mg/m2 per day for 7 days) during the second year of treatment. The primary endpoint was difference in 5-year event-free survival between the experimental group and the control group for both the low-risk and intermediate-to-high-risk cohorts, with a non-inferiority margin of 0·05 (5%). The analysis was by intention to treat. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-14005706. FINDINGS: Between Jan 1, 2015, and Feb 20, 2020, 6141 paediatric patients with newly diagnosed acute lymphoblastic leukaemia were registered to this study. Approximately 1 year after diagnosis and treatment, 5054 patients in continuous remission were randomly assigned, including 2923 (1442 in the control group and 1481 in the experimental group) with low-risk acute lymphoblastic leukaemia and 2131 (1071 control, 1060 experimental) with intermediate-to-high risk acute lymphoblastic leukaemia. Median follow-up for patients who were alive at the time of analysis was 3·7 years (IQR 2·8-4·7). Among patients with low-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (90·3% [95% CI 88·4-92·2] vs 90·2% [88·2-92·2]; p=0·90). The one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·024, establishing non-inferiority. Among patients with intermediate-to-high-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (82·8% [95% CI 80·0-85·7] vs 80·8% [77·7-84·0]; p=0·90), but the one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·055, giving a borderline inferior result for those in the experimental group. In the low-risk cohort, we found no differences in the rates of infections, symptomatic osteonecrosis, or other complications during the second year of maintenance treatment between patients in the control and experimental groups. Patients with intermediate-to-high-risk acute lymphoblastic leukaemia in the control group were more likely to develop grade 3-4 pneumonia (26 [2·4%] of 1071 vs ten [0·9%] of 1060) and vincristine-related peripheral neuropathy (17 [1·6%] vs six [0·6%]) compared with the experimental group. Incidence of grade 5 fatal infection was similar between the control group and the experimental group in both the low-risk cohort (two [0·1%] of 1442 vs five [0·3%] of 1481) and intermediate-to-high risk cohort (six [0·6%] of 1071 vs five [0·5%] of 1060). INTERPRETATION: Vincristine plus dexamethasone pulses might be omitted beyond 1 year of treatment for children with low-risk acute lymphoblastic leukaemia. Additional studies are needed for intermediate-to-high-risk acute lymphoblastic leukaemia. FUNDING: VIVA China Children's Cancer Foundation, the National Natural Science Foundation of China, the China fourth round of Three-Year Public Health Action Plan (2015-2017), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
Assuntos
Dexametasona/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Vincristina/administração & dosagem , Adolescente , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Quimioterapia de Manutenção , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Intervalo Livre de Progressão , Pulsoterapia , Recidiva , Taxa de SobrevidaRESUMO
OBJECTIVES: To carry out a review of clinical characteristics, laboratory profiles, management and outcomes of patients with Kawasaki disease (KD) and macrophage activation syndrome (MAS). METHODS: Medical records of patients treated for KD and MAS between January 1994 and December 2019 were reviewed. Patient demographics, clinical signs, laboratory values, coronary artery abnormalities, treatments and outcomes of patients with KD and MAS were recorded. We also performed a review published studies on the subject. RESULTS: Of the 950 cases with KD, 12 (1.3%; 10 boys, 2 girls) were diagnosed with MAS. The median age at diagnosis was 4 years (range 9 months-7.5 years). The median interval between onset of fever and diagnosis of KD was 11 days (range 6-30). Thrombocytopenia was seen in 11 patients. The median pro-brain natriuretic peptide value was 2101 pg/ml (range 164-75 911). Coronary artery abnormalities were seen in 5 (41.7%) patients; 2 had dilatation of the left main coronary artery (LMCA), 1 had dilatation of both the LMCA and right coronary artery (RCA), 1 had dilatation of the RCA and 1 had bright coronary arteries. All patients received IVIG as first-line therapy for KD. MAS was treated with i.v. methylprednisolone pulses followed by tapering doses of oral prednisolone. Additional therapy included i.v. infliximab (n = 4), second-dose IVIG (n = 1) and oral ciclosporin (n = 1). CONCLUSION: MAS is an unusual and underrecognized complication of KD. In our cohort of 950 patients with KD, 1.3% had developed MAS. KD with MAS is associated with an increased propensity towards development of coronary artery abnormalities.
Assuntos
Glucocorticoides/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndrome de Ativação Macrofágica/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Criança , Pré-Escolar , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/fisiopatologia , Feminino , Humanos , Índia , Lactente , Infliximab/uso terapêutico , Síndrome de Ativação Macrofágica/sangue , Síndrome de Ativação Macrofágica/complicações , Síndrome de Ativação Macrofágica/fisiopatologia , Masculino , Metilprednisolona/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Prednisolona/uso terapêutico , Pulsoterapia , Atenção Terciária à Saúde , Trombocitopenia/sangueRESUMO
BACKGROUND: To observe the effect of corticosteroids in the treatment of children with refractory Mycoplasma pneumoniae pneumonia (RMPP) under different doses, to summarize the clinical features of children treated with glucocorticoid pulse therapy. METHODS: The clinical data of 125 children with RMPP hospitalized in Tianjin Children's Hospital from September 2018 to October 2019 were retrospectively analyzed. They were divided into two groups according to the dose of hormone. Compare the clinical features, laboratory findings, and imaging between the two groups, and use meaningful related indicators as ROC curves to find reference indicators for pulse therapy. RESULTS: (1) The median age of the group II was older than that of the group I(P < 0.05). (2) We found more severe presentations, higher incidence of extra-pulmonary complications and more serious radiological findings in group II, which needed oxygen more often, higher the hormone, higher usage rate of gamma globulin, higher usage rate of bronchoscopy, and higher incidence of plastic bronchitis(P < 0.05). (3) WBC, CRP, LDH, FER, D-D dimer, APTT, TT, PCT, IL-6 and the percentage of neutrophils in peripheral blood in Group II were higher than those in Group I(P < 0.05). (4) In ROC curve analysis, CRP, LDH, FER, and neutrophils of leukocyte classification were independent related factors that could be used as valuable predictors of methylprednisolone pulse therapy for RMPP in children. The cut-off values were CRP44.45 mg/L, LDH590IU/L, FER411ng/L, and neutrophils in leukocyte classification were 73.75%, respectively. CONCLUSION: CRP ≥ 44.45 mg/L, LDH ≥ 590 IU/L, FER ≥ 411 ng/L, neutrophil≥73.75%, lung consolidation, and pleural effusion may be predictors that guide the treatment of RMPP with pulse dose of GC.
Assuntos
Glucocorticoides/administração & dosagem , Mycoplasma pneumoniae , Pneumonia por Mycoplasma/tratamento farmacológico , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/patologia , Pulsoterapia , Curva ROC , Recidiva , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) is thought to cause kidney injury via a variety of mechanisms. The most common reported kidney injury following COVID-19 infection is acute tubular injury (ATI); however, the procoagulant state induced by the virus may also damage the kidneys. CASE-DIAGNOSIS/TREATMENT: Herein, we report two cases of acute necrotizing glomerulonephritis (GN) with fibrinoid necrosis in the context of COVID-19 infection. The one with more chronic features in the kidney biopsy progressed to permanent kidney failure but the second one had an excellent response to glucocorticoid pulse therapy with subsequent normal kidney function at 2-month follow-up. CONCLUSIONS: Both reported cases had an acute presentation of kidney injury with positive nasopharyngeal PCR test for COVID-19. Based on the data review by the researchers, this is the first report of acute necrotizing GN associated with COVID-19 infection.
Assuntos
Injúria Renal Aguda/etiologia , COVID-19/complicações , Glomerulonefrite/etiologia , Glomérulos Renais/patologia , SARS-CoV-2/patogenicidade , Injúria Renal Aguda/patologia , Injúria Renal Aguda/terapia , Adolescente , Biópsia , Coagulação Sanguínea , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/virologia , Glomerulonefrite/patologia , Glomerulonefrite/terapia , Glucocorticoides/administração & dosagem , Humanos , Glomérulos Renais/irrigação sanguínea , Masculino , Necrose/imunologia , Necrose/patologia , Contagem de Plaquetas , Pulsoterapia , Diálise Renal , SARS-CoV-2/isolamento & purificação , Resultado do TratamentoRESUMO
BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a severe and life-threatening disease. Given its heterogeneous clinical presentation, the phenotype of TTP during pregnancy and its management have not been well documented. CASE PRESENTATION: We report here a 25-year-old woman, G1P0 at 36 weeks gestation, who developed severe thrombocytopenia and anemia. She was performed an emergent caesarean section 1 day after admission because of multiple organ failure. As ADAMTS 13 enzyme activity of the patient was 0% and antibodies were identified by enzyme-linked immunosorbent assay, she was diagnosed as acquired thrombotic thrombocytopenic purpura (aTTP). Furthermore, asymptomatic primary Sjögren's syndrome was incidentally diagnosed on screening. After treatment with rituximab in addition to PEX and steroids, the activity of the ADAMTS 13 enzyme increased significantly from 0 to 100%. CONCLUSIONS: To the best of our knowledge, this is the first case report of concomitant TTP and asymptomatic Sjögren's syndrome in a pregnant woman. It highlights the association between pregnancy, autoimmune disease, and TTP. It also emphasizes the importance of an enzyme-linked immunosorbent assay in the diagnosis and rituximab in the treatment of patients with acquired TTP.
Assuntos
Proteína ADAMTS13 , Complicações na Gravidez/diagnóstico , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/diagnóstico , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Corticosteroides/administração & dosagem , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Troca Plasmática , Gravidez , Complicações na Gravidez/terapia , Pulsoterapia , Púrpura Trombocitopênica Trombótica/terapia , Rituximab/uso terapêutico , Síndrome de Sjogren/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) still is a global emergency. According to the studies, pregnant women are of the at risk populations and any underlying disease(s) might even worsen their condition. The aim of this study is reporting a complex case of immune thrombocytopenic purpura (ITP) during pregnancy who has been diagnosed with COVID-19 as well as suspicion of HELLP syndrome. CASE PRESENTATION: A 24-year-old woman with a platelet count of 6000/mL and resistance to conventional therapies was referred. A day after starting 0.5 g/day of methylprednisolone for her, fever and a decrease in SpO2 presented. According to the paraclinical investigations, COVID-19 was diagnosed and the conventional COVID-19 treatments started for her (the methylprednisolone pulse stopped). Due to the increased liver enzymes and low platelet count, with suspicion of HELLP syndrome, cesarean section surgery was performed which resulted in a healthy neonate. Then, the methylprednisolone pulse was restarted for and she developed an increase in the platelet count. CONCLUSION: It is not clear how COVID-19 and pregnancy affected the patient's condition and the underlying disease; however, it seems the delivery and/or restarting the methylprednisolone pulses caused improvement in her condition.
Assuntos
COVID-19/diagnóstico , Metilprednisolona/administração & dosagem , Complicações Hematológicas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/diagnóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Antivirais/uso terapêutico , COVID-19/complicações , COVID-19/virologia , Cesárea , Resistência a Medicamentos , Feminino , Síndrome HELLP/diagnóstico , Humanos , Recém-Nascido , Masculino , Contagem de Plaquetas , Gravidez , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Pulsoterapia , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/diagnóstico , SARS-CoV-2/isolamento & purificação , Resultado do Tratamento , Adulto Jovem , Tratamento Farmacológico da COVID-19RESUMO
PURPOSE: Glucocorticoids are a mainstay treatment for Graves' orbitopathy, yet their exact mechanisms of action remain unclear. We aimed to determine whether the therapeutic effects of systemic steroid therapy in Graves' orbitopathy are mediated by changes in regulatory T lymphocytes (Tregs) and T helper 17 lymphocytes (Th17). METHODS: We assessed Treg and Th17 levels in the peripheral blood of 32 patients with active, moderate-to-severe Graves' orbitopathy who received 12 weekly pulses of methylprednisolone, and determined their association with disease severity, disease activity, and treatment outcomes. The acute orbitopathy phase was confirmed based on clinical evaluation and magnetic resonance imaging, and assessed using the clinical activity score (CAS). The severity of the disease was classified according to ETA/EUGOGO guidelines, and quantified based on the total eye score. Treatment response was determined based on specific criteria (e.g., changes in CAS score, diplopia grade, visual acuity, etc.). Treg and Th17 cells were identified using flow cytometry. RESULTS: Methylprednisolone treatment improved the activity of the disease and altered the Th17/Treg balance (i.e., the percentage of Tregs decreased while the number of Th17 cells remained unchanged). There was no association between the Treg/Th17 ratio and the activity and severity of the disease or the treatment response. CONCLUSIONS: Therapeutic effects of steroid therapy in Graves' orbitopathy are not mediated by Treg and Th17 alterations in the peripheral blood. The decrease in peripheral Treg percentage is likely a consequence of the non-specific effects of steroids and does not impact clinical outcome.
Assuntos
Oftalmopatia de Graves , Contagem de Linfócitos/métodos , Metilprednisolona/administração & dosagem , Pulsoterapia/métodos , Linfócitos T Reguladores/patologia , Células Th17/patologia , Diplopia/diagnóstico , Diplopia/tratamento farmacológico , Diplopia/etiologia , Monitoramento de Medicamentos/métodos , Feminino , Citometria de Fluxo/métodos , Glucocorticoides/administração & dosagem , Oftalmopatia de Graves/sangue , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/tratamento farmacológico , Oftalmopatia de Graves/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Índice de Gravidade de Doença , Resultado do Tratamento , Acuidade VisualRESUMO
Background/aim: High-dose steroid has been shown to reduce the mortality rate in Corona virus disease 2019 (COVID-19) patients who need oxygen support. Here, we evaluated the effectiveness of pulse-steroid in case of unresponsiveness to treatment with high dose steroid. Materials and methods: The study is a retrospective controlled trial. We divided the patients in 3 groups: standard-care therapy alone, high-dose steroid treatment (6 mg/day dexamethasone equivalent), and pulse-steroid treatment (250 mg/day methyl-prednisolone). One hundred and fifty patients were enrolled in each group. All patients were hospitalized and needed oxygen support. We matched the patients according to disease severity at the onset of hypoxia, weight of co-morbidities, age, and sex. We then compared 3 groups in terms of mortality, length of hospitalization, need for intensive care unit (ICU) admission and mechanical ventilation (MV), length of stay in ICU, and duration of MV. Results: The pulse-steroid group had shorter ICU stay. The median ICU stay was 9.0 (CI 95% 6.012.0) days in standard-care group, 8.0 (CI 95% 5.013.0) days in high-dose steroid group and 4.5(CI %95 3.08.0) days in pulse-steroid group. Moreover, although patients in pulse-steroid group were initially unresponsive to high dose steroid therapy, they achieved similar results compared to the high-dose steroid group in other outcomes except for length of hospital stay. Conclusion: Pulse-steroid treatment would be an option for COVID-19 patients who do not respond to the initial high-dose steroid treatment.
Assuntos
Tratamento Farmacológico da COVID-19 , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Metilprednisolona/administração & dosagem , Idoso , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pulsoterapia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: There are no determined treatment agents for severe COVID-19. It is suggested that methylprednisolone, as an immunosuppressive treatment, can reduce the inflammation of the respiratory system in COVID-19 patients. METHODS: We conducted a single-blind, randomised controlled clinical trial involving severe hospitalised patients with confirmed COVID-19 at the early pulmonary phase of the illness in Iran. The patients were randomly allocated in a 1:1 ratio by the block randomisation method to receive standard care with methylprednisolone pulse (intravenous injection, 250â mg·day-1 for 3â days) or standard care alone. The study end-point was the time of clinical improvement or death, whichever came first. Primary and safety analysis was done in the intention-to-treat (ITT) population. RESULTS: 68 eligible patients underwent randomisation (34 patients in each group) from April 20, 2020 to June 20, 2020. In the standard care group, six patients received corticosteroids by the attending physician before the treatment and were excluded from the overall analysis. The percentage of improved patients was higher in the methylprednisolone group than in the standard care group (94.1% versus 57.1%) and the mortality rate was significantly lower in the methylprednisolone group (5.9% versus 42.9%; p<0.001). We demonstrated that patients in the methylprednisolone group had a significantly increased survival time compared with patients in the standard care group (log-rank test: p<0.001; hazard ratio 0.293, 95% CI 0.154-0.556). Two patients (5.8%) in the methylprednisolone group and two patients (7.1%) in the standard care group showed severe adverse events between initiation of treatment and the end of the study. CONCLUSIONS: Our results suggest that methylprednisolone pulse could be an efficient therapeutic agent for hospitalised severe COVID-19 patients at the pulmonary phase.
Assuntos
Anti-Inflamatórios/administração & dosagem , Tratamento Farmacológico da COVID-19 , Metilprednisolona/administração & dosagem , Adulto , Idoso , Feminino , Hospitalização , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Pulsoterapia , Índice de Gravidade de Doença , Método Simples-CegoRESUMO
OBJECTIVES: In patients with LN, clinical and histological responses to treatment have been shown to be discordant. We investigated whether per-protocol repeat kidney biopsies are predictive of LN relapses and long-term renal function impairment. METHODS: Forty-two patients with incident biopsy-proven active proliferative (class III/IV±V) LN from the database of the UCLouvain were included in this retrospective study. Per-protocol repeat biopsies were performed after a median [interquartile range (IQR)] time of 24.3 (21.3-26.2) months. The National Institutes of Health activity index (AI) and chronicity index (CI) scores were assessed in all biopsies. RESULTS: Despite a moderate correlation between urinary protein/creatinine ratios (UPCR) and AI scores at repeat biopsy (r = 0.48; P = 0.001), 10 patients (23.8%) with UPCR < 1.0 g/g still had a high degree of histological activity (AI > 3). High AI scores (continuous) in repeat biopsies were associated with an increased probability and/or shorter time to renal relapse (n = 11) following the repeat biopsy [hazard ratio (HR) = 1.2, 95% CI: 1.1, 1.3; P = 0.007], independently of proteinuria levels. High CI scores (continuous) in repeat biopsies were associated with a sustained increase in serum creatinine levels corresponding to ≥120% of the baseline value (HR = 1.8, 95% CI: 1.1, 2.9; P = 0.016) through a median (IQR) follow-up time of 131.5 (73.8-178.2) months, being also the case for acute tubulointerstitial inflammation and interstitial fibrosis/tubular atrophy in repeat but not baseline biopsies. CONCLUSION: Our results highlight the usefulness of per-protocol repeat biopsies, herein performed after a median time of 24 months from baseline, as an integral part of the treatment evaluation, also in patients showing adequate clinical response.
Assuntos
Rim/patologia , Nefrite Lúpica/patologia , Adulto , Biópsia , Creatinina/urina , Ciclofosfamida/uso terapêutico , Progressão da Doença , Feminino , Glucocorticoides/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Túbulos Renais/patologia , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/urina , Masculino , Metilprednisolona/uso terapêutico , Ácido Micofenólico/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Proteinúria/urina , Pulsoterapia , Recidiva , Estudos Retrospectivos , Rituximab/uso terapêutico , Adulto JovemRESUMO
OBJECTIVES: SSc is a autoimmune disease characterized by fibrosis of the skin and internal organs. There is a lack of evidence for the efficacy of i.v. CYC pulse therapy on skin thickening. We aimed to examine the response of i.v. CYC pulse therapy on skin thickening in our cohort of SSc patients and analysed factors that predict this response. METHODS: We retrospectively evaluated the data for 143 patients with SSc from baseline to 12, 24 and 36 months. All patients were treated with at least 6 i.v. CYC pulses (750 mg/m2/month). We applied the modified Rodnan Skin Score (mRSS) to assess skin thickening. A clinically relevant response was defined as a decrease in mRSS of 5 points and 25% from baseline. Different baseline variables for predicting response on month 12 were tested in logistic regression analyses. RESULTS: Baseline characteristics of the patients with dcSSc and lcSSc were collected. Forty-three percent (n = 42) of dcSSc patients had a clinically relevant response on month 12. Non-responding on month 6 predicts non-response on month 12 (odds ratio 37.1; 95% CI 4.5, 306.4). CONCLUSION: We concluded that i.v. CYC pulse therapy should be considered as an effective treatment option for skin thickening in dcSSc patients, because 43% of this group of patients were found to have a clinically relevant response. Of the dcSSC patients who did not respond by month 6, only 29% had a response by month 12. This finding can help the physician and patient in shared decision making about whether or not to continue therapy.
Assuntos
Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Pele , Adulto , Idoso , Feminino , Humanos , Infusões Intravenosas , Modelos Logísticos , Estudos Longitudinais , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pulsoterapia , Estudos Retrospectivos , Escleroderma Sistêmico/complicações , Resultado do TratamentoRESUMO
Childhood onset chronic inflammatory demyelinating polyneuropathy (CIDP) often requires long-term immunomodulatory therapy. We report a comprehensive review of our treatment of pediatric CIDP with a focus on high-dose weekly corticosteroids ("pulse oral corticosteroids"), a treatment method that is not commonly reported. We retrospectively reviewed medical records of pediatric patients with CIDP treated at our center between 2000 and 2018 for whom we had at least 12 mo follow-up. Here, we describe the demographics, disease course, treatment regimens, and long-term outcomes of these patients. Twenty-five patients were identified for analysis. Pulse oral corticosteroid monotherapy was the predominant maintenance treatment in 56% of patients. Patients were followed for a median of 4 y. Side effects were seen in a minority of patients. The probability of a normal exam or being off treatment at last follow-up was similar regardless of predominant maintenance therapy. Pulse oral corticosteroid therapy is a safe and effective long-term treatment option in children with CIDP.
Assuntos
Glucocorticoides/administração & dosagem , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Prednisona/administração & dosagem , Administração Oral , Adolescente , Corticosteroides/administração & dosagem , Criança , Pré-Escolar , Duração da Terapia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lactente , Humor Irritável , Quimioterapia de Manutenção , Masculino , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/fisiopatologia , Pulsoterapia , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Aumento de Peso , Adulto JovemRESUMO
BACKGROUND: Intravesical administration of Bacillus Calmette-Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy. CASE PRESENTATION: A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident. CONCLUSIONS: We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.
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Antituberculosos/uso terapêutico , Vacina BCG/efeitos adversos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/etiologia , Esteroides/uso terapêutico , Exacerbação dos Sintomas , Administração Intravesical , Idoso , Autopsia , Vacina BCG/administração & dosagem , Vacina BCG/uso terapêutico , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/prevenção & controle , Evolução Fatal , Humanos , Doenças Pulmonares Intersticiais/microbiologia , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium bovis/genética , Resultados Negativos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Pulsoterapia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/prevenção & controleRESUMO
Solid organ transplant recipients are considered at high risk for COVID-19 infection due to chronic immune suppression; little data currently exists on the manifestations and outcomes of COVID-19 infection in lung transplant recipients. Here we report 8 cases of COVID-19 identified in patients with a history of lung transplant. We describe the clinical course of disease as well as preexisting characteristics of these patients.
Assuntos
COVID-19/fisiopatologia , Infecção Hospitalar/fisiopatologia , Imunossupressores/uso terapêutico , Transplante de Pulmão , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Adulto , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , COVID-19/diagnóstico por imagem , COVID-19/imunologia , COVID-19/terapia , Tosse/fisiopatologia , Infecção Hospitalar/diagnóstico por imagem , Infecção Hospitalar/imunologia , Infecção Hospitalar/terapia , Fibrose Cística/cirurgia , Dispneia/fisiopatologia , Feminino , Febre/fisiopatologia , Gastroenteropatias/fisiopatologia , Glucocorticoides/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Humanos , Fibrose Pulmonar Idiopática/cirurgia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Pulmão/diagnóstico por imagem , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Pancreatite Necrosante Aguda , Doença Pulmonar Obstrutiva Crônica/cirurgia , Pulsoterapia , SARS-CoV-2 , Sepse , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: We investigated the efficacy of methylprednisolone pulse therapy (MP) and responder characteristics in patients with refractory epilepsy. METHODS: We reviewed medical records of our center to identify patients with refractory epilepsy treated with MP other than continuous spikes and waves during slow sleep (CSWS), Landau-Kleffner syndrome (LKS), or Rasmussen's syndrome (RS) between 2004 and 2015. A course of MP consisted of intravenous methylprednisolone (30â¯mg/kg/day) on three consecutive days. Patients received multiple courses at intervals of four weeks. We examined seizure outcome, developmental outcome, antibodies to N-methyl-d-aspartate (NMDA)-type glutamate receptors (GluRs), cerebral spinal fluid (CSF)-albumin/serum-albumin ratio, and interictal electroencephalograms (EEGs). Responder to MP was defined as maintaining seizure reduction rate (SRR) ≥50% for three months after the first course of MP. RESULTS: Thirty-one consecutive patients treated with MP at our center were studied. Seizure types were focal onset impaired awareness seizure (FIAS) only (nâ¯=â¯23), FIAS with epileptic spasms (ES) (nâ¯=â¯7), and ES only (nâ¯=â¯1). Responder rate was 32.2% (10/31 patients), and seizure-free rate was 9.7% (3/31). Responders constituted 43.5% of patients without ES. No patient with ES was responder. Behavior and cognition also improved in 6 of 10 responders. History of seizure aggravation after inactivated vaccine before MP was found significantly higher rate in responder patients, comparing with nonresponder patients (pâ¯=â¯0.01). CONCLUSION: Methylprednisolone pulse therapy may be considered for possible treatment in patients with focal epilepsy with drug-resistant seizures without ES, and it may improve cognitive function and behavioral comorbidities.
Assuntos
Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Metilprednisolona/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Administração Intravenosa , Adolescente , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/psicologia , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Pulsoterapia/métodos , Estudos Retrospectivos , Adulto JovemRESUMO
Patients with steroid-resistant nephrotic syndrome (SRNS) who develop resistance to immunosuppressive agents, defined as refractory SRNS, have poor renal outcomes. Although the chimeric anti-CD20 monoclonal antibody rituximab has shown efficacy for frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome, its efficacy for refractory SRNS remains uncertain due to limited data. According to previous case reports, 50.4% of patients with refractory SRNS showed clinical improvements after rituximab treatment. Remission rates in patients with initial steroid resistance and late steroid resistance were 43.9 and 57.7%, respectively, and 41.5 and 63.6% in patients with focal segmental glomerulosclerosis and minor glomerular abnormalities, respectively. However, various factors (race, disease severity, number of rituximab doses, concomitant treatments, and observation period) differed among these observational studies and their consensus may also have been affected by potential publication bias. Rituximab monotherapy may have some degree of efficacy and lead to satisfactory outcomes in a subset of patients with refractory SRNS. However, administration of concomitant treatments during rituximab-mediated B cell depletion, such as methylprednisolone pulse therapy, daily oral prednisolone therapy, and immunosuppressive agents, may lead to better outcomes in these patients. Large-scale, multi-center prospective studies are needed to evaluate the efficacy and safety of such regimens.