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1.
J Med Virol ; 94(1): 349-356, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34542192

RESUMO

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 , COVID-19/tratamento farmacológico , 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 fármacos
2.
J Med Virol ; 94(1): 372-379, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34559436

RESUMO

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 , COVID-19/tratamento farmacológico , 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 fármacos
3.
J Med Virol ; 94(1): 291-297, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34491575

RESUMO

Due to current advances and growing experience in the management of coronavirus Disease 2019 (COVID-19), the outcome of COVID-19 patients with severe/critical illness would be expected to be better in the second wave compared with the first wave. As our hospitalization criteria changed in the second wave, we aimed to investigate whether a favorable outcome occurred in hospitalized COVID-19 patients with only severe/critical illness. Among 642 laboratory-confirmed hospitalized COVID-19 patients in the first wave and 1121 in the second wave, those who met World Health Organization (WHO) definitions for severe or critical illness on admission or during follow-up were surveyed. Data on demographics, comorbidities, C-reactive protein (CRP) levels on admission, and outcomes were obtained from an electronic hospital database. Univariate analysis was performed to compare the characteristics of patients in the first and second waves. There were 228 (35.5%) patients with severe/critical illness in the first wave and 681 (60.7%) in the second wave. Both groups were similar in terms of age, gender, and comorbidities, other than chronic kidney disease. Median serum CRP levels were significantly higher in patients in the second wave compared with those in the first wave [109 mg/L (interquartile range [IQR]: 65-157) vs. 87 mg/L (IQR: 39-140); p < 0.001]. However, intensive care unit admission and mortality rates were similar among the waves. Even though a lower mortality rate in the second wave has been reported in previous studies, including all hospitalized COVID-19 patients, we found similar demographics and outcomes among hospitalized COVID-19 patients with severe/critical illness in the first and second wave.


Assuntos
COVID-19/tratamento farmacológico , COVID-19/mortalidade , Cuidados Críticos/estatística & dados numéricos , Índice de Gravidade de Doença , Idoso , Amidas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Azitromicina/uso terapêutico , Proteína C-Reativa/análise , COVID-19/epidemiologia , COVID-19/patologia , Comorbidade , Combinação de Medicamentos , Enoxaparina/uso terapêutico , Feminino , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Humanos , Hidroxicloroquina/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Pirazinas/uso terapêutico , Estudos Retrospectivos , Ritonavir/uso terapêutico , SARS-CoV-2 , Resultado do Tratamento , Turquia/epidemiologia
4.
Medicine (Baltimore) ; 100(41): e27351, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731107

RESUMO

BACKGROUND: Guillain-Barre syndrome (GBS) is a disease with the features of acuteness, paralysis, inflammation, and in peripheral nerves. There are many current treatment options with varying efficacy, and to assess their effectiveness, we performed a network meta-analysis (NMA). The study protocol was registered at PROSPERO (CRD: 42019119178). Posted history: this manuscript was previously posted to medRxiv: doi: https://doi.org/10.1101/2020.06.03.20121780. METHODS: The literature search database includes Web of Science, PubMed, Embase, and the Cochrane library that meets the requirements. We performed the NMA using controlled trials with 2 kinds of outcomes. We used the gemtc R package to perform the NMA to evaluate different GBS treatments' relative results. The consistency of direct and indirect evidence was also assessed by R software with gemtc package. RESULTS: This NMA study included a total of 2474 subjects from 28 trials with 15 kinds of therapies. No improvement was observed in methylprednisolone and prednisolone compared with placebo. Conversely, plasma exchange (PE) and intravenous immunoglobulin (IVIg) were more effective than placebo. There was no significant difference between different doses and courses of PE and IVIg. For combination treatment, such as IVIg+eculizumab, immunoadsorption followed by IVIg and PE followed by IVIg, they didn't show significant advantages than IVIg and PE in NMA. On the consistency examination between direct and indirect evidence, there was no apparent heterogeneity between them. Funnel plots indicated there was little possibility of publication bias in this study. CONCLUSION: PE or IVIg has significant efficacy for GBS patients. The effects of several kinds of therapies should be further explored. Corticosteroids have no considerable impact on GBS.


Assuntos
Síndrome de Guillain-Barré/terapia , Avaliação de Resultados em Cuidados de Saúde , Terapia Combinada , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Metilprednisolona/uso terapêutico , Metanálise em Rede , Troca Plasmática
5.
DNA Cell Biol ; 40(11): 1396-1406, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34767734

RESUMO

Sepsis has become a major public health problem worldwide. Methylprednisolone sodium succinate (MP) is a commonly used drug to prevent inflammation. However, the role and underlying mechanism of MP in sepsis remain vague. MP inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-17 and suppressed cell growth in alveolar type II epithelial cells (ATII cells). Small nucleolar RNA host gene 5 (SNHG5) expression was inhibited by LPS and restored by MP. Upregulation of SNHG5 inhibited the cellular role of LPS in ATII cells, and further, downregulation of SNHG5 inhibited the cellular role of MP in ATII cells under LPS conditions. SNHG5 elevated the expression of Copine 1 (CPNE1) by enhancing the mRNA stability of CPNE1. Increasing CPNE1 expression restored the silenced SNHG5-induced inhibitor role of MP in ATII cells under LPS conditions. Finally, MP attenuated lung injury and TNF-α and IL-17 secretion in an LPS-induced sepsis mouse model. Overall, this study investigated the mechanism underlying the effect of MP treatment in sepsis and, for the first time, revealed the important role of the SNHG5/CPNE1 pathway in the development and treatment of sepsis and the potential to serve as a diagnostic and therapeutic target for sepsis.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Metilprednisolona/farmacologia , Sepse/tratamento farmacológico , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/genética , Proteínas de Transporte , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/genética , Feminino , Inflamação , Lipopolissacarídeos/farmacologia , Metilprednisolona/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Nucleolar Pequeno/genética , Sepse/metabolismo , Transdução de Sinais/efeitos dos fármacos
6.
BMJ Case Rep ; 14(11)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34799390

RESUMO

This is a case of a young woman who developed neurological and psychiatric symptoms 3 days after resection of an immature teratoma. She was diagnosed with anti-NMDA receptor encephalitis via positive serum antibody titres, which was later confirmed with cerebrospinal fluid antibody titres. Given her cancer diagnosis, she underwent treatment with bleomycin, etoposide and cisplatin chemotherapy in addition to 5 days of high-dose steroids (1 g of intravenous methylprednisolone) for the encephalitis. This treatment regimen led to significant clinical improvement 3 weeks after completion of one cycle of chemotherapy.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Neoplasias Ovarianas , Teratoma , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Feminino , Humanos , Metilprednisolona/uso terapêutico , Receptores de N-Metil-D-Aspartato , Teratoma/tratamento farmacológico , Teratoma/cirurgia
7.
J Med Case Rep ; 15(1): 497, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620236

RESUMO

BACKGROUND: Macrophage activation syndrome is classified as a secondary form of hemophagocytic lymphohistiocytosis. It is a hyperinflammatory complication observed to be comorbid with a variety of autoimmune diseases, including adult-onset Still's disease and systemic juvenile idiopathic arthritis. Macrophage activation syndrome is less commonly detected in adult patients with systemic lupus erythematosus, which, if untreated, can be fatal, though determining the optimum treatment strategy is still a challenge. CASE PRESENTATION: Herein, we report a case of macrophage activation syndrome in a 33-year-old Egyptian female as an unusual complication of a systemic lupus erythematosus flare in adult patients. Our patient was initially treated with a combination of intravenous methylprednisolone pulse therapy and intravenous immunoglobulin therapy, which was followed by a course of oral prednisolone and oral cyclosporine with little response. Switching from oral prednisone to intravenous dexamethasone sodium phosphate showed a more favorable clinical and biochemical response. CONCLUSION: Macrophage activation syndrome is less commonly detected in adult patients with systemic lupus erythematosus. Our case demonstrates that dexamethasone sodium phosphate can be a successful alternative treatment for patients with systemic lupus erythematosus complicated by macrophage activation syndrome in whom the response to pulse methylprednisolone was inadequate to manage their illness, proving to be remarkably effective in a relatively short time frame.


Assuntos
Lúpus Eritematoso Sistêmico , Síndrome de Ativação Macrofágica , Adulto , Ciclosporina/uso terapêutico , Dexametasona/análogos & derivados , Feminino , Humanos , Imunoglobulinas Intravenosas , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Síndrome de Ativação Macrofágica/tratamento farmacológico , Síndrome de Ativação Macrofágica/etiologia , Metilprednisolona/uso terapêutico
8.
JAMA Netw Open ; 4(10): e2127172, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34605919

RESUMO

Importance: Serum ferritin, an acute phase marker of inflammation, has several physiologic functions, including limiting intracellular oxidative stress. Whether the effectiveness of corticosteroids differs according to serum ferritin level in COVID-19 has not been reported. Objective: To examine the association between admission serum ferritin level and methylprednisolone treatment outcomes in nonintubated patients with severe COVID-19. Design, Setting, and Participants: This retrospective cohort study included patients with severe COVID-19 admitted to an academic referral center in Stony Brook, New York, from March 1 to April 15, 2020, receiving high-flow oxygen therapy (fraction of inspired oxygen, ≥50%). The outcomes of treatment with methylprednisolone were estimated using inverse probability of treatment weights, based on a propensity score comprised of clinical and laboratory variables. Patients were followed up for 28 days. Data were analyzed from December 19, 2020, to July 22, 2021. Exposures: Systemic methylprednisolone administered per the discretion of the treating physician. Main Outcomes and Measures: The primary outcome was mortality, and the secondary outcome was a composite of death or mechanical ventilation at 28 days. Results: Among 380 patients with available ferritin data (median [IQR] age, 60 years [49-72] years; 130 [34.2%] women; 250 [65.8%] men; 310 White patients [81.6%]; 47 Black patients [12.4%]; 23 Asian patients [6.1%]), 142 patients (37.4%) received methylprednisolone (median [IQR] daily dose, 160 [120-240] mg). Ferritin levels were similar in patients who received methylprednisolone vs those who did not (median [IQR], 992 [509-1610] ng/mL vs 893 [474-1467] ng/mL; P = .32). In weighted analyses using tertiles of ferritin values (lower: 29-619 ng/mL; middle: 623-1316 ng/mL; upper: 1322-13 418 ng/mL), methylprednisolone was associated with lower mortality in patients with ferritin in the upper tertile (HR, 0.16; 95% CI, 0.06-0.45) and higher mortality in those with ferritin in the middle (HR, 2.46; 95% CI, 1.15-5.28) and lower (HR, 2.43; 95% CI, 1.13-5.22) tertiles (P for interaction < .001). Composite end point rates were lower with methylprednisolone in patients with ferritin in the upper tertile (HR, 0.45; 95% CI, 0.25-0.80) but not in those with ferritin in the middle (HR, 0.83; 95% CI, 0.50-1.39) and lower (HR, 0.89; 95% CI, 0.51-1.55) tertiles (P for interaction = .11). Conclusions and Relevance: In this cohort study of nonintubated patients with severe COVID-19, methylprednisolone was associated with improved clinical outcomes only among patients with admission ferritin in the upper tertile of values.


Assuntos
Anti-Inflamatórios/uso terapêutico , COVID-19/tratamento farmacológico , Ferritinas/sangue , Inflamação/sangue , Metilprednisolona/uso terapêutico , Índice de Gravidade de Doença , Afro-Americanos , Idoso , Grupo com Ancestrais do Continente Asiático , COVID-19/sangue , COVID-19/mortalidade , COVID-19/terapia , Grupo com Ancestrais do Continente Europeu , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , New York , Oxigenoterapia , Pneumonia , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2 , Resultado do Tratamento
9.
Bratisl Lek Listy ; 122(11): 793-798, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34672670

RESUMO

OBJECTIVES: The aim of this study was to determine the efficacy of pulse steroid therapy administered to patients critically ill with COVID-19 progressing into severe pneumonia. METHODS: A total of 600 patients included in this retrospective study were divided into three groups. Group 1 (control group): 200 patients who did not receive steroid treatment, Group 2: 200 patients who received dexamethasone 1x8 milligram (mg) or methylprednisolone 1x80 mg, Group 3: (pulse steroid therapy group): 200 patients who received 1 g methylprednisolone followed by 1x80 mg methylprednisolone. Demographic and laboratory data were recorded. RESULTS: Mortality rates in groups 1, 2 and 3 were 77 %, 53.55 %, and 58.5 %, respectively. The ratios of intubated patients in groups 1, 2 and 3 were 70 %, 45.5 % and 56 %, respectively. The numbers of patients whose D­dimer values were above 2,250 ng/mL (cut-off value for D-dimer in this study) in groups 2, 1 and 3 were 65, 107, and 105, respectively. CONCLUSION: Pulse steroid therapy does not shorten the duration of hospital stay, does not reduce the need for intubation and increases the risk of thrombosis by significantly increasing the level of D-dimer among patients critically and severely ill with COVID-19 (Tab. 4, Fig. 3, Ref. 20) Keywords: COVID-19, pulse steroid therapy, thrombosis, d-dimer, corticosteroid.


Assuntos
COVID-19 , Estado Terminal , Humanos , Metilprednisolona , Estudos Retrospectivos , SARS-CoV-2
10.
BMJ Case Rep ; 14(10)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645637

RESUMO

Primary phlebitis of the central nervous system (PPCNS) is a rare condition that might be a subset of primary angiitis of the CNS. In this case report, the patient was a 39-year-old man with a 2-week history of anterograde amnesia and abnormal behaviours. Black-blood MRI (BB-MRI) showed contrast enhancement of the left basilar vein and cerebral superficial veins. Angiography showed unremarkable change in arteries. After a thorough differential diagnosis, we diagnosed PPCNS and then administered methylprednisolone pulse and cyclophosphamide pulse. The neuropsychological symptoms and MRI findings gradually improved, and after 2 months, the dose of prednisolone was gradually reduced to 20 mg. No recurrence was observed. This case shows that BB-MRI may be useful for diagnosing PPCNS.


Assuntos
Flebite , Vasculite do Sistema Nervoso Central , Adulto , Sistema Nervoso Central , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Metilprednisolona/uso terapêutico , Flebite/diagnóstico por imagem , Flebite/tratamento farmacológico , Vasculite do Sistema Nervoso Central/diagnóstico por imagem , Vasculite do Sistema Nervoso Central/tratamento farmacológico
11.
Medicine (Baltimore) ; 100(40): e27450, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622865

RESUMO

RATIONALE: Adult T-cell leukemia/lymphoma (ATL) and human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are caused by HTLV-1, but the coexistence of both disorders is rare. The estimated incidence is approximately 3%. PATIENT CONCERNS: A 54-year-old man was unable to stand up because of spastic paraparesis 1 month after the onset. He developed lymphadenopathy in the left supraclavicular fossa 5 months after the onset. The spastic paraplegia and sensory symptoms below the thoracic spinal cord level worsened. DIAGNOSES: Both blood and cerebrospinal fluid (CSF) tests were positive for anti-HTLV-1 antibodies. The patient was diagnosed with rapidly progressive HAM/TSP. He was also diagnosed with lymphoma-type ATL by the biopsy specimen of the lymph node. CSF examination at the time of symptom exacerbation showed abnormal lymphocytes, suggesting central infiltration of the ATL in the central nervous system. INTERVENTIONS: Methylprednisolone pulse therapy and oral prednisolone maintenance therapy were administered for rapidly progressive HAM/TSP. Intrathecal injection of methotrexate was administered for the suggested central infiltration of the ATL. OUTCOMES: Methylprednisolone pulse therapy and intrathecal injection of methotrexate did not improve the patient's exacerbated symptoms. Five months later, clumsiness and mild muscle weakness of the fingers appeared, and magnetic resonance imaging showed swelling of the cervical spinal cord. Clonality analysis showed monoclonal proliferation only in the DNA of a lymph node lesion, but not in the CSF and peripheral blood cells. LESSONS: This was a case of rapidly progressive HAM/TSP associated with lymphoma-type ATL that was refractory to steroids and chemotherapy. The pathogenesis was presumed to involve ATL cells in the brain and spinal cord because of the presence of abnormal lymphocytes in the CSF, but DNA analysis could not prove direct invasion. This case suggests that when we encounter cases with refractory HAM/TSP, it should be needed to suspect the presence of ATL in the background.


Assuntos
Leucemia-Linfoma de Células T do Adulto/complicações , Paraparesia Espástica Tropical/complicações , Feminino , Glucocorticoides/administração & dosagem , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Masculino , Metotrexato/administração & dosagem , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/tratamento farmacológico
12.
Am J Case Rep ; 22: e933847, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34716288

RESUMO

BACKGROUND Several cases of herpes simplex virus type 1 meningoencephalitis (HSVE) have been reported in patients receiving steroids, but the exact contribution of steroids to the disorder remains unclear because other risk factors, such as chemotherapy, brain radiation, or surgery, were present in almost all cases. CASE REPORT We report the case of a 76-year-old man who developed HSVE following the administration of pulse-dose steroids. The patient had occupational asbestos exposure and a chronic interstitial lung disease of unclear etiology (sarcoidosis versus hypersensitivity pneumonitis) and was admitted for acute-on-chronic respiratory failure requiring mechanical ventilation. After a negative infectious workup and several days of antibiotics without improvement, pulse-dose steroids were administered. In the following days, the patient developed a fever and worsening encephalopathy. A lumbar puncture showed elevated nucleated cells and positive polymerase chain reaction for herpes simplex virus 1 in the cerebrospinal fluid, confirming the diagnosis of HSVE. Acyclovir treatment was initiated, but the patient later died as a result of persistent severe encephalopathy and respiratory failure with an inability to wean mechanical ventilation. CONCLUSIONS Clinicians should keep in mind that HSVE is a potential complication of steroids and carefully consider the benefit/risk ratio of pulse-dose steroids, taking into account associated factors of immunosuppression. A high level of awareness should be especially maintained in critically ill patients because of associated risk factors (critical illness immune paralysis) and because neurological signs of HSVE may be missed in mechanically ventilated, sedated patients.


Assuntos
Encefalite por Herpes Simples , Herpesvirus Humano 1 , Meningoencefalite , Aciclovir/efeitos adversos , Idoso , Encefalite por Herpes Simples/diagnóstico , Encefalite por Herpes Simples/tratamento farmacológico , Humanos , Masculino , Meningoencefalite/induzido quimicamente , Meningoencefalite/diagnóstico , Metilprednisolona/efeitos adversos
14.
Drugs R D ; 21(4): 419-429, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34655050

RESUMO

OBJECTIVE: The aim of this study was to identify factors affecting blood concentrations of voriconazole following letermovir coadministration using population pharmacokinetic (PPK) analysis in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. METHODS: The following data were retrospectively collected: voriconazole trough levels, patient characteristics, concomitant drugs, and laboratory information. PPK analysis was performed with NONMEM® version 7.4.3, using the first-order conditional estimation method with interaction. We collected data on plasma voriconazole steady-state trough concentrations at 216 timepoints for 47 patients. A nonlinear pharmacokinetic model with the Michaelis-Menten equation was applied to describe the relationship between steady-state trough concentration and daily maintenance dose of voriconazole. After stepwise covariate modeling, the final model was evaluated using a goodness-of-fit plot, case deletion diagnostics, and bootstrap methods. RESULTS: The maximum elimination rate (Vmax) of voriconazole in patients coadministered letermovir and methylprednisolone was 1.72 and 1.30 times larger than that in patients not coadministered these drugs, respectively, resulting in decreased voriconazole trough concentrations. The developed PPK model adequately described the voriconazole trough concentration profiles in allo-HSCT recipients. Simulations clearly showed that increased daily doses of voriconazole were required to achieve an optimal trough voriconazole concentration (1-5 mg/L) when patients received voriconazole with letermovir and/or methylprednisolone. CONCLUSIONS: The development of individualized dose adjustment is critical to achieve optimal voriconazole concentration, especially among allo-HSCT recipients receiving concomitant letermovir and/or methylprednisolone.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Metilprednisolona , Acetatos , Antifúngicos , Humanos , Quinazolinas , Estudos Retrospectivos , Voriconazol
15.
An Acad Bras Cienc ; 93(suppl 4): e20210297, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34706009

RESUMO

Acute myocardial infarction (AMI) is one of the major causes of heart failure and mortality. Glucocorticoids administration post-infarction has long been proposed, but it has shown conflicting results so far. This controversy may be associated with the glucocorticoid type and the period when it is administered. To elucidate these, the present aims to evaluate if the brief methylprednisolone acetate administration is determinant for heart adaptation after AMI. Male Wistar rats were divided into 3 groups: sham-operated (SHAM); infarcted (AMI); infarcted treated with methylprednisolone acetate (AMI+M). Immediately after surgery, the AMI+M group received a single dose of methylprednisolone acetate (40 mg/kg i.m.). After 56 days, the cardiac function was assessed and lungs, liver and heart were collected to determine rates of hypertrophy and congestion. Heart was used for oxidative stress and metalloproteinase activity analyses. Methylprednisolone acetate attenuated matrix metalloproteinase-2 activity, cardiac dilatation, and prevented the onset of pulmonary congestion, as well as avoided cardiac hypertrophy. Our data indicate that administration of methylprednisolone acetate shortly after AMI may be a therapeutic alternative for attenuation of detrimental ventricular remodeling.


Assuntos
Metilprednisolona , Infarto do Miocárdio , Animais , Masculino , Metaloproteinase 2 da Matriz , Metilprednisolona/uso terapêutico , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Miocárdio , Ratos , Ratos Wistar , Remodelação Ventricular
16.
Medicine (Baltimore) ; 100(40): e27373, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622840

RESUMO

BACKGROUND: Since the start of the coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need for effective therapies for patients with COVID-19. In this study, we aimed to assess the therapeutic efficacy of glucocorticoids in severe COVID-19. METHODS: A systematic literature search was performed across PubMed, Web of Science, EMBASE, and the Cochrane Library (up to June 26, 2021). The literature investigated the outcomes of interest were mortality and invasive mechanical ventilation. RESULTS: The search identified 13 studies with 6612 confirmed severe COVID-19 patients. Our meta-analysis found that using glucocorticoids could significantly decrease COVID-19 mortality (hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.45-0.79, P < .001), relative to non-use of glucocorticoids. Meanwhile, using glucocorticoids also could significantly decrease the risk of progression to invasive mechanical ventilation for severe COVID-19 patients (HR = 0.69, 95% CI 0.58-0.83, P < .001). Compared with using dexamethasone (HR = 0.68, 95% CI 0.50-0.92, P = .012), methylprednisolone use had a better therapeutic effect for reducing the mortality of patients (HR = 0.35, 95% CI 0.19-0.64, P = .001). CONCLUSION: The result of this meta-analysis showed that using glucocorticoids could reduce mortality and risk of progression to invasive mechanical ventilation in severe COVID-19 patients.


Assuntos
COVID-19/tratamento farmacológico , COVID-19/mortalidade , Glucocorticoides/uso terapêutico , Dexametasona/uso terapêutico , Humanos , Metilprednisolona/uso terapêutico , Respiração Artificial , SARS-CoV-2 , Índice de Gravidade de Doença
17.
Am J Trop Med Hyg ; 105(4): 942-945, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34614478

RESUMO

Chikungunya virus (CHIKV) is an arbovirus endemic to South Asia with frequent outbreaks. A wide spectrum of neurological complications has been described in Chikungunya infections. Myeloneuropathy is a rare complication seen in Chikungunya and is proposed to have an underlying immune mediated pathogenesis. We report a case of a 45-year-old man presenting to the emergency services with acute onset of quadriparesis, breathlessness, urinary retention, profound pain, and sensory disturbances 6 weeks after the onset of high-grade fever and arthralgia. On examination, the patient had Medical Research Council grade 1 flaccid quadriparesis with prominent wasting and areflexia with distinct sensory level at T4. Immunoglobulin M CHIKV antibodies were positive, tested twice at a 1-week interval. He had notable magnetic resonance imaging (MRI) findings in the form of patchy T2 hyperintensities involving the entire length of the cervical and thoracic cord with normal brain imaging and extensive short tau inversion recovery hyperintense signal changes on muscle MRI. He was treated with five cycles of plasmapheresis and intravenous methylprednisolone followed by oral steroids for 8 weeks. At 20-week follow-up, the patient had improvement in upper limb weakness, but paraparesis persisted. The case highlights the presence of unusual MRI findings and also the importance of early recognition of after infective neurological complications, and prompt treatment with immunomodulation may be beneficial.


Assuntos
Febre de Chikungunya/complicações , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/virologia , Artralgia/diagnóstico por imagem , Artralgia/virologia , Febre de Chikungunya/virologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Plasmaferese , Doenças da Medula Espinal/classificação , Doenças da Medula Espinal/tratamento farmacológico
18.
Radiology ; 301(1): 242-246, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34543144

RESUMO

History A 50-year-old woman presented to the emergency department of our hospital with a 2-day history of lower limb pain associated with unusual asthenia and diffuse arthralgia over the past 3 weeks. She was a native of Guinea and had lived in France for most of her life, working as a personal care assistant. Her only medical history of note was an occurrence of fetal death at 12 weeks gestation when she was 35 years old. She had bilateral lower limb swelling, without changes in skin temperature or color. All proximal and distal arterial pulses were felt. General physical examination findings were otherwise unremarkable. Her laboratory tests showed a decreased hemoglobin concentration of 8.9 g/dL (normal range, 12-16 g/dL), a decreased platelet count of 45 × 109/L (normal range, [150-400] × 109/L), a C-reactive protein level of 158 mg/L (normal range, <5 mg/L), and a d-dimer level of 2000 mg/L (normal range, <500 mg/L]). Compression US of the lower limbs revealed bilateral calf vein thrombosis involving the fibular and posterior tibial veins. Curative anticoagulation using low-molecular-weight heparin (enoxaparin, subcutaneous injection of 100 units per kilogram of body weight twice a day) was started. The day after the start of anticoagulation therapy, the patient reported dyspnea and acute chest and abdominal pain. Her vital signs were assessed, and she had elevated blood pressure and increased heart rate and respiratory rate, but she remained afebrile. Her cardiac auscultation was unremarkable, besides tachycardia. Skin examination revealed small areas of necrosis on the fingertips of her right hand. Laboratory studies were repeated and showed an increase in serum creatinine level from a baseline value of 0.49 mg/dL to a new value of 1.01 mg/dL (normal range, 0.6-1.1 mg/dL), an apparition of low-grade proteinuria of 0.43 g per day (normal range, <0.3 g/ day), and a high serum troponin level of 1066 ng/L (normal range, <14 ng/L), whereas electrocardiography showed no ST segment modification and echocardiography revealed a moderately altered left ventricular ejection fraction (45%). There was no coronary occlusion seen at emergency coronarography. Contrast-enhanced CT of the chest, abdomen, and pelvis was performed (Figs 1, 2) together with cardiac MRI (Figs 3, 4).


Assuntos
Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/terapia , Aspirina/uso terapêutico , Enoxaparina/uso terapêutico , Feminino , Humanos , Extremidade Inferior/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Troca Plasmática/métodos , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia/métodos , Trombose Venosa/terapia
20.
J Int Med Res ; 49(9): 3000605211048366, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34586926

RESUMO

Churg-Strauss syndrome (CSS) is a granulomatous small-vessel vasculitis. Asthma is seen in the majority of patients with CSS, but atypical nonasthmatic forms of CSS are also being recognized. We herein describe a 67-year-old woman with a history of chronic pyelonephritis and drug allergy reactions who was admitted to our hospital because of worsening renal function preceded by fever, purpura, sinusitis, and a positive urine culture that confirmed a urinary infection. She was initially treated with pipemidic acid for 7 days, followed by clarithromycin for sinusitis. Laboratory tests on admission showed an absolute eosinophil count of 1750 cells/µL and serum creatinine concentration of 4.72 mg/dL. Urine and blood cultures showed no growth. Kidney biopsy revealed crescent formations with diffuse interstitial fibrosis and foci of eosinophil infiltration. An atypical form of CSS was diagnosed based on tissue eosinophilia, peripheral eosinophilia, and sinusitis. Intravenous methylprednisolone and cyclophosphamide pulse therapy together with hemodialysis treatment improved the patient's clinical condition but did not resolve the kidney damage. The onset of an atypical form of CSS in our patient manifested as symptoms and signs mimicking those of chronic pyelonephritis and drug allergy reactions. The patient's chronic kidney disease finally progressed to dialysis dependence.


Assuntos
Asma , Síndrome de Churg-Strauss , Pielonefrite , Vasculite , Idoso , Asma/complicações , Asma/tratamento farmacológico , Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/tratamento farmacológico , Feminino , Humanos , Metilprednisolona , Pielonefrite/complicações , Pielonefrite/tratamento farmacológico
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