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1.
Int J Mol Sci ; 24(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36675202

RESUMO

In vitro cell-line cytotoxicity is widely used in the experimental studies of potential antineoplastic agents and evaluation of safety in drug discovery. In silico estimation of cytotoxicity against hundreds of tumor cell lines and dozens of normal cell lines considerably reduces the time and costs of drug development and the assessment of new pharmaceutical agent perspectives. In 2018, we developed the first freely available web application (CLC-Pred) for the qualitative prediction of cytotoxicity against 278 tumor and 27 normal cell lines based on structural formulas of 59,882 compounds. Here, we present a new version of this web application: CLC-Pred 2.0. It also employs the PASS (Prediction of Activity Spectra for Substance) approach based on substructural atom centric MNA descriptors and a Bayesian algorithm. CLC-Pred 2.0 provides three types of qualitative prediction: (1) cytotoxicity against 391 tumor and 47 normal human cell lines based on ChEMBL and PubChem data (128,545 structures) with a mean accuracy of prediction (AUC), calculated by the leave-one-out (LOO CV) and the 20-fold cross-validation (20F CV) procedures, of 0.925 and 0.923, respectively; (2) cytotoxicity against an NCI60 tumor cell-line panel based on the Developmental Therapeutics Program's NCI60 data (22,726 structures) with different thresholds of IG50 data (100, 10 and 1 nM) and a mean accuracy of prediction from 0.870 to 0.945 (LOO CV) and from 0.869 to 0.942 (20F CV), respectively; (3) 2170 molecular mechanisms of actions based on ChEMBL and PubChem data (656,011 structures) with a mean accuracy of prediction 0.979 (LOO CV) and 0.978 (20F CV). Therefore, CLC-Pred 2.0 is a significant extension of the capabilities of the initial web application.


Assuntos
Antineoplásicos , Software , Humanos , Teorema de Bayes , Antineoplásicos/farmacologia , Antineoplásicos/química , Prednisona , Linhagem Celular Tumoral
2.
J Feline Med Surg ; 25(1): 1098612X221143769, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36655881

RESUMO

OBJECTIVES: Feline primary laryngeal or tracheal lymphoma (PLTL) is an uncommon extranodal presentation. Information on long-term survival is scarce, although some small case series describe this being achieved with multiagent protocols; an accurate outcome for cats with PLTL is yet to be determined. The aim of this study was to gather information on the clinical presentation, response to treatment and outcome in a large case series of feline PLTL. METHODS: This retrospective multicentre study included cats with a cytological or histopathological confirmation of PLTL. Histopathology samples, when available, were reassessed for grade and immunophenotype. Clinical (age, signalment, retroviral status, presence of anaemia, clinical signs, location and therapy type) and outcome (response, progression-free survival [PFS] and overall survival [OS]) variables were recorded. Survival analyses to assess the impact of variables on PFS and OS were performed. RESULTS: Twenty-three cases were included; cats had a median age of 11 years (range 2-16) and the male:female ratio was 3.6:1. Common clinical signs at presentation included increased respiratory effort (74%) and abnormal upper respiratory tract sounds (48%). Immunophenotyping was performed in 48% of cases and all were B cell. Debulking surgery was performed in 26% of cases. All cats received chemotherapy, COP (cyclophosphamide, vincristine and prednisolone; 39%), CHOP (cyclophosphamide, vincristine, doxorubicin and prednisolone; 44%) and other protocols (17%); 35% had a partial response and 65% a complete response. Median PFS and OS were 909 days (range 23-1484) and 909 days (range 23-2423), respectively. Complete response was associated with longer PFS (P <0.001) and OS (P = 0.012). Pretreatment with steroids was associated with longer OS (P = 0.003). No other variable was found to be significant. CONCLUSIONS AND RELEVANCE: PLTL in cats is mostly of a B-cell phenotype, could be of a low-to-medium grade, and may respond to surgical and medical treatment with a longer survival time than has previously been reported.


Assuntos
Doenças do Gato , Linfoma , Gatos , Masculino , Animais , Feminino , Vincristina , Ciclofosfamida/uso terapêutico , Prednisolona , Estudos Retrospectivos , Linfoma/diagnóstico , Linfoma/terapia , Linfoma/veterinária , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prednisona/uso terapêutico , Doenças do Gato/diagnóstico , Doenças do Gato/tratamento farmacológico
3.
BMJ Case Rep ; 16(1)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717160

RESUMO

A man in his 50s with metastatic hormone-sensitive prostate cancer, receiving androgen deprivation therapy and abiraterone acetate/prednisone, presented with an uncontrollable 'Irish brogue' accent despite no Irish background, consistent with foreign accent syndrome (FAS). He had no neurological examination abnormalities, psychiatric history or MRI of the brain abnormalities at symptom onset. Imaging revealed progression of his prostate cancer, despite undetectable prostate-specific antigen levels. Biopsy confirmed transformation to small cell neuroendocrine prostate cancer (NEPC). Despite chemotherapy, his NEPC progressed resulting in multifocal brain metastases and a likely paraneoplastic ascending paralysis leading to his death. We report FAS as the presenting manifestation of transformation to small cell NEPC, a previously undescribed phenomenon. His presentation was most consistent with an underlying paraneoplastic neurological disorder (PND), despite a negative serum paraneoplastic panel. This report enhances the minimal existing literature on FAS and PNDs associated with transformed NEPC.


Assuntos
Carcinoma de Células Pequenas , Neoplasias da Próstata , Humanos , Masculino , Antagonistas de Androgênios/uso terapêutico , Carcinoma de Células Pequenas/complicações , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Prednisona/uso terapêutico , Neoplasias da Próstata/patologia , Pessoa de Meia-Idade
4.
PLoS One ; 18(1): e0280044, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36630466

RESUMO

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a high grade non-Hodgkin lymphoma which is common among immunodeficient people. Derangements of peripheral blood immune cells have been described to have a prognostic impact in DLBCL in high income countries, including a monocytosis, the ratios of lymphocytes to both monocytes (L:M) and neutrophils (N:L), as well as the numbers of regulatory T-cells (Tregs) and immunosuppressive monocytes (HLA-DRlow monos). To date, the impact of these variables has not been assessed in the setting of HIV-associated DLBCL (HIV-DLBCL), which is among the most common malignancies seen in people living with HIV. In this study, we assessed these factors in a cohort of South African patients with DLBCL and a high HIV-seropositivity-rate. In addition, we evaluated the prognostic value of monocyte activation (as reflected by monocyte fluorescence (MO-Y) on a Sysmex haematology analyser). This parameter has to date not been assessed in the setting of DLBCL. METHODS: A full blood count and differential count as well as flow cytometry for HLA-DRlow monocyte and Treg enumeration were performed in patients with incident DLBCL referred to the Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa between November 2019 and May 2022. Additional clinical and laboratory data were recorded from the patient charts and laboratory information system. RESULTS: Seventy-six patients were included, of whom 81.3% were people living with HIV with a median CD4 count of 148 cells/ul. Most patients had advanced stage disease (74.8%) and were predominantly treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy (without Rituximab). At a median follow-up period of 19 months, the median survival time was 3.5 months, with a 12-month survival rate of 27.0%. All of the immune-cell-related variables (with the exception of the CD4 count) were similar between the people living with HIV and the HIV-negative individuals. In contrast to previous studies, a high monocyte count, the L:M and increased numbers of HLA-DRlow monocytes were not significantly associated with survival in HIV-DLBCL, while a neutrophilia (>8 x 109/L), the N:L (>6:1), high numbers of Tregs (≥5.17% of CD4s) and lymphopenia (<1.3 x 109/L) were. In addition, increased monocyte fluorescence (MO-Y >115.5) was associated with superior outcomes, which we speculate to reflect a more robust antitumour immune response among individuals with high levels of monocyte activation. On Cox Proportional hazard analysis, immune-cell factors independently associated with survival included a CD4 count <150 cells/ul and a neutrophilia. CONCLUSION: The monocyte count, L:M and the number of HLA-DRlow monos are not strong prognostic indicators in HIV-DLBCL, while a low CD4 count and neutrophilia are. Elevation of the MO-Y shows some promise as a potential biomarker of antitumour immunity; further study in this regard would be of interest.


Assuntos
Infecções por HIV , Linfoma Difuso de Grandes Células B , Humanos , Prognóstico , Monócitos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , África do Sul/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Rituximab/uso terapêutico , Imunossupressores/uso terapêutico , Vincristina/uso terapêutico , Contagem de Leucócitos , Prednisona/uso terapêutico , Infecções por HIV/tratamento farmacológico
5.
Clin Lab ; 69(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36649512

RESUMO

BACKGROUND: Presently, several classification methods are based on diffuse large B-cell lymphoma (DLBCL), but its clinical application has not yet been testified in Asian populations. METHODS: Twenty-five DLBCL patients were subjected to second-generation gene sequencing (NGS), and retrospective analysis of clinical features of the patients was to explore genotyping and survival prognosis biomarkers. RESULTS: The prevalent mutant genes in DLBCL patients cover myeloid differentiation factor 88 (MyD88) (40%), TP53 (32%), B-cell translocation gene 2 (BTG2) (28%), PIM1 (28%), and CREB-binding protein (CREBBP) (24%) in this study. The classical International Prognostic Index (IPI) scores were associated with progression-free survival (PFS) (HR: 7.52, 95% CI 1.51 - 37.6, p = 0.00393) via univariate analysis. Furthermore, patients with ETS-variant gene 6 (ETV6) (HR: 5.1, 95% CI 0.927 - 28.1, p = 0.0371), platelet-derived growth factor receptor A (PDGFRA) (HR: 4.29, 95% CI 0.824 - 22.3, p = 0.0594), platelet-derived growth factor receptor B (PDGFRB) (HR: 10.8, 95% CI 0.979 - 119, p = 0.0149) was distinctively correlated with poor PFS except for the IPI score. Nevertheless, the mutation of PDGFRA/B gene was not distinct in further multivariate analysis (PFS: HR: 2.72, 95% CI 0.52 - 14.23, p = 0.2369). Additionally, better survival prognosis was in DLBCL patients who did not progress within 12 months (POD12). Ultimately, caspase recruitment domain 11 (CARD11) gene mutations were enriched in patients with primary intranodal tumors, but the prognostic relevance was not discovered. CONCLUSIONS: ETV6 and platelet-derived growth factor receptor (PDGFR)A/B gene mutations are supposed to be potential biomarkers for the prognosis of DLBCL patients via the statistical analysis of this small sample, and POD12 is also expected to be an effective endpoint for efficacy assessment.


Assuntos
Proteínas Imediatamente Precoces , Linfoma Difuso de Grandes Células B , Humanos , Rituximab/uso terapêutico , Estudos Retrospectivos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Prognóstico , Biomarcadores , Receptores do Fator de Crescimento Derivado de Plaquetas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prednisona/uso terapêutico , Proteínas Imediatamente Precoces/uso terapêutico , Proteínas Supressoras de Tumor
6.
Int J Mol Sci ; 24(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36674612

RESUMO

Ataxia-telangiectasia (AT) is a multisystemic neurodegenerative inborn error of immunity (IEI) characterized by DNA repair defect, chromosomal instability, and hypersensitivity to ionizing radiation. Impaired DNA double-strand break repair determines a high risk of developing hematological malignancies, especially lymphoproliferative diseases. Poor response to treatment, excessive chemotherapy toxicities, and the need for avoiding exposure to ionizing radiation make the successful clinical management of patients with AT challenging for oncologists. We describe the favorable outcome of the LBCL with IRF4 rearrangement at stage III in a 7-year-old female patient diagnosed with AT. The patient was treated according to the B-HR arm of the INTER-B-NHL-COP 2010 protocol, including the administration of rituximab, cyclophosphamide, methotrexate, prednisone, etc. She presented excessive treatment toxicities despite individually reduced doses of methotrexate and cyclophosphamide. However, in the MRI there was no significant reduction in pathologic lymph nodes after three immunochemotherapy courses. Therefore, a lymph node biopsy was taken. Its subsequent histopathological examination revealed tuberculosis-like changes, though tuberculosis suspicion was excluded. After two following immunochemotherapy courses, PET-CT confirmed complete remission. From March 2022 onwards, the patient has remained in remission under the care of the outpatient children's oncology clinic.


Assuntos
Ataxia Telangiectasia , Linfoma Difuso de Grandes Células B , Feminino , Humanos , Criança , Metotrexato/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Rituximab/genética , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Ataxia Telangiectasia/tratamento farmacológico , Ataxia Telangiectasia/genética , Prednisona/uso terapêutico , Ciclofosfamida/uso terapêutico , Mutação , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Vincristina/uso terapêutico , Doxorrubicina/uso terapêutico , Proteínas Mutadas de Ataxia Telangiectasia/genética
7.
Reumatol Clin (Engl Ed) ; 19(1): 1-5, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36603961

RESUMO

INTRODUCTION: Glucocorticoids are associated with serious side effects related to dosing and time of use. Unfortunately, there is no standard method for determining glucocorticoid exposure, especially in patients undergoing long-term treatment. OBJECTIVE: The aim of this work was to create a free and easy-to-use web application to calculate, in a systematic way, the total cumulative dose of corticosteroids. METHODS: The total cumulative dose is calculated as the sum of all periods of treatment with different doses of corticosteroids, and is expressed as the equivalent dose of prednisone in mg. Glucocorticoid doses during periods in which the available information is missing or incomplete are estimated by systematic assumptions. RESULTS: A simulation exercise using standard patterns of steroid use in polymyalgia rheumatica, and giant cell arteritis showed that even when the period of no information reached 50% of the time, the accuracy of the calculator had a mean absolute percentage error (MAPE)<7%. CONCLUSION: This tool simplifies and standardizes the glucocorticoids cumulative dose calculation, thereby minimizing bias in the assessment of glucocorticoid cumulative dose.


Assuntos
Arterite de Células Gigantes , Polimialgia Reumática , Humanos , Glucocorticoides/uso terapêutico , Prednisona/efeitos adversos , Arterite de Células Gigantes/tratamento farmacológico , Polimialgia Reumática/tratamento farmacológico
8.
Artigo em Inglês | MEDLINE | ID: mdl-36396449

RESUMO

OBJECTIVE: We report a case of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) who achieved durable and steroid-free remission after IV cladribine. METHODS: A 25 year-old man presented with progressively worsening headaches, polydipsia, dysarthria, diplopia and vertigo, and obtundation requiring respiratory support. CSF revealed lymphocytosis, and MRI revealed a perivascular pattern of punctate enhancement involving the pons. An extensive workup for inflammatory, autoimmune, infective, and malignant explanations was unrevealing. He responded dramatically to steroids, compatible with CLIPPERS as a diagnosis of exclusion. Attempts to wean prednisone over the ensuing year resulted in 2 clinical relapses and persistent punctate enhancement. Given significant steroid side effects, steroid-sparing agents were considered. RESULTS: IV cladribine IV (0.0875 mg/kg adjusted body weight daily × 4 days at 0, 4, 8, and 16 months) was selected, given its favorable side effect profile including lower risks of malignancy and infertility and the potential for long-lasting effects. The only side effect was short-term fatigue at the time of infusion. At 20 months after cladribine initiation, he was able to wean-off prednisone altogether. Now at 33 months, he remains in clinical and MRI remission. DISCUSSION: Cladribine is a rational candidate steroid-sparing treatment for presumed neurologic autoimmune conditions such as CLIPPERS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that cladribine is a steroid-sparing treatment consideration in CLIPPERS.


Assuntos
Doenças do Sistema Nervoso Central , Cladribina , Masculino , Humanos , Adulto , Cladribina/farmacologia , Doenças do Sistema Nervoso Central/diagnóstico , Prednisona/uso terapêutico , Ponte , Imageamento por Ressonância Magnética
9.
JCI Insight ; 8(2)2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36512421

RESUMO

BACKGROUNDChronotherapy is a drug intervention at specific times of the day to optimize efficacy and minimize adverse effects. Its value in hematologic malignancy remains to be explored, in particular in adult patients.METHODSWe performed chronotherapeutic analysis using 2 cohorts of patients with diffuse large B cell lymphoma (DLBCL) undergoing chemotherapy with a dichotomized schedule (morning or afternoon). The effect of a morning or afternoon schedule of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on survival and drug tolerability was evaluated in a survival cohort (n = 210) and an adverse event cohort (n = 129), respectively. Analysis of about 14,000 healthy individuals followed to identify the circadian variation in hematologic parameters.RESULTSBoth progression-free survival (PFS) and overall survival (OS) of female, but not male, patients were significantly shorter when patients received chemotherapy mostly in the morning (PFS HR 0.357, P = 0.033; and OS HR 0.141, P = 0.032). The dose intensity was reduced in female patients treated in the morning (cyclophosphamide 10%, P = 0.002; doxorubicin 8%, P = 0.002; and rituximab 7%, P = 0.003). This was mainly attributable to infection and neutropenic fever: female patients treated in the morning had a higher incidence of infections (16.7% vs. 2.4%) and febrile neutropenia (20.8% vs. 9.8%) as compared with those treated in the afternoon. The sex-specific chronotherapeutic effects can be explained by the larger daily fluctuation of circulating leukocytes and neutrophils in female than in male patients.CONCLUSIONIn female DLBCL patients, R-CHOP treatment in the afternoon can reduce toxicity while it improves efficacy and survival outcome.FUNDINGNational Research Foundation of Korea (NRF) grant funded by the Korean government (grant number NRF-2021R1A4A2001553), Institute for Basic Science IBS-R029-C3, and Human Frontiers Science Program Organization Grant RGY0063/2017.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Adulto , Masculino , Humanos , Feminino , Rituximab/uso terapêutico , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Linfoma Difuso de Grandes Células B/terapia , Vincristina , Ciclofosfamida , Prednisona , Doxorrubicina
10.
Clinics (Sao Paulo) ; 78: 100150, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36529052

RESUMO

OBJECTIVE: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. METHODS: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). RESULTS: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05‒0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05‒0.88, p = 0.034). After six months (D69‒D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. CONCLUSION: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698).


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , COVID-19 , Humanos , Anticorpos Antivirais , Imunoglobulina G , Prednisona
11.
Mol Biol Rep ; 50(2): 1447-1458, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36478296

RESUMO

BACKGROUND: Multiple myeloma is one of the most common hematological malignancies worldwide. Genetic alterations may lead to the progression from monoclonal gammopathy to multiple myeloma. Additionally, the genetic background of the disease might influence therapy outcomes, including survival time. SLCO1B1, belonging to the OATPs family, is a membrane protein that mediates the uptake of a wide range of endogenous and exogenous (including drugs) compounds. METHODS AND RESULTS: In this study, the A388G single nucleotide polymorphism in the SLCO1B1 gene in Polish multiple myeloma patients was determined. This polymorphism affects the amino acid change of the protein, so it may be responsible for treatment effectiveness or risk of disease development. A388G was evaluated by the PCR-RFLP method. The presented study showed a statistically significant association between the GG genotype with longer survival of patients with multiple myeloma with Melphalan-Prednisone therapy compared to other treatment regimens (p = 0.0271). There was no statistically significant association in the frequency of genotypes (p = 0.8211) and alleles: allele A (p = 0.5442); allele G (p = 0.8020) between multiple myeloma patients and a control group. CONCLUSIONS: The A388G polymorphism does not seem to affect the increased risk of the development of multiple myeloma. However, the occurrence of the GG genotype may prolong of patients overall survival in the case of Melphalan-Prednisone therapy.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Polimorfismo de Nucleotídeo Único/genética , Melfalan/uso terapêutico , Polônia/epidemiologia , Prednisona/uso terapêutico , Genótipo , Transportador 1 de Ânion Orgânico Específico do Fígado/genética
12.
J Neuromuscul Dis ; 10(1): 67-79, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36565131

RESUMO

BACKGROUND: Evidence on the long-term efficacy of steroids in Duchenne muscular dystrophy (DMD) after loss of ambulation is limited. OBJECTIVE: Characterize and compare disease progression by steroid treatment (prednisone, deflazacort, or no steroids) among non-ambulatory boys with DMD. METHODS: Disease progression was measured by functional status (Performance of Upper Limb Module for DMD 1.2 [PUL] and Egen Klassifikation Scale Version 2 [EK] scale) and by cardiac and pulmonary function (left ventricular ejection fraction [LVEF], forced vital capacity [FVC] % -predicted, cough peak flow [CPF]). Longitudinal changes in outcomes, progression to key disease milestones, and dosing and body composition metrics were analyzed descriptively and in multivariate models. RESULTS: This longitudinal cohort study included 86 non-ambulatory patients with DMD (mean age 13.4 years; n = 40 [deflazacort], n = 29 [prednisone], n = 17 [no steroids]). Deflazacort use resulted in slower average declines in FVC % -predicted vs. no steroids (+3.73 percentage points/year, p < 0.05). Both steroids were associated with significantly slower average declines in LVEF, improvement in CPF, and slower declines in total PUL score and EK total score vs. no steroids; deflazacort was associated with slower declines in total PUL score vs. prednisone (all p < 0.05). Both steroids also preserved functional abilities considered especially important to quality of life, including the abilities to perform hand-to-mouth function and to turn in bed at night unaided (all p < 0.05 vs. no steroids). CONCLUSIONS: Steroid use after loss of ambulation in DMD was associated with delayed progression of important pulmonary, cardiac, and upper extremity functional deficits, suggesting some benefits of deflazacort over prednisone.


Assuntos
Distrofia Muscular de Duchenne , Qualidade de Vida , Masculino , Humanos , Adolescente , Prednisona/uso terapêutico , Volume Sistólico , Estudos Longitudinais , Função Ventricular Esquerda , Progressão da Doença
13.
J Am Anim Hosp Assoc ; 59(1): 40-44, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36584318

RESUMO

A 7 yr old female spayed mixed-breed dog was presented for a 1 wk history of neck pain and pelvic limb weakness. Examination revealed nonambulatory paraparesis and thoracolumbar hyperesthesia. MRI revealed extensive intramedullary T2-weighted/short tau inversion recovery hyperintensity and diffuse severe T1-post contrast meningeal enhancement of the thoracolumbar spinal cord. An L5-L6 cerebrospinal fluid sample revealed a suppurative pleocytosis (81% neutrophils, total protein 4362.5 mg/dL and nucleated cell count 352,000/µL). While awaiting the results of infectious disease testing, the dog was treated for suspected meningoencephalitis of unknown etiology with corticosteroids, cyclosporine, and a cytarabine arabinoside infusion. The dog neurologically declined and was started on broad-spectrum antibiotics. The dog continued to decline despite antibiotics, and infectious disease titers subsequently revealed serum antibody positivity for blastomycosis. The dog was then referred to a multispecialty referral hospital and was treated with amphotericin B followed by fluconazole. Prednisone was continued at anti-inflammatory doses. Urine blastomycosis antigen testing was submitted for subsequent disease monitoring but was negative. Five months after presentation the dog was clinically doing well with no identifiable neurologic deficits. This case demonstrates that neurologic blastomycosis may have negative urine antigen concentrations in some dogs and that other diagnostic modalities should be pursued when central nervous system fungal disease is suspected.


Assuntos
Blastomicose , Doenças do Cão , Cães , Feminino , Animais , Blastomicose/diagnóstico , Blastomicose/tratamento farmacológico , Blastomicose/veterinária , Doenças do Cão/diagnóstico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/cirurgia , Prednisona/uso terapêutico , Sistema Nervoso Central , Antibacterianos/uso terapêutico
14.
Anticancer Res ; 43(1): 463-471, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36585174

RESUMO

BACKGROUND/AIM: Enzalutamide (ENZ) and abiraterone acetate with prednisone (AAP) represent novel hormonal therapies used in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The aim of the study was to assess the long-term outcome of mCRPC patients treated with ENZ or AAP in real-life clinical practice. PATIENTS AND METHODS: The outcomes of 337 mCRPC patients treated with ENZ or AAP were retrospectively analysed. RESULTS: Median radiographic progression-free (rPFS) and overall survival (OS) of patients treated in the first line (pre-chemotherapy) was 13.89 (95% CI=12.40-16.80) and 31.02 (95% CI=24.27-37.44) months vs. 10.97 (95% CI=8.97-14.82) and 26.57 (95% CI=15.97-33.92) months for those treated in the second line (post-chemotherapy). We found inferior survival for patients with synchronous metastases, high Gleason score (GS) and visceral metastases. CONCLUSION: The efficacy of both ENZ and AAP in mCRPC patients is herein confirmed. Synchronous metastases, high GS and visceral metastases were identified as significant adverse prognostic factors.


Assuntos
Acetato de Abiraterona , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Acetato de Abiraterona/uso terapêutico , Prednisona/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Nitrilas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento
15.
J Clin Exp Hematop ; 62(4): 202-207, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36575000

RESUMO

The cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) regimen, containing doxorubicin (DXR), which is a key drug for aggressive non-Hodgkin lymphoma (NHL), is a standard chemotherapeutic regimen; however, its administration in elderly patients is often intolerable. Pirarubicin (tetrahydropyranyl adriamycin [THP]) is an anthracycline developed in Japan. We have conducted a phase II trial of a full-dose THP-COP (modified CHOP regimen with DXR replaced by THP) regimen for elderly patients with newly diagnosed, advanced-stage, aggressive NHL. Patients aged 70-79 years old with previously untreated NHL according to the Working Formulation (D through H and J), disease stage I with a bulky mass or stage II-IV, and performance status of 0-1 were eligible. The THP-COP regimen, which consisted of 750-mg/m2 cyclophosphamide, 50-mg/m2 THP, 1.4-mg/m2 vincristine (capped at 2.0 mg) on day 1, and 100-mg prednisolone daily on days 1 to 5, was delivered every 3 weeks for 6 cycles. The primary endpoint was complete response (CR) rate. Twenty-nine patients were enrolled in the study. The CR rate was 65.5% (95% confidence interval, 45.7-82.1%). The 3-year failure-free and overall survival rates were 54.1% and 53.9%, respectively. The most frequent observed grade 3 or 4 toxicity was neutropenia, which occurred in 80% of the patients. Grade 3 cardiac dysfunction was observed in one patient. The full-dose THP-COP regimen exhibited similar efficacy and safety, and a tendency for less cardiac toxicity, when compared with the standard CHOP regimen in elderly Japanese patients with newly diagnosed, advanced-stage, aggressive NHL.


Assuntos
Linfoma não Hodgkin , Idoso , Humanos , Vincristina/efeitos adversos , Linfoma não Hodgkin/diagnóstico , Ciclofosfamida , Doxorrubicina/uso terapêutico , Prednisona , Prednisolona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento
16.
Arerugi ; 71(10): 1214-1219, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-36543200

RESUMO

A 56-year-old woman who had allergic bronchopulmonary mycosis (ABPM) with nontuberculous mycobacteriosis (NTM) was treated with prednisone. After treatment, her respiratory symptoms, eosinophil count, and infiltrative shadow diminished. However, when the dosage of prednisone was tapered and finally stopped, the eosinophil count increased and the infiltrative shadow returned. Since there was a risk of exacerbation of NTM, benralizumab without prednisone was administrated, which improved the patient's respiratory symptoms and eosinophil count, while the infiltrative shadow remained. When the dosage of prednisone was restarted, the shadow disappeared. After prednisone discontinuation, no exacerbation of the shadows nor relapse were observed. In recent years, clinical usefulness of biologics like benralizumab for ABPM has been reported, but evidence to support their use is insufficient. Furthermore, it is expected that the number of the combined cases of NTM and ABPM will increase with the increase in NTM; however, reports of biologics for the management of both cases are extremely rare. The risk of complications of infectious diseases, interaction with antifungal drugs, and steroid sparing effects should be considered when deciding the treatment strategy. Accumulation of more cases in the future may lead to the establishment of a treatment method for the combined cases of NTM and ABPM.


Assuntos
Produtos Biológicos , Aspergilose Pulmonar Invasiva , Infecções por Mycobacterium não Tuberculosas , Humanos , Feminino , Pessoa de Meia-Idade , Prednisona , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/diagnóstico
17.
Beijing Da Xue Xue Bao Yi Xue Ban ; 54(6): 1208-1213, 2022 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-36533357

RESUMO

Hemophagocytic syndrome (HPS) is a severe disease characterized by excessive release of inflammatory cytokines caused by abnormal activation of lymphocytes and macrophages, which can cause multiple organ damage and even death. Panniculitis is a disease characterized by inflammation of subcutaneous adipose tissue. We effectively treated 2 patients with panniculitis-associated HPS with ruxolitinib. Case 1: A 70-year-old male started with intermittent plantar swelling and pain, and then developed leukocytosis, mild anemia, multiple red maculopapules with painless subcutaneous nodules on the forehead, neck and bilateral lower legs. The patient was treated with prednisone and leflunomide for improvement. After that, repeated fever and rash occurred again. After admission to our hospital, we found his leukocyte and hemoglobin decreased, ferritin raised, fibrinogen and natural killer (NK) cell activity decreased, and hemophagocytic cells were found in bone marrow aspiration. The skin pathology was consistent with non-suppurative nodular panniculitis. He was diagnosed with nodular panniculitis associa-ted HPS. He was treated with glucocorticoid, cyclosporine, etoposide and gamma globule, but the disease was not completely controlled. After adjusting etoposide to ruxolitinib, his symptoms and abnormal laboratory findings returned to normal. After 2 months he stopped using ruxolitinib due to repeated infections. During the follow-up, though the prednisone dose was tapered, his condition was stable. Case 2: A 46-year-old female patient developed from intermittent fever, erythematous nodular rash with tenderness, leukopenia, and abnormal liver function. antibiotic therapy was ineffective. She improved after glucocorticoid treatment, and relapsed after glucocorticoid reduction. There were fever, limb nodules, erythema with ulcerative necrosis, intermittent abdominal pain when she came to our hospital. Blood examination showed that her white blood cells, red blood cells and platelets were decreased, fibrinogen was decreased, triglyceride was increased, ferritin and soluble interleukin-2 receptor(SIL-2R/sCD25) were significantly raised, and hemophagocytic cells were found in bone marrow aspiration. It was found that Epstein-Barr virus DNA was transiently positive, skin Staphylococcus aureus infection, and pulmonary Aspergillus flavus infection, but C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were normal, and no evidence of tumor and other infection was found. Skin pathology was considered panniculitis. The diagnosis was panniculitis, HPS and complicated infection. Antibiotic therapy and symptomatic blood transfusion were given first, but the disease was not controlled. Later, dexamethasone was given, and the condition improved, but the disease recurred after reducing the dose of dexamethasone. Due to the combination of multiple infections, the application of etoposide had a high risk of infection spread. Ruxolitinib, dexamethasone, and anti-infective therapy were given, and her condition remained stable after dexamethasone withdrawal. After 2 months of medication, she stopped using ruxolitinib. One week after stopping using ruxolitinib, she developed fever and died after 2 weeks of antibiotic therapy treatment in a local hospital. In conclusion, panniculitis and HPS are related in etiology, pathogenic mechanism and clinical manifestations. Abnormal activation of Janus-kinase and signal transduction activator of transcription pathway and abnormal release of inflammatory factors play an important role in the pathogenesis of the two diseases. The report suggests that ruxolitinib is effective and has broad prospects in the treatment of panniculitis associated HPS.


Assuntos
Infecções por Vírus Epstein-Barr , Exantema , Linfo-Histiocitose Hemofagocítica , Paniculite , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Glucocorticoides/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Etoposídeo/uso terapêutico , Prednisona/uso terapêutico , Herpesvirus Humano 4 , Paniculite/etiologia , Paniculite/complicações , Dexametasona/uso terapêutico , Exantema/complicações , Ferritinas/uso terapêutico , Antibacterianos/uso terapêutico , Fibrinogênio/uso terapêutico
18.
Gan To Kagaku Ryoho ; 49(12): 1377-1379, 2022 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-36539254

RESUMO

A 83-year-old man was diagnosed with diffuse large B-cell lymphoma and scheduled for treatment. However, he developed abdominal pain, and computed tomography revealed a gastrointestinal perforation. Emergency surgery was performed, upon which we identified perforations in the small intestine, and we therefore performed resection of the small intestine. R-CHOP therapy was performed postoperatively, resulting in successful tumor shrinkage. Malignant lymphoma of the small intestine often causes intestinal perforations, and the prognosis of patients with perforations is unfavorable. We report a case of a patient with multiple intestinal perforations owing to malignant lymphoma of the small intestine, in whom minimal surgery was performed and intervention in the early postoperative period was successful.


Assuntos
Perfuração Intestinal , Linfoma Difuso de Grandes Células B , Masculino , Humanos , Idoso de 80 Anos ou mais , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/cirurgia , Intestino Delgado , Prednisona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
19.
Zhonghua Yi Xue Za Zhi ; 102(48): 3881-3885, 2022 Dec 27.
Artigo em Chinês | MEDLINE | ID: mdl-36540927

RESUMO

Objective: To evaluate the efficacy and safety of belimumab in children with systemic lupus erythematosus (cSLE). Methods: The clinical data of 49 cSLE patients admitted into the Department of Rheumatology and Immunology, Children's Hospital affiliated to the Capital Institute of Pediatrics, from August 2018 to December 2021 were collected. They were divided into the belimumab treatment group (18 cases) and the traditional treatment group (31 cases) according to whether they received belimumab treatment. The cSLE patients in the traditional group had similar baseline SLEDAI scores with the belimumab group and were treated with traditional immunosuppressive drugs. The clinical symptoms and improvements before and after treatment, as well as the differences in adverse events during follow-up were compared between the two groups. Results: In belimumab group, the age was (11.9±1.8) years old, the median (Q1, Q3) of disease duration was 7.5 (2.0, 16.8) months, 3 patients were male, and 15 patients completed 24 weeks of treatment. In the traditional treatment group, 31 patients with cSLE were enrolled, with an average age of (11.3±2.4) years, a median (Q1, Q3) of disease duration of 7.0 (2.5, 10.5) months, among whom 6 patients were male, and 25 patients completed 24 weeks of treatment. At baseline, the belimumab treatment group had a significantly lower oral prednisone dose than the conventional treatment group [(29.58±12.43) mg/d vs (38.20±14.11) mg/d, P=0.037]. After 24 weeks of treatment, the dosage of prednisone in both groups was reduced, and the dosage of prednisone in the belimumab group was (14.12±5.86) mg/d, which was lower than that in the traditional treatment group [(23.51±9.79) mg/d] (P=0.002). After 24 weeks of treatment, the levels of complement C3 and C4 increased, the dsDNA levels and SLEDAI score decreased in both groups (all P>0.05). The incidence of adverse events in belimumab group (3/15, 3 cases) was lower than that in traditional treatment group (32.0%, 8/25) (P>0.05). Conclusions: Belimumab in the treatment of cSLE can reduce the initial dose of prednisone and facilitate the reduction of prednisone dose, significantly improve the clinical symptoms and organ involvement, and reduce the disease activity. The incidence of adverse events was low during belimumab treatment.


Assuntos
Anticorpos Monoclonais Humanizados , Lúpus Eritematoso Sistêmico , Humanos , Masculino , Criança , Adolescente , Feminino , Prednisona/uso terapêutico , Resultado do Tratamento , Anticorpos Monoclonais Humanizados/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Imunossupressores/uso terapêutico
20.
Front Immunol ; 13: 1049444, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36524109

RESUMO

Anti-erythropoietin (anti-EPO) antibody-mediated pure red cell aplasia (PRCA) is a rarely seen disease. Anti-EPO antibodies were mostly found in patients with chronic kidney disease who received recombinant human erythropoietin (rHuEPO) injections subcutaneously. The treatment against anti-EPO antibody-mediated PRCA included discontinuation of rHuEPO, immunosuppressive agents, intravenous immunoglobulin, plasmapheresis, or kidney transplantation. We reported a case of kidney transplant recipient with anti-EPO antibody-mediated PRCA, who had no trend of recovery after stopping rHuEPO, receiving regular induction and maintenance immunosuppressive regimens. He was further given 6 consecutive plasmapheresis sessions, cyclophosphamide, and adjusted maintenance immunosuppressive regimen into cyclosporine, sirolimus and prednisone. We monitored his anti-EPO antibody levels with a self-created simple mixing test. At 10 months post kidney transplant, his anti-EPO antibody finally turned negative, and his reticulocyte count dramatically increased. Cyclosporine, sirolimus and prednisone combined with roxadustat eventually alleviated the patient's anti-EPO antibody-mediated PRCA. Our self-created simple mixing test for anti-EPO antibody titer was very helpful in disease monitoring and therapeutic guidance.


Assuntos
Transplante de Rim , Aplasia Pura de Série Vermelha , Masculino , Humanos , Transplante de Rim/efeitos adversos , Prednisona/uso terapêutico , Aplasia Pura de Série Vermelha/tratamento farmacológico , Aplasia Pura de Série Vermelha/etiologia , Anticorpos , Imunossupressores/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Ciclosporina/uso terapêutico , Sirolimo/uso terapêutico
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