RESUMO
A boy with nonambulatory Duchenne muscular dystrophy (DMD) tested positive for exon 63 duplication and exhibited intellectual disability, overweight and dyslipidaemia. The patient underwent a comprehensive multidisciplinary approach involving pharmacological and non-pharmacological interventions. Despite challenges, such as socioeconomic constraints and limited access to advanced therapies, the patient received tailored care. The management included prednisone medication, dietary modifications and psychological support. The patient's journey highlighted the complex interplay of medical and psychosocial factors affecting DMD patients in resource-limited settings. Regular monitoring and the involvement of the patient's family in a peer group were arranged to improve overall quality of life. The case underscores the need for accessible and holistic care for DMD patients, addressing both medical and psychosocial challenges.
Assuntos
Éxons , Distrofia Muscular de Duchenne , Humanos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Masculino , Criança , Qualidade de Vida , Prednisona/uso terapêutico , Deficiência Intelectual/genéticaRESUMO
INTRODUCTION: The diffuse large B-cell lymphoma (Dlbcl) is the most common non-Hodgkin lymphoma and at highest incidence among the elderly. Despite the improved outcomes of patients treated with the first-line (1L) standard of care until the end of 2022, composed by rituximab and polychemotherapy (R-Chop), during the last 20 years, the rate of relapsed and refractory Dlbcl (rrDlbcl) remains elevated. This study has identified and analyzed patients newly diagnosed with Dlbcl and treated with 1L, from the perspective of the Italian National Health Service (Ssn). METHODS: From the administrative database of Fondazione Ricerca e Salute (ReS) including ~5.5 million inhabitants/year in Italy, adults with a new in-hospital Dlbcl diagnosis (index date) and treated with 1L in 2018, 2019, 2020 and 2021 were identified and characterized in terms of demographics and comorbidities during a period (from 4 to 8 years) preceding index date. From 1 to 4 years following index date (follow-up), overall survival (Kaplan-Meier curves), percentage distribution of patients by line of therapy including dispensation/administration of chemo-immunotherapy, hemopoietic stem cell transplantation (Hsct), and direct healthcare costs charge to the Ssn, were evaluated. RESULTS: Overall, from the ReS database, 206 patients newly diagnosed with Dlbcl and treated with 1L from 2018 to 2021 in Italy (incidence from 0.9 to 1.7 x100,000 adult inhabitants) were identified. They were mainly older (median age 68 [56; 75] years), males (56%) and affected by ≥2 comorbidities (52%), mostly cardiometabolic. During 4 years of follow-up, 56% of cases in 2018 survived. During the first follow-up year: 73%, 80%, 100% and 35% of cases in 2018, 2019, 2020 and 2021, respectively, received a 2L; 42% and 64% of cases in 2018 and 2020, respectively, received a 3L. At least one Hsct was found as a 2L among cases in 2018, 2020 and 2021. On average, each patient newly diagnosed with Dlbcl and treated with 1L from 2018 to 2021 caused a total expenditure directly charged to the Ssn ranging from 20,000 to 30,000 during the first follow-up year (chemo-immunotherapy accounted for 40-53%), which reduced with time in favor of other drugs and Hsct. CONCLUSIONS: This analysis confirms the high rate of rrDlbcl and the high economic impact charged to the SSN to support first the chemo-immunotherapy, then the chronic care and the absence of standardized further lines of therapy for patients with rrDlbcl.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bases de Dados Factuais , Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/epidemiologia , Itália , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Idoso de 80 Anos ou mais , Adulto , Rituximab/administração & dosagem , Estimativa de Kaplan-Meier , Transplante de Células-Tronco Hematopoéticas , Custos de Cuidados de Saúde/estatística & dados numéricos , Vincristina/administração & dosagem , Seguimentos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Doxorrubicina/administração & dosagem , Prednisona/administração & dosagem , Prednisona/uso terapêuticoRESUMO
First-line treatment for advanced-stage diffuse large B-cell lymphoma (DLBCL) typically involves 6x R-CHOP21 or 6x R-CHOP21 with two additional rituximab administrations (6x R-CHOP21 + 2 R). In contemporary practice, this treatment choice might be guided by interim PET scan results. This nationwide, population-based study investigates the comparative effectiveness of these treatment regimens in an era where interim PET-guided treatment decisions were not standard practice. Utilizing the Netherlands Cancer Registry, we identified 1577 adult patients diagnosed with advanced-stage DLBCL between 2014-2018 who completed either 6x R-CHOP21 (43%) or 6x R-CHOP21 + 2 R (57%). We used propensity scores to assess differences in event-free survival (EFS) and overall survival (OS). At five years, EFS (hazard ratio of 6x R-CHOP21 + 2 R versus 6x R-CHOP21 [HR] = 0.89; 95% confidence interval [CI], 0.72-1.09) and OS (HR = 0.93; 95% CI, 0.73-1.18) were not significantly different between both regimens. In exploratory risk-stratified analysis according to the International Prognostic Index (IPI), high-IPI patients (i.e., scores of 4-5) benefit most from 6x R-CHOP21 + 2 R (5-year absolute risk difference of EFS = 16.8%; 95% CI, -0.4%-34.1% and OS = 12.1%; 95% CI, -5.4-29.6%). Collectively, this analysis reveals no significant differences on average in EFS and OS between the two treatments. However, the potential benefits for high-risk patients treated with 6x R-CHOP21 + 2 R underscore the need for future research.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Linfoma Difuso de Grandes Células B , Prednisona , Rituximab , Vincristina , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Vincristina/uso terapêutico , Vincristina/administração & dosagem , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Prednisona/uso terapêutico , Prednisona/administração & dosagem , Adulto , Idoso de 80 Anos ou mais , Estadiamento de Neoplasias , Resultado do Tratamento , Países Baixos/epidemiologiaRESUMO
PURPOSE: To better characterise the effects of corticosteroids on the course of pure idiopathic orbital inflammation syndrome (pIOIS). METHODS: This was a national, multicentre, prospective, non-interventional cohort study (SIOI). Among the 35 patients with histologically proven orbital inflammation who had previously been studied for their IgG4 immunostaining status, we selected those with a negative IgG4 status (ie, pIOIS) who received corticosteroids as single first-line treatment. Clinical, morphological and pathological findings at diagnosis and during follow-up from treatment initiation to study completion were analysed. Patients were assessed for their response to prednisone after the 24-month prospective phase in terms of remission (≤10 mg/d) or failure (>10 mg/d). Daily standard doses of prednisone (DSDP) were calculated at different time-points and compared between response groups. RESULTS: Of the 17 patients with pIOIS included in the final analysis, two-thirds received corticosteroids only. DSDP (mg/kg-day) were significantly higher at the time of failure in eight patients (47%) than in nine (53%) remitting at M24 (0.16 vs 0.045; p: 0.03). Notably, patients with pIOIS with a cellular pattern or orbital fat involvement tended to receive higher daily corticosteroid doses in the event of failure than remission (0.16 vs 0.045 and 0.12 vs 0.042, respectively). During treatment, maximal DSDP was 0.52 in failed patients. CONCLUSION: The highest corticosteroid doses were insufficient to prevent failure in patients with pIOIS, particularly in those with a cellular pattern or orbital fat involvement. Large-scale interventional studies are now necessary to clarify prognostic factors and optimise corticosteroid management in patients with pIOIS.
Assuntos
Glucocorticoides , Pseudotumor Orbitário , Humanos , Estudos Prospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto , Pseudotumor Orbitário/tratamento farmacológico , Glucocorticoides/uso terapêutico , França/epidemiologia , Idoso , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Tecido Adiposo/metabolismo , Falha de Tratamento , Prednisona/uso terapêutico , Prednisona/administração & dosagem , Seguimentos , Órbita/patologia , Órbita/efeitos dos fármacosRESUMO
BACKGROUND: Results of conventional induction chemotherapies in primary central nervous system lymphoma (PCNSL) need to be improved. Ibrutinib, a BTK inhibitor, and lenalidomide, an immunomodulatory drug, have shown promising results at relapse, supporting to further assess their individual use in combination with high-dose methotrexate-based chemotherapy. METHODS: Patients with newly diagnosed PCNSL were randomized to receive four 28-day cycles of ibrutinib or lenalidomide in combination with R-MPV (rituximab, methotrexate, procarbazine, vincristine and prednisone) in a 3 + 3 design. Responders then received a consolidation with R-Cytarabine and an intensive chemotherapy with autologous stem cell transplantation. The objective of the phase IB study was to define the recommended phase II dose (RP2D) based on the dose-limiting toxicity (DLT) occurring during the first induction cycle. RESULTS: Twenty-six patients (median age 52) were randomized. Four DLTs were observed: one grade 5 aspergillosis and pneumocystosis, one grade 4 catheter-related infection and two grade 3 increased alanine aminotransferase levels. RP2D of ibrutinib and lenalidomide were 560 mg daily (D3-14 and D17-28) and 15 mg daily (D1-21) respectively, in combination with R-MPV. In both arms, the most frequent grade ≥3 treatment-related adverse events were hepatic cytolysis, neutropenia and infections. One grade 4 Lyell's syndrome was reported at cycle 2 in the lenalidomide arm. After 4 induction cycles, the overall response rates were 76.9% and 83.3% in the lenalidomide and ibrutinib arm, respectively. CONCLUSION: Targeted induction therapies combining lenalidomide or ibrutinib with R-MPV are feasible for first-line PCNSL. The safety profile is consistent with the known safety profiles of R-MPV and both targeted therapies. The phase II part of the study is ongoing. TRIAL REGISTRATION: NCT04446962.
Assuntos
Adenina , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Nervoso Central , Lenalidomida , Piperidinas , Pirazóis , Pirimidinas , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Lenalidomida/efeitos adversos , Adenina/análogos & derivados , Adenina/administração & dosagem , Pessoa de Meia-Idade , Piperidinas/administração & dosagem , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Masculino , Feminino , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Idoso , Adulto , Pirimidinas/administração & dosagem , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Vincristina/administração & dosagem , Vincristina/uso terapêutico , Vincristina/efeitos adversos , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Prednisona/efeitos adversos , Linfoma/tratamento farmacológicoRESUMO
The potential of RNA-based liquid biopsy is increasingly being recognized in diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma. This study explores the cell-free transcriptome in a humanized DLBCL patient-derived tumor xenograft (PDTX) model. Blood plasma samples (n = 171) derived from a DLBCL PDTX model, including 27 humanized (HIS) PDTX, 8 HIS non-PDTX, and 21 non-HIS PDTX non-obese diabetic (NOD)-scid IL2Rgnull (NSG) mice were collected during humanization, xenografting, treatment, and sacrifice. The mice were treated with either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), CD20-targeted human IFNα2-based AcTaferon combined with CHOP (huCD20-Fc-AFN-CHOP), or phosphate-buffered saline (PBS). RNA was extracted using the miRNeasy serum/plasma kit and sequenced on the NovaSeq 6000 platform. RNA sequencing data of the formalin-fixed paraffin-embedded (FFPE) tissue and blood plasma samples of the original patient were included. Flow cytometry was performed on immune cells isolated from whole blood, spleen, and bone marrow. Bulk deconvolution was performed using the Tabula Sapiens v1 basis matrix. Both R-CHOP and huCD20-Fc-AFN-CHOP were able to control tumor growth in most mice. Xenograft tumor volume was strongly associated with circulating tumor RNA (ctRNA) concentration (p < 0.001, R = 0.89), as well as with the number of detected human genes (p < 0.001, R = 0.79). Abundance analysis identified tumor-specific biomarkers that were dynamically tracked during tumor growth or treatment. An 8-gene signature demonstrated high accuracy for assessing therapy response (AUC 0.92). The tumoral gene detectability in the ctRNA of the PDTX-derived plasma was associated with RNA abundance levels in the patient's tumor tissue and blood plasma (p < 0.001), confirming that tumoral gene abundance contributes to the cell-free RNA (cfRNA) profile. Decomposing the transcriptome, however, revealed high inter- and intra-mouse variability, which was lower in the HIS PDTX mice, indicating an impact of human engraftment on the stability and profile of cfRNA. Immunochemotherapy resulted in B cell depletion, and tumor clearance was reflected by a decrease in the fraction of human CD45+ cells. Lastly, bulk deconvolution provided complementary biological insights into the composition of the tumor and circulating immune system. In conclusion, the blood plasma-derived transcriptome serves as a biomarker source in a preclinical PDTX model, enables the assessment of biological pathways, and enhances the understanding of cfRNA dynamics.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Linfoma Difuso de Grandes Células B , Camundongos Endogâmicos NOD , Camundongos SCID , Prednisona , Rituximab , Transcriptoma , Vincristina , Ensaios Antitumorais Modelo de Xenoenxerto , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Animais , Humanos , Camundongos , Biópsia Líquida/métodos , Rituximab/uso terapêutico , Prednisona/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina , Biomarcadores Tumorais/genética , Masculino , Ácidos Nucleicos Livres/genética , Ácidos Nucleicos Livres/sangue , Feminino , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Systemic inflammation can significantly impact gliomas' onset, progression, and prognosis. Glioblastoma multiforme (GBM) represents the glioma subtype characterized by the most profound inflammatory and immunosuppressive states. Consequently, various blood-borne biomarkers have been scrutinized concerning their prognostic value in GBM patients. OBJECTIVE: We sought to investigate whether the recently introduced Global Immune-Nutrition-Inflammation Index (GINI) holds prognostic significance for GBM patients treated with the standard Stupp protocol. METHODS: We retrospectively analyzed the data from a cohort of newly diagnosed GBM patients receiving the standard Stupp regimen using the propensity score-matching methodology. The GINI was computed using the original formula: GINI = [(C-reactive protein × Monocytes × Platelets × Neutrophils) ÷ (Albumin × Lymphocytes)]. We employed receiver operating characteristic (ROC) curve analysis to identify the optimal cutoff values for GINI, which could help distinguish between different survival outcomes. The primary and secondary objectives were the differences in overall survival (OS) and progression-free survival (PFS) between the GINI groups. RESULTS: The optimal GINI cutoff value was 1350. Out of 294 eligible patients, 211 were PSM-matched: GINI<1350 (N = 95) and GINI≥1350 (N = 116). Comparative Kaplan-Meier estimates indicated that the GINI≥1350 patients had substantially worse median PFS (8.0 vs 16.8 months; p < .001) and OS (14.3 vs 22.9 months; p < .001) durations than their GINI<1350 counterparts. CONCLUSION: High pretreatment GINI values are robustly and independently associated with inferior PFS and OS outcomes in selected GBM patients who receive standard Stupp protocol. These findings suggest that if further confirmed, the novel GINI could serve as a valuable biological marker for the prognostic stratification of GBM patients.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Inflamação , Humanos , Glioblastoma/imunologia , Glioblastoma/mortalidade , Glioblastoma/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Inflamação/imunologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/sangue , Idoso , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Intervalo Livre de Progressão , Neutrófilos/imunologia , Estado Nutricional , Prednisona/uso terapêutico , Prednisona/administração & dosagemRESUMO
Importance: Anti-double-stranded DNA (dsDNA) antibody has been reported to have a close relationship with systemic lupus erythematosus (SLE) flares and participates in the pathogenesis of lupus nephritis (LN) as well as causing damage to other organs. However, whether early use of mycophenolate mofetil (MMF) could prevent SLE flares is not clear. Objective: To assess the efficacy and safety of MMF plus prednisone and hydroxychloroquine sulfate compared with prednisone and hydroxychloroquine sulfate alone in patients with SLE. Design, Setting, and Participants: This investigator-initiated, multicenter, observer-blinded randomized clinical trial enrolled 130 participants aged 18 to 65 years and was conducted in 3 hospitals across China. Treatment-naive patients with newly diagnosed SLE, a high titer of anti-dsDNA antibody, and no major organ involvement were included. The study was started September 1, 2018, and the follow-up was completed September 30, 2021. Data were analyzed from December 1, 2021, to March 31, 2022. Interventions: Patients were randomized 1:1 to receive oral prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) (control group) or prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) plus MMF (500 mg twice daily) (MMF group) for 96 weeks. Main Outcomes and Measures: The primary outcome was the proportion of patients presenting with flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare Index. The secondary outcomes included the proportion with lupus low disease activity state at week 96, 36-Item Short Form Health Survey scores before and after treatment, proportion of adverse events (AEs), and changes in SLEDAI-2000 scores and prednisone doses. Results: Among 130 randomized patients (mean [SD] age, 34.5 [12.5] years; 112 [86.2%] women), 119 (91.5%) completed the follow-up. The risk of severe flare was significantly lower in the MMF group (7 of 65 [10.8%]) vs the control group (18 of 65 [27.7%]) (relative risk [RR], 0.39 [95% CI, 0.17-0.87]; P = .01). Additionally, 1 of 65 patients in the MMF group (1.5%) and 9 of 65 in the control group (13.8%) manifested LN (RR, 0.11 [95% CI, 0.01-0.85]; P = .008). Most common serious study drug-related AEs were infections (20 of 65 [30.8%] in the control group and 22 of 65 [33.8%] in the MMF group). Conclusions and Relevance: The findings of this randomized clinical trial suggest that MMF may reduce the rate of severe flare and lower the incidence of LN in patients with new-onset SLE and a high titer of anti-dsDNA antibody without major organ involvement. Trial Registration: Chinese Clinical Trial Registry: ChiCTR1800017540.
Assuntos
Hidroxicloroquina , Lúpus Eritematoso Sistêmico , Ácido Micofenólico , Prednisona , Humanos , Ácido Micofenólico/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Feminino , Adulto , Masculino , Hidroxicloroquina/uso terapêutico , Hidroxicloroquina/efeitos adversos , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Prednisona/efeitos adversos , Quimioterapia Combinada , Adolescente , Imunossupressores/uso terapêutico , Adulto Jovem , China , Resultado do TratamentoAssuntos
Linfadenopatia Imunoblástica , Linfonodos , Linfoma de Células T , Plasmócitos , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Plasmócitos/patologia , Linfonodos/patologia , Linfadenopatia Imunoblástica/patologia , Linfadenopatia Imunoblástica/genética , Linfoma de Células T/patologia , Linfoma de Células T/genética , Imunofenotipagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vincristina/uso terapêutico , Prednisona/uso terapêutico , Ciclofosfamida , DoxorrubicinaRESUMO
Background: Angioimmunoblastic T-cell lymphoma (AITL) is known for its unfavorable survival prognosis. Chidamide has shown efficacy in relapsed/refractory AITL, but its efficacy in newly diagnosed AITL is uncertain. Objective: This retrospective research aimed to evaluate the effectiveness and safety of chidamide when used with doxorubicin, cyclophosphamide, prednisone, and vincristine (CHOP) in comparison to CHOP by itself for individuals newly diagnosed with AITL, and to examine the impact of transplantation. Method: This was an analysis that compared outcomes among patients who received chidamide + CHOP on a clinical trial vs. historical controls who received CHOP alone, enrolling a total of sixty-six treatment-naive AITL patients between April 2014 and November 2022. Among them, thirty-three received chidamide in addition to CHOP (chidamide group), while thirty-three received CHOP alone (control group). The clinical characteristics were balanced between the two groups. All patients were scheduled to undergo up to six courses of treatment before transplantation. Results: The chidamide group had a significantly longer median overall survival (OS) compared to the control group, with a median OS that was not reached, as opposed to 20 months in the control group (p = 0.002). In the control group, the median progression-free survival (PFS) was 11 months, while in the chidamide group, it was 22 months (p = 0.080). In the high-risk group (IPI ≥ 3), the chidamide group demonstrated notably superior complete response (CR) and overall response rate (ORR) compared to the control cohort (p = 0.002, p = 0.034). The PFS and OS in the chidamide group were not reached, and there were significant differences compared to the control group (p = 0.007, p = 0.003). The median OS of the transplanted group was longer than the non-transplanted group (p = 0.004). On multivariate analysis, chidamide group reduced the hazards of death in the total cohort. Conclusion: As the study was non-random and retrospective, Chidamide combined with chemotherapy should be tested in randomized trials given its potential to improve prognosis in treatment-naive AITL patients. Furthermore, autologous hematopoietic stem cell transplantation (auto-HSCT) has demonstrated enhanced overall survival in individuals with AITL. Clinical trial registration: https://clinicaltrials.gov/, NCT03268889.
Assuntos
Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aminopiridinas/uso terapêutico , Aminopiridinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzamidas/uso terapêutico , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Linfoma de Células T/mortalidade , Linfoma de Células T/terapia , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/diagnóstico , Prednisona/uso terapêutico , Prednisona/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/uso terapêutico , Vincristina/administração & dosagemRESUMO
Colonic lymphoma is a rare malignant gastrointestinal tumor that can be revealed by an exceptional and serious complication: intestinal obstruction. Treatment is based on surgery and chemotherapy. We here report a case of diffuse colonic large B-cell lymphoma revealed by occlusion and diagnosed based on the examination of surgical specimen in a 64-year-old man who was in complete remission after six courses of R-CHOP.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Colo , Ciclofosfamida , Doxorrubicina , Obstrução Intestinal , Linfoma Difuso de Grandes Células B , Prednisona , Rituximab , Vincristina , Humanos , Masculino , Pessoa de Meia-Idade , Obstrução Intestinal/etiologia , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/cirurgia , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/complicações , Neoplasias do Colo/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/patologia , Ciclofosfamida/administração & dosagem , Vincristina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Prednisona/administração & dosagem , Doxorrubicina/administração & dosagem , Rituximab/administração & dosagem , Indução de RemissãoRESUMO
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma entity, and its incidence increases with age. There is a paucity of data regarding use of biweekly R-CHOP (R-CHOP-14) in patients ≥80 years of age. We performed a retrospective cohort study of patients with DLBCL aged ≥80 years treated with R-CHOP-14 and R-miniCHOP in two academic tertiary centers in Germany between 01/01/2005 and 12/30/2019. Overall, 79 patients were included. Median age was 84 years (range 80-91). Despite higher CR rates with R-CHOP-14 (71.4% vs. 52.4%), no statistically significant difference could be found between patients treated with R-CHOP-14 and R-miniCHOP regarding overall survival (OS) (p = .88, HR 0.94, 95% CI = 0.47-1.90) and progression-free survival (PFS) (p = .26, HR 0.66, 95% CI = 0.32-1.36). At a median follow-up of 40 months, the 2-year OS rates were 56% with R-CHOP-14 and 53% with R-miniCHOP. Two-year PFS rates were 46% for R-CHOP-14 and 50% for R-mini-CHOP. Relative dose intensity of chemotherapy did not correlate with OS (p = .72). With the caveat of a retrospective cohort study, we conclude that lacking a difference in OS, R-miniCHOP should be preferred for most patients with untreated DLBCL aged ≥80 years.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Linfoma Difuso de Grandes Células B , Prednisona , Rituximab , Vincristina , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Estudos Retrospectivos , Vincristina/uso terapêutico , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Idoso de 80 Anos ou mais , Masculino , Feminino , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Prednisona/uso terapêutico , Prednisona/administração & dosagem , Rituximab/administração & dosagem , Resultado do TratamentoRESUMO
INTRODUCTION/OBJECTIVES: Optic nerve sheath (ONS) enhancement using magnetic resonance imaging of the orbits was observed in patients with giant cell arteritis (GCA). We previously showed that ONS diameter (ONSD) by bedside ultrasound is increased in patient with active GCA. This study aims to assess whether ONSD decreases with clinical remission in patients with GCA. METHODS: A prospective cohort study was conducted from June 2022 to January 2023. Patients who had an optic nerve ultrasound at GCA diagnosis as part of a previous crosssectional study were eligible. Optic nerve ultrasound was performed by the same investigator at diagnosis and month 3. ONSD (includes the optic nerve and its sheath) and optic nerve diameter (OND) were measured. Descriptive statistics for baseline characteristics and paired sample t-test were performed to assess the mean difference in OND and ONSD between diagnosis and month 3. RESULTS: Nine patients with GCA were included. The median age at disease onset was 79 years (interquartile range (IQR) of 79-82 years), and 7 patients were males. All patients were in clinical remission at month 3 on prednisone (median dose of 15 mg/day, IQR of 10-25 mg). The mean ONSD was lower at month 3 (3.76 mm) compared to baseline (5.98 mm), with a paired mean difference of 2.22 mm (95% CI 1.41-3.03 mm, p < 0.001). As anticipated, OND measurements did not vary between diagnosis and month 3. CONCLUSION: ONSD on ultrasound improves after 3 months of therapy in patients with GCA. A longer prospective study is required to determine if ONSD is useful to assess disease activity in GCA. Key Points ⢠ONS ultrasound can identify patients with active GCA. ⢠The ONSD on ultrasound is dynamic and improved after 3 months of GCA therapy. ⢠ONS ultrasound may be useful to monitor disease activity in GCA.
Assuntos
Arterite de Células Gigantes , Nervo Óptico , Ultrassonografia , Humanos , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/tratamento farmacológico , Masculino , Feminino , Projetos Piloto , Idoso , Nervo Óptico/diagnóstico por imagem , Nervo Óptico/patologia , Estudos Prospectivos , Idoso de 80 Anos ou mais , Prednisona/uso terapêutico , Estudos TransversaisRESUMO
BACKGROUND: Managing metastatic castration-resistant prostate cancer (mCRPC) in men aged ≥ 75 is challenging due to limited data. Regardless of age, in real-world clinical practice, most mCRPC still derive from failure of androgen deprivation therapy (ADT) with or without docetaxel (D) for metastatic castration-sensitive prostate cancer (mCSPC). As abiraterone acetate plus prednisone (AA) and enzalutamide (Enza) are common first-line treatments for mCRPC. The impact of prior use of D for mCSPC on the efficacy and safety of AA or Enza in this older population remains unclear. METHODS: A cohort of patients aged ≥ 75 years starting AA or Enza as first-line therapy for mCRPC from January 2015 to April 2019 was identified from the registries of 10 institutions. Patients were categorized into 2 groups based on previous use of D for mCSPC. Primary endpoints were cancer-specific survival (CSS) from AA or Enza start, CSS from ADT onset, and safety. We used Kaplan-Meier method to estimate the endpoints distribution, including median values with 95% confidence intervals (95% CI). RESULTS: Of the 337 patients identified, 24 (7.1%) received ADT+D and 313 (92.9%) received ADT alone for mCSPC. Median follow-up from AA/Enza start was 18.8 months. Median CSS from ADT or AA/Enza was not significantly different between ADT+D and ADT alone cohorts (71.9 vs. 52.7 months, P = .97; 25.4 vs. 27.2 months, P = .89, respectively). No statistically significant difference in adverse events (AEs) of any grade rate (58.3% vs. 52.1%, respectively; P = .67) or grade ≥ 3 (12.5% vs. 15.7%, respectively; P = 1.0) was found between ADT+D and ADT alone cohorts. CONCLUSIONS: Despite the innate limitations of a retrospective design and relatively small size of the ADT+D cohort, this analysis suggests that elderly men receiving AA or Enza as first-line therapy for mCRPC have similar survival outcomes and tolerability, regardless of previous D for mCSPC.
Assuntos
Acetato de Abiraterona , Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Docetaxel , Nitrilas , Feniltioidantoína , Neoplasias de Próstata Resistentes à Castração , Sistema de Registros , Humanos , Masculino , Feniltioidantoína/administração & dosagem , Feniltioidantoína/uso terapêutico , Feniltioidantoína/análogos & derivados , Feniltioidantoína/efeitos adversos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/mortalidade , Idoso , Acetato de Abiraterona/uso terapêutico , Acetato de Abiraterona/administração & dosagem , Nitrilas/administração & dosagem , Docetaxel/administração & dosagem , Docetaxel/uso terapêutico , Idoso de 80 Anos ou mais , Sistema de Registros/estatística & dados numéricos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Prednisona/administração & dosagem , Prednisona/uso terapêuticoRESUMO
Cold atmospheric plasma (CAP) has been employed as a therapy against both acute and chronic skin lesions, contaminated or not, and has effects on angiogenesis and reepithelialization promoting healing. In this context, the present study aimed to evaluate the effects of a CAP jet associated with pharmacological treatment described by the 2015 AAHA/AAFP pain management guidelines and the 2022 WSAVA guidelines for the recognition, assessment, and treatment of pain, on the healing of chronic skin lesions caused by a pruritic reaction resulting from post-surgical neuropathic pain. To this end, a single CAP application was performed on a feline patient with a 6 months old recurrent contaminated cervical skin lesions along with administration of ketamine (10 µg/kg/min) following the prescription of prednisone (1 mg/kg, SID, 6 days), gabapentin (8 mg/kg, BID, 60 days) and amitriptyline (0.5 mg /kg, SID, 60 days). A single application of plasma associated with an NMDA antagonist, anti-inflammatory steroid, tricyclic antidepressant and gabapentinoid thus provided a significant improvement in the macroscopic appearance of the lesion within 10 days, and the owner reported the cessation of intense itching within the first four hours after treatment and a consequent improvement in the animal's quality of life. The medical treatment was finished almost a year since the writing of this paper, without clinical or reported recurrent signs of the condition. Therefore, we observed that single dose CAP application associated with ketamine, gabapentin, amitriptyline and prednisone leads to significant healing of chronically infected skin lesions resulting from post-surgical neuropathic pain.
Assuntos
Analgésicos , Doenças do Gato , Ketamina , Neuralgia , Gases em Plasma , Animais , Gatos , Neuralgia/veterinária , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Gases em Plasma/uso terapêutico , Gases em Plasma/farmacologia , Doenças do Gato/tratamento farmacológico , Ketamina/administração & dosagem , Ketamina/uso terapêutico , Analgésicos/uso terapêutico , Analgésicos/administração & dosagem , Dor Pós-Operatória/veterinária , Dor Pós-Operatória/tratamento farmacológico , Gabapentina/uso terapêutico , Gabapentina/administração & dosagem , Masculino , Amitriptilina/uso terapêutico , Amitriptilina/administração & dosagem , Prednisona/uso terapêutico , Prednisona/administração & dosagem , Terapia Combinada/veterinária , FemininoRESUMO
This study aims to test the hypothesis that disease duration may affect the response to generic tofacitinib (TOF) and investigate the influence of concomitant medications with TOF on elderly rheumatoid arthritis (RA). This study retrospectively collected 76 elderly patients (age > 60) treated with TOF from 2019 to 2023 and grouped them according to age of disease onset. Data were collected from baseline to the last follow-up visit within 24 months. The demographic characteristics and follow-up results were compared. TOF retention and the effect of concomitant drugs (methotrexate, MTX, prednisone) were analyzed using Kaplan-Meier plots and COX regression analysis. Canonical correlation analysis (CCA) was used to explore the correlation among demographic characteristics, medication regimen, and improved clinical outcomes. There was no significant difference in the proportion of patients achieving low disease activity (LDA) between different disease duration groups. Patients in the group of MTX had a shorter time of using TOF in follow-up (log-rank p = 0.041). Prednisone dosage at baseline had a predictive value for functionally disabled situation. We found significant associations between discontinuation of TOF in the last follow-up and getting LDA. A total result of CCA yielded a significant positive correlation with set 1 (demographic characteristics and medication regimen) and set 2 (improved clinical outcomes) (canonical coefficient = 0.887, p < 0.001). Disease duration may not affect response to generic TOF and medication regimen was the factor related to efficacy of generic TOF in elderly RA in the real world. Demographic characteristics and medication regimen were correlated positively with improved clinical outcomes. Key Points ⢠There is scarce data from the western area of China regarding the use of tofacitinib in elderly rheumatoid arthritis patients, despite widespread use. ⢠In this retrospective analysis of 76 elderly patients at a single center, we found disease duration may not affect response to generic TOF. ⢠Concomitant MTX might contribute to better control of the disease activity. ⢠Concomitant prednisone dosage at baseline was the independent risk factor for functionally disabled situation.
Assuntos
Antirreumáticos , Artrite Reumatoide , Metotrexato , Piperidinas , Pirimidinas , Humanos , Artrite Reumatoide/tratamento farmacológico , Pirimidinas/uso terapêutico , Masculino , Feminino , Idoso , Piperidinas/uso terapêutico , Estudos Retrospectivos , Antirreumáticos/uso terapêutico , Metotrexato/uso terapêutico , Resultado do Tratamento , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Quimioterapia Combinada , Inibidores de Proteínas Quinases/uso terapêutico , Idoso de 80 Anos ou maisRESUMO
BACKGROUND Fermenting bacilli producing lactic acid, including Bifidobacterium spp., are supposed to have low pathogenicity and no virulence for humans. Probiotics consisting of those fermenting bacilli can prevent and treat symptomatic gastrointestinal conditions, such as diarrhea. We use probiotics even in cancer patients, those who are immunocompromised, because a preferable effect to the intestinal commensal microbiome has been shown in a recent report. Some case reports warn of a rare risk of bloodstream infection caused by probiotics. However, complete prohibition of probiotic use in cancer patients abandons the benefits. CASE REPORT A 75-year-old Japanese woman with malignant lymphoma was treated with immune-chemotherapy regimen consisting of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). The patient had onset of febrile neutropenia during chemotherapy and had Bifidobacterium breve bloodstream infection on day 8 after the eighth R-CHOP treatment. She had usually eaten commercial yogurt every morning. This yogurt was produced from only Lactobacillus bulgaricus and Streptococcus thermophilus. It did not contain Bifidobacterium breve. The bloodstream infection in this case looked like it derived from her food; however, it was not associated with her habitual foods. The patient was treated with meropenem for 8 days and experienced complete remission of the bloodstream infection. CONCLUSIONS We speculate that fermenting bacilli can also be a source of bloodstream infection, not necessarily associated with probiotic strains, in cancer patients treated with chemotherapy. Additionally, we recommend that probiotics can alleviate alimentary tract symptoms in immunocompromised patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Probióticos , Humanos , Feminino , Idoso , Probióticos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Doxorrubicina/efeitos adversos , Vincristina/uso terapêutico , Infecções por Bifidobacteriales/microbiologia , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Prednisona/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bifidobacterium breve , Linfoma/tratamento farmacológicoRESUMO
Due to the lack of treatment guidelines for the management of advanced-stage marginal zone lymphoma (MZL), only one chemoimmunotherapy-cyclophosphamide, vincristine, and prednisone plus rituximab (R-CVP)-is reimbursed in the first-line setting in South Korea. The aim of this study was to develop a consensus-based recommendation for the treatment of patients with advanced-stage MZL. Twelve hematologist oncologists participated in a two-round Delphi process to identify consensus on the management of patients with advanced-stage MZL in South Korea. Physicians rated their level of agreement with each statement on a four-point Likert scale. Statements were divided into two sections: definitions used in clinical practice and clinical management of patients with advanced-stage MZL. Consensus was reached for 23 of 33 (69.7%) and 5 of 13 statements (38.5%) in rounds 1 and 2, respectively. There was strong consensus (91.7%) that advanced-stage MZL subtypes are defined according to the Lugano staging system. First-line systemic treatment should be prescribed for patients with symptomatic advanced-stage MZL. Although there was unanimous agreement that R-CVP is the standard first-line treatment for advanced-stage MZL, physicians also agreed that bendamustine with rituximab (BR) has greater efficacy than R-CVP as first-line treatment (91.7%). For the treatment of relapsed/refractory advanced-stage MZL, BR and R-CVP can be repeated in patients with short (< 24 months) and long remission periods (≥ 24 months), respectively. This study provides insights on the management of patients with advanced-stage MZL in South Korea. This may enhance clinical decision-making, thus improving patient outcomes.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Técnica Delphi , Linfoma de Zona Marginal Tipo Células B , Humanos , República da Coreia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Estadiamento de Neoplasias , Rituximab/administração & dosagem , Consenso , Vincristina/administração & dosagem , Vincristina/uso terapêutico , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Masculino , Feminino , Guias de Prática Clínica como AssuntoAssuntos
Linfoma Difuso de Grandes Células B , Neoplasias Primárias Múltiplas , Humanos , Masculino , Idoso , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/genética , Linfoma de Células T/patologia , Linfoma de Células T/genética , Linfoma de Células T/metabolismo , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/genética , Intestino Delgado/patologia , Ciclofosfamida/uso terapêutico , Vincristina/uso terapêutico , Doxorrubicina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diagnóstico Diferencial , Prednisona/uso terapêuticoRESUMO
The mechanism underlying intestinal fibrosis, the main complication of inflammatory bowel disease (IBD), is not yet fully understood, and there is no therapy to prevent or reverse fibrosis. We evaluated, in in vitro cellular models, the ability of different classes of drugs currently used in IBD to counteract two pivotal processes of intestinal fibrosis, the differentiation of intestinal fibroblasts to activated myofibroblasts using CCD-18Co cells, and the epithelial-to-mesenchymal transition (EMT) of intestinal epithelial cells using Caco-2 cells (IEC), both being processes induced by transforming growth factor-ß1 (TGF-ß1). The drugs tested included mesalamine, azathioprine, methotrexate, prednisone, methylprednisolone, budesonide, infliximab, and adalimumab. The expression of fibrosis and EMT markers (collagen-I, α-SMA, pSmad2/3, occludin) was assessed by Western blot analysis and by immunofluorescence. Of the drugs used, only prednisone, methylprednisolone, budesonide, and adalimumab were able to antagonize the pro-fibrotic effects induced by TGF-ß1 on CCD-18Co cells, reducing the fibrosis marker expression. Methylprednisolone, budesonide, and adalimumab were also able to significantly counteract the TGF-ß1-induced EMT process on Caco-2 IEC by increasing occludin and decreasing α-SMA expression. This is the first study that evaluates, using in vitro cellular models, the direct antifibrotic effects of drugs currently used in IBD, highlighting which drugs have potential antifibrotic effects.