RESUMO
BACKGROUND: Trastuzumab deruxtecan (T-DXd) has shown promising results in patients with breast cancer brain metastases (BCBMs). We conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of T-DXd in the human epidermal growth factor receptor 2 (HER2)-positive BCBM population. PATIENTS AND METHODS: We searched PubMed, Embase, and Cochrane Library databases as well as American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and San Antonio Breast Cancer Symposium (SABCS) websites for clinical trials (CTs) and observational studies evaluating T-DXd in patients with HER2-positive BCBM. Heterogeneity was assessed with I2 statistics. Random effects models were used for all statistical analyses, which were carried out using R software (version 4.2.2). RESULTS: Ten studies were included, six CTs (n = 189) and four observational studies (n = 130), with a total of 319 patients. The median progression-free survival was 15 months [95% confidence interval (CI) 13.9-16.1 months]. The objective response rate (ORR) was 61% (95% CI 52% to 70%), and the intracranial (IC)-ORR was 61% (95% CI 54% to 69%). No significant differences in ORR and IC-ORR were observed between CTs and observational studies (P = 0.31 and 0.58, respectively). The clinical benefit rate (CBR) was 80% (95% CI 52% to 94%), and the IC-CBR was 70% (95% CI 54% to 82%). The ORR was 68% (95% CI 57% to 77%) in the subgroup of patients with stable BMs and 60% (95% CI 48%-72%) in patients with active BM, with no significant difference between groups (P = 0.35). CONCLUSIONS: Our systematic review and meta-analysis supports the IC activity of T-DXd in patients with stable BM and active BM. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) under the protocol number CRD42023422589.
Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Camptotecina/análogos & derivados , Imunoconjugados , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológicoRESUMO
Abstract This study evaluated the effect of the volatile oil of Alpinia zerumbet (VOAz) on caveolin-1 gene expression and muscular fibrosis. The rats were immobilized to induce fibrosis of the gastrocnemius muscle, and they were treated with VOAz. Collagen quality was assessed by histology and the expression of the caveolin-1 (CAV-1) gene was evaluated using qPCR. Histomorphological analysis indicated a significant reduction in the perimeter, width, and intensity of collagen in the treated groups, thus showing that the oil was effective in regulating the quality of collagen at the three concentrations. The results of expression levels suggested a decrease in the lesioned group and in two treatment groups (0.0115 µg/g and 0.009 µg/g). However, with the lowest concentration (0.0065 µg/g), no significant difference was observed, with levels similar to those found in healthy tissue. Therefore, the results showed that VOAz has the potential to be a non-invasive and low-cost alternative to aid in the treatment of muscular fibrosis.
Resumo Este estudo avaliou o efeito do óleo volátil de Alpinia zerumbet (OVAz) na expressão do gene da caveolina-1 e na fibrose muscular. Os ratos foram imobilizados para induzir a fibrose do músculo gastrocnêmio, e foram tratados com OVAz. A qualidade do colágeno foi avaliada com histologia e à expressão do gene caveolina-1 (CAV-1) foi avaliada usando qPCR. A análise histomorfológica indicou uma redução significativa no perímetro, largura e intensidade do colágeno nos grupos tratados. Os resultados dos níveis de expressão sugeriram diminuição nos grupos de lesão e em dois grupos de tratamento (0,0115 µg/g e 0,009 µg/g). No entanto, com a menor concentração (0,0065 µg/g), não foi observada diferença significativa, apresentando níveis semelhantes aos encontrados em tecido saudável. O uso do OVAz foi eficaz para reverter as alterações do colágeno causadas pela fibrose, e sua menor concentração apresentou uma possível tendência de aumento na expressão do CAV-1. Portanto, os resultados mostraram que o OVAz tem potencial para ser uma alternativa não invasiva e de baixo custo para auxiliar no tratamento da fibrose muscular.
Assuntos
Animais , Ratos , Óleos Voláteis/farmacologia , Colágeno/metabolismo , Alpinia/química , Caveolina 1/metabolismo , Músculos/efeitos dos fármacos , Fibrose , Óleos de Plantas/farmacologia , Brasil , Ratos Wistar , Modelos Animais de Doenças , Músculos/patologiaRESUMO
Abstract This study evaluated the effect of the volatile oil of Alpinia zerumbet (VOAz) on caveolin-1 gene expression and muscular fibrosis. The rats were immobilized to induce fibrosis of the gastrocnemius muscle, and they were treated with VOAz. Collagen quality was assessed by histology and the expression of the caveolin-1 (CAV-1) gene was evaluated using qPCR. Histomorphological analysis indicated a significant reduction in the perimeter, width, and intensity of collagen in the treated groups, thus showing that the oil was effective in regulating the quality of collagen at the three concentrations. The results of expression levels suggested a decrease in the lesioned group and in two treatment groups (0.0115 µg/g and 0.009 µg/g). However, with the lowest concentration (0.0065 µg/g), no significant difference was observed, with levels similar to those found in healthy tissue. Therefore, the results showed that VOAz has the potential to be a non-invasive and low-cost alternative to aid in the treatment of muscular fibrosis.
Resumo Este estudo avaliou o efeito do óleo volátil de Alpinia zerumbet (OVAz) na expressão do gene da caveolina-1 e na fibrose muscular. Os ratos foram imobilizados para induzir a fibrose do músculo gastrocnêmio, e foram tratados com OVAz. A qualidade do colágeno foi avaliada com histologia e à expressão do gene caveolina-1 (CAV-1) foi avaliada usando qPCR. A análise histomorfológica indicou uma redução significativa no perímetro, largura e intensidade do colágeno nos grupos tratados. Os resultados dos níveis de expressão sugeriram diminuição nos grupos de lesão e em dois grupos de tratamento (0,0115 µg/g e 0,009 µg/g). No entanto, com a menor concentração (0,0065 µg/g), não foi observada diferença significativa, apresentando níveis semelhantes aos encontrados em tecido saudável. O uso do OVAz foi eficaz para reverter as alterações do colágeno causadas pela fibrose, e sua menor concentração apresentou uma possível tendência de aumento na expressão do CAV-1. Portanto, os resultados mostraram que o OVAz tem potencial para ser uma alternativa não invasiva e de baixo custo para auxiliar no tratamento da fibrose muscular.
RESUMO
This study evaluated the effect of the volatile oil of Alpinia zerumbet (VOAz) on caveolin-1 gene expression and muscular fibrosis. The rats were immobilized to induce fibrosis of the gastrocnemius muscle, and they were treated with VOAz. Collagen quality was assessed by histology and the expression of the caveolin-1 (CAV-1) gene was evaluated using qPCR. Histomorphological analysis indicated a significant reduction in the perimeter, width, and intensity of collagen in the treated groups, thus showing that the oil was effective in regulating the quality of collagen at the three concentrations. The results of expression levels suggested a decrease in the lesioned group and in two treatment groups (0.0115 µg/g and 0.009 µg/g). However, with the lowest concentration (0.0065 µg/g), no significant difference was observed, with levels similar to those found in healthy tissue. Therefore, the results showed that VOAz has the potential to be a non-invasive and low-cost alternative to aid in the treatment of muscular fibrosis.
Assuntos
Alpinia , Caveolina 1/metabolismo , Colágeno/metabolismo , Músculos/efeitos dos fármacos , Óleos Voláteis/farmacologia , Alpinia/química , Animais , Brasil , Modelos Animais de Doenças , Fibrose , Músculos/patologia , Óleos de Plantas/farmacologia , Ratos , Ratos WistarRESUMO
Persistent infection with high-risk human papillomavirus (HPV) is the main cause of cervical cancer and the prevalence of HPV types varies depending on the geographic region. Therefore, this study assessed the prevalence of HPV types in women with cervical lesions from Sergipe state, Northeastern Brazil. A cross-sectional study was conducted in women with cervical lesions from March to December 2014. These lesions were investigated by PCR and HPV types were identified by DNA sequencing. 432 patients were included, of which 337 patients tested positive for HPV. Eighteen different HPV types were detected, and high-risk HPV types were detected in 69.2%. HPV 16 (63.4%) was the most prevalent HPV type found, followed by HPV 66 (4.6%), HPV 18 (1.6%) and HPV 45 (1.4%). These results highlight the importance of the high prevalence of HPV 66, which is a possibly carcinogenic virus type not covered by the available vaccines. The prevalence of HPV 16 was high in the studied population, reaffirming the importance of young vaccination. However, the high prevalence of HPV 66 found in this study shows the importance of monitoring the diversity of HPV types in different populations and geographic regions to better understand the impacts of current HPV vaccines.
Assuntos
Alphapapillomavirus/classificação , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Idoso , Alphapapillomavirus/genética , Alphapapillomavirus/isolamento & purificação , Brasil/epidemiologia , Estudos Transversais , DNA Viral/análise , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Prevalência , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Bloodstream infections (BSI) are a major complication in the early phase of a haematopoietic stem cell transplant (HSCT). AIM: To describe the incidence and risk factors for BSI occurring in the pre-engraftment phase of HSCT, and its impact on mortality. METHODS: Clinical variables of 232 HSCT patients were analysed retrospectively between 2014 and 2015. Univariate Cox regression analyses were performed to test the association between each covariate and the outcome. Covariates with P < 0.10 on univariate analysis were included in a multiple Cox regression analysis using a backward elimination method. FINDINGS: The cumulative incidence of BSI was 25.4%, mainly caused by Gram-negative bacteria (GNB) (55.2%). Approximately 40.5% of the patients had gut colonization by multi-drug-resistant (MDR) bacteria (vancomycin-resistant enterococcus and carbapenem-resistant GNB). Among patients colonized by MDR GNB, 20% developed an overt BSI due to MDR bacteria with the same pattern of sensitivity. Of the 13 deaths related to infection, 10 were patients with BSI caused by MDR GNB. The independent risk factors for BSI were gut colonization by MDR bacteria including GNB (P < 0.001) and duration of neutropenia >10 days (P = 0.005), and those associated with BSI caused by MDR bacteria were age >62 years (P = 0.03), use of total parenteral nutrition (TPN) (P < 0.001) and previous gut colonization by MDR GNB (P = 0.002). CONCLUSIONS: Previous gut colonization by MDR was an independent risk factor for BSI, together with TPN and age, and had an impact on outcome. These findings suggest that gut decolonization may be a potential strategy to prevent BSI.
Assuntos
Farmacorresistência Bacteriana Múltipla , Trato Gastrointestinal/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sepse/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Enterococcus , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sepse/microbiologia , Sepse/mortalidade , Análise de Sobrevida , Adulto JovemRESUMO
Bovine papillomavirus (BPV) is a diverse group of double-stranded DNA oncogenic viruses, which have been detected in epithelial lesions and body fluids. Most studies of BPV infection rely on a single method for DNA detection; however the use of any single method or technique may underestimate the true prevalence of this virus. The purpose of this study was to compare two PCR strategies for the detection of BPV in skin lesions and fluids: these involve the use of BPV type-specific and consensus primers. Seventy-two cutaneous lesions, 57 blood samples and 59 semen samples were collected. PCR was used with the FAP consensus primers and BPV type-specific primers (for BPVs 2, 3, 4, 5, 8, 9 and 10), along with sequencing assays, to detect the BPV types. Phylogenetic analysis was carried out by means of the maximum likelihood method. It was found that both FAP and BPV type-specific primer sets could amplify BPV types of DNA in skin lesions, blood and semen samples. However, the BPV type-specific primers were more sensitive than the consensus primers and were able to detect co-infection of BPV in the samples. The consensus primers amplified five BPV types and were more suitable for detecting new putative BPV types. Thus, account should be taken of both PCR primer systems to identify co-infection, the presence of novel viruses, and avoid false-negative results.
Assuntos
Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/virologia , Técnicas de Diagnóstico Molecular/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/veterinária , Reação em Cadeia da Polimerase/métodos , Virologia/métodos , Animais , Sangue/virologia , Bovinos , Primers do DNA/genética , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Sêmen/virologia , Sensibilidade e Especificidade , Pele/virologia , Dermatopatias/diagnóstico , Dermatopatias/veterinária , Dermatopatias/virologiaRESUMO
Invasive pulmonary aspergillosis is a major cause of morbidity and mortality in immunocompromised patients, particularly those with hematological malignancies in the setting of profound neutropenia and/or hematopoietic stem cell transplant recipients. The optimal therapy for invasive aspergillosis relies on the restoration of leukocyte counts and effective antifungal treatment initiated at the earliest stage of infection. Several alternative antifungal compounds are currently available. A rational approach should take into account not only the degree of certainty of infection (as codified by the EORTC/MSG classification), but also previous exposure to other antifungals, the pharmacokinetic and pharmacodynamic characteristics of the antifungals employed and the clinical characteristics of the patient.
Assuntos
Antifúngicos/uso terapêutico , Hospedeiro Imunocomprometido , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Humanos , Aspergilose Pulmonar Invasiva/prevenção & controle , Contagem de Leucócitos , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/microbiologia , Fatores de TempoRESUMO
Bovine papillomaviruses (BPVs) cause many benign and malignant lesions in cattle and other animals. Twelve BPV types have been identified so far, and several putative novel BPV types have been detected based on the analysis of L1 gene fragments, generated by FAP59/64 and MY11/09 primers. Phylogenetic trees are important in studies that describe novel BPV types. However, topological mistakes could be a problem in such studies. Therefore, we made use of entropy to find phylogenetic informative regions in the BPV L1 gene sequences from all 12 BPVs. Six data sets were created and phylogenetically compared to each other using neighbor-joining and maximum likelihood methods of phylogenetic tree reconstruction. We found two major regions in the L1 gene, using an entropy-based approach, which selects regions with low information complexity. More robust phylogenetic trees were obtained with these regions, when compared to the ones obtained with FAP59/64 and MY11/09 primers. More robust phylogenetic trees are important to accurately position novel BPV types, subtypes and variants. We conclude that an entropy-based approach is a good methodology for selecting regions of the L1 gene of BPVs that could be used to design more specific and sensitive degenerate primers, for the development of improved diagnostic methods.
Assuntos
Primers do DNA/química , Genes Virais , Papillomaviridae/genética , Animais , Bovinos , Entropia , Filogenia , Reação em Cadeia da Polimerase/métodosRESUMO
BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of seasonal respiratory viral infection in hematopoietic stem cell transplantations (HSCT) patients. The efficacy of treatment, however, remains controversial. We describe an outbreak of 31 cases of RSV that occurred in an HSCT outpatient care unit in the fall season from March through May 2010, with a good outcome without any specific antiviral treatment. METHODS: During these 3 months, 222 nasal wash samples were tested and, of these, 31 outpatients were positive for RSV. In 2009, 99 samples had been tested and only 10 outpatients were positive for RSV in the same period. RESULTS: Seven (22.5%) patients had severe neutropenia (<500 cells/µL); severe lymphopenia (<200 cells/µL) was present in 13 (41.9%) patients, and 14 (45%) had received intravenous broad-spectrum antibiotics. Hospitalization was necessary only for 8 patients (25.8%); 20 had lower respiratory tract infection (64.5%). Only 1 patient died as a result of proven invasive aspergillosis. CONCLUSION: This report suggests that HSCT outpatients with no risk factors may not always require specific treatment for RSV.
Assuntos
Antivirais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Pacientes Ambulatoriais , Infecções por Vírus Respiratório Sincicial/epidemiologia , Adolescente , Adulto , Idoso , Criança , Infecção Hospitalar , Surtos de Doenças , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Líquido da Lavagem Nasal/virologia , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Vírus Sinciciais Respiratórios/isolamento & purificação , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
The aim of this study was to evaluate the presence of different types of Bovine papillomavirus (BPV) in cattle skin lesions and to identify new viral types in Brazil. A total of 72 skin lesions were analysed from 66 different bovines by PCR using degenerate and specific primers, and subsequent sequencing. Sequencing quality was determined using Staden package with Phred 30. Similarity analysis was performed with BioEdit and BLAST programs to verify the identity with known BPV types. Phylogenetic analysis was carried out using Maximum Likelihood method with TIM3 + G as nucleotide substitution model in PAUP*, and 1000 non-parametric bootstrap replicates. Analyses revealed the presence of ten different types of BPV in the samples, with the exception of BPV7. The presence of co-infections was very high as almost all samples (89%) were co-infected. A putative new BPV11 subtype was also found in lesions from different animals. These results add significant knowledge about the prevalence and diversity of BPV infection in Brazilian cattle, which could be used in future studies aiming at the development of more specific treatment and diagnostic methods.
Assuntos
Doenças dos Bovinos/virologia , Coinfecção/veterinária , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/veterinária , Infecções por Papillomavirus/virologia , Animais , Bovinos , Coinfecção/virologia , FilogeniaRESUMO
The diversity of papillomavirus (PV) found in bovine cutaneous warts from Brazilian cattle was evaluated using the PCR technique with the utilization of consensus primers MY09/11 and by PCR using Bovine Papillomavirus (BPV) type-specific primers followed by sequencing. Eleven cutaneous warts from 6 cattle herds were selected. Six warts were positive for the presence of PV. The presence of BPV types 1, 2, 3, 6 and feline sarcoid-associated PV (FeSarPV) in cutaneous wart lesions, as well as the presence of co-infections, was found. To the best of our knowledge, this is the first time that FeSarPV is described co-infecting a cutaneous wart in Brazil. The present study confirms the previous finding of FeSarPV infecting cattle. These results show the necessity of more studies to investigate the diversity of PV in cattle, its diversity and the possibility of co-infection in cattle and other animals.
Assuntos
Doenças dos Bovinos/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/veterinária , Dermatopatias Virais/veterinária , Verrugas/veterinária , Animais , Brasil/epidemiologia , Doenças do Gato/epidemiologia , Doenças do Gato/virologia , Gatos , Bovinos , Doenças dos Bovinos/epidemiologia , Coinfecção/epidemiologia , Coinfecção/veterinária , Coinfecção/virologia , Feminino , Masculino , Papillomaviridae/classificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Filogenia , Sarcoidose/epidemiologia , Sarcoidose/veterinária , Sarcoidose/virologia , Dermatopatias Virais/epidemiologia , Dermatopatias Virais/virologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/veterinária , Neoplasias Cutâneas/virologia , Verrugas/epidemiologia , Verrugas/virologiaRESUMO
Este trabalho objetivou avaliar a qualidade sanitária de 50 lotes comerciais de sementes de braquiária, produzidos em diferentes regiões nas safras de 2004-2005 e 2005-2006. Sementes de Brachiaria brizantha cvs. Marandu e Xaraés, B. decumbens cv. Basilisk, B. humidicola cv. Humidicola e B. ruziziensis cv. Ruziziensis, destinadas ao comércio interno, foram submetidas ao teste de sanidade pelo método de papel de filtro. Adicionalmente, avaliou-se a sanidade de sementes de 'Marandu' (2 lotes) e 'Basilisk' (1 lote) destinadas à exportação. As sementes foram distribuídas sobre papel de filtro acondicionado em gerbox e incubadas a 20º C, com fotoperíodo de 12h, durante sete dias. Os fungos secundários ou de armazenamento (FSA) mais frequentemente detectados nos lotes de braquiária foram Aspergillus sp. e Rhizopus sp. Quanto aos fungos potencialmente patogênicos (FP), constatou-se elevada frequência dos gêneros Bipolaris. Curvularia. Fusarium e Phoma. Em geral, foi elevada a incidência de Bipolaris sp., Fusarium sp. e Phoma sp. nas sementes. A ocorrência de Phoma sp. foi crítica, pois 42% dos lotes registraram índices superiores a 70%. Bipolaris sp., Fusarium sp. e Phoma sp. também foram associados às sementes de braquiária tipo exportação, em alguns casos, com incidência considerável. Os resultados revelaram que as sementes comerciais de braquiária apresentam baixa qualidade sanitária e que, em todas as regiões produtoras, existe pelo menos um fator afetando a sanidade dessas sementes.
This work aimed to evaluate the sanitary quality of 50 commercial lots of seeds of braquiaria grass, produced in different regions in the crop of 20042005 and 20052006. The lots consisted of seeds of the cultivars Brachiaria brizantha cvs. Marandu and Xaraes, B. decumbens cv. Basilisk, B. humidicola cv. Humidicola and B. ruziziensis cv. Ruziziensis. Additionally, seeds of 'Marandu' (2 lots) and 'Basilisk' (1 lot) for exportation were analyzed. The blotter test was used, at 20º C under alternating light and darkness in a 12h photoperiod, for 7 days. Aspergillus sp. and Rhizopus sp. were the secondary or storage fungi with greatest frequency in lots of seeds. High frequency of potential pathogenic fungi, specifically of the Bipolaris. Curvularia. Fusarium and Phoma genera, was observed. In general, there was a high incidence of Bipolaris sp., Fusarium sp. and Phoma sp. in braquiaria grass seeds. The occurrence of Phoma sp. was severe, because 42% of the lots showed incidence superior to 70%. Bipolaris sp., Fusarium sp. and Phoma sp. were associated to braquiaria grass seeds for exportation, in some cases, with significant incidence. The results evidenced the low sanitary quality of commercial seeds of braquiaria grass, and demonstrated that in all producer regions there is at least one factor affecting the sanitary quality of these seeds.