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T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive mature T-cell malignancy characterized by marked lymphocytosis, B symptoms, lymphadenopathy, and hepatosplenomegaly. There is no standard treatment approach, and in the absence of an allogeneic transplant, the prognosis remains poor. The disease-defining cytogenetic abnormality in T-PLL is the juxtaposition of the TCL1-family oncogene to the TCR gene enhancer locus primarily due to an inversion of chromosome 14, that is, inv(14). The application of next-generation sequencing technologies led to the discovery of highly recurrent gain-of-function mutations in JAK1/3 and STAT5B in over 70% of T-PLL providing opportunities for therapeutic intervention using small molecule inhibitors. Additional genetic mechanisms that may contribute to the pathogenesis of T-PLL remain unknown. Herein we describe the identification of a novel gene fusion SMCHD1::JAK2 resulting from a translocation between chromosome 9 and 18 involving SMCHD1 exon 45 and JAK2 exon 14 (t(9;18)(p24.1;p11.32)(chr9:g.5080171::chr18:g.2793269)), a previously undescribed genetic event in a patient with T-PLL harboring the key disease defining inv(14) resulting in rearrangement of TCL1 and TRA/D. In this manuscript, we describe the clinical and genetic features of the patient's disease course over a 25-month post-treatment duration using ruxolitinib and duvelisib.
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Janus Quinase 2 , Leucemia Prolinfocítica de Células T , Humanos , Leucemia Prolinfocítica de Células T/genética , Leucemia Prolinfocítica de Células T/tratamento farmacológico , Leucemia Prolinfocítica de Células T/patologia , Janus Quinase 2/genética , Proteínas de Fusão Oncogênica/genética , Masculino , Translocação Genética , Pirimidinas/uso terapêutico , Pirazóis/uso terapêutico , Pessoa de Meia-Idade , Nitrilas/uso terapêutico , Cromossomos Humanos Par 9/genéticaRESUMO
Nonhematopoietic lymph node stromal cells (LNSCs) regulate lymphocyte trafficking, survival, and function for key roles in host defense, autoimmunity, alloimmunity, and lymphoproliferative disorders. However, the study of LNSCs in human diseases is complicated by a dependence on viable lymphoid tissues, which are most often excised prior to establishment of a specific diagnosis. Here, we demonstrate that cryopreservation can be used to bank lymphoid tissue for the study of LNSCs in human disease. Using human tonsils and lymph nodes (LN), lymphoid tissue fragments were cryopreserved for subsequent enzymatic digestion and recovery of viable nonhematopoietic cells. Flow cytometry and single-cell transcriptomics identified comparable proportions of LN stromal cell types in fresh and cryopreserved tissue. Moreover, cryopreservation had little effect on transcriptional profiles, which showed significant overlap between tonsils and LN. The presence and spatial distribution of transcriptionally defined cell types were confirmed by in situ analyses. Our broadly applicable approach promises to greatly enable research into the roles of LNSCs in human disease.
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Bancos de Espécimes Biológicos , Criopreservação , Humanos , Linfócitos , Linfonodos/patologia , Células EstromaisRESUMO
Idiopathic multicentric Castleman disease (iMCD) is a rare hematologic disorder with heterogeneous presentations ranging from moderate constitutional symptoms to life-threatening multiorgan system involvement. There are vastly different clinical subtypes, with some patients demonstrating thrombocytopenia, anasarca, fever/elevated C-reactive protein, reticulin fibrosis/renal failure, and organomegaly (TAFRO) and others having milder/more moderate symptoms with potential for severe disease (not otherwise specified, NOS). Due to its rarity and heterogeneity, the natural history and long-term burden of iMCD are poorly understood. We investigated real-world medical data from ACCELERATE, a large natural history registry of patients with Castleman disease, to better characterize the long-term disease burden experienced by these patients. We found that iMCD-TAFRO patients face a significant hospitalization burden, requiring more time in the hospital than iMCDNOS patients during the year surrounding diagnosis (median [interquartile range]: 36 [18-61] days vs. 0 [0-4] days; P<0.001). In addition, we found life-sustaining interventions, such as mechanical ventilation (17%) and dialysis (27%), were required among iMCD patients, predominantly those with iMCD-TAFRO. iMCD-NOS patients, however, spent a significantly greater proportion of time following disease onset in a state of disease flare (median 52.3% vs. 18.9%; P=0.004). Lastly, we observed severe iMCD-related morbidities, such as acute renal failure, sepsis and pneumonia, among others, arising after iMCD diagnosis, impairing the patients' quality of life. These data demonstrate a substantial disease burden experienced by iMCD patients and emphasize the importance of ongoing research into iMCD to aid disease control.
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Hiperplasia do Linfonodo Gigante , Humanos , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Longitudinais , Idoso , Efeitos Psicossociais da Doença , Hospitalização , Sistema de RegistrosRESUMO
The World Health Organization and the International Consensus Classification have both addressed and categorized T-cell lymphomas and histiocytic and dendritic tumours. Differences in the classification systems has generated considerable debate. Falini and colleagues now provide some clarity for the readership, with a framework for navigating the current classifications. They highlight the importance of finding a common path to formulate a single classification scheme in the near future. Commentary on: Falini et al. A comparison of the International Consensus and 5th WHO classifications of T-cell lymphomas and histiocytic/dendritic cell tumours. Br J Haematol 2023;203:369-383.
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High-grade B-cell lymphomas with 11q aberrations (HGBL-11q) represent a World Health Organization-defined group of lymphomas that harbor recurrent chromosome 11q aberrations involving proximal gains and telomeric losses. Although a limited number of HGBL-11q cases evaluated thus far appear to show a similar course and prognosis as Burkitt lymphoma (BL), many molecular differences have been appreciated, most notably the absence of MYC rearrangement. Despite biological differences between BL and HGBL-11q, histomorphologic and immunophenotypic distinction remains challenging. Here, we provide a comparative whole proteomic profile of BL- and HGBL-11q-derived cell lines, identifying numerous shared and differentially expressed proteins. Transcriptome profiling performed on paraffin-embedded tissue samples from primary BL and HGBL-11q lymphomas was additionally performed to provide further molecular characterization. Overlap of proteomic and transcriptomic data sets identified several potential novel biomarkers of HGBL-11q, including diminished lymphoid enhancer-binding factor 1 expression, which was validated by immunohistochemistry staining in a cohort of 23 cases. Altogether, these findings provide a comprehensive multimodal and comparative molecular profiling of BL and HGBL-11q and suggest the use of enhancer-binding factor 1 as an immunohistochemistry target to distinguish between these aggressive lymphomas.
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Linfoma de Burkitt , Linfoma de Células B , Linfoma Difuso de Grandes Células B , Proteogenômica , Humanos , Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Fator 1 de Ligação ao Facilitador Linfoide , Proteômica , Linfoma de Células B/genética , Linfoma de Células B/patologia , Aberrações Cromossômicas , Biomarcadores , Linfoma Difuso de Grandes Células B/patologiaRESUMO
Approximately 30% of pediatric patients with anaplastic large cell lymphoma (ALCL) relapse. Although brentuximab vedotin has demonstrated excellent activity in ALCL, it has not been used for newly diagnosed patients. Children's Oncology Group (COG) trial ANHL12P1 determined the toxicity and efficacy of brentuximab vedotin with chemotherapy in children with newly diagnosed nonlocalized anaplastic large cell lymphoma kinase (ALK)+/CD30+ ALCL. From 2013 to 2017, 68 children with ALK+ ALCL were enrolled and received brentuximab vedotin. All patients received 5-day prophase, followed by 6 cycles of chemotherapy. Brentuximab vedotin was given on day 1 of each of the 6 cycles. Of the 67 patients eligible for toxicity evaluation, 66 completed all 6 cycles of chemotherapy, resulting in 399 evaluable cycles. There were no toxic deaths, no case of progressive multifocal leukoencephalopathy syndrome, and no case of grade 3 or 4 neuropathy. The 2-year event-free survival (EFS) was 79.1% (95% confidence interval [CI], 67.2-87.1). The 2-year overall survival (OS) was 97.0% (95% CI, 88.1-99.2). Fourteen patients relapsed. Eleven of 14 (79%) relapses occurred within 10 months of diagnosis; only 1 patient (1.5%) relapsed during therapy. Quantitative reverse transcription polymerase chain reaction for NPM-ALK at baseline (minimal disseminated disease) demonstrated prognostic value for EFS (P = .0004). Overall, the addition of brentuximab vedotin to standard chemotherapy does not add significant toxicity or alter the desired interval between cycles. The addition of brentuximab vedotin prevented relapses during therapy, and the OS and EFS estimates compare favorably with results obtained using conventional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01979536.
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Quinase do Linfoma Anaplásico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Brentuximab Vedotin/administração & dosagem , Linfoma Anaplásico de Células Grandes , Proteínas de Neoplasias , Adolescente , Adulto , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brentuximab Vedotin/efeitos adversos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/enzimologia , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/mortalidade , Masculino , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Taxa de SobrevidaRESUMO
BACKGROUND: Reusable menstrual products have expanded the choices available for menstrual care and can offer long-term cost and environmental benefits. Yet, in high-income settings, efforts to support period product access focus on disposable products. There is limited research to understand young people's product use and preferences in Australia. METHODS: Quantitative and open-text qualitative data were collected through an annual cross-sectional survey of young people (aged 15-29) in Victoria, Australia. The convenience sample was recruited through targeted social media advertisements. Young people who reported menstruating in the past 6 months (n = 596) were asked questions about their menstrual product use, use of reusable materials, product priorities and preferences. RESULTS: Among participants, 37% had used a reusable product during their last menstrual period (24% period underwear, 17% menstrual cup, 5% reusable pads), and a further 11% had tried using a reusable product in the past. Reusable product use was associated with older age (age 25-29 PR = 3.35 95%CI = 2.09-5.37), being born in Australia (PR = 1.74 95%CI = 1.05-2.87), and having greater discretionary income (PR = 1.53 95%CI = 1.01-2.32). Participants nominated comfort, protection from leakage and environmental sustainability as the most important features of menstrual products, followed by cost. Overall, 37% of participants reported not having enough information about reusable products. Having enough information was less common among younger participants (age 25-29 PR = 1.42 95%CI = 1.20-1.68) and high school students (PR = 0.68 95%CI = 0.52-0.88). Respondents highlighted the need for earlier and better information, challenges navigating the upfront cost and availability of reusables, positive experiences with reusables, and challenges for use, including cleaning reusables and changing them outside the home. CONCLUSIONS: Many young people are using reusable products, with environmental impacts an important motivator. Educators should incorporate better menstrual care information in puberty education and advocates should raise awareness of how bathroom facilities may support product choice.
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Produtos de Higiene Menstrual , Puberdade , Humanos , Adolescente , Vitória , Estudos Transversais , Escolaridade , Menstruação , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
Castleman disease (CD) describes a group of rare, potentially fatal lymphoproliferative disorders. To determine factors associated with mortality in CD, we analysed data from deceased patients in the ACCELERATE registry and compared them with matched controls. We analysed demographic, treatment and laboratory data from all deceased CD patients, matched controls and a subgroup of idiopathic multicentric Castleman disease (iMCD) patients. Of the 140 patients in ACCELERATE with a confirmed CD diagnosis, 10 had died. There were 72 patients with confirmed iMCD; six were deceased. The deceased CD cohort had more hospitalisations per year, higher overall hospitalisations and more days hospitalised per month, and received more treatment regimens per year than the matched-control group. Analysis of laboratory values showed a significantly decreased absolute lymphocyte count at months 3 and 6 in the deceased cohort compared with controls. Among iMCD patients, there was a higher proportion of iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction and organomegaly) cases in the deceased group. The deceased iMCD group had significantly lower immunoglobulin M, international normalised ratio and platelet count. These data demonstrate that there may be differences between patients who have fatal and non-fatal outcomes, and provide preliminary suggestions for parameters to evaluate further.
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Hiperplasia do Linfonodo Gigante , Trombocitopenia , Hiperplasia do Linfonodo Gigante/diagnóstico , Progressão da Doença , Febre , Humanos , Sistema de Registros , Trombocitopenia/diagnósticoRESUMO
Castleman disease (CD) represents a group of rare, heterogeneous and poorly understood disorders that share characteristic histopathological features. Unicentric CD (UCD) typically involves a single enlarged lymph node whereas multicentric CD (MCD) involves multiple lymph node stations. To understand the cellular basis of CD, we undertook a multi-platform analysis using targeted RNA sequencing, RNA in-situ hybridization (ISH), and adaptive immune receptor rearrangements (AIRR) profiling of archived tissue from 26 UCD, 14 MCD, and 31 non-CD reactive controls. UCD showed differential expression and upregulation of follicular dendritic cell markers (CXCL13, clusterin), angiogenesis factors (LPL, DLL4), extracellular matrix remodeling factors (TGFß, SKIL, LOXL1, IL-1ß, ADAM33, CLEC4A), complement components (C3, CR2) and germinal center activation markers (ZDHHC2 and BLK) compared to controls. MCD showed upregulation of IL-6 (IL-6ST, OSMR and LIFR), IL-2, plasma cell differentiation (XBP1), FDC marker (CXCL13, clusterin), fibroblastic reticular cell cytokine (CCL21), angiogenesis factor (VEGF), and mTORC1 pathway genes compared to UCD and controls. ISH studies demonstrated that VEGF was increased in the follicular dendritic cell-predominant atretic follicles and the interfollicular macrophages of MCD compared to UCD and controls. IL-6 expression was higher along interfollicular vasculature-associated cells of MCD. Immune repertoire analysis revealed oligoclonal expansions of T-cell populations in MCD cases (2/6) and UCD cases (1/9) that are consistent with antigen-driven T cell activation. The findings highlight the unique genes, pathways and cell types involved in UCD and MCD. We identify potential novel targets in CD that may be harnessed for therapeutics.
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Hiperplasia do Linfonodo Gigante , Proteínas ADAM , Hiperplasia do Linfonodo Gigante/genética , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/terapia , Clusterina , Citocinas , Humanos , Interleucina-6 , Transcriptoma , Fator A de Crescimento do Endotélio VascularRESUMO
Idiopathic multicentric Castleman disease (iMCD) is a polyclonal lymphoproliferative disorder characterized by constitutional symptoms, generalized lymphadenopathy, cytopenias, and multi-organ dysfunction due to excessive cytokines, notably Interleukin-6. Idiopathic multicentric Castleman disease is often sub-classified into iMCD-TAFRO, which is associated with thrombocytopenia (T), anasarca (A), fever/elevated C-reactive protein (F), renal dysfunction (R), and organomegaly (O), and iMCD not otherwise specified (iMCD-NOS), which is typically associated with thrombocytosis and hypergammaglobulinemia. The diagnosis of iMCD is challenging as consensus clinico-pathological diagnostic criteria were only recently established and include several non-specific lymph node histopathological features. Identification of further clinico-pathological features commonly found in iMCD could contribute to more accurate and timely diagnoses. We set out to characterize bone marrow (BM) histopathological features in iMCD, assess differences between iMCD-TAFRO and iMCD-NOS, and determine if these findings are specific to iMCD. Examination of BM specimens from 24 iMCD patients revealed a high proportion with hypercellularity, megakaryocytic atypia, reticulin fibrosis, and plasmacytosis across patients with both iMCD-NOS and iMCD-TAFRO with significantly more megakaryocytic hyperplasia (p = 0.001) in the iMCD-TAFRO cases. These findings were also consistent with BM findings from 185 published cases of iMCD-NOS and iMCD-TAFRO. However, these findings are relatively nonspecific as they can be seen in various other infectious, malignant, and autoimmune diseases.
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Hiperplasia do Linfonodo Gigante , Trombocitopenia , Medula Óssea/patologia , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/patologia , Febre/diagnóstico , Febre/patologia , Humanos , Linfonodos/patologiaRESUMO
BACKGROUND: Social media-delivered health promotion has demonstrated limited uptake and effectiveness among young adults. Understanding how young adults interact with existing social media platforms for health might provide insight for future health promotion interventions. OBJECTIVE: The aim of this study is to describe how young adults interact with different social media platforms for health and health information. METHODS: We used a web-based conversation methodology to collect data from 165 young adults aged 18 to 24 years. Participants participated in an extended conversation with moderators and other participants about health and social media. They were prompted to discuss how they find health information, how they use different social media platforms, and how they evaluate the trustworthiness of information. A thematic qualitative analysis was applied to the data. RESULTS: Young adults spent a lot of time scrolling through Facebook newsfeeds, which often resulted in seeing health-related content either from their friends, news sources, or advertisements. Some actively sought out information about specific health areas by joining groups or following relevant pages. YouTube was considered a useful source for learning about everything and was often the go-to when searching for information or advice (after Google). Young adults found the video format easy to learn from. They stated that they could identify accurate YouTube health content by cross-checking multiple videos, by feeling that the presenter was real and relatable, or just through instinctively judging a video's credibility. Instagram was a source of inspiration for health and wellness from those whose lives were dedicated to healthy lifestyles and fitness. Twitter, Tumblr, and Snapchat were rarely used for health information. CONCLUSIONS: Most young adults obtain health information from social media, both actively and through passive exposure. Participants indicated looking to social media influencers for health and lifestyle inspiration and judged the credibility of sources by appearance and instinct. Health experts should try to use the channels in the way that young adults already use them; use relatable role models on Instagram and YouTube, eye-catching headlines and support groups on Facebook, and easy to follow instruction videos via YouTube. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1111/1747-0080.12448.
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Mídias Sociais , Comunicação , Promoção da Saúde , Humanos , Estilo de Vida , Adulto JovemRESUMO
BACKGROUND: Globally, suboptimal dietary choices are a leading cause of noncommunicable diseases. Evidence for effective interventions to address these behaviors, particularly in young adults, is limited. Given the substantial time young adults spend in using social media, there is interest in understanding the current and potential role of these platforms in shaping dietary behavior. OBJECTIVE: This study aims to explore the influence of social media on young adults' dietary behaviors. METHODS: We recruited 234 young adults aged 18-24 years and living in Australia, using market and social research panels. We applied a digital ethnography approach to collect data from web-based conversations in a series of forums, where participants responded to different health-themed questions related to health behavior change and persuasion on social media. We conducted a qualitative thematic analysis. RESULTS: Participants described how social media influenced their decisions to change their health behaviors. Access to social support and health information through web-based communities was juxtaposed with exposure to highly persuasive fast-food advertisements. Some participants expressed that exposure to web-based health-focused content induced feelings of guilt about their behavior, which was more prominent among women. Fast-food advertisements were discussed as a contributor to poor health behaviors and indicated as a major barrier to change. CONCLUSIONS: Young adults reported that social media is highly persuasive toward dietary behavior through different pathways of social influence. This suggests that social norms on the web are an important aspect of changing young adults' health behaviors. The commercialization of social media also encourages poor health behaviors, largely through fast-food advertisements. Future social media-delivered dietary interventions should acknowledge the social and environmental factors that challenge the ability of young adults to make individual health behavior improvements. Care should also be taken to ensure that future interventions do not further elicit guilt in a way that contributes to poor mental health within this community.
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Mídias Sociais , Comunicação , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Estado Nutricional , Comunicação Persuasiva , Adulto JovemRESUMO
BACKGROUND: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals are at higher risk of poor mental health and well-being. Social media platforms can provide LGBTQ youths with a space that counters heteronormative environments and potentially supports mental health and well-being. Mental health includes an individual's state of psychological and emotional well-being and not merely the absence of mental disorders. OBJECTIVE: We sought to identify how LGBTQ youths and adolescents use social media for connection with other LGBTQ peers and groups, identity development, and social support and how these affect mental health and well-being. METHODS: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) procedures were used to guide this review. Searches were conducted in ACM Digital Library, CINAHL, Ovid Embase, Ovid MEDLINE, and Web of Science in March 2021. This review focused on LGBTQ youths aged 10 to 24 years. Included peer-reviewed studies must comprise social media; explore peer connection, identity development, or social support; and be published from 2012 onward. In total, 2 researchers extracted data and performed quality assessments independently using the Newcastle-Ottawa Scale for quantitative articles and the Critical Appraisal Skills Programme for qualitative articles. Qualitative synthesis was performed on articles that satisfied the eligibility criteria. RESULTS: A total of 26 studies (n=15, 58% qualitative; n=8, 31% quantitative; n=3, 12% mixed methods) met the inclusion criteria. Of the 8 quantitative studies, 6 (75%) were cross-sectional, and 2 (25%) were cohort studies. All studies ranged from moderate to high quality. Social media was a popular tool used by LGBTQ youths to connect with LGBTQ communities. In qualitative data, we found that LGBTQ youths negotiated and explored identity and obtained support from peers on social media. Instagram, Tumblr, and Twitter were commonly used to access LGBTQ content owing to ease of anonymity. Identity management was the most studied social media affordance, important to LGBTQ youths for strategic disclosure. Key strategies for managing identities included being anonymous, censoring locations or content, restricting audiences, and using multiple accounts. Quantitative studies (3/8, 38%) showed that social media was associated with reduced mental health concerns and increased well-being among LGBTQ youths. Mental health concerns arising from social media use were attributed to discrimination, victimization, and policies that did not accommodate changed identities. CONCLUSIONS: We found that social media may support the mental health and well-being of LGBTQ youths through peer connection, identity management, and social support, but findings were limited by weaknesses in the evidence. More robust and longitudinal studies are needed to determine the relationship between social media use and LGBTQ mental health, particularly among adolescents. The findings may inform interventions to promote social media health literacy and the mental health and well-being of this vulnerable group. TRIAL REGISTRATION: PROSPERO CRD42020222535; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=222535.
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Minorias Sexuais e de Gênero , Mídias Sociais , Pessoas Transgênero , Adolescente , Feminino , Identidade de Gênero , Humanos , Comportamento SexualRESUMO
Migrant and ethnic minority groups are underrepresented in alcohol and other drug (AOD) research. This qualitative study explored AOD use among young people from migrant and ethnic minority backgrounds in Melbourne, Australia. We conducted one focus group and 16 interviews and thematically analyzed data drawing on the social-ecological model of health. Theme one showed AOD use was considered a "normal" part of youth identity, particularly for participants who had grown up with peer groups in Australia. Theme two highlighted participant's sense of responsibility to meet expectations and make informed decisions about AOD use to protect themselves and their friends. Theme three highlighted participant's risk of experiencing AOD-related stigma through negative stereotypes and fear of consequences within families and communities, particularly among female participants. Participants' perceptions and experiences differed by individual factors, interpersonal relationships, AOD accessibility across settings and broader gender, cultural and religious norms. Interventions developed with young people from migrant and ethnic minority backgrounds are needed to target the social-ecological factors underpinning AOD use, particularly stigma.
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Background Adolescents use social media more frequently than other age groups. Social media has been described as a safe environment for lesbian, gay, bisexual, transgender and queer and/or questioning (LGBTQ) adolescents. As part of mixed-methods research investigating the association between social networks and sexual agency, we present qualitative findings on how LGBTQ adolescents connect online to form support networks. Methods We recruited 30 adolescents aged 14-17years who identified as LGBTQ in terms of their gender or attraction in the longitudinal Social Networks and Agency Project. Semi-structured interviews were conducted online or face-to-face across Australia. Thematic analysis was used to explore perceptions and experiences of participants in relation to social media use and relationships. Results Two overarching themes were identified: LGBTQ adolescents use social media for identity, relationships and wellbeing support. Social media is not always free of discrimination for LGBTQ adolescents. Many LGBTQ participants joined Facebook groups to connect with LGBTQ peers. Facebook was considered a vital support for those with mental health concerns including suicidal ideation. Participants gave and received support from group members, which was considered useful for those feeling isolated or victimised. LGBTQ adolescents formed friendships, romantic relationships and gained information on sex, relationships, and sexual health from these groups. Participants described negative experiences including discrimination within Facebook groups, mismanaged groups and exposure to anti-LGBTQ sentiments. Conclusion Social media is an environment where LGBTQ adolescents can connect, educate and support each other, which may have beneficial effects for this marginalised group. There remain issues with social media including discrimination against and within LGBTQ communities.
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Minorias Sexuais e de Gênero , Mídias Sociais , Adolescente , Bissexualidade/psicologia , Feminino , Identidade de Gênero , Humanos , Comportamento Sexual/psicologiaRESUMO
Background:Adolescents use social media more frequently than other age groups. Social media has been described as a safe environment for lesbian, gay, bisexual, transgender and queer and/or questioning (LGBTQ) adolescents. As part of mixed-methods research investigating the association between social networks and sexual agency, we present qualitative findings on how LGBTQ adolescents connect online to form support networks.Methods:We recruited 30 adolescents aged 14-17years who identified as LGBTQ in terms of their gender or attraction in the longitudinal Social Networks and Agency Project. Semi-structured interviews were conducted online or face-to-face across Australia. Thematic analysis was used to explore perceptions and experiences of participants in relation to social media use and relationships.Results:Two overarching themes were identified: LGBTQ adolescents use social media for identity, relationships and wellbeing support. Social media is not always free of discrimination for LGBTQ adolescents. Many LGBTQ participants joined Facebook groups to connect with LGBTQ peers. Facebook was considered a vital support for those with mental health concerns including suicidal ideation. Participants gave and received support from group members, which was considered useful for those feeling isolated or victimised. LGBTQ adolescents formed friendships, romantic relationships and gained information on sex, relationships, and sexual health from these groups. Participants described negative experiences including discrimination within Facebook groups, mismanaged groups and exposure to anti-LGBTQ sentiments.Conclusion:Social media is an environment where LGBTQ adolescents can connect, educate and support each other, which may have beneficial effects for this marginalised group. There remain issues with social media including discrimination against and within LGBTQ communities.
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T-cell lymphomas are a heterogeneous group of rare malignancies with overlapping clinical, immunologic, and histologic features. Recent advances in our understanding of T-cell differentiation based on gene expression profiling, next-generation sequencing, and transgenic mouse modeling studies have better elucidated the pathogenetic mechanisms underlying the diverse biology of T-cell lymphomas. These studies show that although genetic alterations in epigenetic modifiers are implicated in all subtypes of T-cell lymphomas, specific subtypes demonstrate enrichment for particular recurrent alterations targeting specific genes. In this regard, RHOA and TET2 alterations are prevalent in nodal T-cell lymphomas, particularly angioimmunoblastic T-cell lymphomas, peripheral T-cell lymphomas (PTCLs) not otherwise specified, and nodal PTCLs with T-follicular helper phenotype. JAK-STAT signaling pathways are mutationally activated in many extranodal T-cell lymphomas, such as natural killer/T-cell and hepatosplenic T-cell lymphomas. The functional significance of many of these genetic alterations is becoming better understood. Altogether these advances will continue to refine diagnostic criteria, improve prognostication, and identify novel therapeutic targets, resulting in improved outcomes for patient with T-cell lymphomas.
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Linfoma de Células T/etiologia , Animais , Biomarcadores , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Suscetibilidade a Doenças , Metabolismo Energético , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma de Células T/diagnóstico , Linfoma de Células T/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Linfócitos T/metabolismo , Linfócitos T/patologiaRESUMO
Castleman disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8), whereas others are HHV-8-negative/idiopathic (iMCD). Treatment of iMCD is challenging, and outcomes can be poor because no uniform treatment guidelines exist, few systematic studies have been conducted, and no agreed upon response criteria have been described. The purpose of this paper is to establish consensus, evidence-based treatment guidelines based on the severity of iMCD to improve outcomes. An international Working Group of 42 experts from 10 countries was convened by the Castleman Disease Collaborative Network to establish consensus guidelines for the management of iMCD based on published literature, review of treatment effectiveness for 344 cases, and expert opinion. The anti-interleukin-6 monoclonal antibody siltuximab (or tocilizumab, if siltuximab is not available) with or without corticosteroids is the preferred first-line therapy for iMCD. In the most severe cases, adjuvant combination chemotherapy is recommended. Additional agents are recommended, tailored by disease severity, as second- and third-line therapies for treatment failures. Response criteria were formulated to facilitate the evaluation of treatment failure or success. These guidelines should help treating physicians to stratify patients based on disease severity in order to select the best available therapeutic option. An international registry for patients with CD (ACCELERATE, #NCT02817997) was established in October 2016 to collect patient outcomes to increase the evidence base for selection of therapies in the future.
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Corticosteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/terapia , Ensaios Clínicos como Assunto , Estado Terminal/terapia , Gerenciamento Clínico , Medicina Baseada em Evidências , Humanos , Guias de Prática Clínica como AssuntoRESUMO
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are characterized by a progressive accumulation of leukemic cells in the peripheral blood, bone marrow, and lymphoid tissues. Treatment of CLL/SLL has evolved significantly in recent years because of the improved understanding of the disease biology and the development of novel targeted therapies. In patients with indications for initiating treatment, the selection of treatment should be based on the disease stage, patient's age and overall fitness (performance status and comorbid conditions), and cytogenetic abnormalities. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CLL/SLL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/normas , Transplante de Células-Tronco Hematopoéticas/normas , Leucemia Linfocítica Crônica de Células B/terapia , Oncologia/normas , Recidiva Local de Neoplasia/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Medula Óssea/patologia , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunofenotipagem , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/mortalidade , Linfonodos/citologia , Linfonodos/patologia , Linfócitos/patologia , Oncologia/métodos , Mutação , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Organizações sem Fins Lucrativos/normas , Prognóstico , Indução de Remissão/métodos , Transplante Homólogo/normas , Estados Unidos/epidemiologiaRESUMO
Idiopathic multicentric Castleman disease (iMCD) is a rare immunologic disorder characterized by systemic inflammation, multicentric lymphadenopathy, and organ dysfunction. Enlarged lymph nodes demonstrate a spectrum of characteristic but variable histopathologic features historically categorized into hyaline vascular (HV) (or hypervascular [HyperV] more recently), plasmacytic, or "mixed." Though the etiology is unknown, a pro-inflammatory cytokine storm, often involving interleukin-6 (IL-6), contributes to pathogenesis. Anti-IL-6 therapy with siltuximab is the only FDA- or EMA-approved treatment based on efficacy and safety in multiple studies. Importantly, no patients considered to have HV histopathology achieved the primary endpoint in the Phase II study. NCCN currently recommends siltuximab first-line for iMCD, except for patients considered to have HV histopathology. We investigated whether histopathologic subtype should guide siltuximab treatment decisions. Secondary analyses of clinical trial and real-world data revealed similar clinical benefit across histopathologic subtypes. Notably, only 18 of 79 patients in the Phase II study were consistently classified into histopathologic subtype by three independent review panels, demonstrating limited reliability to guide treatment decisions. Real-world data further demonstrate siltuximab's effectiveness in patients considered to have HV (or HyperV). Though histopathology is a critical component for diagnosis, there is insufficient evidence to guide treatment based solely on lymph node histopathologic subtype.