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1.
Int J Drug Policy ; 94: 103205, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33839598

RESUMO

BACKGROUND: Little is known about how socioeconomic circumstances relate to injection frequencies among people who inject drugs (PWID) with diverse trajectories of injection. We aimed to characterize trajectories of injection drug use in a community-based sample of PWID over 7.5 years and to investigate the extent to which two modifiable factors reflecting socioeconomic stability-stable housing and stable income-relate to injection frequencies across distinct trajectories. METHODS: HEPCO is an open, prospective cohort study of PWID living in Montréal with repeated follow-up at three-month or one-year intervals. Self-reported data on injection frequency, housing and income are collected at each visit. Injection frequency was defined as the number of injection days (0-30), reported for each of the past three months. Using group-based trajectory modeling, we first estimated average trajectories of injection frequency. Then, we estimated the trajectory group-specific average shift upward or downward associated with periods of stable housing and stable income relative to periods when these conditions were unstable. RESULTS: Based on 19,527 injection frequency observations accrued by 529 participants followed over 2011-2019 (18.3% female, median age: 41), we identified five trajectories of injection frequency: three characterized by sustained injection at different frequencies (28% infrequent; 19% fluctuating; 19% frequent), one by a gradual decline (12%), and another by cessation (28%). Periods of stable housing and stable income were each independently associated with a lower injection frequency, on average, in all five trajectory groups (2.2-7.5 fewer injection days/month, depending on the factor and trajectory group). CONCLUSION: Trajectories of injection drug use frequency were diverse and long-lasting for many PWID. Despite this diversity, socioeconomic stability was consistently associated with a lower injection frequency, emphasizing the close relationship between access to fundamental necessities and injection patterns in all PWID, irrespective of whether they are on a path to cessation or sustained injecting.

2.
Lab Invest ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33692440

RESUMO

Indolent T cell lymphoproliferative disorder (LPD) of the gastrointestinal tract (GI-TLPD) is a rare human primary gastrointestinal T cell lymphoma that was recently included in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Low-grade intestinal T cell lymphoma (LGITL), an emerging disease in the domestic cat, shares a number of features with human GI-TLPD. In this prospective study, we determined whether feline LGITL might serve as a model of human GI-TLPD. We analyzed clinical, laboratory, and radiological data and performed histopathological and molecular studies on small intestinal biopsies from 22 domestic cats diagnosed with LGITL. This cancer mostly affects aging cats, is associated with nonspecific gastrointestinal tract signs, and is usually characterized by an indolent course. A histopathological analysis indicated that LGITL was mainly located in the jejunum. The small intestinal lamina propria was infiltrated by large numbers of small CD3+ T cell lymphocytes with various CD4 and CD8 expression profiles (CD4+ CD8- (4 out of 11, 36%), CD4- CD8+ (3 out of 11, 27%), and CD4- CD8- (4 out of 11, 36%)). Intraepithelial lymphocyte (IEL) counts were elevated in all cases. Ki67 was expressed in lamina propria lymphocytes and IELs at a low level (<30%). Most LGITLs were labelled by antibodies against phosphorylated STAT5, but were negative for CD56 and phosphorylated STAT3. T cell receptor gamma chain gene monoclonality was found in 86% of cases. These findings confirmed that feline LGITL shares clinical and histopathological features with human GI-TLPD. Feline LGITL may therefore constitute a relevant model of the human disease.

3.
Int J Drug Policy ; : 103127, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33549464

RESUMO

BACKGROUND: "Big Events" are major disruptions to physical, political, and economic environments that can influence vulnerability to drug-related harms. We reviewed the impacts of Big Events with relevance to the COVID-19 pandemic on drug-related risk and harms and access to drug treatment and harm reduction services. METHODS: We conducted a rapid review of quantitative, qualitative, and mixed methods literature relating to the following Big Events: respiratory infection pandemics, natural disasters, financial crises, and heroin shortages. Included studies reported data on changes to risks, harms, and/or service provisioning for people who use illicit drugs (other than cannabis) in the context of these Big Events. Searches were conducted in PubMed in May 2020, and two reviewers screened studies for inclusion. Peer-reviewed studies published in English or French were included. We used a narrative synthesis approach and mapped risk pathways identified in the literature. RESULTS: No studies reporting on respiratory infection pandemics were identified. Twelve studies reporting on natural disaster outcomes noted marked disruption to drug markets, increased violence and risk of drug-related harm, and significant barriers to service provision caused by infrastructure damage. Five studies of the 2008 global financial crisis indicated increases in the frequency of drug use and associated harms as incomes and service funding declined. Finally, 17 studies of heroin shortages noted increases in heroin price and adulteration, potentiating drug substitutions and risk behaviors, as well as growing demand for drug treatment. CONCLUSION: Current evidence reveals numerous risk pathways and service impacts emanating from Big Events. Risk pathway maps derived from this literature provide groundwork for future research and policy analyses, including in the context of the COVID-19 pandemic. In light of the findings, we recommend responding to the pandemic with legislative and financial support for the flexible delivery of harm reduction services, opioid agonist treatment, and mental health care.

4.
Haematologica ; 106(5): 1443-1456, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33567810

RESUMO

Adult T cell leukemia/lymphoma (ATL) is associated to chronic human T cell leukemia virus type 1 (HTLV-1) infection and carries a poor prognosis. Arsenic trioxide (AS) and interferon-alpha (IFNα) together selectively trigger Tax viral oncoprotein degradation and cure Tax-driven murine ATL. AS/IFNα/zidovudine treatment achieves a high response rate in patients with chronic ATL. Interleukin 10 (IL-10) is an immuno-suppressive cytokine whose expression is activated by Tax. Here we show that, in ATL, AS/IFNα-induced abrogation of leukemia initiating cell activity requires IL-10 expression shutoff. Loss of IL-10 secretion drives production of inflammatory cytokines by the microenvironment, followed by innate immunity-mediated clearance of Taxdriven leukemic cells. Accordingly, anti-IL-10 monoclonal antibodies significantly increased the efficiency of AS/IFNα therapy. These results emphasize the sequential targeting of malignant ATL cells and their immune microenvironment in leukemia initiating cell (LIC) eradication and provide a strong rational to test AS/IFNα/anti-IL10 combination in ATL.

5.
Gut ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579790

RESUMO

OBJECTIVE: Enteropathy-associated T-cell lymphoma (EATL) is a rare but severe complication of coeliac disease (CeD), often preceded by low-grade clonal intraepithelial lymphoproliferation, referred to as type II refractory CeD (RCDII). Knowledge on underlying oncogenic mechanisms remains scarce. Here, we analysed and compared the mutational landscape of RCDII and EATL in order to identify genetic drivers of CeD-associated lymphomagenesis. DESIGN: Pure populations of RCDII-cells derived from intestinal biopsies (n=9) or sorted from blood (n=2) were analysed by whole exome sequencing, comparative genomic hybridisation and RNA sequencing. Biopsies from RCDII (n=50), EATL (n=19), type I refractory CeD (n=7) and uncomplicated CeD (n=18) were analysed by targeted next-generation sequencing. Moreover, functional in vitro studies and drug testing were performed in RCDII-derived cell lines. RESULTS: 80% of RCDII and 90% of EATL displayed somatic gain-of-functions mutations in the JAK1-STAT3 pathway, including a remarkable p.G1097 hotspot mutation in the JAK1 kinase domain in approximately 50% of cases. Other recurrent somatic events were deleterious mutations in nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) regulators TNFAIP3 and TNIP3 and potentially oncogenic mutations in TET2, KMT2D and DDX3X. JAK1 inhibitors, and the proteasome inhibitor bortezomib could block survival and proliferation of malignant RCDII-cell lines. CONCLUSION: Mutations activating the JAK1-STAT3 pathway appear to be the main drivers of CeD-associated lymphomagenesis. In concert with mutations in negative regulators of NF-κB, they may favour the clonal emergence of malignant lymphocytes in the cytokine-rich coeliac intestine. The identified mutations are attractive therapeutic targets to treat RCDII and block progression towards EATL.

6.
Addiction ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33464660

RESUMO

BACKGROUND AND AIMS: Cocaine use disorder (CUD) is a significant public health concern for which no efficacious pharmacological interventions are available. Cannabidiol (CBD) has attracted considerable interest as a promising treatment for addiction. This study tested CBD efficacy for reducing craving and preventing relapse in people with CUD. DESIGN: Single-site double-blind randomized controlled superiority trial comparing CBD with placebo. SETTING AND PARTICIPANTS: Centre Hospitalier de l'Université de Montréal, Canada. Seventy-eight adults (14 women) with moderate to severe CUD participated. INTERVENTION: Participants were randomly assigned (1 : 1) by stratified blocks to daily 800 mg CBD (n = 40) or placebo (n = 38). They first underwent an inpatient detoxification phase lasting 10 days. Those who completed this phase entered a 12-week outpatient follow-up. MEASUREMENTS: Primary outcomes were drug-cue-induced craving during detoxication and time-to-cocaine relapse during subsequent outpatient treatment. FINDINGS: During drug-cue exposure, craving scores [mean ± standard deviation (SD)] increased from baseline by 4.69 (2.89) versus 3.21 (2.78) points, respectively, in CBD (n = 36) and placebo (n = 28) participants [confidence interval (CI) = -0.33 to 3.04; P = 0.069; Bayes factor = 0.498]. All but three participants relapsed to cocaine by week 12 with similar risk for CBD (n = 34) and placebo (n = 27) participants (hazard ratio = 1.20, CI = 0.65-2.20, P = 0.51; Bayes factor = 0.152). CBD treatment was well tolerated and associated mainly with diarrhoea. CONCLUSIONS: CBD did not reduce cocaine craving or relapse among people being treated for CUD.

7.
J Clin Invest ; 131(2)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33463551

RESUMO

Early appearance of neutralizing antibodies during acute hepatitis C virus (HCV) infection is associated with spontaneous viral clearance. However, the longitudinal changes in antigen-specific memory B cell (MBCs) associated with divergent HCV infection outcomes remain undefined. We characterized longitudinal changes in E2 glycoprotein-specific MBCs from subjects who either spontaneously resolved acute HCV infection or progressed to chronic infection, using single-cell RNA-seq and functional assays. HCV-specific antibodies in plasma from chronically infected subjects recognized multiple E2 genotypes, while those from spontaneous resolvers exhibited variable cross-reactivity to heterotypic E2. E2-specific MBCs from spontaneous resolvers peaked early after infection (4-6 months), following expansion of activated circulating T follicular helper cells (cTfh) expressing interleukin 21. In contrast, E2-specific MBCs from chronically infected subjects, enriched in VH1-69, expanded during persistent infection (> 1 year), in the absence of significantly activated cTfh expansion. Early E2-specific MBCs from spontaneous resolvers produced monoclonal antibodies (mAbs) with fewer somatic hypermutations and lower E2 binding but similar neutralization as mAbs from late E2-specific MBCs of chronically infected subjects. These findings indicate that early cTfh activity accelerates expansion of E2-specific MBCs during acute infection, which might contribute to spontaneous clearance of HCV.

8.
Transpl Infect Dis ; : e13552, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33352001

RESUMO

EBV-positive mucocutaneous ulcer (EBV-MCU) is a rare EBV-positive B-cell lymphoproliferative disorder occurring in immunocompromised patients such as patients with solid organ or hematopoietic stem cells transplantation. EBV-MCU often consists of an isolated and circumscribed cutaneous or mucosal ulcerative lesion with a self-limited growth potential and a high regression rate upon immunosuppressive treatment withdrawal or rituximab therapy. Nevertheless, the pathophysiology of this latent infection leading to clonal lymphoproliferation is not well established. We report here two cases of EBV-MCU in kidney transplant recipients with a dissociated immune response to EBV with the absence of EBV-related antibodies and a positive T-cell response to EBV suggesting a potential specific oncogenic mechanism in this lymphoproliferative disorder.

9.
Open Forum Infect Dis ; 7(11): ofaa175, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33204743

RESUMO

We report a case of chronic hepatosplenic aspergillosis following immune reconstitution complicating colic aspergillosis in an AIDS patient with multicentric Castleman disease. Symptoms mimicked the clinical presentation of chronic disseminated candidiasis and responded to corticosteroid. This emerging entity enlarges the spectrum of fungal immune reconstitution inflammatory syndrome in the HIV setting.

12.
BMJ Open ; 10(9): e036102, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32912944

RESUMO

INTRODUCTION: Despite a recent meta-analysis including 31 randomised controlled trials comparing methadone and buprenorphine for the treatment of opioid use disorder, important knowledge gaps remain regarding the long-term effectiveness of different treatment modalities across individuals, including rigorously collected data on retention rates and other treatment outcomes. Evidence from real-world data represents a valuable opportunity to improve personalised treatment and patient-centred guidelines for vulnerable populations and inform strategies to reduce opioid-related mortality. Our objective is to determine the comparative effectiveness of methadone versus buprenorphine/naloxone, both overall and within key populations, in a setting where both medications are simultaneously available in office-based practices and specialised clinics. METHODS AND ANALYSIS: We propose a retrospective cohort study of all adults living in British Columbia receiving opioid agonist treatment (OAT) with methadone or buprenorphine/naloxone between 1 January 2008 and 30 September 2018. The study will draw on seven linked population-level administrative databases. The primary outcomes include retention in OAT and all-cause mortality. We will determine the effectiveness of buprenorphine/naloxone vs methadone using intention-to-treat and per-protocol analyses-the former emulating flexible-dose trials and the latter focusing on the comparison of the two medication regimens offered at the optimal dose. Sensitivity analyses will be used to assess the robustness of results to heterogeneity in the patient population and threats to internal validity. ETHICS AND DISSEMINATION: The protocol, cohort creation and analysis plan have been approved and classified as a quality improvement initiative exempt from ethical review (Providence Health Care Research Institute and the Simon Fraser University Office of Research Ethics). Dissemination is planned via conferences and publications, and through direct engagement and collaboration with entities that issue clinical guidelines, such as professional medical societies and public health organisations.

13.
Pain Med ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32869088

RESUMO

INTRODUCTION: Most studies on chronic noncancer pain (CNCP) in people who use drugs (PWUD) are restricted to people attending substance use disorder treatment programs. This study assessed the prevalence of CNCP in a community-based sample of PWUD, identified factors associated with pain, and documented strategies used for pain relief. METHODS: This was a cross-sectional study nested in an ongoing cohort of PWUD in Montreal, Canada. Questionnaires were administered to PWUD seen between February 2017 and January 2018. CNCP was defined as pain lasting three or more months and not associated with cancer. RESULTS: A total of 417 PWUD were included (mean age = 44.6 ± 10.6 years, 84% men). The prevalence of CNCP was 44.8%, and the median pain duration (interquartile range) was 12 (5-18) years. The presence of CNCP was associated with older age (>45 years old; odds ratio [OR] = 1.8, 95% CI = 1.2-2.7), male sex (OR = 2.3, 95% CI = 1.2-4.2), poor health condition (OR = 1.9, 95% CI = 1.3-3.0), moderate to severe psychological distress (OR = 2.9, 95% CI = 1.8-4.7), and less frequent cocaine use (OR = 0.5, 95% CI = 0.3-0.9). Among CNCP participants, 20.3% used pain medication from other people, whereas 22.5% used alcohol, cannabis, or illicit drugs to relieve pain. Among those who asked for pain medication (N = 24), 29.2% faced a refusal from the doctor. CONCLUSIONS: CNCP was common among PWUD, and a good proportion of them used substances other than prescribed pain medication to relieve pain. Close collaboration of pain and addiction specialists as well as better pain assessment and access to nonpharmacological treatments could improve pain management in PWUD.

14.
J Exp Med ; 217(11)2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-32812031

RESUMO

Epstein-Barr virus (EBV) preferentially infects epithelial cells and B lymphocytes and sometimes T and NK lymphocytes. Persistence of EBV-infected cells results in severe lymphoproliferative disorders (LPDs). Diagnosis of EBV-driven T or NK cell LPD and chronic active EBV diseases (CAEBV) is difficult, often requiring biopsies. Herein, we report a flow-FISH cytometry assay that detects cells expressing EBV-encoded small RNAs (EBERs), allowing rapid identification of EBV-infected cells among PBMCs. EBV-infected B, T, and/or NK cells were detectable in various LPD conditions. Diagnosis of CAEBV in 22 patients of Caucasian and African origins was established. All exhibited circulating EBV-infected T and/or NK cells, highlighting that CAEBV is not restricted to native American and Asian populations. Proportions of EBV-infected cells correlated with blood EBV loads. We showed that EBV-infected T cells had an effector memory activated phenotype, whereas EBV-infected B cells expressed plasma cell differentiation markers. Thus, this method achieves accurate and unambiguous diagnoses of different forms of EBV-driven LPD and represents a powerful tool to study their pathophysiological mechanisms.

15.
Subst Abus ; 41(3): 269-274, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697171

RESUMO

Medications for opioid use disorder (MOUD), such as methadone and buprenorphine, are effective strategies for treatment of opioid use disorder (OUD) and reducing overdose risk. MOUD treatment rates continue to be low across the US, and currently, some evidence suggests access to evidence-based treatment is becoming increasingly difficult for those with OUD as a result of the 2019 novel corona virus (COVID-19). A major underutilized source to address these serious challenges in the US is community pharmacy given the specialized training of pharmacists, high levels of consumer trust, and general availability for accessing these service settings. Canadian, Australian, and European pharmacists have made important contributions to the treatment and care of those with OUD over the past decades. Unfortunately, US pharmacists are not permitted to prescribe MOUD and are only currently allowed to dispense methadone for the treatment of pain, not OUD. US policymakers, regulators, and practitioners must work to facilitate this advancement of community pharmacy-based through research, education, practice, and industry. Advancing community pharmacy-based MOUD for leading clinical management of OUD and dispensation of treatment medications will afford the US a critical innovation for addressing the opioid epidemic, fallout from COVID-19, and getting individuals the care they need.


Assuntos
Analgésicos Opioides/uso terapêutico , Serviços Comunitários de Farmácia , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Farmacêuticos , Âmbito da Prática , Austrália , Betacoronavirus , Buprenorfina/uso terapêutico , Canadá , Infecções por Coronavirus , Assistência à Saúde , Acesso aos Serviços de Saúde , Humanos , Metadona/uso terapêutico , Pandemias , Pneumonia Viral , Reino Unido , Estados Unidos
16.
Addiction ; 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32649010

RESUMO

BACKGROUND AND AIMS: Disbursement of income assistance has been temporally associated with intensified drug use and related harms (coined the 'cheque effect'). However, relationships to injection drug use (IDU) remain understudied. We examined short-term 'cheque effects' and associated factors among people who inject drugs (PWID). DESIGN: Cross-sectional analysis nested within a cohort study. SETTING: Montreal, Quebec, Canada. PARTICIPANTS: PWID receiving income assistance, with no employment income. A total of 613 PWID (median age 41, 83% male) contributed 3269 observations from 2011 to 2017. MEASUREMENTS AND METHODS: At each cohort visit, an interviewer-administered questionnaire captured retrospective reports of injection-related behaviour during the 2-day periods (i) before and (ii) including/after receiving last month's income assistance payment (number of injections; drugs injected; any receptive syringe-sharing). The relative likelihood (odds) and magnitude (rate) of an increase in injection frequency ('cheque effect') were estimated in relation to social and behavioural factors using logistic and negative binomial regression in a covariate-adjusted two-part model. FINDINGS: Prevalence of IDU and syringe-sharing were, respectively, 1.80 and 2.50 times higher in the days following versus preceding cheque receipt (P < 0.001). Among people with past-month IDU, most observations showed increased injection frequency (52%) or no change in injection frequency (44%). The likelihood of a 'cheque effect' was positively associated with cocaine injection [versus injection of other substances, odds ratio (OR) = 2.639, 95% confidence interval (CI) = 2.04-3.41], unstable housing (OR = 1.272, 95% CI = 1.03-1.57) and receiving opioid agonist therapy (OR =1.597, 95% CI = 1.27-2.00) during the same month. Magnitude of the 'cheque effect' was positively associated with cocaine injection [rate ratio (RR) = 1.795, 95% CI = 1.43-2.16], unstable housing (RR = 1.198, 95% CI = 1.02-1.38) and frequent injection (RR = 2.938, 95% CI = 2.43-3.44), but inversely associated with opioid agonist therapy (RR = 0.817, 95% CI = 0.68-0.95) and prescription opioid injection (RR = 0.794, 95% CI = 0.66-0.93). CONCLUSION: Among people who inject drugs in Montreal, Canada, injection drug use and receptive syringe-sharing appear to be more prevalent in the 2 days after versus before receiving income assistance. The odds and rate of individual-level increases in injection frequency appear to be positively associated with cocaine injection (versus injection of other substances) and unstable housing.

17.
Drug Alcohol Depend ; 213: 108135, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32603976

RESUMO

BACKGROUND: Stimulants, such as amphetamines and cocaine, are widely injected among people who inject drugs (PWID). Systematic reviews indicate stimulant injection is associated with HIV and HCV among PWID. Using these associations, we estimated the contribution of stimulant injection to HIV and HCV transmission among PWID. METHODS: We modeled HIV and HCV transmission among PWID, incorporating excess injecting and sexual risk among PWID who inject stimulants. We simulated three illustrative settings with different stimulants injected, prevalence of stimulant injecting, and HIV/HCV epidemiology. We estimated one-year population attributable fractions of stimulant injection on new HIV and HCV infections, and impact of scaling up needle-syringe programs (NSP). RESULTS: In low prevalence settings of stimulant injection (St. Petersburg-like, where 13 % inject amphetamine), 9% (2.5-97.5 % interval [95 %I]: 6-15 %) and 7% (95 %I 4-11 %) of incident HIV and HCV cases, respectively, could be associated with stimulant injection in the next year. With moderate stimulant injection (Montreal-like, where 34 % inject cocaine), 29 % (95 %I: 19-37 %) and 19 % (95 %I: 16-21 %) of incident HIV and HCV cases, respectively, could be associated with stimulant injection. In high-burden settings like Bangkok where 65 % inject methamphetamine, 23 % (95%I:10-34%) and 20 % (95%I: 9-27%) of incident HIV and HCV cases could be due to stimulant injection. High-coverage NSP (60 %) among PWID who inject stimulants could reduce HIV (by 22-65 %) and HCV incidence (by 7-11 %) in a decade. DISCUSSION: Stimulant injection contributes substantially to HIV and HCV among PWID. NSP scale-up and development of novel interventions among PWID who inject stimulants are warranted.

18.
Leukemia ; 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32555298

RESUMO

Adult T-cell leukemia/lymphoma (ATL) carries a poor prognosis even in indolent subtypes. We performed targeted deep sequencing combined with mapping of HTLV-1 proviral integration sites of 61 ATL patients of African and Caribbean origin. This revealed mutations mainly affecting TCR/NF-kB (74%), T-cell trafficking (46%), immune escape (29%), and cell cycle (26%) related pathways, consistent with the genomic landscape previously reported in a large Japanese cohort. To examine the evolution of mutational signatures upon disease progression while tracking the viral integration architecture of the malignant clone, we carried out a longitudinal study of patients who either relapsed or progressed from an indolent to an aggressive subtype. Serial analysis of relapsing patients identified several patterns of clonal evolution. In progressing patients, the longitudinal study revealed NF-kB/NFAT mutations at progression that were present at a subclonal level at diagnosis (allelic frequency < 5%). Moreover, the presence in indolent subtypes of mutations affecting the TCR/NF-kB pathway, whether clonal or subclonal, was associated with significantly shorter time to progression and overall survival. Our observations reveal the clonal dynamics of ATL mutational signatures at relapse and during progression. Our study defines a new subgroup of indolent ATLs characterized by a mutational signature at high risk of transformation.

19.
Pediatr Blood Cancer ; 67(8): e28416, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32452165

RESUMO

Pediatric-type follicular (PTFL), marginal zone (MZL), and peripheral T-cell lymphoma (PTCL) account each for <2% of childhood non-Hodgkin lymphoma. We present clinical and histopathological features of PTFL, MZL, and few subtypes of PTCL and provide treatment recommendations. For localized PTFL and MZL, watchful waiting after complete resection is the therapy of choice. For PTCL, therapy is subtype-dependent and ranges from a block-like anaplastic large cell lymphoma (ALCL)-derived and, alternatively, leukemia-derived therapy in PTCL not otherwise specified and subcutaneous panniculitis-like T-cell lymphoma to a block-like mature B-NHL-derived or, preferentially, ALCL-derived treatment followed by hematopoietic stem cell transplantation in first remission in hepatosplenic and angioimmunoblastic T-cell lymphoma.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Zona Marginal Tipo Células B , Linfoma Folicular , Linfoma de Células T Periférico , Adolescente , Aloenxertos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma Folicular/diagnóstico , Linfoma Folicular/terapia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapia , Masculino
20.
Am J Prev Med ; 58(6): 845-853, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32444003

RESUMO

INTRODUCTION: Needle and syringe programs and opioid agonist therapy are essential for harm reduction among people who inject drugs. Few studies assess their combined potential in preventing hepatitis C virus infection. No studies have assessed whether they perform similarly among individuals at risk of primary and recurrent infection. This study aimed to estimate the rates of hepatitis C virus acquisition according to harm reduction coverage among hepatitis C virus-naive and previously infected people who inject drugs in Montreal, Canada. METHODS: This prospective cohort study involved regular interviews and hepatitis C antibody and RNA testing (data collection: 2010-2017, analysis: 2018). Opioid agonist therapy coverage was defined by current dose: high (≥60 mg/day methadone, ≥16 mg buprenorphine), low, or none. Complete needle and syringe program coverage was defined as exclusively reporting safe needle and syringe sources (past 6 or 3 months). Combined coverage was defined as full (high-dose agonist/complete needle/syringe coverage), minimal (low-dose agonist/incomplete needle/syringe coverage), and partial (remaining combinations). Cox regression models were fit. RESULTS: A total of 106 events were observed over 1,183.1 person-years for primary and recurrent incidence rates of 10.6 (95% CI=8.0, 13.8) and 7.6 (95% CI=5.6, 9.9) per 100 years, respectively. High-dose opioid agonist therapy was associated with a 77% reduction in hepatitis C virus acquisition (hazard ratio=0.23, 95% CI=0.10, 0.50) compared with not receiving opioid agonist therapy. Needle and syringe coverage was not associated with infection rates. Estimates considering their combination reflected opioid agonist therapy coverage. Associations were similar among hepatitis C virus-naive and previously infected people who inject drugs. CONCLUSIONS: High-dose opioid agonist therapy seems particularly important to reduce drug-related harms among hepatitis C virus-naive and previously infected people who inject drugs in Montreal.

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