Current perspectives on the management of refractory or relapsed classic hodgkin lymphoma in brazil: Balancing efficacy, safety, and tolerability.

Classic Hodgkin lymphoma (CHL), which accounts for 90-95% of all cases of Hodgkin lymphoma, is the most frequent cancer in adolescents and the most frequent lymphoma in adolescents and young adults. Despite progressive improvements over past decades and the general sensitivity of CHL to frontline chemotherapy, approximately 10-15% of patients have refractory disease that either does not respond to such therapy or progresses after an initial partial response. In patients with refractory or relapsed disease, standard treatment until recently consisted mainly of salvage chemotherapy, in many cases followed by high-dose chemotherapy and autologous stem-cell transplantation. However, improved understanding of the pathobiology of CHL, coupled with the introduction of novel agents, has markedly changed the treatment landscape in the past decade. Although refractory or relapsed CHL continues to be challenging, the therapeutic landscape is undergoing profound changes brought about by novel agents, particularly brentuximab vedotin and immunotherapy. In this review, we discuss the most salient treatment options for adult patients with refractory or relapsed CHL, with a special focus on the Brazilian healthcare setting, which is constrained by inherent characteristics of this system. In the attempt to balance efficacy, safety and tolerability, practicing physicians must rely on clinical trials and on results from real-world studies, and use their own point of view and experience, as well as patient characteristics and previous therapy, to make treatment decisions for refractory or relapsed CHL.

Ixazomib Versus Placebo as Postinduction Maintenance Therapy in Newly Diagnosed Multiple Myeloma Patients: An Analysis by Age and Frailty Status of the TOURMALINE-MM4 Study.

BACKGROUND: The TOURMALINE-MM4 trial demonstrated a significant and clinically meaningful progression-free survival (PFS) benefit with ixazomib versus placebo as postinduction maintenance in nontransplant, newly-diagnosed multiple myeloma patients, with a manageable and well-tolerated toxicity profile. MATERIALS AND METHODS: In this subgroup analysis, efficacy and safety were assessed by age (< 65, 65-74, and ≥ 75 years) and frailty status (fit, intermediate-fit, and frail). RESULTS: In this analysis, PFS benefit with ixazomib versus placebo was seen across age subgroups, including patients aged < 65 years (hazard ratio [HR], 0.576; 95% confidence interval [CI], 0.299-1.108; P = .095), 65-74 years (HR, 0.615; 95% CI, 0.467-0.810; P < .001), and ≥ 75 years (HR, 0.740; 95% CI, 0.537-1.019; P = .064). PFS benefit was also seen across frailty subgroups, including fit (HR, 0.530; 95% CI, 0.387-0.727; P < .001), intermediate-fit (HR, 0.746; 95% CI, 0.526-1.058; P = .098), and frail (HR, 0.733; 95% CI, 0.481-1.117; P = .147) patients. With ixazomib versus placebo, rates of grade ≥ 3 treatment-emergent adverse events (TEAEs; 28-44% vs. 10-36%), serious TEAEs (15-29% vs. 3-29%), and discontinuation due to TEAEs (7-19% vs. 5-11%) were higher or similar across age and frailty subgroups, and generally somewhat higher in older age groups and intermediate-fit/frail patients in both arms. Treatment with ixazomib versus placebo did not adversely affect patient-reported quality-of-life scores across age and frailty status subgroups. CONCLUSION: Ixazomib is a feasible and effective maintenance option for prolonging PFS across this heterogeneous patient population.

Imunoexpressão de ING 4, VEGF e NF-κB em lesões periapicais inflamatórias / Immunoexpression of ING 4, VEGF and NF-κB in inflammatory periapical lesions

As lesões periapicais inflamatórias (LPIs) são condições patológicas decorrentes de infecções de origem odontogênica, principalmente representadas pelos granulomas periapicais (GPs) e cistos radiculares (CRs). Sua patogênese está associada a mecanismos imunológicos e angiogênicos. O presente estudo, do tipo retrospectivo, teve como objetivo analisar, de forma semiquantitativa, a expressão imuno-histoquímica de ING-4, VEGF e NF-κB em LPIs, e correlacionar o padrão de expressão dessas proteínas. A amostra consistiu de 26 GPs, 17 CRs e 19 cistos radiculares residuais (CRRs). Foram avaliados espessura epitelial e infiltrado inflamatório, e a associação desses achados com o padrão de expressão das proteínas ING-4, VEGF e NF-κB nas LPIs selecionadas. Para a realização da análise estatística, foram utilizados os testes de qui-quadrado, Kruskal-Wallis, Mann-Whitney e correlação de Spearman (p < 0,05). O infiltrado inflamatório exibiu maior intensidade no GP, seguido pelo CR, e por último, o CRR (p < 0,05). Apesar de não haver associação estatisticamente significativa ao associar a expressão de ING-4 nas células inflamatórias do tecido conjuntivo ou cápsula fibrosa entre os grupos de LPIs, o GP e CR evidenciaram, através da média de postos, maior expressão dessa proteína. Não foi evidenciada associação estatisticamente significativa de ING-4 com a intensidade do infiltrado inflamatório. A imunoexpressão de VEGF no núcleo das células inflamatórias do tecido conjuntivo ou cápsula fibrosa exibem associação significativa com as LPIs, que ocorre maior expressão dessa proteína nos cistos (p= 0,002). A maior expressão de NF-κB foi evidenciada nos casos de GPs, tanto a nível nuclear quanto citoplasmático das células inflamatórias (p = 0,005; p = 0,002). Não houve associação estatisticamente significativa quando comparada a expressão de NF-κB entre os cistos, mas a mediana da expressão dessa proteína foi maior para os CRs. Na cápsula fibrosa, a imunoexpressão nuclear e citoplasmática de NF-κB nas células inflamatórias foi superior nas lesões periapicais com intenso infiltrado inflamatório (p < 0,001). Portanto, sugere-se que ING-4, VEGF e NF-κB participam do desenvolvimento das LPIs, e apesar de ocorrer relação diretamente proporcional entre a expressão dessas proteínas, ING-4 não exerceu atividade reguladora na inflamação associada a essas lesões (AU).

Inflammatory periapical lesions (IPLs) are pathological conditions resulting from infections of odontogenic origin, being mainly represented by periapical granulomas (PGs) and radicular cysts (RCs). Its pathogenesis is associated with immunological and angiogenic mechanisms. This retrospective study, semi-quantitative and comparative aimed to analyze the immunohistochemical expression of ING-4, VEGF and NF-κB in IPLs, and to correlate the pattern of expression of these proteins. The sample consisted of 26 were PGs, 17 RCs and 19 residual radicular cysts (RRCs). Epithelial thickness and inflammatory infiltrate were evaluated, and the correlation of these findings with the expression pattern of ING-4, VEGF and NF-κB proteins in selected IPLs. To perform the statistical analysis, the chi-square, Kruskal-Wallis, Mann-Whitney and Spearman correlation tests were used (p < 0.05). The inflammatory infiltrate exhibited greater intensity in the PG, followed by the RC, and finally, the RRC (p < 0.05). Although there was no statistically significant association when associating the expression of ING-4 in inflammatory cells of the connective tissue or fibrous capsule the groups of IPLs, the PG and RC showed higher expression of this protein. There was no statistically significant association between ING-4 and the intensity of the inflammatory infiltrate. Immunoexpression of VEGF in the nucleus of inflammatory cells in the connective tissue or fibrous capsule shows a significant association with IPLs, in which there is greater expression of this protein occurring in cysts (p= 0,002). The highest expression of NF-κB was evidenced in cases of PGs, both at the nuclear and cytoplasmic level of inflammatory cells (p=0,005; p= 0,002). There was no statistically significant association when comparing the expression of NF-κB between the cysts, but the median expression of this protein was expression was higher for the RCs. In the fibrous capsule, nuclear and cytoplasmic NF-κB immunoexpression in inflammatory cells was higher in periapical lesions with intense inflammatory infiltrate (p<0.001). Therefore, it is suggested that ING-4, VEGF and NF-κB participate in the etiopathogenesis of IPLs, and that there is a directly proportional relationship between the expression of these proteins. ING-4 did not exert regulatory activity in the inflammation associated with these lesions (AU).

Thromboembolic and bleeding events in intensive care unit patients with COVID-19: results from a Brazilian tertiary hospital.

OBJECTIVES: To describe the incidence of thromboembolic events in adult patients with severe COVID-19 and identify clinical and laboratory factors associated with these events. DESIGN: Observational retrospective cohort study of 243 adult patients with severe COVID-19 admitted to an intensive care unit (ICU) at a Brazilian tertiary hospital. RESULTS: The incidence of all thromboembolic events was 14.8%, in which 3.8% developed deep vein thrombosis, 7.8% pulmonary embolism, 2.5% acute myocardial infarction, 1.2% stroke, and 1.2% peripheral artery occlusion. Risk factors identified were D-dimer at admission >3000 ng/mL (P=<0.0013) and major bleeding (P=0.001). The cumulative risk of developing thromboembolic events at day 28 after ICU admission was 16.0%. The rate of major bleeding was 4.1%. After receiver operating characteristic curve analysis, the D-dimer cut-off at admission correlating with thromboembolic events was 1140.5 ng/mL. CONCLUSIONS: The rate of thromboembolic events in our study was lower than previously described. High D-dimer level at admission was the leading risk factor; the optimal cut-off was 1140.5 ng/mL. The occurrence of thromboembolic events did not have an impact on the median overall survival rate. The optimal anticoagulant strategy in this context still needs to be established.

Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial.

OBJECTIVE: To determine whether tocilizumab improves clinical outcomes for patients with severe or critical coronavirus disease 2019 (covid-19). DESIGN: Randomised, open label trial. SETTING: Nine hospitals in Brazil, 8 May to 17 July 2020. PARTICIPANTS: Adults with confirmed covid-19 who were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two serum biomarkers (C reactive protein, D dimer, lactate dehydrogenase, or ferritin). The data monitoring committee recommended stopping the trial early, after 129 patients had been enrolled, because of an increased number of deaths at 15 days in the tocilizumab group. INTERVENTIONS: Tocilizumab (single intravenous infusion of 8 mg/kg) plus standard care (n=65) versus standard care alone (n=64). MAIN OUTCOME MEASURE: The primary outcome, clinical status measured at 15 days using a seven level ordinal scale, was analysed as a composite of death or mechanical ventilation because the assumption of odds proportionality was not met. RESULTS: A total of 129 patients were enrolled (mean age 57 (SD 14) years; 68% men) and all completed follow-up. All patients in the tocilizumab group and two in the standard care group received tocilizumab. 18 of 65 (28%) patients in the tocilizumab group and 13 of 64 (20%) in the standard care group were receiving mechanical ventilation or died at day 15 (odds ratio 1.54, 95% confidence interval 0.66 to 3.66; P=0.32). Death at 15 days occurred in 11 (17%) patients in the tocilizumab group compared with 2 (3%) in the standard care group (odds ratio 6.42, 95% confidence interval 1.59 to 43.2). Adverse events were reported in 29 of 67 (43%) patients who received tocilizumab and 21 of 62 (34%) who did not receive tocilizumab. CONCLUSIONS: In patients with severe or critical covid-19, tocilizumab plus standard care was not superior to standard care alone in improving clinical outcomes at 15 days, and it might increase mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT04403685.

Social Validity of the Strengthening Families Program in Northeastern Brazil: the Voices of Parents, Adolescents, and Facilitators.

In 2013, Brazil's Ministry of Health adopted the Strengthening Families Program (SFP 10-14), developed internationally for preventing drug abuse by enhancing family bonds. The social validity of the objectives, procedures, and perceived impacts of the program were investigated for participants and facilitators in northeastern Brazil. Focus groups with parents/guardians (N = 199), adolescents (N = 111), and facilitators (N = 100) were implemented. Content analysis revealed that the program's objectives were considered socially relevant and that there was a positive short-term perceived impact on family cohesion, authoritative parenting style, adolescent life skills, and the facilitators' professional capacity. The parents/guardians and adolescents presented a positive perception of the appropriateness of the program's methodology, while facilitators indicated the need to adapt it to vulnerable families and improve its implementation conditions. Future studies may benefit from these findings when developing similarly viable and scalable interventions in low-resource settings. Brazilian Trial Register RBR-7q9xh5. Registered 5 August 2017, http://www.ensaiosclinicos.gov.br/rg/RBR-7q9xh5/.

Real-world analysis of treatment patterns and clinical outcomes in patients with newly diagnosed chronic lymphocytic leukemia from seven Latin American countries.

OBJECTIVE: To describe chronic lymphocytic leukemia (CLL) treatment patterns and patient outcomes in Latin America. METHODS: This chart review study (NCT02559583; 2008-2015)evaluated time to progression (TTP) and overall survival (OS) outcomes among patients with CLL who initiate done (n = 261) to two (n = 96) lines of therapy (LOT) since diagnosis. Differences in TTP and OS were assessed by Kaplan-Meier analysis, with a log-rank test for statistical significance. Association between therapeutic regimen and risk for disease progression or death was estimated using Cox proportional hazard regression. RESULTS: The most commonly prescribed therapies in both LOTs were chlorambucil-, followed by fludarabine- and cyclophosphamide (C)/CHOP-based therapies. Chlorambucil- and C/CHOP-based therapies were largely prescribed to elderly patients (≥65 years) while fludarabine-based therapy was predominantly used by younger patients (≤65 years). In LOT1, relative to chlorambucil-administered patients, those prescribed fludarabine-based therapies had lower risk of disease progression (hazard ratio [HR] and 95% confidence interval [CI] 0.32 [0.19-0.54]), whereas C/CHOP-prescribed patients had higher risk (HR 95%CI 1.88 [1.17-3.04]). Similar results were observed in LOT2. There was no difference in OS between treatments in both LOTs. DISCUSSION: Novel therapies such as kinase inhibitors were rarely prescribed in LOT1 or LOT2in Latin America. The greater TTP observed forfludarabine-based therapies could be attributed to the fact that fludarabine-based therapies are predominantly administered to young and healthy patients. CONCLUSION: Chlorambucil-based therapy, which has limited benefits, is frequently prescribed in Latin America. Prescribing novel agents for fludarabine-based therapy-ineligible patients with CLL is the need of the hour. Trial registration: ClinicalTrials.gov identifier: NCT02559583.

Barriers and Facilitators in the Strengthening Families Program (SFP 10-14) Implementation Process in Northeast Brazil: A Retrospective Qualitative Study.

This study analyzed contextual barriers and facilitators in the implementation of Strengthening Families Program (SFP 10-14), Brazilian version, a family-based preventive program focused on the prevention of risk behaviors for adolescent health. SFP 10-14 was implemented between 2016 and 2017 for socioeconomically vulnerable families in four Northeast Brazilian states as a tool of the National Drug Policy. A retrospective qualitative study was carried out in which 26 implementation agents participated. Data from 16 individual interviews and two group interviews were analyzed through content analysis. The most recurrent barriers were the group facilitators' working conditions, weak municipal administration, precarious infrastructure, inadequate group facilitator training methodologies, low adherence of managers and professionals, and funding scarcity. The conditions highlighted as favorable to the implementation were proper intersectoral coordination, engagement of involved actors, awareness of public agency administrators, municipal management efficacy, and efficient family recruitment strategies. Favorable political contexts, engagement of implementation agents, and intersectoral implementation strategies were identified as central to the success of the implementation of SFP 10-14, especially in the adoption of the intervention, community mobilization, and intervention delivery stages. Further studies should combine contexts, mechanisms, and results for a broad understanding of the effectiveness of this intervention in the public sector.

Rationale and design of the "Tocilizumab in patients with moderate to severe COVID-19: an open-label multicentre randomized controlled" trial (TOCIBRAS). / Justificativa e delineamento do estudo "Tocilizumabe em pacientes com COVID-19 moderado a grave: estudo aberto, multicêntrico, randomizado, controlado" (TOCIBRAS).

INTRODUCTION: Pro-inflammatory markers play a significant role in the disease severity of patients with COVID-19. Thus, anti-inflammatory therapies are attractive agents for potentially combating the uncontrolled inflammatory cascade in these patients. We designed a trial testing tocilizumab versus standard of care intending to improve the outcomes by inhibiting interleukin-6, an important inflammatory mediator in COVID-19. METHODS AND ANALYSIS: This open-label multicentre randomized controlled trial will compare clinical outcomes of tocilizumab plus standard of care versus standard of care alone in patients with moderate to severe COVID-19. Two of the following four criteria are required for protocol enrolment: D-dimer > 1,000ng/mL; C reactive protein > 5mg/dL, ferritin > 300mg/dL, and lactate dehydrogenase > upper limit of normal. The primary objective will be to compare the clinical status on day 15, as measured by a 7-point ordinal scale applied in COVID-19 trials worldwide. The primary endpoint will be assessed by an ordinal logistic regression assuming proportional odds ratios adjusted for stratification variables (age and sex). ETHICS AND DISSEMINATION: The TOCIBRAS protocol was approved by local and central (national) ethical committees in Brazil following current national and international guidelines/directives. Each participating center had the study protocol approved by their institutional review boards before initiating protocol enrolment. The data derived from this trial will be published regardless of the results. If proven active, this strategy could alleviate the consequences of the inflammatory response in COVID-19 patients and improve their clinical outcomes.

INTRODUÇÃO: Os marcadores pró-inflamatórios desempenham papel importante na severidade de pacientes com COVID-19. Assim, terapêuticas anti-inflamatórias são agentes interessantes para potencialmente combater a cascata inflamatória descontrolada em tais pacientes. Delineamos um ensaio para testar tocilizumabe em comparação com o tratamento padrão, tendo como objetivo melhorar os desfechos por meio da inibição da interleucina 6, um importante mediador inflamatório na COVID-19. MÉTODOS E ANÁLISES: Este será um estudo aberto multicêntrico, randomizado e controlado, que comparará os desfechos de pacientes tratados com tocilizumabe mais tratamento padrão com o tratamento padrão isoladamente em pacientes com COVID-19 moderada a grave. Como critérios de inclusão, serão exigidos dois dos quatro critérios a seguir: dosagens de dímero D acima de 1.000ng/mL, proteína C-reativa acima de 5mg/dL, ferritina acima de 300mg/dL e desidrogenase lática acima do limite superior do normal. O objetivo primário será comparar a condição clínica no dia 15, conforme avaliação por meio de escala ordinal de 7 pontos aplicada nos estudos de COVID-19 em todo o mundo. O desfecho primário será avaliado por regressão logística ordinal assumindo razões de propensão proporcionais ajustadas pelas variáveis de estratificação (idade e sexo). ÉTICA E DISSEMINAÇÃO: O TOCIBRAS foi aprovado pelos comitês de ética locais e central (nacional) do Brasil em conformidade com as atuais diretrizes e orientações nacionais e internacionais. Cada centro participante obteve aprovação do estudo por parte de seu comitê de ética em pesquisa, antes de iniciar as inscrições no protocolo. Os dados derivados deste ensaio serão publicados independentemente de seus resultados. Se tiver sua efetividade comprovada, esta estratégia terapêutica poderá aliviar as consequências da resposta inflamatória na COVID-19 e melhorar os resultados clínicos.

Managing patients with multiple myeloma during the COVID-19 pandemic: recommendations from an expert panel - ABHH monoclonal gammopathies committe

ABSTRACT Since the World has been facing the COVID-19 pandemic, special attention has been taken concerning cancer patients; related to their immunosuppression status, adding risk for more aggressive COVID-19 and mortality, but also concerns about the access and the quality of care in cancer therapy. The COVID-19 pandemic impacts the number of infected, its related mortality, as well as the care of cancer patients. Multiple myeloma patients are a particular group with several important aspects to be considered during pandemic times. In essence, they are immunosuppressed in different intensities during their treatment. Most of them are elderly and all of them require long-term therapy, with prolonged contact with the health care system, possibly including a stem cell transplant during the treatment. A panel of experts in multiple myeloma and infectious diseases discusses pieces of evidence and the lack of the same in the scenario of COVID-19 in myeloma patients, while also exposing what is expected for the next phases of the COVID-19 pandemic.

Justificativa e delineamento do estudo Tocilizumabe em pacientes com COVID-19 moderado a grave: estudo aberto, multicêntrico, randomizado, controlado (TOCIBRAS) / Rationale and design of the Tocilizumab in patients with moderate to severe COVID-19: an open-label multicentre randomized controlled trial (TOCIBRAS)

RESUMO Introdução: Os marcadores pró-inflamatórios desempenham papel importante na severidade de pacientes com COVID-19. Assim, terapêuticas anti-inflamatórias são agentes interessantes para potencialmente combater a cascata inflamatória descontrolada em tais pacientes. Delineamos um ensaio para testar tocilizumabe em comparação com o tratamento padrão, tendo como objetivo melhorar os desfechos por meio da inibição da interleucina 6, um importante mediador inflamatório na COVID-19. Métodos e análises: Este será um estudo aberto multicêntrico, randomizado e controlado, que comparará os desfechos de pacientes tratados com tocilizumabe mais tratamento padrão com o tratamento padrão isoladamente em pacientes com COVID-19 moderada a grave. Como critérios de inclusão, serão exigidos dois dos quatro critérios a seguir: dosagens de dímero D acima de 1.000ng/mL, proteína C-reativa acima de 5mg/dL, ferritina acima de 300mg/dL e desidrogenase lática acima do limite superior do normal. O objetivo primário será comparar a condição clínica no dia 15, conforme avaliação por meio de escala ordinal de 7 pontos aplicada nos estudos de COVID-19 em todo o mundo. O desfecho primário será avaliado por regressão logística ordinal assumindo razões de propensão proporcionais ajustadas pelas variáveis de estratificação (idade e sexo). Ética e disseminação: O TOCIBRAS foi aprovado pelos comitês de ética locais e central (nacional) do Brasil em conformidade com as atuais diretrizes e orientações nacionais e internacionais. Cada centro participante obteve aprovação do estudo por parte de seu comitê de ética em pesquisa, antes de iniciar as inscrições no protocolo. Os dados derivados deste ensaio serão publicados independentemente de seus resultados. Se tiver sua efetividade comprovada, esta estratégia terapêutica poderá aliviar as consequências da resposta inflamatória na COVID-19 e melhorar os resultados clínicos.

ABSTRACT Introduction: Pro-inflammatory markers play a significant role in the disease severity of patients with COVID-19. Thus, anti-inflammatory therapies are attractive agents for potentially combating the uncontrolled inflammatory cascade in these patients. We designed a trial testing tocilizumab versus standard of care intending to improve the outcomes by inhibiting interleukin-6, an important inflammatory mediator in COVID-19. Methods and analysis: This open-label multicentre randomized controlled trial will compare clinical outcomes of tocilizumab plus standard of care versus standard of care alone in patients with moderate to severe COVID-19. Two of the following four criteria are required for protocol enrolment: D-dimer > 1,000ng/mL; C reactive protein > 5mg/dL, ferritin > 300mg/dL, and lactate dehydrogenase > upper limit of normal. The primary objective will be to compare the clinical status on day 15, as measured by a 7-point ordinal scale applied in COVID-19 trials worldwide. The primary endpoint will be assessed by an ordinal logistic regression assuming proportional odds ratios adjusted for stratification variables (age and sex). Ethics and dissemination: The TOCIBRAS protocol was approved by local and central (national) ethical committees in Brazil following current national and international guidelines/directives. Each participating center had the study protocol approved by their institutional review boards before initiating protocol enrolment. The data derived from this trial will be published regardless of the results. If proven active, this strategy could alleviate the consequences of the inflammatory response in COVID-19 patients and improve their clinical outcomes.

Managing patients with multiple myeloma during the COVID-19 pandemic: recommendations from an expert panel - ABHH monoclonal gammopathies committe.

Since the World has been facing the COVID-19 pandemic, special attention has been taken concerning cancer patients; related to their immunosuppression status, adding risk for more aggressive COVID-19 and mortality, but also concerns about the access and the quality of care in cancer therapy. The COVID-19 pandemic impacts the number of infected, its related mortality, as well as the care of cancer patients. Multiple myeloma patients are a particular group with several important aspects to be considered during pandemic times. In essence, they are immunosuppressed in different intensities during their treatment. Most of them are elderly and all of them require long-term therapy, with prolonged contact with the health care system, possibly including a stem cell transplant during the treatment. A panel of experts in multiple myeloma and infectious diseases discusses pieces of evidence and the lack of the same in the scenario of COVID-19 in myeloma patients, while also exposing what is expected for the next phases of the COVID-19 pandemic.

Epidemiology of Hematologic Malignancies in Real-World Settings: Findings From the Hemato-Oncology Latin America Observational Registry Study.

PURPOSE: Limited information is available on multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL) management in Latin America. The primary objective of the Hemato-Oncology Latin America (HOLA) study was to describe patient characteristics and treatment patterns of Latin American patients with MM, CLL, and NHL. METHODS: This study was a multicenter, retrospective, medical chart review of patients with MM, CLL, and NHL in Latin America identified between January 1, 2006, and December 31, 2015. Included were adults with at least 1 year of follow-up (except in cases of death within 1 year of diagnosis) treated at 30 oncology hospitals (Argentina, 5; Brazil, 9; Chile, 1; Colombia, 5; Mexico, 6; Panama/Guatemala, 4). RESULTS: Of 5,140 patients, 2,967 (57.7%) had NHL, 1,518 (29.5%) MM, and 655 (12.7%) CLL. Median follow-up was 2.2 years for MM, 3.0 years for CLL, and 2.2 years for NHL, and approximately 26% died during the study observation period. Most patients had at least one comorbidity at diagnosis. The most frequent induction regimen was thalidomide-based chemotherapy for MM and chlorambucil with or without prednisone for CLL. Most patients with NHL had diffuse large B-cell lymphoma (DLBCL; 49.1%) or follicular lymphoma (FL; 19.5%). The majority of patients with DLBCL or FL received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. CONCLUSION: The HOLA study generated an unprecedented level of high-quality, real-world evidence on characteristics and treatment patterns of patients with hematologic malignancies. Regional disparities in patient characteristics may reflect differences in ethnoracial identity and level of access to care. These data provide needed real-world evidence to understand the disease landscape in Latin America and may be used to inform clinical and health policy decision making.

The influence of MTHFR C677T polymorphism in chronic lymphocytic leukemia.

Some factors have been associated with the etiology of chronic lymphocytic leukemia (CLL), among them the Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. The aim of this study was to evaluate the role of MTHFR C677T polymorphism in CLL. A case-control study was conducted with 219 individuals from Brazilian central population. MTHFR C677T polymorphism was determined through PCR-RFLP followed by PAGE. The T allele frequence was higher in patients diagnosed with CLL than healthy subjects. However, when stratified by gender, the TT genotype was exclusively found in men diagnosed with CLL (p < 0.05). Adjusted multiple logistic regression analysis demonstrated that age was significantly linked to CLL predisposition (odds ratio = 1.08; p < 0.001). Studies evaluating the influence of genetic factors may provide insights on susceptibility for CLL.

Technical Quality of Complete Dentures: Influence on Masticatory Efficiency and Quality of Life.

PURPOSE: To evaluate the effect of the technical quality of conventional complete dentures (CD) on masticatory efficiency and quality of life (QoL) of denture wearers during a 1-year follow-up. MATERIALS AND METHODS: A prospective clinical trial with 32 edentulous patients (mean age of 60.2 years) wearing mandibular and maxillary dentures was conducted. All patients were evaluated wearing their preexisting dentures and after 3, 6, and 12 months postinsertion of new dentures. A reproducible method for objective evaluation of the technical quality of CDs was employed. Masticatory efficiency was evaluated by the colorimetric method using beads as artificial testing food. The oral health impact on patient QoL was measured using the OHIP-EDENT (Oral Health Impact Profile in Edentulous Adults) questionnaire. The nonparametric Wilcoxon test was applied to reveal any differences in technical quality between the preexisting and new dentures. The Friedman test was used to detect differences in masticatory efficiency and oral health impact on QoL. Spearman's correlation was applied to reveal correlation between the variables. RESULTS: Comparing preexisting and new dentures, significant improvement was found in technical quality between the dentures (p < 0.001). There was no statistically significant difference in masticatory efficiency. A significant decrease was found in the total OHIP-EDENT scores after denture replacement. A positive correlation was found between technical quality and OHIP in the new denture wearers (p = 0.011). CONCLUSIONS: According to the results of this study, denture quality significantly improved patients' oral health-related QoL; however, insertion of new dentures did not influence masticatory efficiency.

Splenic marginal zone lymphoma: a literature review of diagnostic and therapeutic challenges.

Splenic marginal zone lymphoma (SMZL) is a low-grade B-cell non-Hodgkin's lymphoma characterized by massive splenomegaly, moderate lymphocytosis with or without villous lymphocytes, rare involvement of peripheral lymph nodes and indolent clinical course. As a rare disease, with no randomized prospective trials, there is no standard of care for SMZL so far. Splenectomy has been done for many years as an attempt to control disease, but nowadays it has not been encouraged as first line because of new advances in therapy as rituximab, that are as effective with minimal toxicity. Facing these controversies, this review highlights advances in the literature regarding diagnosis, prognostic factors, treatment indications and therapeutic options.

Splenic marginal zone lymphoma: a literature review of diagnostic and therapeutic challenges

ABSTRACT Splenic marginal zone lymphoma (SMZL) is a low-grade B-cell non-Hodgkin's lymphoma characterized by massive splenomegaly, moderate lymphocytosis with or without villous lymphocytes, rare involvement of peripheral lymph nodes and indolent clinical course. As a rare disease, with no randomized prospective trials, there is no standard of care for SMZL so far. Splenectomy has been done for many years as an attempt to control disease, but nowadays it has not been encouraged as first line because of new advances in therapy as rituximab, that are as effective with minimal toxicity. Facing these controversies, this review highlights advances in the literature regarding diagnosis, prognostic factors, treatment indications and therapeutic options.