Efficacy and safety of bendamustine-containing bridging therapy in R/R LBCL patients receiving CD19 CAR T-cells.

Bridging therapy (BT) after leukapheresis is required in most relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients receiving chimeric antigen receptor (CAR) T cells. Bendamustine-containing regimens are a potential BT option. We aimed to assess if this agent had a negative impact on CAR-T outcomes when it was administered as BT. We included R/R LBCL patients from six centers who received systemic BT after leukapheresis from February 2019 to September 2022; patients who only received steroids or had pre-apheresis bendamustine exposure were excluded. Patients were divided into two BT groups, with and without bendamustine. Separate safety and efficacy analyses were carried out for axi-cel and tisa-cel. Of 243 patients who received BT, bendamustine (benda) was included in 62 (26%). There was a higher rate of BT progressors in the non-benda group (62% vs. 45%, p = 0.02). Concerning CAR-T efficacy, complete responses were comparable for benda versus non-benda BT cohorts with axi-cel (70% vs. 53%, p = 0.12) and tisa-cel (44% vs. 36%, p = 0.70). Also, 12-month progression-free and overall survival were not significantly different between BT groups with axi-cel (56% vs. 43% and 71% vs. 63%) and tisa-cel (25% vs. 26% and 52% vs. 48%); there were no differences when BT response was considered. CAR T-cell expansion for each construct was similar between BT groups. Regarding safety, CRS G ≥3 (6% vs. 6%, p = 0.79), ICANS G ≥3 (15% vs. 17%, p = 0.68), severe infections, and neutropenia post-infusion were comparable among BT regimens. BT with bendamustine-containing regimens is safe for patients requiring disease control during CAR T-cell manufacturing.

Treatment outcomes in patients with large B-cell lymphoma after progression to chimeric antigen receptor T-cell therapy.

Over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients who receive chimeric antigen receptor (CAR) T cells will experience disease progression. There is no standard next line of therapy and information in this setting is scarce and heterogeneous. We analyzed 387 R/R LBCL patients who progressed after CAR T cells from July 2018 until March 2022 in Spain and the United Kingdom. Median overall survival (OS) was 5.3 months, with significant differences according to the interval between infusion and progression (<2 months [1.9 months], 2-6 months [5.2 months], and >6 months [not reached]). After progression, 237 (61%) patients received treatment. Focusing on the first subsequent therapy, overall (complete) response rates were 67% (38%) for polatuzumab-bendamustine-rituximab (POLA), 51% (36%) for bispecific antibodies (BsAb), 45% (35%) for radiotherapy (RT), 33% (26%) for immune checkpoint inhibitors (ICIs), 25% (0%) for lenalidomide (LENA), and 25% (14%) for chemotherapy (CT). In terms of survival, 12-month progression-free survival and OS was 36.2% and 51.0% for POLA, 32.0% and 50.1% for BsAb, 30.8% and 37.5% for RT, 29.9% and 27.8% for ICI, 7.3% and 20.8% for LENA, and 6.1% and 18.3% for CT. Thirty-two (14%) patients received an allogeneic hematopoietic cell transplant with median OS not reached after a median follow-up of 15.1 months. In conclusion, patients with R/R LBCL who progress within the first 2 months after CAR T-cell therapy have dismal outcomes. Novel targeted agents, such as polatuzumab and BsAbs, can achieve prolonged survival after CAR T-cell therapy failure.

Recent Bendamustine Treatment Before Apheresis Has a Negative Impact on Outcomes in Patients With Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy.

PURPOSE: Approximately 30%-40% of patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) infused with CD19-targeted chimeric antigen receptor (CAR) T cells achieve durable responses. Consensus guidelines suggest avoiding bendamustine before apheresis, but specific data in this setting are lacking. We report distinct outcomes after CAR T-cell therapy according to previous bendamustine exposure. METHODS: The study included CAR T-cell recipients from seven European sites. Safety, efficacy, and CAR T-cell expansion kinetics were analyzed according to preapheresis bendamustine exposure. Additional studies on the impact of the washout period and bendamustine dose were performed. Inverse probability treatment weighting (IPTW) and propensity score matching (PSM) analyses were carried out for all efficacy comparisons between bendamustine-exposed and bendamustine-naïve patients. RESULTS: The study included 439 patients with R/R LBCL infused with CD19-targeted commercial CAR T cells, of whom 80 had received bendamustine before apheresis. Exposed patients had significantly lower CD3+ cells and platelets at apheresis. These patients had a lower overall response rate (ORR, 53% v 72%; P < .01), a shorter progression-free survival (PFS, 3.1 v 6.2 months; P = .04), and overall survival (OS, 10.3 v 23.5 months; P = .01) in comparison with the bendamustine-naïve group. Following adjustment methods for baseline variables, these differences were mitigated. Focusing on the impact of bendamustine washout before apheresis, those with recent (<9 months) exposure (N = 42) displayed a lower ORR (40% v 72%; P < .01), shorter PFS (1.3 v 6.2 months; P < .01), and OS (4.6 v 23.5 months; P < .01) in comparison with bendamustine-naïve patients. These differences remained significant after IPTW and PSM analysis. Conversely, the cumulative dose of bendamustine before apheresis did not affect CAR-T efficacy outcomes. CONCLUSION: Recent bendamustine exposure before apheresis was associated with negative treatment outcomes after CD19-targeted CAR T-cell therapy and should be therefore avoided in CAR T-cell candidates.

Lacunas e propostas de práticas educativas de saúde sexual e reprodutiva para população LGBTQIA+: revisão integrativa / Gap and proposals for educational practices of sexual and reproductive health for the LGBTQIA+ population: an integrative review / Lagunas y propuestas de prácticas educativas de salud sexual y reproductiva para la población LGBTQIA+: una revisión integrativa

Objetivo: analisar as publicações científicas nacionais sobre a atenção à saúde sexual e reprodutiva oferecida para população LGBTQIA+ com relação às principais lacunas e possibilidades das práticas educativas referentes a essa temática no contexto brasileiro. Método: revisão integrativa, em seis etapas, com busca dos estudos realizada em junho de 2022 nas bases de dados LILACS, MEDLINE, SCIELO e Web of Science e SCOPUS. Resultados: foram recuperados 5.643 estudos e selecionados 14 para análise e discussão. Destacaram-se os temas: saúde sexual e reprodutiva com foco na reprodução e nas técnicas reprodutivas, infecções sexualmente transmissíveis e educação em saúde sexual e, por fim, direitos sexuais e reprodutivos. Conclusão: foram evidenciadas as principais lacunas quanto ao tema de saúde sexual e reprodutiva, assim como sugestões para práticas educativas ligadas à temática.

Objective: to analyze national scientific publications on the attention to sexual and reproductive health offered to the LGBTQIA+ population about the main gaps and possibilities of educational practices referring to this topic in the Brazilian context. Method: integrative review in six stages, with two studies, carried out in June 2022 in the LILACS, MEDLINE, SCIELO Web of Science, and SCOPUS databases. Results: 5,643 studies were recovered 14 were selected for analysis and discussion. Highlights the topics: sexual and reproductive health with a focus on reproduction and techniques, sexually transmitted infections, education in sexual health, and finally sexual and reproductive rights. Conclusion: found highlighted the main gaps regarding the topics of sexual and reproductive health, as well as suggestions for educational practices.

Objetivos: analizar las publicaciones científicas nacionales sobre la atención a la salud sexual y reproductiva ofrecida para la población LGBTQIA+ con la relación con las principales lagunas y posibilidades de las prácticas educativas referentes a esa temática en el contexto brasileño. Método: revisión integrativa, en seis etapas, con búsqueda de estudios realizados en junio de 2022 en bases de datos LILACS, MEDLINE, SCIELO y Web of Science y SCOPUS. Resultados: foram recuperados 5.643 estudios y seleccionados 14 para análisis y discusión. Destacaram-se os temas: saúde sexual e reprodutiva com foco na reprodução e nas técnicas reproductivas, infecções sexualmente transmissíveis e educação em saúde sexual e, por fim, direitos sexuais e reprodutivos. Conclusión: foram evidenciadas como principales lagunas en cuanto al tema de salud sexual y reproductiva, así como sugerencias para prácticas educativas ligadas a temáticas.

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study.

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February-June 2020; n = 769 (66%)) and later (July 2020-February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11-0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01-3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22-0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81-1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.

Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) following treatment with tisagenlecleucel.

Chimeric antigen receptor (CAR) T cell-related HLH/MAS is an unusual manifestation of severe cytokine release syndrome (CRS) with poor prognosis and a challenging diagnosis. The establishment of specific diagnosis criteria is essential, and the combination of several techniques for CAR T-cell follow-up, allows a more precise management of this complication.

BCL2 translocation in high grade B cell lymphoma (NOS, DH/TH) is associated with reduced progression free survival.

High Grade B Cell Lymphoma, NOS, and High Grade B Cell Lymphoma with Dual Hit or Triple Hit have been recently recategorized in the 2016 revision of the WHO classification of lymphoid neoplasms. In this study we have characterized the genetic, histopathological, and clinical features of a series of this type of lymphoid neoplasia (17 HGBCL NOS and 53 HGBCL DH/TH).HGBCL NOS showed better response to first line treatment than HGBCL with DH/TH but no significant differences in PFS or OS were found between the two categories. Survival analysis in the whole cohort of cases found that only the presence of BCL2 translocation was significantly associated with PFS. Other clinical features such as IPI, LDH or stage were equivalent in both categories. Furthermore, both high grade and DLBCL morphological patterns showed equivalent PFS and OS in this set of High grade BCL NOS/DH/TH.Key pointsBCL2 translocation in High Grade B Cell Lymphoma NOS and High Grade B Cell Lymphoma with DH/TH is associated with reduced progression free survival.Both high grade and DLBCL morphological patterns showed equivalent outcome regarding PFS and OS in HGBCL.

Allogeneic Stem Cell Transplantation in Mature T Cell and Natural Killer/T Neoplasias: A Registry Study from Spanish GETH/GELTAMO Centers.

Despite advances in understanding the biology of mature T and natural killer (NK)/T cell neoplasia, current therapies, even the most innovative ones, are still far from ensuring its cure. The only treatment to date that has been shown to control aggressive T cell neoplasms in the long term is allogeneic stem cell transplantation (alloSCT). We aim to report the results of alloSCT for advanced mature T and NK/T neoplasias performed in centers from our national GELTAMO/GETH (Grupo Español de Linfoma y Trasplante de Médula Ósea/Grupo Español de Trasplante Hematopoyético y Terapia Celular) over the past 25 years. As a secondary objective, we analyzed the results of alloSCT from haploidentical donors. We performed a retrospective analysis of all patients who received an alloSCT in Spanish centers (n = 201) from September 1995 to August 2018. The 2-year overall survival (OS) and disease-free survival (DFS) were 65.5% and 58.2%, respectively. The univariate for OS and DFS showed statistically different hazard ratios for conditioning intensity, response pre-alloSCT, comorbidity index, donor/receptor cytomegalovirus status and Eastern Cooperative Oncology Group (ECOG) pre-alloSCT, but only a better ECOG pre-alloSCT remained significant in the multivariate analysis. There was an increased incidence of relapse in those patients who did not develop chronic graft-versus-host disease (GVHD) and an increased risk of death in those developing moderate to severe acute GVHD. The 1-year nonrelapse mortality was 21.9% and was mainly due to GVHD (30%) and bacterial infections (17%). When comparing unrelated donors with haploidentical donors, we found similar results in terms of OS and DFS. There was, however, a reduction of acute GVHD in the haploidentical group (P = .04) and trend to a reduction of chronic GVHD. In conclusion, alloSCT is the only curative option for most aggressive T cell neoplasias. Haploidentical donors offer similar results to related donors in terms of survival with a reduction of acute GVHD.

Clinical utility of targeted next-generation sequencing for the diagnosis of myeloid neoplasms with germline predisposition.

Myeloid neoplasms (MN) with germline predisposition (MNGP) are likely to be more common than currently appreciated. Many of the genes involved in MNGP are also recurrently mutated in sporadic MN. Therefore, routine analysis of gene panels by next-generation sequencing provides an effective approach to detect germline variants with clinical significance in patients with hematological malignancies. Gene panel sequencing was performed in 88 consecutive and five nonconsecutive patients with MN diagnosis. Disease-causing germline mutations in CEBPα, ASXL1, TP53, MPL, GATA2, DDX41, and ETV6 genes were identified in nine patients. Six out of the nine patients with germline variants had a strong family history. These patients presented great heterogeneity in the age of diagnosis and phenotypic characteristics. In our study, there were families in which all the affected members presented the same subtype of disease, whereas members of other families presented various disease phenotypes. This intrafamiliar heterogeneity suggests that the acquisition of particular somatic variants may drive the evolution of the disease. This approach enabled high-throughput detection of MNGP in patients with MN diagnosis, which is of great relevance for both the patients themselves and the asymptomatic mutation carriers within the family. It is crucial to make a proper diagnosis of these patients to provide them with the most suitable treatment, follow-up, and genetic counseling.

R-COMP versus R-CHOP as first-line therapy for diffuse large B-cell lymphoma in patients ≥60 years: Results of a randomized phase 2 study from the Spanish GELTAMO group.

The use of non-pegylated liposomal doxorubicin (Myocet® ) in diffuse large B-cell lymphoma (DLBCL) has been investigated in retrospective and single-arm prospective studies. This was a prospective phase 2 trial of DLBCL patients ≥60 years old with left ventricular ejection fraction (LVEF) ≥55% randomized to standard R-CHOP or investigational R-COMP (with Myocet® instead of conventional doxorubicin). The primary end point was to evaluate the differences in subclinical cardiotoxicity, defined as decrease in LVEF to <55% at the end of treatment. Secondary objectives were efficacy, safety, and variations of troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and LVEF along follow-up. Ninety patients were included, 45 in each group. No differences were observed in the percentage of patients with LVEF <55% at end of treatment (11% in R-CHOP arm vs. 7% in R-COMP arm, p = 0.697) or at 4 months (10% vs. 6%, respectively, p = 0.667) and 12 months (8% vs. 7%, respectively, p = 1). However, a higher percentage of R-CHOP compared with R-COMP patients showed increased troponin levels in cycle 6 (100% vs. 63%, p = 0.001) and at 1 month after treatment (88% vs. 56%, respectively, p = 0.015). Cardiovascular adverse events were seen in five R-CHOP patients (nine episodes, four grade ≥3) and in four R-COMP patients (five episodes, all grade 1-2). No significant differences in efficacy were observed. In conclusion, R-COMP is a feasible immunochemotherapy schedule for DLBCL patients ≥60 years, with similar efficacy to R-CHOP. However, the use of non-pegylated doxorubicin instead of conventional doxorubicin was not associated with less early cardiotoxicity, although some reduced cardiac safety signals were observed. Trial registration: ClinicalTrials.gov Identifier: NCT02012088.

Health-related quality of life associated with risk of death in Brazilian dialysis patients: an eight-year cohort.

PURPOSE: Despite the advancements in renal replacement therapy, patients with end-stage renal disease face several limitations, with significant impacts on health-related quality of life (HRQoL) and mortality. This study aims to examine associations between quality of life and risk of death in Brazilian patients who underwent dialysis therapy between 2007 and 2015. METHODS: Observational, prospective, non-concurrent cohort study of patients who underwent dialysis therapy at the Brazilian Public Health System (SUS) and were followed up for 8 years. Semi-structured questionnaires interrogating socioeconomic and demographic characteristics, as well as HRQoL measures (36 Item Short-Form Health Survey, SF-36), were employed. The Cox proportional risk model was used to investigate associations between HRQoL and risk of death. RESULTS: Our sample comprised 1162 patients; of these, 884 were on hemodialysis (HD) and 278 on peritoneal dialysis (PD). Among the HD patients, death was associated with the physical (HR: 0.993; 95% CI: 0.989-0.997) and physical summary component (HR: 0.994; 95% CI: 0.989-0.999) domains of HRQoL. Regarding the PD patients, death was associated with the bodily pain (HR: 0.994; 95% CI: 0.990-0.998), mental health (HR: 0.094; 95% CI: 0.990-0.998), emotional problems (HR: 0.993; 95% CI: 0.987-0.998), social functioning (HR: 1.012; 95% CI: 1.002-1.023), physical problems (HR: 0.992; 95% CI: 0.986-0.998) and mental summary component (HR: 0.989; 95% CI: 0.981-0.997) domains of HRQoL. CONCLUSIONS: Our data suggest that early and timely intervention measures aiming to enhance the HRQoL of dialysis patients are an essential component of professional practice and may contribute to improving the management of factors associated with dialysis patients' mortality.

New prognosis score including absolute lymphocyte/monocyte ratio, red blood cell distribution width and beta-2 microglobulin in patients with diffuse large B-cell lymphoma treated with R-CHOP: Spanish Lymphoma Group Experience (GELTAMO).

The International Prognostic Index (IPI) is the most widely used score for non-Hodgkin lymphoma but lacks the ability to identify a high-risk population in diffuse large B-cell lymphoma (DLBCL). Low absolute lymphocyte count and high monocytes have proved to be unfavourable factors. Red-cell distribution width (RDW) has been associated with inflammation and beta-2 microglobulin (B2M) with tumour load. The retrospective study included 992 patients with DLBCL treated with R-CHOP. In the multivariate analysis, age, Eastern Cooperative Oncology Group performance status (ECOG-PS), stage, bulky mass, B2M, RDW, and lymphocyte/monocyte ratio (LMR) were independently related to progression-free survival (PFS). A new prognosis score was generated with these variables including age categorized into three groups (0, 1, 2 points); ECOG ≥ 3-4 with two; stage III/IV, bulky mass, high B2M, LMR < 2·25 and RDW > 0·96 with one each; for a maximum of 9. This score could improve the discrimination of a very high-risk subgroup with five-year PFS and overall survival (OS) of 19% and 24% versus 45% and 59% of R (revised)-IPI respectively. This score also showed greater predictive ability than IPI. A new score is presented including complete blood cell count variables and B2M, which are readily available in real-life practice without additional tests. Compared to R-IPI, it shows a more precise high-risk assessment and risk discrimination for both PFS and OS.

Vídeo com Pacientes Virtuais na Avaliação do Conhecimento dos Internos de Medicina sobre Cefaleias / Video with Virtual Patients in the Assessment of Medical Interns' Knowledge on Headache

Resumo: Introdução: As Diretrizes Curriculares Nacionais enfatizam que os currículos médicos devem se basear nas necessidades de saúde da população. Por entender que a cefaleia é um problema de saúde pública, ela deve estar entre as competências exigidas para a atuação profissional em nível da atenção primária. Assim, a avaliação do ensino das cefaleias na graduação de Medicina é fundamental. O objetivo do trabalho é apresentar uma metodologia inovadora de avaliação que utiliza vídeo com personagens virtuais para avaliar o conhecimento dos estudantes de Medicina sobre as cefaleias. Método: Trata-se de uma pesquisa exploratória, quantitativa, em que o conhecimento dos internos de Medicina de uma universidade pública federal foi avaliado por meio de casos clínicos com pacientes virtuais. Os dados foram analisados de acordo com as categorias a priori: 1. diagnóstico da cefaleia, 2. tratamento agudo da cefaleia, 3. tratamento profilático da cefaleia e 4. necessidade de exames complementares ou avaliação com especialista. Resultados: Dentre os 155 estudantes matriculados no internato, 31 participaram da pesquisa. A análise mostrou que apenas 16,13% identificaram a enxaqueca crônica, 93,55% reconheceram os sinais de alarme para a cefaleia secundária e 96,77% diagnosticaram a cefaleia tensional. No tratamento da fase aguda da enxaqueca, as classes mais prescritas foram os anti-inflamatórios e analgésicos simples. No caso da cefaleia secundária, de etiologia infecciosa, a maioria (69,56%) prescreveu antibioticoterapia empírica. Com relação à terapia profilática, 87,09% a indicaram na enxaqueca e apenas 29,03%, na cefaleia tensional. Na indicação de exames complementares, 77,42% não a consideraram adequada na enxaqueca, enquanto 77,42% indicaram o estudo do líquido cefalorraquidiano na cefaleia secundária. A maioria dos estudantes solicitou parecer da neurologia para a cefaleia secundária e não o solicitaram na cefaleia tensional. A ferramenta avaliativa foi eficaz na avaliação do conhecimento sobre cefaleia. A utilização de vídeos com pacientes virtuais é uma ferramenta útil na avaliação do conhecimento sobre cefaleias. Conclusões: Os resultados obtidos permitem concluir que existem lacunas no diagnóstico e manejo das cefaleias durante a graduação de Medicina da universidade estudada, e, por isso, é imperativa a definição de uma matriz de competências mínimas para o ensino, no Brasil, da cefaleia na graduação de Medicina.

Abstract: Introduction: The National Curriculum Directive emphasizes that medical curricula should be based on the health needs of the population. Understanding that headache is a public health problem, it must be among the competences required for professional practice at the primary care level. Thus, the assessment of the headache education in undergraduate medical school is fundamental. The aim of this paper is to present an innovative assessment methodology that uses video with virtual characters to assess medical students´ knowledge about headache. Method: This is an exploratory, quantitative research, where the knowledge of the medical interns of a federal public university was evaluated through clinical cases with virtual patients. Data were analyzed according to the a priori categories: 1) headache diagnosis; 2) acute treatment of headache; 3) prophylactic treatment of headache; and 4) need for further exams or expert assessment. Results: Of the 155 students regularly enrolled in the medical Internship, 31 participated in the research. The analysis showed that only 16.13% recognized chronic migraine, 93.55% recognized the warning signs for secondary headache, and 96.77% diagnosed tension headache. In the treatment of acute migraine phase, the most often prescribed drug classes were anti-inflammatory and simple analgesic drugs. In the case of secondary headache of infectious etiology, the majority (69.56%) prescribed empirical antibiotic therapy. Treatment of the acute phase of tension headache was adequately prescribed by 64.51% of the students. Regarding prophylactic therapy, 87.09% indicated it for migraine and only 29.03% for tension headache. As for the indication of complementary exams, 77.42% did not consider it adequate in migraine cases, while 77.42% indicated the study of CSF in secondary headache. Most students requested neurological evaluation for secondary headache and did not request it for tension headache. The assessment tool was effective in assessing headache knowledge. The use of videos with virtual patients is a useful tool in the assessment of headache knowledge. Conclusion: The results allow us to conclude that there are gaps in the diagnosis and management of headache during the undergraduate medical degree of the assessed university, so it is imperative to define a matrix of minimum competences for headache education in undergraduate medical school in Brazil.

Sickle cell retinopathy: What we now understand using optical coherence tomography angiography. A systematic review.

For over four decades, efforts have been underway for the evaluation of sickle cell retinopathy (SCR) in an attempt to identify peripheral high-risk vascular abnormalities based on Goldberg's classification (gold-standard) (1971). The macula is an area in the center of the retina that is responsible for high-resolution central vision and is also affected in SCR. With the development of new technologies for retinal imaging, the macula became a main focus of interest in the study of sickle cell disease (SCD). Optical coherence tomography angiography is a modern non-invasive method that allows qualitative and quantitative analysis of the retinal vascular network in the macular region. We identified 86 studies on SCD and optical coherence tomography angiography. Of those, 12 met the inclusion criteria for this systematic review. The prevalence of sickle cell maculopathy was 45.6% in the SCD population and it increased with age. We present the main vascular findings and discuss visual impairment and pathophysiology, genotypes, and peripheral high-risk vascular abnormalities. The role of the hematologist, general practitioner, and pediatrician in treatment is also reviewed.

Angiopoetin-like 4 in sickle cell retinopathy.

This correspondence provides a comment on the recent review article by Yang et al. [Biosci. Rep. (2018) 38, BSR20180557, https://doi.org/10.1042/BSR20180557].

Differential prognostic impact of GELTAMO-IPI in cell of origin subtypes of Diffuse Large B Cell Lymphoma as defined by the Hans algorithm.

The Grupo Español de Linfomas y Trasplantes de Médula Ósea International Prognostic Index (GELTAMO-IPI) stratifies four risk groups in diffuse large B cell lymphoma (DLBCL) patients treated with immunochaemotherapy: low (LR), low-intermediate (LIR), high-intermediate (HIR), and high (HR). The present study explores the effect of GELTAMO-IPI in the DLBCL subtypes defined by the immunohistochaemistry-based Hans algorithm, Germinal Centre B (GCB) and non-GCB. A multivariate Cox regression model including GELTAMO-IPI risk groups, cell of origin (COO) subtypes and their product was developed to evaluate interaction between the two variables. The COO subtype was available in 839 patients (380 GCB; 459 non-GCB) and both the GELTAMO-IPI and the COO subtype in 780 (353 GCB; 427 non-GCB). There were no differences in 5-year overall survival (OS) between the two subtypes. The Cox model revealed interaction between the GELTAMO-IPI risk groups and the COO subtypes (P = 0·005), indicating that GELTAMO-IPI has a different effect in the two subtypes. Three risk groups were stratified in both COO subtypes: in the GCB subtype, LR, LIR and the combined HIR+HR had 5-year OS of 100%, 75% and 52%, respectively. In the non-GCB subtype, LR, the combined LIR+HIR and HR had a 5-year OS of, 97%, 82% and 35% respectively. GELTAMO-IPI identifies a genuine poor outcome group of patients in the DLBCL non-GCB subtype.

Itinerário terapêutico de pessoas diagnosticadas com câncer: aproximações e distanciamentos da rede de atenção oncológica / Therapeutic itinerary of people with cancer: approximations and distances of the oncologic healthcare system

O objetivo deste estudo é discutir a forma como confi gura-se o Itinerário Terapêutico de pessoas com diagnóstico de câncer, do município da Zona da Mata Mineira. Estudo de natureza qualitativa realizado com 4 pacientes com câncer, diagnosticados entre os anos de 2014 e 2015. Os dados foram coletados por meio de entrevista em janeiro de 2016, e apresentados sob a forma de narrativa. Os preceitos éticos foram respeitados. A análise dos itinerários terapêuticos permitiu perceber que o sistema de saúde apresenta difi culdades relacionadas ao diagnóstico e ações de prevenção e promoção à saúde, ao passo que os tratamentos se apresentaram como efetivos, aproximando-se da rede de cuidados de atenção oncológica ideal. O itinerário terapêutico permite visualizar a trajetória dos pacientes e torna-se uma ferramenta fundamental no estabelecimento de um plano de cuidados mais efi caz pelos profi ssionais de saúde, com destaque para a Enfermagem

This study aims to discuss the way that the Therapeutic Itinerary is built on of cancer patients of the Mata Mineira Zone. A qualitative study carried out with 4 cancer patients which had the diagnoses between 2014 and 2015. Data were collected through interviews on January 2016 and analyzed by the narrative. Ethical precepts have been respected. The analysis of the therapeutic itineraries allowed to perceive that the health system presents diffi culties related to the diagnosis, prevention and promotion of health, considering that the treatments were effective, getting closer to the ideal oncology healthcare system. The therapeutic itinerary allows visualizing the patients' trajectory and becomes a fundamental tool in the establishment of a more effective care plan by health professionals, with emphasis on Nursing care

Topographic and Chemical Analysis of Reciprocating and Rotary Instruments Surface after Continuous Use.

This study aimed at evaluating the changes in surface characteristics and NiTi content of reciprocating and rotary instruments after continuous use. Thirty brand-new instruments were assigned to 3 groups (n=10): PNX1 Group - ProTaper Next system - instrument X1; PNX2 Group - ProTaper Next system - instrument X2 and WO Group - WaveOne system - Primary instrument 25.08. The instruments were used to prepare 60 simulated root canals. Analysis of surface characteristics by scanning electron microscopy (SEM) and chemical analysis of Ni and Ti content by energy-dispersive spectroscopy (EDS) were performed before and after the first and third use of the instruments. Only WO Group had significant increase in the quantity of defects and deformations after the third use (p<0.05). PNX1 Group had significant decrease in Ni content after the third use, in comparison with the unused instruments (p<0.05). PNX1 Group had no decrease in Ti content throughout the time of use (p>0.05), however, in PNX2 Group, there was significant decrease in the different time interval of analysis (p<0.05). Continuous use promoted increase in defects and deformations only for WaveOne instruments. Chemical composition presented significant changes according to the time of instruments use.

Topographic and Chemical Analysis of Reciprocating and Rotary Instruments Surface after Continuous Use

Abstract This study aimed at evaluating the changes in surface characteristics and NiTi content of reciprocating and rotary instruments after continuous use. Thirty brand-new instruments were assigned to 3 groups (n=10): PNX1 Group - ProTaper Next system - instrument X1; PNX2 Group - ProTaper Next system - instrument X2 and WO Group - WaveOne system - Primary instrument 25.08. The instruments were used to prepare 60 simulated root canals. Analysis of surface characteristics by scanning electron microscopy (SEM) and chemical analysis of Ni and Ti content by energy-dispersive spectroscopy (EDS) were performed before and after the first and third use of the instruments. Only WO Group had significant increase in the quantity of defects and deformations after the third use (p<0.05). PNX1 Group had significant decrease in Ni content after the third use, in comparison with the unused instruments (p<0.05). PNX1 Group had no decrease in Ti content throughout the time of use (p>0.05), however, in PNX2 Group, there was significant decrease in the different time interval of analysis (p<0.05). Continuous use promoted increase in defects and deformations only for WaveOne instruments. Chemical composition presented significant changes according to the time of instruments use.

Resumo Este estudo teve como objetivo avaliar as alterações nas características de superfície e teor de NiTi de instrumentos reciprocantes e rotatórios após uso contínuo. Trinta instrumentos novos foram separados em três grupos (n=10): Grupo PNX1 - ProTaper Next system - instrumento X1; Grupo PNX2 - ProTaper Next system - instrumento X2 e Grupo WO - WaveOne system - instrumento Primary 25.08. Os instrumentos foram utilizados para o preparo de 60 canais radiculares simulados. Análise por microscopia eletronica de varredura (MEV), a análise química do conteúdo de Ni e Ti por espectroscopia de energia dispersiva (EED) foram realizadas antes e após o primeiro e terceiro uso dos instrumentos. Apenas o Grupo WO apresentou aumento significativo na quantidade de defeitos e deformações após o terceiro uso (p<0,05). O grupo PNX1 teve diminuição significativa no teor de Ni após o terceiro uso, em comparação aos instrumentos não utilizados (p<0,05). O grupo PNX1 não apresentou diminuição do teor de Ti ao longo do tempo de uso (p>0,05), no entanto, no Grupo PNX2, houve diminuição significativa nos diferentes intervalos de tempo de análise (p<0,05). O uso contínuo promoveu aumento nos defeitos e deformações somente para os instrumentos WaveOne. A composição química apresentou alterações significativas de acordo com o tempo de uso dos instrumentos.