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Objective:\ud \ud To summarize the latest evidence on head and neck cancer epidemiology from the International Head and Neck Cancer Epidemiology (INHANCE) consortium.\ud \ud Subjects and Methods:\ud \ud INHANCE was established in 2004 to elucidate the etiology of head and neck cancer through pooled analyses of individual‐level data on a large scale. We summarize results from recent INHANCE‐based publications updating our 2015 overview.\ud \ud Results:\ud \ud Seventeen papers were published between 2015 and May 2020. These studies further define the nature of risks associated with tobacco and alcohol, and occupational exposures on head and neck cancer. The beneficial effects on incidence of head and neck cancer were identified for good oral health, endogenous and exogenous hormonal factors, and selected aspects of diet related to fruit and vegetables. INHANCE has begun to develop risk prediction models and to pool follow‐up data on their studies, finding that ~30% of cases had cancer recurrence and 9% second primary cancers, with overall‐ and disease‐specific 5‐year‐survival of 51% and 57%, respectively.\ud \ud Conclusions:\ud \ud The number and importance of INHANCE scientific findings provides further evidence of the advantages of large‐scale internationally collaborative projects and will support the development of prevention strategies.

Haploidentical hematopoietic-cell transplantation using post-transplant cyclophosphamide(Haplo-PTCy) is a feasible procedure in children with haematologic malignancies. However, data of a large series of children with acute leukaemia(AL) in this setting is missing. We analysed 144 AL Haplo-PTCy paediatric recipients; median age was 10 years. Patients had acute lymphoblastic(ALL; n = 86) or myeloblastic leukaemia(AML; n = 58) and were transplanted in remission(CR1: n = 40; CR2: n = 57; CR3+: n = 27) or relapse (n = 20). Bone marrow was the graft source in 57%; donors were father (54%), mother (35%), or sibling (11%). Myeloablative conditioning was used in 87%. Median follow-up was 31 months. At day +100, cumulative incidence (CI) of neutrophil recovery and acute GVHD (II-IV) were 94% and 40%, respectively. At 2-years, CI of chronic GVHD and relapse, were 31%, 40%, and estimated 2-year overall survival (OS), leukaemia-free survival (LFS) and graft-versus-host-relapse-free survival (GRFS) were 52%, 44% and 34% respectively. For patients transplanted in remission, positive measurable residual disease (MRD) prior to transplant was associated with decreased LFS (p = 0.05) and GRFS (p = 0.003) and increased risk of relapse (p = 0.02). Mother donor was associated with increased risk of chronic GVHD (p = 0.001), decreased OS (p = 0.03) and GRFS (p = 0.004). Use of PBSC was associated with increased risk of chronic GVHD (p = 0.04). In conclusion, achieving MRD negativity pre-transplant, avoiding use of mother donors and PBSC as graft source may improve outcomes of Haplo-PTCy in children with AL.

Objective: The objective of this study was to estimate treatment costs of Hematopoietic stem cell transplantation (HSCT) at a reference center in Brazil. Methods: The study population consisted of patients from the Unified Health System HSCT who underwent HSCT in southern Brazil between 2016 and 2019. Costs were measured using a micro-costing approach, based on Time-Driven Activity-based Costing (TDABC) adapted for economic studies in health and included the following steps: definition of the research question, structured data collection, and statistical analysis of results. Results: The total cost of HSCT was $155,110 ($92,794 – $249,146 USD). Matched unrelated donor HSCT was more expensive than matched related donor HSCT. The major cost factors involve post-ransplant complications, mainly the occurrence of infections. Concerning cost composition, exams and procedures represent the largest expense in HSCT (45%). Conclusion: These estimates could be applicable to further evaluations for HSCT cost-effectiveness and help healthcare decision-makers in middle-income countries

Objective This study aims to describe the epidemiological characteristics and survival rates of children with acute myeloid leukemia treated in hospitals in southern Brazil and compare them with international data. Methods A multicenter cohort study was conducted with retrospective data collection of all new patients with acute myeloid leukemia under 18 treated at five referral centers in pediatric hematology-oncology in southern Brazil between January 2005 and December 2015. Results Of the 149 patients with acute myeloid leukemia, 63.0% (n = 94) were male. The median age at diagnosis was 10.5 years (range 0–18 years) and 40.3% (n = 60) had a white blood cell count below 50,000/mm2. The most common Franco-American-British (FAB) subtype was M3 (n = 43, 28.9%). Nine (6.0%) patients had central nervous system disease. In M3 patients, overall survival (OS) was 69.2% and 3-year event-free survival was 67.7%; in non-M3 patients, these rates were 45.3% and 36.7%, respectively. In non-M3 patients, OS was significantly different between transplanted (61.8%) and non-transplanted (38.2%) patients (p = 0.031). Conclusions These results show a higher prevalence of the Franco-American-British M3 subtype than that reported in the international literature, as well as a decreased OS compared with that of developed countries. Further multicenter Brazilian studies with a larger sample size are encouraged to better understand the characteristics of acute myeloid leukemia, and to improve the treatment and prognosis in this population.

Peri-intraventricular hemorrhage is one of the main causes of neurological impairment in premature newborns. To control their risk factors is necessary in view of the increasing survival of extreme preterm infants. Objective: To evaluate the prevalence of peri-intraventricular hemorrhage in premature newborns, identify the risk factors and observe the frequencies of intra-hospital outcomes of interests. Methods: This study was done in Brazil. This was an observational, analytical longitudinal and prospective study. The subjects included were newborns of gestational age less than 34 weeks who were admitted to two public hospitals between May and November 2015. To assess possible associated factors, obstetric, perinatal and neonatal data were analyzed (chorioamnionitis, antenatal corticosteroids, gestational age, newborn weight, Apgar score at 1 and 5 minutes, resuscitation in the delivery room, surfactant in the delivery room, newborn transferred from another hospital, respiratory distress syndrome: RDS, sepsis, umbilical vein catheterization, assisted ventilation, exogenous surfactant in the Neonatal ICU, use of sodium bicarbonate, inotropic agents, adrenaline, volume expanders and blood products). The hospital outcomes studied were assisted ventilation time, hospital stay and death. The data analysis was performed by chi-square test or Fisher’s test, with a significance level of 5%. Results: Out of 156 newborns, 46 (29.9%) presented peri-intraventricular hemorrhage and 28.2% of these had a severe form of the disease. There were significant associations (p 0.05) with the following risk factors: gestational age, birth weight, low Apgar score, delivery room resuscitation, RDS, surfactant use, sepsis, packed red blood cell transfusion, mechanical ventilation and umbilical vein catheterization. The newborns with peri-intraventricular hemorrhage presented longer times on assisted ventilation, longer hospital stays and higher risk of death. Conclusion: The prevalence of peri-intraventricular hemorrhage was high in the population studied, especially the severe form. Perinatal and neonatal risk factors were associated with a higher risk of developing the disease and the outcomes studied were more evident in these newborns.

Severe aplastic anemia (SAA) is a life-threatening disease that can be cured with allogeneic cell transplantation (HCT). Haploidentical donor transplantation with post-transplantation cyclophosphamide (haplo-PTCy) is an option for patients lacking an HLA-matched donor. We analyzed 87 patients who underwent haplo-PTCy between 2010 and 2019. The median patient age was 14 years (range, 1 to 69 years), most were heavily transfused, and all received previous immunosuppression (25% without antithymocyte globulin). Almost two-thirds (63%) received standard fludarabine (Flu)/cyclophosphamide (Cy) 29/total body irradiation (TBI) 200 cGy conditioning, and the remaining patients received an augmented conditioning: Flu/Cy29/TBI 300-400 (16%), Flu/Cy50/TBI 200 (10%), or Flu/Cy50/TBI 400 (10%). All patients received PTCy-based graft-versus-host disease (GVHD) prophylaxis. Most grafts (93%) were bone marrow (BM). The median duration of follow-up was 2 years and 2 months. The median time to neutrophil recovery was 17 days. Primary graft failure occurred in 15% of the patients, and secondary or poor graft function occurred in 5%. The incidences of grade II-IV acute GVHD was 14%, and that of chronic GVHD was 9%. Two-year overall survival and event-free survival (EFS) were 79% and 70%, respectively. EFS was higher for patients who received augmented Flu/Cy/TBI (hazard ratio [HR], .28; P = .02), and those who received higher BM CD34 cell doses (3.2 × 10E6/kg) (HR, .29; P = .004). The presence of donor-specific antibodies before HSCT was associated with lower EFS (HR, 3.92; P = .01). Graft failure (HR, 7.20; P.0001) was associated with an elevated risk of death. Cytomegalovirus reactivation was frequent (62%). Haploidentical HCT for SAA is a feasible procedure; outcomes are improved with augmented conditioning regimens and BM grafts with higher CD34 cell doses.

Acute lymphoid leukemia is a childhood cancer that in high-income countries has event-free survival rates of 80% and global survival rates of 90%. In Brazil these rates are under 70%. This difference may be due to the implementation of supportive care, including the assessment of asparaginase (ASNase) activity. ASNase may cause hypersensitivity reactions and silent drug inactivation. For this reason, ASNase activity monitoring is an essential tool to ensure an effective treatment. Our aim was to implement an ASNase activity measurement technique at a hospital setting. samples from children who were given Escherichia coli-derived ASNase were collected. The results of the analyses conducted in our laboratory Hospital de Clínicas de Porto Alegre were compared to those of two institutions: Centro Infantil Boldrini and University of Munster. 262 samples were assessed. The results of the first analyses were compared with those obtained at Centro Infantil Boldrini and showed an ICC of 0.954. Thirty samples were sent to the University of Munster and presented an ICC was 0.960. Our results, when compared to those of national and international centers, showed an excellent agreement. The study was able to implement an ASNase activity test to monitor the treatment.

This is an observational and cross-sectional study, carried out in May 2020, targeting adult individuals of both sexes who are members of multiprofessional teams working in Brazilian HSCT units in the current period of the pandemic by completing and analyzing a questionnaire. pre-formulated. HSCT units that cannot access the questionnaire were excluded from the study. The analysis of the operation profile of HSCT units in Brazil, through the application of a pre-structured questionnaire, is not an accurate tool, since it assumes some premises that may prove to be wrong, especially in this current scenario in Brazil. However, the data reveal the vulnerability of patients with onco-hematological diseases to infection by COVID-19, especially during HSCT procedures, in relation to the general population. Despite its limitations, it can be valuable to plan policies.

Allogeneic hematopoietic stem cell transplantation (HCT) can cure primary immunodeficiency diseases (PID). When a HLA-matched donor is not available, a haploidentical family donor may be considered. The use of T cell-replete haploidentical HCT with post-transplantation cyclophosphamide (haplo-PTCy) in children with PID has been reported in few case series. A donor is usually readily available, and haplo-PTCy can be used in urgent cases. We studied the outcomes of 73 patients with PID who underwent haplo-PTCy, including 55 patients who did so as a first transplantation and 18 who did so as a salvage transplantation after graft failure of previous HCT. The median patient age was 1.6 years. Most of the children were male (n = 54) and had active infection at the time of transplantation (n = 50); 10 children had severe organ damage. The diagnosis was severe combined immunodeficiency (SCID) in 34 patients and non-SCID in 39 (Wiskott-Aldrich syndrome; n = 14; chronic granulomatous disease, n = 10; other PID, n = 15). The median duration of follow-up of survivors was 2 years. The cumulative incidence of neutrophil recovery was 88% in the SCID group and 84% in non-SCID group and was 81% for first transplantations and 83% after a salvage graft. At 100 days, the cumulative incidence of acute GVHD grade II-IV and III-IV was 33% and 14%, respectively. The majority of patients reached 200/μL CD4+ and 1000/μL CD3+ cell counts between 3 and 6 months. The estimated 2-year overall survival was 66%; it was 64% for SCID patients and 65% for non-SCID patients and 63% for first HCT and 77% for salvage transplantations. Twenty-five patients died, most of them due to infection early after transplantation (before 100 days). In conclusion, haplo-PTCy is a feasible procedure, can cure two-thirds of children with PID, and can be used as rescue treatment for previous graft failure. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Agentes químicos com capacidade de ação no biofilme dental e com propriedades anti-inflamatórias têm sido amplamente inseridos em produtos para uso caseiro na Odontologia. Esses podem representar um recurso adjuvante no tratamento da gengivite, de maneira a otimizar resultados clínicos de pacientes em tratamento. Diante da diversidade dos produtos disponíveis no mercado, faz-se necessário que o cirurgião-dentista conheça o desempenho clínico desses agentes a fim de prescrever, com propriedade, os mais adequados para cada paciente. O objetivo deste trabalho foi abordar o uso de dentifrícios contendo fluoreto estanhoso como alternativa terapêutica no tratamento da gengivite através de uma revisão de literatura. Para esse fim, foi realizada pesquisa nas bases de dados PubMed, Scielo e Google Acadêmico em busca de artigos que utilizaram os seguintes descritores: "stannous fluoride", "gingivitis control" e “antimicrobial dentifrices”, sem filtros para restringir período de tempo. De acordo com os artigos incluídos nesta revisão, pode-se afirmar que o uso de dentifrícios com fluoreto estanhoso possibilita uma redução significativa tanto nos índices de placa visível, quanto nos índices de sangramento gengival. Através da revisão de literatura realizada, pode-se afirmar que a indicação de dentifrícios contendo fluoreto estanhoso é segura e representa um bom recurso como controle coadjuvante do biofilme supragengival e no tratamento da gengivite.

Large scale datasets created from crowdsourced labels or openly available data have become crucial to provide training data for large scale learning algorithms. While these datasets are easier to acquire, the data are frequently noisy and unreliable, which is motivating research on weakly supervised learning techniques. In this paper we propose original ideas that help us to leverage such datasets in the context of change detection. First, we propose the guided anisotropic diffusion (GAD) algorithm, which improves semantic segmentation results using the input images as guides to perform edge preserving filtering. We then show its potential in two weakly-supervised learning strategies tailored for change detection. The first strategy is an iterative learning method that combines model optimisation and data cleansing using GAD to extract the useful information from a large scale change detection dataset generated from open vector data. The second one incorporates GAD within a novel spatial attention layer that increases the accuracy of weakly supervised networks trained to perform pixel-level predictions from image-level labels. Improvements with respect to state-of-the-art are demonstrated on 4 different public datasets., Machine Learning Journal 2021. arXiv admin note: substantial text overlap with arXiv:1904.08208

Background Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. Methods Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. Results For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). Conclusions Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

Objectives: \ud This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures.\ud \ud Materials and Methods: \ud We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework.\ud \ud Results: \ud For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30 years. In former smokers who quit ≥10 years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers.\ud \ud Conclusion: \ud Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.

BackgroundThe association between socioeconomic disadvantage (low education and/or income) and head and neck cancer is well established, with smoking and alcohol consumption explaining up to three-quarters of the risk. We aimed to investigate the nature of and explanations for head and neck cancer risk associated with occupational socioeconomic prestige (a perceptual measure of psychosocial status), occupational socioeconomic position and manual-work experience, and to assess the potential explanatory role of occupational exposures.MethodsPooled analysis included 5818 patients with head and neck cancer (and 7326 control participants) from five studies in Europe and South America. Lifetime job histories were coded to: (1) occupational social prestige—Treiman’s Standard International Occupational Prestige Scale (SIOPS); (2) occupational socioeconomic position—International Socio-Economic Index (ISEI); and (3) manual/non-manual jobs.ResultsFor the longest held job, adjusting for smoking, alcohol and nature of occupation, increased head and neck cancer risk estimates were observed for low SIOPS OR=1.88 (95% CI: 1.64 to 2.17), low ISEI OR=1.74 (95% CI: 1.51 to 1.99) and manual occupations OR=1.49 (95% CI: 1.35 to 1.64). Following mutual adjustment by socioeconomic exposures, risk associated with low SIOPS remained OR=1.59 (95% CI: 1.30 to 1.94).ConclusionsThese findings indicate that low occupational socioeconomic prestige, position and manual work are associated with head and neck cancer, and such risks are only partly explained by smoking, alcohol and occupational exposures. Perceptual occupational psychosocial status (SIOPS) appears to be the strongest socioeconomic factor, relative to socioeconomic position and manual/non-manual work.

Introduction: Treatment of childhood acute lymphoblastic leukemia (ALL) is based on risk stratification. This study aimed to assess the agreement between risk group classifications in the different childhood ALL treatment protocols used in a referral hospital in southern Brazil. Methods: We retrospectively reviewed the medical records of patients aged 1 to 18 years with B-cell ALL treated at a hospital from January 2013 to April 2017. Agreement between risk classifications was assessed by the kappa coefficient. Results: Seventy-five patients were analyzed. There was poor agreement between risk stratification by GBTLI 2009 and BFM 95 protocols (kappa=0.22; p = 0.003) and by GBTLI 2009 and IC-BFM 2002 protocols (kappa=0.24; p = 0.002). Risk group distribution was 13.3% for low risk, 32.0% for intermediate risk, and 54.7% for high risk based on stratification by the GBTLI 2009 protocol, and 28.0% for low risk, 42.7% for intermediate risk, and 29.3% for high risk based on stratification by the IC-BFM 2002 protocol. Overall survival was 68.6%. Conclusion: This study provides numerous points to ponder about the treatment of leukemia in Brazil. The percentage of patients classified as high risk in our sample was higher than that reported in the international literature. This difference, however, had no impact on overall survival, which was shorter than that reported in the international literature.

HSCT is performed in Brazil since the 70’s, most of them in public centers. Transplant numbers are regularly reported by most centers to the Brazilian Transplant Registry/ Brazilian Solid Organ Association (ABTO/RBT), Latin American Bone Marrow Transplant Group/ Worldwide Network for Blood and Marrow Transplantation (LABMT/WBMT), but transplant outcomes are not available in our country. The objective of this work is to understand HSCT activity and outcomes of Brazilian children. Methods The Brazilian Society of Bone Marrow Transplant and Cellular Therapy (SBTMO) has developed the initiative to collaborate with the Center for International Blood and Marrow Transplant Research (CIBMTR) to receive back deidentified aggregate nationwide data reported by Brazilian transplant centers. This was approved by the national central IRB in 2019 (Conep CAAE: 65575317.5.1001.0071, principal investigator Dr. Nelson Hamerschlak) as a research project, including data from 2008 through 2027. This is the first report of the Brazilian Pediatric Hematopoietic Stem Cell Transplant activity prepared by the SBTMO Data Managers Working Group with the data reported to the CIBMTR and returned to the country as an enhanced Data Back to Center file. Results Between 2008 and 2019, 16 of the 19 institutions reporting to the CIBMTR also reported pediatric transplants. A total of 1,929 transplants were reported in children younger than 18 years of age and, different from the adult experience, most of them are allogeneic transplants. Within the past three years, the number of allogeneic transplants from unrelated and mismatched donors have increased and are now performed more often than transplants from matched sibling donors. Unrelated cord blood grafts were rarely used. Marrow was the preferred graft source for all allogeneic transplants. Acute leukemias and severe aplastic anemia were the most common indications for HSCT. Infections were the first cause of death within 100 days post HSCT. The 2-year overall survival after HSCT with HLA-identical sibling, unrelated donors and mismatched related donors for acute lymphoblastic leukemia was 56%, 60% and 37% (p = 0.2) and for acute myelogenous leukemia, 57%, 55% and 62% (p = 0.8), respectively. Pediatric myelodysplastic syndrome and chronic myelogenous leukemia had overall survival over 80%. Severe aplastic anemia was the most common non-malignant HSCT indication and the results with matched related and unrelated transplants are excellent, > 85% survival. In conclusion, this is the first report on transplant outcomes in Brazilian children. The collaboration with the CIBMTR may be a feasible way for Latin American countries to know their transplant outcomes using a mature registry structure with several tools already in place to enhance the collaboration. We would like to acknowledge Dr Nelson Hamerschlak, principal investigator of the National protocol, Dr. Marcelo Pasquini, for his help with the collaboration between CIBMTR and SBTMO, the Brazilian institutions reporting their data, the Data Manager Working Group and the Pediatric Working Group of the SBTMO and SOBOPE.

Study objectives : This paper aimed to analyze the factors that affect international operations for e-commerce to Argentina, Chile and Colombia, in the case of Brazilian footwear industry. This study also sought to identify the main barriers to the internationalization and level of control required by Brazilian footwear firms into South American markets. Method/approach: It was conducted a qualitative research with a data collection composed by in-depth interviews with three experts in e-commerce and executives from three Brazilian footwear firms. These firms produce their own branded shoes by e-commerce operations in Brazil and are current exporters to Argentina, Chile and Colombia. Originality/Relevance: Despite of the significant growth of e-commerce in the recent years in South America, there is still a lack of research related to the topic with a specific focus for this region. Main results: The findings suggest that the similar logistics and telecommunication infrastructure, the related services, the electronic payment options and the South American consumer propensity regarding to Brazil shoes are external factors with influence on international operations by e-commerce. However, the discrepancies regarding local legislation are the main barriers for the internationalization of Brazilian footwear e-commerce. Theoretical contributions: Firms from emerging markets tend to internationalize e-commerce operations through low risk strategies, focusing only on marketing and sales activities. Managerial contributions: The need for a high level of control on the commercial activities and the brand management abroad are internal factors that can affect costs and pace of Brazilian footwear e-commerce internationalization.

Background: Evidence shows the benefits of having a family physician (FP) at the heart of a care team that delivers palliative and end-of-life care (PEoLC). However, FPs have limitations on their ability to provide PEoLC. Objectives: We conducted a quality improvement study to (1) explore the barriers FPs encounter in providing PEoLC in our metropolitan context and (2) identify potential strategies to overcome these challenges. Methods: We interviewed a cohort of FPs from 10 different clinical practices within a metropolitan area (British Columbia [BC], Canada); this cohort is not regularly engaged with our Specialist Palliative Care Team. Verbatim transcripts were examined using inductive thematic analysis. Results: All FPs identified home visits as a critical aspect of being able to provide PEoLC. Despite this consensus, work-life balance, time, and compensation are major barriers to providing home visits and PEoLC. Local healthcare system awareness (available resources, why and how to access them) was identified as a barrier that can potentially be addressed through education sessions. Although 5 out of 10 FPs had not had formal palliative care education or training, clinical education was not considered a barrier to provide PEoLC. Conclusion: Providing FPs with tools and resources through education, including why and how to access them, and adjusting the BC compensation model to address home visit's travel time and time modifiers may better support FPs to provide PEoLC.

Background Strategies to mitigate the impact of COVID‐19 in special populations are complex and challenging. Few studies have addressed the impact of COVID‐19 on pediatric patients with cancer in low‐ and middle‐income countries. Methods Multicenter observational cohort study with prospective records and retrospective analyses starting in April 2020 in 21 pediatric oncology centers distributed throughout Brazil. Participants: Patients under 18 years of age who are infected by the SARS‐CoV‐2 virus (confirmed diagnosis through reverse transcriptase‐polymerase chain reaction [RT‐PCR]) while under treatment at pediatric oncology centers. The variables of interest included clinical symptoms, diagnostic and therapeutic measures. The repercussions of SARS‐CoV‐2 infection on cancer treatment and general prognosis were monitored. Results One hundred seventy‐nine patients were included (median age 6 [4–13] years, 58% male). Of these, 55.9% had acute leukemia and 34.1% had solid tumors. The presence of SARS‐CoV‐2 was diagnosed by RT‐PCR. Various laboratory markers were analyzed, but showed no correlation with outcome. Children with low or high BMI for age had lower overall survival (71.4% and 82.6%, respectively) than those with age‐appropriate BMI (92.7%) (p = .007). The severity of presentation at diagnosis was significantly associated with outcome (p

Artificial intelligence (AI) has become part of our daily lives and is commonly used in a wide range of industries. However, most of users have little visibility and knowledge about how AI systems reach a particular decision and their outcomes in the various fields where AI and machine learning are being applied. Many of the algorithms' results cannot be understood and explained in terms of how and why a specific decision was taken. With the advance of artificial intelligence researches, several techniques and approaches have emerged over the last few years, but only a few studies have been produced with regards to the end-user perspective and comprehension of the algorithms outcomes. This paper aims to evaluate the comprehensibility of the explanations from the perspective of the different types of users, aiming to generate confidence and understanding of the results produced by the AI.

Introduction: Peritoneal dialysis (PD) has been considered a safe option of therapy in end-stage renal disease patients with urgent need of dialysis. Recently, it was proposed that Urgent-Start-PD (US-PD) be defined when PD starts within 72 hours after catheter placement and “early start” PD (ES-PD) when PD starts between 3 and 14 days after. We aimed to compare demographic and clinical characteristics between patients in US-PD and ES-PD as well as 30-day complications, 6-month hospitalization, and dropout rate. Methods: Adult patients starting PD within 14 days after catheter insertion (October/2016 - February/2019) were included and divided into US-PD group and ES-PD group based on the their PD initiation time. Clinical and demographic data, fill volume for the first PD session, 30-day complications, 6-month hospitalization, and dropout rate were assessed. Results: In our study, 72 patients were analyzed (US-PD=40, ES-PD=32) with mean age of 53.2±15.2 years old. No differences between US-PD and ES-PD regarding demographic characteristics, 30-day complications, 6-month hospitalization, and dropout events were found. The most frequent short-term complication in patients who started PD urgently was leakage. The most common cause of dropout was transfer to HD. Conclusion: Fifty five percent of our sample started PD less than 72 hours after catheter insertion. The lack of difference in the measured outcomes compared to patients that had therapy initiated after this period encourages the use of urgent PD when needed. RESUMO Introdução: A diálise peritoneal (DP) tem sido considerada uma opção segura de terapia em pacientes com doença renal terminal com necessidade urgente de diálise. Recentemente, foi proposto que a DP de início urgente (US-PD) fosse definida quando a DP iniciar dentro de 72 horas após o implante do cateter, e a DP de "início precoce" (ES-PD) quando a DP iniciar entre 3 e 14 dias após o procedimento. Nosso objetivo foi comparar características demográficas e clínicas entre pacientes em US-PD e ES-PD, bem como complicações em 30 dias, internação por 6 meses e taxa de saída do tratamento. Métodos: Pacientes adultos iniciando DP em até 14 dias após a inserção do cateter (outubro/2016 - fevereiro/2019) foram incluídos e divididos no grupo US-PD ou ES-PD com base no tempo de início da DP. Dados clínicos e demográficos, volume de preenchimento na primeira sessão de DP, complicações em 30 dias, hospitalização por 6 meses e taxa de saída foram avaliados. Resultados: Em nosso estudo, 72 pacientes foram analisados (US-PD = 40, ES-PD = 32) com média de idade de 53,2 ± 15,2 anos. Não foram encontradas diferenças entre US-PD e ES-PD em relação às características demográficas, complicações em 30 dias, hospitalização por 6 meses e saída do tratamento. A complicação de curto prazo mais frequente nos pacientes que iniciaram a DP com urgência foi o extravasamento de líquido peritoneal. A causa mais comum de saída foi a transferência para HD. Conclusão: Mais da metade da nossa amostra iniciou a DP menos de 72 horas após a inserção do cateter. A falta de diferença nos desfechos mensurados em comparação com os pacientes que iniciaram o tratamento após esse período incentiva o uso de US-PD quando necessário.

Background: The minimal residual disease (MRD) is the most important prognostic factor for acute lymphoblastic leukemia (ALL) in children. This study aimed to investigate the influence of detecting the MRD by the multiparametric flow cytometry (MFC) at day 15 (D15) of the induction on the analysis of the risk group classifications of the different childhood ALL treatment protocols used in a referral hospital in southern Brazil. Method: We retrospectively reviewed the medical records of patients with B-cell ALL, aged 1 to 18 years, treated at a hospital from January 2013 to April 2017. Main results: Seventy-five patients were analyzed. Regarding the MRD by the MFC at D15, the analyses showed statistical significance when the MRD was grouped into three categories, < 0.1%, 0.1–10%, and > 10%, with the following distribution: 30.7%, 52.0%, and 17.3%, respectively. There was a significant association between D15 MRD-MFC < 0.1% and the likelihood of dying or relapsing and between D15 MRD-MFC > 10% and the likelihood of dying or relapsing. The cumulative hazard ratio for the relapse of patients with D15 MRD-MFC < 0.1%, 0.1–10%, and > 10% was 19.2%, 59.8%, and 80.1%, respectively. Conclusion: Our analysis suggests D15 MRD-MFC < 0.1% as a cut-off point for patients with more favorable outcomes and that the MRD at D15 in risk classifications is particularly useful for the stratification of patients with a more favorable prognosis.

The present study aims to present a view on Stela do Patrocinio's oeuvre Reino dos bichos e dos animais e o meu nome [Kingdom of beasts and animals is my name] (DO PATROCINIO, 2001), a work that was poetically produced orally by Stela do Patrocinio and transcribed by Viviane Mose. In our research, we consider that there is a living poetic voice in poems, and our first interest was to discuss how it moves from orality to the writing form. For this purpose, we analyzed Stela do Patrocinio's poetics from two approaches. On the one hand, our interest was centered on the way in which how the question of authorship is refracted, when transposing poetics to written poetry. On the other hand, we turn to the reader's relationship with this poetic voice, understanding the two in their bodily dimensions, taking in account their places in space. For that, we used the theoretical propositions mainly by Foucault (2002, 2009), Gumbrecht (2010) and Zumthor (2014). Amid the debate, the poetic voice is evident in the verses, since, when making a critical reading of these, it is also necessary that they be vocalized. Finally, through the theoretical and critical path, we believe that, transposed to writing, the poetic voice of Stela do Patrocinio (2001) continues to pulse in the reader, in a dynamic where the tension changes, but the production of presence remains.

In digital culture, we recognize new delivery options for media (audio, films, games, texts) – not only a new storage paradigm, but a transition to interactivity with proliferating screens of all sizes. These networks of transmission and circulation (including but not limited to UseNet or BitTorrent, iTunes or Tidal, Napster or Pandora, YouTube or Vimeo, SnapChat or Vine, Hulu or Netflix, Aereo or FilmOn, Steam or GOG.com, Twitch or TikTok, to name but a few) challenge some fundamental precepts of the media industries, and produce new configurations of information and entertainment. Even a casual survey of digital distribution reveals that online content delivery means different things for audiovisual content in a variety of formats, and the consequences need to be discussed from the perspective of consumers, distributors, and creators. What we still call newspapers, television programs, books, films, music albums, games, etc. became increasingly available not only on physical data carriers but as streaming or downloadable data. This shift is not only overriding physical media (what used to come on paper/tape/floppy/cartridge/vinyl/CD/DVD/BluRay, etc.), it means we need to reformulate certain questions that used to be medium-specific: what will happen to retro-gaming? What are the rights of used-book owners? Digital distribution has multiple consequences for just what exactly becomes available how and to whom.

Brazil is the largest country in South America with continental dimensions and significant regional differences. Recently, the country has faced a great challenge in establishing adequate strategies to mitigate the strong impact caused by the arrival of COVID-19 in the national territory. Since the first case diagnosed on February 26th, 2020, we have gone through a 18 week period that resulted in 58.300 deaths and more than 1.370.000 confirmed cases¹. Despite having a public and universal health system, most pediatric oncology centers are located in more urbanized regions, such as state capitals or economic centers. Few reports describe the impact of SARS-CoV-2 on the population of pediatric patients accompanied by cancer or undergoing hematopoietic stem cell transplantation (HSCT)2,3,4. Less frequent still are the descriptions of the situation of these children in low or middle income countries⁵. Faced with this new and unknown scenario, the present study aims to describe the clinical presentation and the evolution of children affected by COVID-19 undergoing treatment in units of oncology, hematology or HSCT. We are analyzing the interregional differences in the presentation, management and prognosis of these children, while drawing a national panorama that can be compared with other countries through a national and multicenter registry of children evaluated for SARS-CoV-2.Through dissemination by the Brazilian Society of Pediatric Oncology (SOBOPE), Brazilian Association of Hematology and Hemotherapy (ABHH) and Brazilian Society of Bone Marrow Transplantation (SBTMO). 36 centers across the country agreed to participate in this project (Figure 1). All regions of the country are included. The variables evaluated are clinical symptoms, diagnostic method, therapeutic measures and treatment location. In addition, the repercussions of infection on baseline treatment and overall prognosis are being assessed. Despite being in an initial phase, the database already counts with 64 registered cases.This joint work of the centers for pediatric oncology and bone marrow transplantation in our country is an advance that is allowing the development of one of the largest databases on the influence of COVID19 in the treatment of children in developing countries. Considering the small number of current literature on this subject, the heterogeneity of our population and regional differences, centralization of records is essential to better understand the extent and impact of this epidemic in our country, in addition to comparing the effect of local health strategies. It is important to highlight that the Sistema Unico de Saude (SUS), one of the largest and most complex public health systems in the world, guarantees universal health care and presents itself as a significant differential in combating the pandemic in Brazil through primary care, as well as medium and high complexity assistance.The development of this study will contribute to a better understanding of the clinical presentation, evolution and impact of that of COVID-19 in pediatric cancer patients or those undergoing HSCT in middle-income countries.

Objetivo: Descrever um caso de um paciente pediátrico que apresentou linfo-histiocitose hemofagocítica (LHH) associada à leucemia monocítica aguda pós-quimioterapia, com hemofagocitose causada pelas próprias células leucêmicas. Descrição do caso: Em um hospital universitário do Sul do Brasil, uma menina de três anos foi diagnosticada com leucemia monocítica aguda com cariótipo normal. Após receber protocolo quimioterápico, atingiu remissão seis meses depois do início do tratamento, recaíndo quatro meses após com um cariótipo complexo envolvendo ambos os cromossomos, 8p e 16q. A medula óssea mostrava-se infiltrada por células blásticas vacuolizadas com aspecto monocítico, com evidências de hemofagocitose. A criança apresentou um declínio clínico progressivo e dois meses após a recaída foi a óbito. Comentários: A LHH é uma condição inflamatória rara e agressiva caracterizada por citopenias, hepatoesplenomegalia, febre e hemofagocitose na medula óssea, linfonodos, baço e fígado. A LHH associada a doenças malignas, embora seja uma condição rara, é potencialmente fatal. A paciente deste caso apresentou cinco dos oito critérios estabelecidos para o diagnóstico de LHH. A evolução do cariótipo do paciente, independentemente do perfil do diagnóstico, pareceu ser secundária ao tratamento da leucemia monocítica aguda, sendo que a instabilidade citogenética pode ter influenciado o comportamento atípico observado nas células leucêmicas. Este é um dos raros casos de LHH em uma criança com leucemia monocítica aguda. Objective: To describe the case of a child who presented hemophagocytic lymphohistiocytosis (HLH) associated with acute monocytic leukemia after chemotherapy, with hemophagocytosis caused by leukemic cells. Case description: In a university hospital in Southern Brazil, a 3-yearold female was diagnosed with acute monocytic leukemia with normal karyotype. The chemotherapy regimen was initiated, and she achieved complete remission six months later, relapsing after four months with a complex karyotype involving chromosomes 8p and 16q. The bone marrow showed vacuolated blasts with a monocytic aspect and evidence of hemophagocytosis. The child presented progressive clinical deterioration and died two months after the relapse. Comments: HLH is a rare and aggressive inflammatory condition characterized by cytopenias, hepatosplenomegaly, fever, and hemophagocytosis in the bone marrow, lymph nodes, spleen, and liver. Although rare, malignancy-associated HLH (M-HLH) is fatal. The patient in this case report met five out of the eight established criteria for HLH. The evolution of the patient’s karyotype, regardless of the diagnostic profile, seemed secondary to the treatment for acute monocytic leukemia. In this case, the cytogenetic instability might have influenced the abnormal behavior of leukemic cells. This is a rare case of HLH in a child with acute monocytic leukemia.

Background and Aims In the last ten years, peritoneal dialysis (PD) has been considered a safe option to start renal replacement therapy (RRT) in end-stage renal disease patients in need to start dialysis urgently. The definition applied to the Urgent Start PD (US-PD) varies widely worldwide. Recently, it was proposed that US-PD definition should be according to patients’ necessity of starting dialysis, considering “urgent start” when PD started up to 72 hours of catheter placement and “early start” PD when it is starts between 3 and 14 days after catheter placement. Considering this new definition, we aimed to compare demographical and clinical characteristics of patients´ that started PD therapy as urgent and early starts as well as 30-day complications, 6-month hospitalization and dropout rate. Method All adult patients that started PD therapy up to 14 days after catheter insertion in our institution between October 2016 and February 2019 were included in the analyses. Patients were placed on urgent-start (US-PD) group if therapy started until 72-h after catheter insertion or early-start (ES-PD) group if PD initiated between 3 and 14 days. Dialysis records were reviewed to obtain clinical and demographic data, fill volume prescribed for the first PD session, 30-days complications (leakage, bleeding, catheter tip migration and peritonitis) and 6-month hospitalization and dropout rate. Results In our study, 72 patients were analyzed (US-PD=52, ES-PD=20), mean age was 53.2 ± 15.2 years old. No differences between US-PD and ES-PD regarding demographic characteristics, 30-day complications and 6-month hospitalization and dropout events were found. The most frequent short-term complication in patients who started PD urgently was leakage (US-PD 6 (11%) x ES-PD 2(10%) patients). The most common cause of patient’s dropout was transfer to HD.Only patients from the US-PD group needed to switch to that modality (5 (10%)). Conclusion Almost three-quarters of our sample started PD less than 72 hours after catheter insertion. The lack of difference in the measured outcomes compared to patients that had therapy initiated after this period encourages the use of PD when urgent dialysis is needed.

Research into self-care practices suggests the need for conscientious and systematic support of nurses and other health care providers. The purpose of this study was to explore the impact of an innovative self-care initiative. The goals were to explore the experience of nurses and other health care providers participating in a reflective, creative nonfiction storytelling event called “Dinner and Stories” and the potential benefits and limitations of using an informal, storytelling model for self-care. A qualitative narrative design was used. Twenty-seven participants including nurses, social workers, and hospice volunteers wrote creative nonfiction stories about a lingering experience of providing care. At predefined dates, groups of up to six met for dinner in a home setting. Participants read aloud, listened deeply, and discussed their narrated stories. Four sources of data were collected: creative nonfiction stories, online forum discussions, in-depth interviews, and host facilitator field notes. Researchers identified four themes: (1) needing a self-care culture, (2) storytelling and writing as healing, (3) co-creating layers of connection, and (4) preferring face-to-face contact. Results add to knowledge about the therapeutic benefits of writing and storytelling for nurses and other health care providers including enriched meaning-making, emotional conveyance, and therapeutic connections between storytellers and listeners.

The results of hematopoietic stem cell transplant (HSCT) for primary immunodeficiency diseases (PID) have been improving over time. Unfortunately, developing countries do not experience the same results. This first report of Brazilian experience of HSCT for PID describes the development and results in the field. We included data from transplants in 221 patients, performed at 11 centers which participated in the Brazilian collaborative group, from July 1990 to December 2015. The majority of transplants were concentrated in one center (n = 123). The median age at HSCT was 22 months, and the most common diseases were severe combined immunodeficiency (SCID) (n = 67) and Wiskott-Aldrich syndrome (WAS) (n = 67). Only 15 patients received unconditioned transplants. Cumulative incidence of GVHD grades II to IV was 23%, and GVHD grades III to IV was 10%. The 5-year overall survival was 71.6%. WAS patients had better survival compared to other diseases. Most deaths (n = 53) occurred in the first year after transplantation mainly due to infection (55%) and GVHD (13%). Although transplant for PID patients in Brazil has evolved since its beginning, we still face some challenges like delayed diagnosis and referral, severe infections before transplant, a limited number of transplant centers with expertise, and resources for more advanced techniques. Measures like newborn screening for SCID may hasten the diagnosis and ameliorate patients' conditions at the moment of transplant.

Aims The aim of this study is to develop a population pharmacokinetic (PopPK) model for intravenous busulfan in children that incorporates variants of GSTA1, gene coding for the main enzyme in busulfan metabolism. Methods Busulfan concentration-time data was collected from 112 children and adolescents (median 5.4 years old, range: 0.1-20) who received intravenous busulfan during the conditioning regimen prior to stem cell transplantation. Weight, sex, baseline disease (malignant vs. non-malignant), age, conditioning regimen and GSTA1 diplotypes were evaluated as covariates of pharmacokinetic parameters by using nonlinear mixed effects analysis. The ability to achieve the target AUC24h (3600-6000 μM min-1 ) was assessed by estimating the first dose based on the present PopPK model and by comparing the results with other available models in children. Results A one-compartment model with first-order elimination best described the data. Allometric scaling of weight and a factor of busulfan metabolism maturation were included in the base model. GSTA1 diplotypes were found to be a significant covariate of busulfan clearance, which was 7% faster in rapid metabolizers and 12% slower in poor metabolizers, in comparison with normal ones. Busulfan doses calculated using the parameters of the proposed PopPK model were estimated to achieve the target AUC in 85.2% of the cases (95% CI 78.7-91.7%). Conclusion This is the first PopPK for busulfan that successfully incorporated GSTA1 genotype in a paediatric population. Its use may contribute to better prediction of busulfan exposure in children and adolescents since the first dose, by tailoring the dose according to the individual metabolic capacity.

ObjectiveSpiritual care has formed an integral part of palliative care since its inception. People with advanced illnesses, however, frequently report that their spiritual needs are not attended to by their medical care team. The present study examines and describes the impact of a spiritual care training program on practice and cultural change in our Canadian hospice.MethodA qualitative case study approach was adopted to gather feedback from hospice staff and volunteers using purposive sampling. In-depth interviews were conducted, transcribed, and analyzed using thematic (semantic and latent) analysis.ResultOur data suggest that the program had a profound personal impact on attendees and contributed to a slight shift in practice patterns in our organization. Using a program not specifically tailored to our local and organizational cultural contexts resulted in some unanticipated challenges such as the range of tensions between personal and cultural boundaries. Although some people criticized parts of the program or questioned the program's value, a general agreement suggests that the program had a positive impact and meaningfully benefited our hospice. “What will happen next?” was the question most frequently voiced by interviewees.Significance of resultsAlthough the program may not have been a perfect fit for our organization, its use instigated a process of cultural change that unfolds today. The present study suggests that a systematic approach to spiritual care training that includes the concepts of workplace spirituality and sensitive practice offer useful frameworks for the development and implementation of spiritual care training in other institutions.

Hematopoietic stem cell transplantation (HSCT) has the potential to cure a significant proportion of patients with malignant and nonmalignant diseases. The main rationale for HSCT in inborn errors of metabolism (IEM) is based on correcting the decreases enzymes by the donor cells within and outside the intravascular compartment. In this article, Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society of Bone Marrow Transplantation and Cellular Therapy (SBTMO) provides a review of HSCT indications in IEM.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach to children and adolescents with high-risk acute lymphoblastic leukemia (ALL) at diagnosis or relapsed disease. Nonetheless, despite the graft versus leukemia (GVL) effect, treatment-related morbidity and mortality remains a major challenge. Moreover, the significant heterogeneity of the available data on the selection of patients, type of conditioning regimen, and type of donor hampers any definitive conclusions in the pediatric population. In 2020, the Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society of Bone Marrow Transplantation and Cellular Therapy (SBTMO) and the Brazilian Society for Pediatric Oncology (SOBOPE) convened a task force to provide general guidance on HSCT for childhood ALL to providing evidence-based guidance for the appropriate management of this disease.

In recent years, there has been an expansion in the use of flow cytometry (FC) immunophenotyping in the diagnosis and monitoring of childhood solid neoplasms. Neuroblastoma (NB), in turn, is the most common extracranial solid tumor in childhood. In the present study, we sought to compare FC and anatomopathological examination (PA) / immunohistochemistry (IHC) of children diagnosed or suspected with NB. The median age was 59 months (minimum 0; maximum 325 months), of these 12 were male (57.1%, 12/21). Forty-eight samples (27 bone marrow (BM), 10 peripheral blood (PB), 8 primary tumors (PT) and 2 liver nodules (HN) and 1 rib fragment (RF)) from 21 patients were evaluated. Twenty-nine samples were from patients with clinical suspicion while 19 samples were from patients with previously confirmed diagnosis. Thirteen samples (7 BM, 5 PT and 1 HN) presented NB when analyzed in FC while 8 (3 BM and 5 PT) samples were positive for NB in the PA/IHC. They were concordant in 88.9% of the cases. No NB cells were identified in any PB. Considering the PA as the gold standard, the FC obtained a sensitivity of 100%, a specificity of 86%, a positive predictive value of 67% and a negative predictive value of 100%. This study demonstrates that FC can be used as a methodology for diagnosis and assessment of NB involvement. In addition, FC has the advantage of allowing a quick diagnosis and accurate classification of the disease, and can also assist in monitoring the treatment.

Busulfan (Bu) is a key component of conditioning regimens used before hematopoietic stem cell transplantation (SCT) in children. Different predictive methods have been used to calculate the first dose of Bu. To evaluate the necessity of further improvements, we retrospectively analyzed the currently available weight- and age-based guidelines to calculate the first doses in 101 children who underwent allogenic SCT in CHU Sainte-Justine, Montreal, after an intravenous Bu-containing conditioning regimen according to genetic and clinical factors. The measured areas under the curve (AUCs) were within target (900 to 1500 µM/min) in 38.7% of patients after the administration of the first dose calculated based on age and weight, as locally recommended. GSTA1 diplotypes linked to poor Bu metabolism (G3) and fludarabine-containing regimens were the only factors associated with AUC within target (OR, 4.7 [95% CI, 1.1 to 19.8, P = .04]; and OR, 9.9 [95% CI, 1.6 to 61.7, P = .01], respectively). From the 11 methods selected for dose calculation, the percentage of AUCs within the target varied between 16% and 74%. In some models G3 was associated with AUCs within the therapeutic and the toxic range, whereas rapid metabolizers (G1) were correlated with subtherapeutic AUCs when different methods were used. These associations were confirmed by clearance-prediction analysis, in which GSTA1 diplotypes consistently influenced the prediction errors of the methods. These findings suggest that these factors should be considered in Bu dose prediction in addition to the anthropometric data from patients. Furthermore, our data indicated that GSTA1 diplotypes was a factor that should be included in future population pharmacokinetic models, including similar conditioning regiments, to improve the prediction of Bu exposure after its initial dose.

Oral mucositis (OM) is an adverse side effect among hematopoietic stem cell transplantation (HSCT) recipients. The objective of this retrospective study was to evaluate the preventive effect of photobiomodulation (PBM) applied three times per week versus seven times per week in patients undergoing HSCT. The risk factors related to the incidence and severity of OM were also assessed. This was a retrospective study that evaluated 99 HSCT recipients who received different PBM protocols. Group I received three sessions per week, and group II received daily treatment. PBM was applied using a continuous-wave diode laser (InGaAlP; MM Optics, Sao Carlos, SP, Brazil) at a wavelength of 660 nm (visible-red) and a total radiant energy of 0.24 J per point. The baseline disease, type of transplant, type of conditioning, prophylaxis against graft-versus-host disease, OM grade, absolute leukocyte and platelet counts, and levels of liver and renal function markers were collected from medical records. The patients’ age ranged from 13 to 71 years (mean/SD, 40.54 ± 16.45). No significant difference was observed between groups I and II regarding sex, age, ethnic, diagnosis, donor type, and conditioning treatment. Both PBM protocols were equally efficient in preventing OM (p = 0.34, ANOVA). Independent of the PBM protocol used, patients who received allogeneic transplant (p

Complicated grief (CG) is one of the central themes in bereavement research and advanced clinical practice today. Using a mixed-methods approach, we wanted to learn (a) what tools Canadian practitioners used to identify or diagnose CG and (b) what interventions or strategies they used to address CG. Sixty-three professionals responded to our survey. There were no straightforward answers to these questions: the state-of-the art of CG in Canada is, in fact, complicated. Practitioners used a wide assortment of tools and strategies with no consensus on any one approach or tool. Building a Canadian CG community of practice was recommended.

Objetivo: Elaborar a matriz de competências a serem desenvolvidas pelos estudantes durante os três meses de estágio no internato em Medicina de Família e Comunidade na Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA). Métodos: Foi realizada revisão de literatura sobre o referencial teórico do ensino baseado em competências sobre escolas médicas que utilizassem o ensino baseado em competências na especialidade e sobre as principais diretrizes nacionais e internacionais sobre o tema. Diante da revisão de literatura, foi discutida a aplicabilidade das recomendações no contexto do internato da UFCSPA. Resultados: Dezoito competências foram elaboradas e divididas em quatro eixos: Geral; Abordagem Individual; Abordagem Familiar e Abordagem Comunitária. Cada competência foi detalhada em um ou mais componentes. Para cada componente, foram identificados os métodos de ensino e de avaliação atualmente utilizados no programa do internato. Conclusão: Com a definição da matriz, as competências, antes desenvolvidas de forma intuitiva, foram organizadas de modo a viabilizar a revisão e adequação dos processos de ensino e avaliação.

The choice of alternative donors for HCT for patients without an HLA-matched related donor depends on several factors. We compared major HCT outcomes in 212 consecutive children transplanted at 11 centers in Brazil for acute leukemia or MDS from an HLA-matched unrelated donor (MUD, n = 95), mismatched unrelated donor (MMUD, n = 47) or unrelated umbilical cord blood (UCB, n = 70). Most had ALL (61%), bone marrow (57%) as the graft source and 95% received a MAC regimen. The 3-year OS probability were 57, 55, and 37% after HCT from MUD, MMUD, and UCB, respectively (HR 1.68, 95%CI 1.07-2.63; P = .02). In comparison with MUD, OS was similar after transplantation of a ≥ 6/8 HLA-matched or a high cell dose (>5 × 107 TNC/kg) CB unit (HR 1.41, 95%CI 0.88-2.27; P = .15). NRM was higher for UCB (HR 3.90, 95%CI 1.43-10.7; P = .01) but not for MMUD (HR 1.03, 95%CI 0.53-2.00; P > .20). Advanced disease (HR 2.05, 95%CI 1.26-3.33; P < .001) and UCB with high probability of being < 6/8 HLA-matched (HR 5.34, 95%CI 2.0-13.9; P < .001) were associated with higher mortality. Relapse and acute GVHD were similar among groups, while PGF was higher among UCB transplants (P = .002) and chronic GVHD among MMUD group (HR 2.88, 95% CI 1.05-7.88; P = .04). Our results suggest that in Brazil HCT outcomes performed with MMUD and MUD donors were comparable, while with UCB units < 6/8 HLA-matched were associated with higher NRM for children with acute leukemia or MDS.

Background: Our research group recently showed that the only ASNase formulation available in Brazil from 2017 to 2018 when used at the same dose and frequency as the formulation provided previously did not reach, in most cases, the serum activity considered therapeutic. Based on these data, our goal was to assess the impact of these facts on the prognosis of children with ALL at 10 different pediatric oncology centers in our country. Methods: a multicenter retrospective observational study followed by prospective follow-up. Patients aged >1 and

The long-term outcome of acute lymphoblastic leukemia has improved dramatically due to the development of more effective treatment strategies. L-asparaginase (ASNase) is one of the main drugs used and causes death of leukemic cells by systematically depleting the non-essential amino acid asparagine. Three main types of ASNase have been used so far: native ASNase derived from Escherichia coli, an enzyme isolated from Erwinia chrysanthemi and a pegylated form of the native E. coli ASNase, the ASNase PEG. Hypersensitivity reactions are the main complication related to this drug. Although clinical allergies may be important, a major concern is that antibodies produced in response to ASNase may cause rapid inactivation of ASNase, leading to a worse prognosis. This reaction is commonly referred to as "silent hypersensitivity" or "silent inactivation". We are able to analyze hypersensitivity and inactivation processes by the measurement of the ASNase activity. The ability to individualize the ASNase therapy in patients, adjusting the dose or switching patients with silent inactivation to an alternate ASNase preparation may help improve outcomes in those patients. This review article aims to describe the pathophysiology of the inactivation process, how to diagnose it and finally how to manage it.

Introduction: Various established occupational lung carcinogens are also suspected risk factors for laryngeal cancer. However, individual studies are often inadequate in size to investigate this relatively rare outcome. Other limitations include imprecise exposure assessment and inadequate adjustment for confounders. Methods: This study applied a quantitative job exposure matrix (SYN-JEM) for four established occupational lung carcinogens to five case-control studies within the International Head and Neck Cancer Epidemiology Consortium. We used occupational histories for 2256 laryngeal cancer cases and 7857 controls recruited from 1989 to 2007. We assigned quantitative exposure levels for asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined (to address highly correlated exposures) via SYN-JEM. We assessed effects of occupational exposure on cancer risk for males (asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined) and females (asbestos and respirable crystalline silica), adjusting for age, study, tobacco smoking, alcohol consumption, and asbestos exposure where relevant. Results: Among females, odds ratios (ORs) were increased for ever versus never exposed. Among males, P values for linear trend were 90th percentile cumulative exposure (OR = 1.3, 95% confidence interval [CI] = 1.0, 1.6), respirable crystalline silica at 30+ years duration (OR = 1.4, 95% CI = 1.2, 1.7) and 75th-90th percentile cumulative exposure (OR = 1.4, 95% CI = 1.1, 1.8), chromium-VI at >75th percentile cumulative exposure (OR = 1.9, 95% CI = 1.2, 3.0), and chromium-VI and nickel combined at 20-29 years duration (OR = 1.5, 95% CI = 1.1, 2.2). Conclusions: These findings support hypotheses of causal links between four lung carcinogens (asbestos, respirable crystalline silica, chromium-VI, and nickel) and laryngeal cancer.

International audience; Change detection is one of the main problems in remote sensing, and is essential to the accurate processing and understanding of the large scale Earth observation data available. Most of the recently proposed change detection methods bring deep learning to this context, but change detection labelled datasets which are openly available are still very scarce, which limits the methods that can be proposed and tested. In this paper we present the first large scale very high resolution semantic change detection dataset, which enables the usage of deep supervised learning methods for semantic change detection with very high resolution images. The dataset contains coregistered RGB image pairs, pixel-wise change information and land cover information. We then propose several supervised learning methods using fully convolutional neural networks to perform semantic change detection. Most notably, we present a network architecture that performs change detection and land cover mapping simultaneously, while using the predicted land cover information to help to predict changes. We also describe a sequential training scheme that allows this network to be trained without setting a hyperparameter that balances different loss functions and achieves the best overall results.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a therapeutic modality commonly used to treat hematological and immunological disorders. Among the main complications of allo-HSCT is the acute graft-versus-host disease (a-GVHD), a condition which accounts for a high incidence of mortality. Several genes encoding inflammatory mediators may present polymorphisms, which have been implicated in the risk of developing a-GVHD. In our study, we investigated the association between genotypes of cytokine-encoding genes and the incidence and severity of a-GVHD and survival of HSCT recipients. No statistically significant association was found between IL and 6-174 G/C, INF-γ + 874 T/A, TNF-α -238 A/G, -308 A/G and IL-10-819C/T, -592 A/C polymorphisms and the presence or severity of a-GVHD. A higher risk of a-GVHD was associated with the IL-10-1082 GG genotype compared to the AA + AG genotypes of recipients and donors. The IL-10-1082 genotype can be used as a prognostic determinant to predict which HSCT recipient will be more responsive to the transplant. Thus, cytokine gene assays may be useful in the individualization of prophylactic regimens and for an appropriate selection of immunosuppressants based on the HSCT recipient’s responsiveness.