Whole-Genome Analysis of Extensively Drug-Resistant Enterobacter hormaechei Isolated from a Patient with Non-Hodgkin's Lymphoma.

BACKGROUND: Currently, the Enterobacteriaceae species are responsible for a variety of serious infections and are already considered a global public health problem, especially in underdeveloped countries, where surveillance and monitoring programs are still scarce and limited. Analyses were performed on the complete genome of an extensively antibiotic-resistant strain of Enterobater hormaechei, which was isolated from a patient with non-Hodgkin's lymphoma, who had been admitted to a hospital in the city of Manaus, Brazil. METHODS: Phenotypical identification and susceptibility tests were performed in automated equipment. Total DNA extraction was performed using the PureLink genomic DNA mini-Kit. The genomic DNA library was prepared with Illumina Microbial Amplicon Prep and sequenced in the MiSeq Illumina Platform. The assembly of the whole-genome and individual analyses of specific resistance genes extracted were carried out using online tools and the Geneious Prime software. RESULTS: The analyses identified an extensively resistant ST90 clone of E. hormaechei carrying different genes, including blaCTX-M-15, blaGES-2, blaTEM-1A, blaACT-15, blaOXA-1 and blaNDM-1, [aac(3)-IIa, aac(6')-Ian, ant(2″)-Ia], [aac(6')-Ib-cr, (qnrB1)], dfrA25, sul1 and sul2, catB3, fosA, and qnrB, in addition to resistance to chlorhexidine, which is widely used in patient antisepsis. CONCLUSIONS: These findings highlight the need for actions to control and monitor these pathogens in the hospital environment.

Incidence, management and outcomes in hepatic artery complications after paediatric liver transplantation: protocol of the retrospective, international, multicentre HEPATIC Registry.

INTRODUCTION: Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications. METHODS AND ANALYSIS: The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC. ETHICS AND DISSEMINATION: All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644.

Personalized lung care: Bronchopulmonary dysplasia risk prediction tool tailored for neonates born in resource-limited settings.

PURPOSE: Predicting bronchopulmonary dysplasia (BPD) to assess the risk-benefit of therapy is necessary considering the side effects of medications. We developed and validated an instrument for predicting BPD and compared it with an instrument currently used for neonates born in a Brazilian hospital. METHODS: This was a retrospective cohort study of patients born between 2016 and 2020 with a gestational age (GA) between 23 and 30 weeks. Predictive equations were elaborated using methods of component variable selection collected on the 14th day of life; 70% of the sample was randomly selected for the construction of risk prediction equations and the remaining 30% for their validation, application, and comparison with the National Institute of Child Health and Human Development (NICHD) instrument. The sensitivity, specificity, and predictive values of the equations were calculated. RESULTS: The equation that used variables with p < 5% in Fisher's exact test presented the best results: specificity of 98% and positive predictive value of 93% and could be used for BPD prediction of all small-for-gestational-age (SGA) infants. The NICHD calculator applied to our population had a specificity of 93% and a positive predictive value of 75% and could not be applied to extremely SGA infants. CONCLUSION: Our tool can predict the risk of BPD on the 14th day of life, has higher specificity and positive predictive value to our population than the NICHD instrument, and can be suitable for SGA infants. The results must be confirmed by applying it to other populations to validate our tool.

Primary liver transplantation vs transplant after Kasai portoenterostomy in children with biliary atresia: A retrospective Brazilian single-center cohort.

BACKGROUND: Biliary atresia (BA) is the most common indication for pediatric liver trans plantation, although portoenterostomy is usually performed first. However, due to the high failure rate of portoenterostomy, liver transplantation has been advocated as the primary procedure for patients with BA. It is still unclear if a previous portoenterostomy has a negative impact on liver transplantation outcomes. AIM: To investigate the effect of prior portoenterostomy in infants un dergoing liver transplantation for BA. METHODS: This was a retrospective cohort study of 42 pediatric patients with BA who underwent primary liver transplantation from 2013 to 2023 at a single tertiary center in Brazil. Patients with BA were divided into two groups: Those under going primary liver transplantation without portoenterostomy and those undergoing liver transplantation with prior portoenterostomy. Continuous variables were compared using the Student's t-test or the Kruskal-Wallis test, and categorical variables were compared using the χ2 or Fisher's exact test, as appropriate. Multivariable Cox regression analysis was performed to determine risk factors for portal vein thrombosis. Patient and graft survival analyses were conducted with the Kaplan-Meier product-limit estimator, and patient subgroups were compared using the two-sided log-rank test. RESULTS: Forty-two patients were included in the study (25 [60%] girls), 23 undergoing liver transplantation without prior portoenterostomy, and 19 undergoing liver transplantation with prior portoenterostomy. Patients with prior portoenterostomy were older (12 vs 8 months; P = 0.02) at the time of liver transplantation and had lower Pediatric End-Stage Liver Disease scores (13.2 vs 21.4; P = 0.01). The majority of the patients (35/42, 83%) underwent living-donor liver transplantation. The group of patients without prior portoenterostomy appeared to have a higher incidence of portal vein thrombosis (39 vs 11%), but this result did not reach statistical significance. Prior portoenterostomy was not a protective factor against portal vein thrombosis in the multivariable analysis after adjusting for age at liver transplantation, graft-to-recipient weight ratio, and use of vascular grafts. Finally, the groups did not significantly differ in terms of post-transplant survival. CONCLUSION: In our study, prior portoenterostomy did not significantly affect the outcomes of liver transplantation.

High prevalence of response to PPI treatment in children and adolescents with eosinophilic esophagitis in southern Brazil.

Introduction: Eosinophilic esophagitis is a newly recognized entity, in which there is significant evidence available that clearly demonstrates the positive impact of PPIs on reducing esophageal eosinophilia in individuals across different age groups, including children, adolescents, and adults. Multiple mechanisms have been proposed to explain how this treatment effect occurs. In Brazil, there seems to be a lack of studies that have prospectively assessed the clinical and therapeutic response rate in pediatric patients with EoE. The objective of this study was to prospectively evaluate the clinical and therapeutic response of pediatric patients with EoE in a medical center located in southern Brazil, by investigating the effectiveness of PPI treatment. Methods: This study is a clinical, prospective, open trial that took place in a pediatric hospital located in southern Brazil. The focus of the study was on patients diagnosed with Eosinophilic Esophagitis (EoE) who were given treatment using omeprazole/esomeprazole at a dosage of 1 mg.kg per dose, twice daily, for a period of 8-12 weeks. Following the treatment period, the patients underwent another endoscopy. Patients who exhibited 15 or less eosinophils in the biopsy conducted after the treatment were considered as responders. Results: A total of 27 patients was evaluated (74.1% boys). The average age (± standard deviation) was 8 years (±4). Nineteen patients (70.3%) were considered as responders to PPI treatment: 6 patients-22.2%-exhibited a complete response (defined as having 5 or fewer eosinophil per high power field. Additionally, 13 patients-48.1%-demonstrated a partial response, characterized by eosinophil counts exceeding 5 but less than 15 eos/hpf. When comparing the responder and non-responder groups at presentation, a statistical difference was observed in the prevalence of food refusal as a presenting symptom. Food refusal was found to be more prevalent in the non-responder group (87.5% vs. 26.3%, P = 0.008). No differences were observed in terms of atopy history and endoscopic scores. Upon comparing the histological findings from the post-treatment endoscopy of the two groups, it was observed that PPI responders exhibited a greater tendency to decrease basal cell hyperplasia (P = 0.06) and intercellular edema (P = 0.08). Conclusion: In this group of pediatric patients with EoE in Southern Brazil most patients showed a high prevalence of histological, endoscopic, and clinical response to PPI treatment. PPIs showed efficacy in Brazilian patients with EoE, most of whom would probably not be able to adequately undergo other treatments. Clinical Trial Registration: https://ensaiosclinicos.gov.br/rg/RBR-2ntbth9, identifier (U1111-1301-1842).

Immune response stability to the SARS-CoV-2 mRNA vaccine booster is influenced by differential splicing of HLA genes.

Many molecular mechanisms that lead to the host antibody response to COVID-19 vaccines remain largely unknown. In this study, we used serum antibody detection combined with whole blood RNA-based transcriptome analysis to investigate variability in vaccine response in healthy recipients of a booster (third) dose schedule of the mRNA BNT162b2 vaccine against COVID-19. The cohort was divided into two groups: (1) low-stable individuals, with antibody concentration anti-SARS-CoV IgG S1 below 0.4 percentile at 180 days after boosting vaccination; and (2) high-stable individuals, with antibody values greater than 0.6 percentile of the range in the same period (median 9525 [185-80,000] AU/mL). Differential gene expression, expressed single nucleotide variants and insertions/deletions, differential splicing events, and allelic imbalance were explored to broaden our understanding of the immune response sustenance. Our analysis revealed a differential expression of genes with immunological functions in individuals with low antibody titers, compared to those with higher antibody titers, underscoring the fundamental importance of the innate immune response for boosting immunity. Our findings also provide new insights into the determinants of the immune response variability to the SARS-CoV-2 mRNA vaccine booster, highlighting the significance of differential splicing regulatory mechanisms, mainly concerning HLA alleles, in delineating vaccine immunogenicity.

The behavior of thermally modified wood after exposure in maritime/industrial and urban environments.

Natural and thermally modified Pine, Ash, and Acacia woods were exposed in two different environments: urban and maritime/industrial. The weathering effects were evaluated during 24 months regarding color, chemical, and structural changes. In all wood species, thermal modification induced color, chemical, and structural changes. All woods became darker (Pine ΔL*: -32.01; Ash ΔL*: -36.83; Acacia ΔL*: -27.50), total extractives content increased (Pine: 19 %; Ash: 32 % and Acacia: 18 %), and the samples presented deformation and damaged cells. Total lignin was not significantly changed, although there were detected changes in lignin, namely the reduction of G-units in Pine (≈2 %) and reduction of S/G ratio in Acacia (≈0.04 %). Ash remained almost the same. After weathering, modified woods suffered fewer color changes, indicating that the thermal modification could improve the resistance to color change. Acacia wood, when exposed to maritime/industrial conditions, revealed a higher color change (ΔE: 35.7 at 24 months) when compared with urban conditions (ΔE: 23.5 at 24 months). Delignification, possibly caused by photodegradation, occurred in all wood samples, and the loss of extractive happened, perhaps caused by rain. Modified woods were slightly less resistant to weathering in maritime/industrial environments. Some structural damage, namely cracked cells, the appearance of molds, blue staining, and particle deposition, was observed. The thermal modification enables color stabilization but does not seem to improve the weathering resistance in all studied wood species. Exposure to the different environments did not lead to significant differences in the morphology and chemical composition of the three natural and modified wood species.

Neuronal substrates of egg-laying behaviour at the abdominal ganglion of Drosophila melanogaster.

Egg-laying in Drosophila is the product of post-mating physiological and behavioural changes that culminate in a stereotyped sequence of actions. Egg-laying harbours a great potential as a paradigm to uncover how the appropriate motor circuits are organized and activated to generate behaviour. To study this programme, we first describe the different phases of the egg-laying programme and the specific actions associated with each phase. Using a combination of neuronal activation and silencing experiments, we identify neurons (OvAbg) in the abdominal ganglion as key players in egg-laying. To generate and functionally characterise subsets of OvAbg, we used an intersectional approach with neurotransmitter specific lines-VGlut, Cha and Gad1. We show that OvAbg/VGlut neurons promote initiation of egg deposition in a mating status dependent way. OvAbg/Cha neurons are required in exploration and egg deposition phases, though activation leads specifically to egg expulsion. Experiments with the OvAbg/Gad1 neurons show they participate in egg deposition. We further show a functional connection of OvAbg neurons with brain neurons. This study provides insight into the organization of neuronal circuits underlying complex motor behaviour.

Cardio-Oncology Rehabilitation for Cancer Survivors With High Cardiovascular Risk: A Randomized Clinical Trial.

Importance: Cardiovascular disease is a leading cause of morbidity in cancer survivors, which makes strategies aimed at mitigating cardiovascular risk a subject of major contemporary importance. Objective: To assess whether a center-based cardiac rehabilitation (CBCR) framework compared with usual care encompassing community-based exercise training (CBET) is superior for cardiorespiratory fitness improvement and cardiovascular risk factor control among cancer survivors with high cardiovascular risk. Design, Setting, and Participants: This prospective, single-center, randomized clinical trial (CORE trial) included adult cancer survivors who had exposure to cardiotoxic cancer treatment and/or previous cardiovascular disease. Enrollment took place from March 1, 2021, to March 31, 2022. End points were assessed at baseline and after the 8-week intervention. Interventions: Participants were randomly assigned in a 1:1 ratio to 8 weeks of CBCR or CBET. The combined aerobic and resistance exercise sessions were performed twice a week. Main Outcomes and Measures: The powered primary efficacy measure was change in peak oxygen consumption (V̇o2) at 2 months. Secondary outcomes included handgrip maximal strength, functional performance, blood pressure (BP), body composition, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), lipid profile, plasma biomarker levels, physical activity (PA) levels, psychological distress, quality of life (QOL), and health literacy. Results: A total of 75 participants completed the study (mean [SD] age, 53.6 [12.3] years; 58 [77.3%] female), with 38 in the CBCR group and 37 in the CBET group. Participants in CBCR achieved a greater mean (SD) increase in peak V̇o2 than those in CBET (2.1 [2.8] mL/kg/min vs 0.8 [2.5] mL/kg/min), with a between-group mean difference of 1.3 mL/kg/min (95% CI, 0.1-2.6 mL/kg/min; P = .03). Compared with the CBET group, the CBCR group also attained a greater mean (SD) reduction in systolic BP (-12.3 [11.8] mm Hg vs -1.9 [12.9] mm Hg; P < .001), diastolic BP (-5.0 [5.7] mm Hg vs -0.5 [7.0] mm Hg; P = .003), and BMI (-1.2 [0.9] vs 0.2 [0.7]; P < .001) and greater mean (SD) improvements in PA levels (1035.2 [735.7] metabolic equivalents [METs]/min/wk vs 34.1 [424.4] METs/min/wk; P < .001), QOL (14.0 [10.0] points vs 0.4 [12.9] points; P < .001), and health literacy scores (2.7 [1.6] points vs 0.1 [1.4] points; P < .001). Exercise adherence was significantly higher in the CBCR group than in the CBET group (mean [SD] sessions completed, 90.3% [11.8%] vs 68.4% [22.1%]; P < .001). Conclusion and Relevance: The CORE trial showed that a cardio-oncology rehabilitation model among cancer survivors with high cardiovascular risk was associated with greater improvements in peak V̇o2 compared with usual care encompassing an exercise intervention in a community setting. The CBCR also showed superior results in exercise adherence, cardiovascular risk factor control, QOL, and health literacy. Trial Registration: ClinicalTrials.gov Identifier: NCT05132998.

Simultaneous Gastric and Colonic Metastasis of Breast Cancer.

Although breast cancer (BC) is the most common malignancy in women, metastasization to the gastrointestinal tract is rare. We present a 59-year-old woman with simultaneous gastric and colonic metastasis of invasive lobular breast carcinoma. She had been diagnosed with BC and underwent surgery and systemic therapy. Two years later, an increase in tumor markers motivated investigation, including upper and lower gastrointestinal endoscopy, which identified gastric ulcers and mucosal irregularity in the cecum. Histopathological analysis was compatible with gastric and colonic metastases from BC. We highlight the importance of biopsying every endoscopically visible lesion in patients with BC history.

Análise sobre o conhecimento do pediatra brasileiro sobre a alergia à proteína do leite de vaca / Analysis of brazilian pediatricians' knowledge of cow's milk protein allergy

Analisar o conhecimento de pediatras brasileiros sobre alergia à proteína do leite de vaca (APLV) por meio de um questionário validado. Estudo quantitativo com delineamento transversal no qual foi aplicado um questionário online sobre conhecimentos de APLV. O cálculo amostral foi de 294. O formulário online foi dividido em dois blocos, sendo o primeiro composto por questões de identificação dos pediatras e o segundo composto pelo questionário validado, construído a partir do Consenso Brasileiro de Alergia Alimentar (2018). A avaliação geral do questionário mostrou um percentual de concordância de 91% e Índice de Validade de Conteúdo de 0,95. Os resultados dos questionários aplicados foram apresentados em frequências absolutas e relativas, média, mediana, desvio padrão e percentis. O nível de significância foi estabelecido em 5% (p < 0,05). O questionário validado foi respondido por 1.316 médicos brasileiros, dos quais 1.017 (77,3%) eram do sexo feminino. A média de idade observada foi de 45,50 ± 13,20 anos. Ao analisar o número total de acertos, notou-se que a média de acertos foi de 80,66 ± 10,42%. Os pediatras responderam principalmente a perguntas sobre o conceito e o tratamento da APLV. A questão com menor índice de acertos foi relacionada à investigação clínica e laboratorial. A maioria dos médicos que respondeu ao questionário demonstrou compreender o conceito e as principais recomendações terapêuticas da APLV.

To analyze the knowledge of Brazilian pediatricians about cow's milk protein allergy (CMPA) using a validated questionnaire. Quantitative study with a cross-sectional design in which an online questionnaire on CMPA knowledge was applied. The sample calculation indicated 1024 participants. The online form was divided into two blocks, the first comprising questions on the identification of pediatricians, and the second comprising the validated questionnaire, built from the Brazilian Consensus on Food Allergy (2018). The general evaluation of the questionnaire showed a percentage of agreement of 91% and a Content Validity Index of 0.95. The results of the applied questionnaires were presented in absolute and relative frequencies, mean, median, standard deviation, and percentiles. The level of significance was set at 5% (p <0.05). The validated questionnaire was answered by 1316 Brazilian doctors, of whom 1017 (77.3%) were females, and their mean age was 45.50 ± 13.20 years. The mean total number of correct answers was 80.66 ± 10.42%. Pediatricians mostly answered questions about the concept and treatment of CMPA. The question with the lowest rate of correct answers was related to clinical and laboratory investigation. Most physicians who answered the questionnaire demonstrated they understood the concept and the main CMPA therapeutic recommendations.

CD8+ tissue-resident memory T-cell development depends on infection-matching regulatory T-cell types.

Immunological memory is critical for immune protection, particularly at epithelial sites, which are under constant risk of pathogen invasions. To counter invading pathogens, CD8+ memory T cells develop at the location of infection: tissue-resident memory T cells (TRM). CD8+ T-cell responses are associated with type-1 infections and type-1 regulatory T cells (TREG) are important for CD8+ T-cell development, however, if CD8+ TRM cells develop under other infection types and require immune type-specific TREG cells is unknown. We used three distinct lung infection models, to show that type-2 helminth infection does not establish CD8+ TRM cells. Intracellular (type-1) and extracellular (type-3) infections do and rely on the recruitment of response type-matching TREG population contributing transforming growth factor-ß. Nevertheless, type-1 TREG cells remain the most important population for TRM cell development. Once established, TRM cells maintain their immune type profile. These results may have implications in the development of vaccines inducing CD8+ TRM cells.

Genetic screening in a Brazilian cohort with inborn errors of immunity.

BACKGROUND: Inherited genetic defects in immune system-related genes can result in Inborn Errors of Immunity (IEI), also known as Primary Immunodeficiencies (PID). Diagnosis of IEI disorders is challenging due to overlapping clinical manifestations. Accurate identification of disease-causing germline variants is crucial for appropriate treatment, prognosis, and genetic counseling. However, genetic sequencing is challenging in low-income countries like Brazil. This study aimed to perform genetic screening on patients treated within Brazil's public Unified Health System to identify candidate genetic variants associated with the patient's phenotype. METHODS: Thirteen singleton unrelated patients from three hospitals in Rio de Janeiro were enrolled in this study. Genomic DNA was extracted from the peripheral blood lymphocytes of each patient, and whole exome sequencing (WES) analyses were conducted using Illumina NextSeq. Germline genetic variants in IEI-related genes were prioritized using a computational framework considering their molecular consequence in coding regions; minor allele frequency ≤ 0.01; pathogenicity classification based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines gathered from the VarSome clinical database; and IEI-related phenotype using the Franklin tool. The genes classification into IEI categories follows internationally recognized guidelines informed by the International Union of Immunological Societies Expert Committee. Additional methods for confirmation of the variant included Sanger sequencing, phasing analysis, and splice site prediction. RESULTS: A total of 16 disease-causing variants in nine genes, encompassing six different IEI categories, were identified. X-Linked Agammaglobulinemia, caused by BTK variations, emerged as the most prevalent IEI disorder in the cohort. However, pathogenic and likely pathogenic variants were also reported in other known IEI-related genes, namely CD40LG, CARD11, WAS, CYBB, C6, and LRBA. Interestingly, two patients with suspected IEI exhibited pathogenic variants in non-IEI-related genes, ABCA12 and SLC25A13, potentially explaining their phenotypes. CONCLUSIONS: Genetic screening through WES enabled the detection of potentially harmful variants associated with IEI disorders. These findings contribute to a better understanding of patients' clinical manifestations by elucidating the genetic basis underlying their phenotypes.

Fate of microbial contamination in a South European Coastal Lagoon (Ria Formosa) under the influence of treated effluents dispersal.

AIM: Assessment of the fate of microbial contamination driven from treated wastewater disposal at a highly productive zone on a South European coastal lagoon (Ria Formosa). METHODS AND RESULTS: Microbial indicators of contamination (Total coliforms, Escherichia coli, and Enterococci) were evaluated monthly during September 2018-September 2020 at three study areas (Faro, Olhão, and Tavira) under different wastewater discharge flows and hydrodynamic conditions. Additional data on E. coli monitoring in bivalves, available from the national institution responsible for their surveillance was also considered. The maximum microbial contamination was found at Faro, the highest-load and less-flushed study area, contrasting the lowest contamination at Olhão, a lower-load and strongly flushed area. The wastewater impact decreased along the spatial dispersal gradients and during high water, particularly at Faro and Tavira study areas, due to a considerable dilution effect. Microbial contamination at Olhão increased during the summer, while at the other study areas seasonal evidence was not clear. Data also indicate that E. coli in bivalves from bivalve production zones next to the three study areas reflected the differentiated impact of the wastewater treatment plants effluents on the water quality of those areas. CONCLUSIONS: Effluent loads together with local hydrodynamics, water temperature, solar radiation, precipitation, and land runoff as well as seabirds populations and environmentally adapted faecal or renaturelized bacterial communities, contributed to microbial contamination of the study areas.

Prevalence, management and efficacy of treatment in portal vein obstruction after paediatric liver transplantation: protocol of the retrospective international multicentre PORTAL registry.

INTRODUCTION: Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO. METHODS AND ANALYSIS: The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged <18 years) with a diagnosed PVO between 1 January 2001 and 1 January 2021 after liver transplantation will be eligible for inclusion. The primary endpoints are the prevalence of PVO, primary and secondary patency after PVO intervention and current management practices. Secondary endpoints are patient and graft survival, severe complications of PVO and technical success of revascularisation techniques. ETHICS AND DISSEMINATION: Medical Ethics Review Board of the University Medical Center Groningen has approved the study (METc 2021/072). The results of this study will be disseminated via peer-reviewed publications and scientific presentations at national and international conferences. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL9261).

Assessing whole-exome sequencing data from undiagnosed Brazilian patients to improve the diagnostic yield of inborn errors of immunity.

OBJECTIVES: Inborn error of immunity (IEI) comprises a broad group of inherited immunological disorders that usually display an overlap in many clinical manifestations challenging their diagnosis. The identification of disease-causing variants from whole-exome sequencing (WES) data comprises the gold-standard approach to ascertain IEI diagnosis. The efforts to increase the availability of clinically relevant genomic data for these disorders constitute an important improvement in the study of rare genetic disorders. This work aims to make available WES data of Brazilian patients' suspicion of IEI without a genetic diagnosis. We foresee a broad use of this dataset by the scientific community in order to provide a more accurate diagnosis of IEI disorders. DATA DESCRIPTION: Twenty singleton unrelated patients treated at four different hospitals in the state of Rio de Janeiro, Brazil were enrolled in our study. Half of the patients were male with mean ages of 9 ± 3, while females were 12 ± 10 years old. The WES was performed in the Illumina NextSeq platform with at least 90% of sequenced bases with a minimum of 30 reads depth. Each sample had an average of 20,274 variants, comprising 116 classified as rare pathogenic or likely pathogenic according to American College of Medical Genetics and Genomics and the Association (ACMG) guidelines. The genotype-phenotype association was impaired by the lack of detailed clinical and laboratory information, besides the unavailability of molecular and functional studies which, comprise the limitations of this study. Overall, the access to clinical exome sequencing data is limited, challenging exploratory analyses and the understanding of genetic mechanisms underlying disorders. Therefore, by making these data available, we aim to increase the number of WES data from Brazilian samples despite contributing to the study of monogenic IEI-disorders.

Adherence, safety, and satisfaction of a cardio-oncology rehabilitation program framework versus community exercise training for cancer survivors: findings from the CORE trial.

PURPOSE: To assess safety, satisfaction, and overall adherence of a center-based cardiac rehabilitation (CBCR) program for cancer survivors at increased cardiovascular (CV) risk, compared to community-based exercise training (CBET). METHODS: The CORE study was a single-center, prospective, randomized controlled trial enrolling cancer survivors exposed to cardiotoxic cancer treatment and/or with previous CV disease. Participants were randomized to an 8-week CBCR program or CBET, twice a week. Overall feasibility (consent, retention, and completion rates), intervention adherence (percentage of exercise sessions attended), and safety were assessed. Adverse events (AEs) were registered, and participants' satisfaction was measured at the end of the study. RESULTS: Eighty out of 116 potentially eligible individuals were included; consent rate was 72.4%, and 77 (96.2%) started the study (retention rate 100% in CBCR vs 92.5% in CBET); completion rate was 92.5%. Intervention adherence was higher in CBCR (90.3 ± 11.8% vs 68.4 ± 22.1%, p < 0.001). Exercise-related AEs were mainly related to musculoskeletal conditions in both groups (7 in CBCR vs 20 in CBET, p < 0.001), accounting for exercise prescription modification in 47 sessions (18 (3.3%) in CBCR vs 29 (7.2%) in CBET, p = 0.006), none motivating exercise discontinuation. No participants reported major CV events. Overall, the satisfaction with the different aspects of the programs (e.g., expectations, monitoring) was higher in the CBCR. CONCLUSION: This exploratory analysis of the CORE trial suggests that both exercise-based interventions are feasible and safe in this setting. The higher intervention adherence and patient satisfaction in CBCR suggest that this comprehensive approach could be of interest in this population.