Brazilian Patients Research Articles

A pilot study of mitochondrial genomic ancestry in admixed Brazilian patients with type 1 diabetes

Interactions between multiple genes and environmental factors could be related to the pathogenesis of type 1 diabetes (T1D). The Brazilian population results from different historical miscegenation events, resulting in a highly diverse genetic pool. This study aimed to analyze the mtDNA of patients with T1D and to investigate whether there is a relationship between maternal ancestry, self-reported color and the presence of T1D. The mtDNA control region of 204 patients with T1D residing in three geographic regions of Brazil was sequenced following the International Society for Forensic Genetics (ISFG) recommendations. We obtained a frequency of Native American matrilineal origin (43.6%), African origin (38.2%), and European origin (18.1%). For self-declared color, 42.6% of the patients with diabetes reported that they were White, 50.9% were Brown, and 5.4% were Black. Finally, when we compared the self-declaration data with maternal ancestral origin, we found that for the self-declared White group, there was a greater percentage of haplogroups of Native American origin (50.6%); for the self-declared Black group, there was a greater percentage of African haplogroups (90.9%); and for the Brown group, there was a similar percentage of Native American and African haplogroups (42.3% and 45.2%, respectively). The Brazilian population with diabetic has a maternal heritage of more than 80% Native American and African origin, corroborating the country’s colonization history.

Mapping Strategies for Strengthening Safety Culture: A Scoping Review.

Twenty years after the "To Err Is Human" report, one in ten patients still suffer harm in hospitals in high-income countries, highlighting the need to strengthen the culture of safety in healthcare. This scoping review aims to map patient safety culture strengthening strategies described in the literature. This scoping review follows the JBI methodology. It adhered to all scoping review checklist items (PRISMA-ScR) with searches in the Lilacs, MedLine, IBECS, and PubMed databases and on the official websites of Brazilian and North American patient safety organizations. The research took place during the year 2023. In total, 58 studies comprising 52 articles and 6 documents from health organizations were included. Various strategies were identified and grouped into seven categories based on similarity, highlighting the need for a comprehensive organizational approach to improve patient care. The most described strategies were communication (69%), followed by teamwork (58.6%) and active leadership (56.9%). The identified strategies can promote the development of a culture in which an organization can achieve patient safety, involving practices and attitudes that reduce risks and errors in healthcare. However, the identification of strategies is limited because it is restricted to certain databases and websites of international organizations and does not cover a broader spectrum of sources. Furthermore, the effectiveness of these strategies in improving patient safety culture has not yet been evaluated.

Identification of a founder effect involving n.197C>T variant in RMRP gene associated to cartilage-hair hypoplasia syndrome in Brazilian patients

Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder frequently linked to n.72A>G (previously known as n.70A>G and n.71A>G), the most common RMRP variant worldwide. More than 130 pathogenic variants in this gene have already been described associated with CHH, and founder alterations were reported in the Finnish and Japanese populations. Our previous study in Brazilian CHH patients showed a high prevalence of n.197C>T variant (former n.195C>T and n.196C>T) when compared to other populations. The aim of this study was to investigate a possible founder effect of the n.197C>T variant in the RMRP gene in a series of CHH Brazilian patients. We have selected four TAG SNPs within chromosome 9 and genotyped the probands and their parents (23 patients previously described and nine novel). A common haplotype to the n.197C>T variant carriers was identified. Patients were also characterized for 46 autosomal Ancestry Informative Markers (AIMs). European ancestry was the most prevalent (58%), followed by African (24%) and Native American (18%). Our results strengthen the hypothesis of a founder effect for the n.197C>T variant in Brazil and indicate that this variant in the RMRP gene originated from a single event on chromosome 9 with a possible European origin.

Haplotype testing of MTTP alleles on insulin resistance in patients with chronic hepatitis C

BackgroundInsulin resistance is a common manifestation among patients with chronic hepatitis C. The aim of this study was to investigate the effect of haplotypes in the microsomal triglyceride transfer protein (MTTP) gene on insulin resistance in Brazilian patients with chronic hepatitis C. MethodsGenetic variants in the MTTP gene were genotyped by PCR-RFLP.Results: Of the 232 patients with chronic hepatitis C, 34.5 % had insulin resistance (HOMA-IR ≥3) and the majority were ≥50 years old. The minor allele frequencies for the -400A/T (rs1800803), -164T/C (rs1800804), H297Q (rs2306985), I128T (rs3816873), Q95H (rs61733139), Q244E (rs17599091) and -493G/T (rs1800591) variants in the MTTP gene were 0.41, 0.30, 0.49, 0.30, 0.08, 0.06 and 0.32. In multivariate analysis, elevated levels of gamma-glutamyl transpeptidase (GGT) was associated with insulin resistance (p = 0.006). Haplotype-based association testing presented that the haplotype ATCTGGG of the -400A/T, -164T/C, H297Q, I128T, Q95H, Q244E and -493G/T variants was associated with the presence of insulin resistance (p = 0.028) and the haplotype TTGTGCG may be a protective factor (p = 0.012). ConclusionThe combination of alleles in the -400A/T, -164T/C, H297Q, I128T, Q95H, Q244E and -493G/T genetic variants in the MTTP gene may play a relevant role in insulin resistance among patients with chronic hepatitis C.

Real-World Study of Adjuvant Biosimilar Trastuzumab-dkst for HER2-Positive Breast Cancer Treatment in a Brazilian Population.

Biological monoclonal antibodies play a pivotal role in cancer treatment, with biosimilars significantly enhancing their accessibility. In Brazil's ethnically diverse setting, real-world evidence is crucial for assessing the effectiveness and applicability of these therapies in routine clinical practice. We performed a multicentric, observational, prospective real-world study on biosimilar trastuzumab-dkst for adjuvant treatment of early HER2-positive breast cancer in Brazilian patients. Data were collected using a case-report form. Of the 176 recruited, we present data from the first 59 patients (mean age 51.7 ± 12.9years) who had completed treatment with trastuzumab-dkst. The mean time from diagnosis to the first adjuvant treatment with trastuzumab-dkst was 5.5 ± 2.7months. Of the patients, 59% of patients achieved at least a 30-month follow-up. The 31.7-month invasive disease-free survival rate (IDFS) was 94.5% (95% CI 83.9-98.2%) and median IDFS was not achieved, since only three patients had invasive disease recurrence. The overall survival rate was 100% until the last assessment. The observed adverse events were similar to those presented by other studies using biosimilar or reference trastuzumab. Four serious adverse events (8.5%) were observed. A reduction in left ventricular ejection fraction of at least 10% was observed in 16.9% of participants. There was no treatment interruption, and three participants (5.1%) had their trastuzumab-dkst dose reduced. Our study reinforces the existing pivotal data, underscoring the real-world efficacy and safety of biosimilar trastuzumab-dkst in the adjuvant treatment for early HER2-positive breast cancer. The preliminary long-term effectiveness and safety data we present further validate trastuzumab-dkst's role as a cost-saving alternative in oncological care. These findings have important implications for improving patient access to crucial treatments and for the more efficient use of healthcare resources. NCT03892655.

Long-Term Safety and Effectiveness of Rituximab Biosimilar RTXM83: A Retrospective Extension Study in Brazilian Patients with Diffuse Large B-Cell Lymphoma.

RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical,and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption. In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01-11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment. The median follow-up period was 77.0months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group. This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care. ClinicalTrials.gov Identifier:NCT04928573. June 16, 2021, "retrospectively registered".

Comprehensive analysis of morbidity and mortality patterns in familial partial lipodystrophy patients: insights from a population study.

There is a lack of information on the clinical and molecular presentation of familial partial lipodystrophy (FPLD), a rare genetic disorder characterized by partial subcutaneous fat loss. This study aimed to provide a comprehensive assessment of the clinical, metabolic, and genetic features of FPLD in the Brazilian population. In a multicenter cross-sectional investigation we evaluated patients with FPLD across five Brazilian reference centers for lipodystrophies. Diagnosis of FPLD was made by clinical evaluation and genetic confirmation. Data on genetic, clinical, and metabolic characteristics were captured. Statistical analysis involved the utilization of the Kruskal-Wallis test to identify differences. The study included 106 patients with genetic confirmation of FPLD. The mean age was 44 ± 15 years, and they were predominantly female (78.3%). LMNA pathogenic variants were identified in 85.8% of patients, PPARG in 10.4%, PLIN1 in 2.8%, and MFN2 in 0.9%. Diabetes mellitus (DM) was highly prevalent (57.5%), affecting 54 females (50.9%). Median triglycerides levels were 199 mg/dL (54-2724 mg/dL), severe hypertriglyceridemia (≥ 500 mg/dL) was found in 34.9% and pancreatitis in 8.5%. Metabolic-associated fatty liver disease (MAFLD) was observed in 56.6%, and cardiovascular disease in 10.4%. The overall mortality rate was 3.8%, due to cardiovascular events. This study presents an extensive cohort of Brazilian patients with FPLD, predominantly DM with several multisystem complications. A comprehensive characterization of lipodystrophy syndromes is crucial for effective patient management and care.

Advance care planning and predictive factors among Brazilian patients with cancer from an outpatient palliative care program.

e24062 Background: Advance care planning (ACP) is crucial for informed decision-making in patient care. However, barriers such as time constraints and discomfort with discussions hinder widespread ACP adoption. A previous study (Cohen et al. JNCCN 2023) indicated a low ACP engagement rate (17%), but participation in a palliative care program has shown potential to increase this proportion. Therefore, we sought to determine the prevalence of ACP and identify associated predictor factors among patients with cancer in Brazil enrolled in an outpatient palliative care (OPC) program. Methods: A retrospective analysis was performed from November 2022 to December 2023. Eligible patients were those who passed away during the study period and had received care from an OPC program at one of the largest private joint cancer centers in Latin America. We assessed the prevalence of ACP and explored its potential associations with clinical characteristics (age, gender and type of cancer), OCP support (follow-up period, appointments and family support), and end-of-life care (treatment in the past month, intensive care unit (ICU) admission in the past month, home care service referrals, and place of death).Comparative analyses involved two groups: those who had undergone ACP and those who had not (no-ACP). Logistic models were employed. Results: A total of 849 patients were included in the final analyses. Patients’ characteristics were well balanced between groups. Most patients were women (56%), with an average of 68.2 years (SD =15.3). Patients were mostly diagnosed with gastrointestinal (36%), breast (13%), and lung (13%) cancers. Notably, 43% of patients had ACP, significantly higher than literature controls (95% confidence interval [CI]= 22-31%, P = 0.001). Among the factors associated with ACP, clinical characteristics were not significant. However, OCP support and end-of-life care were significantly predicted by ACP, including the follow-up period (MACP= 179 vs. Mno-ACP= 101; P = 0.001), family support (MACP= 0.6 vs. Mno-ACP= 0.3; P < 0.001) , ICU admission at the last 30 days of life (ACP = 28% vs. no-ACP = 72%; P < 0.001), and home care service referral (ACP = 72% vs. no-ACP = 28%; P < 0.001). Conclusions: These findings underscore that prolonged engagement with the OPC program is associated with increased adoption of ACP among Brazilian patients with cancer. Given the scarcity of data from developing countries, our findings suggest that the OPC program plays a pivotal role in optimizing end-of life care support through ACP.

Pediatric Asthma Therapy Assessment Questionnaire for the Brazilian population: Cross-cultural adaptation and measurement properties.

To cross-culturally adapt the Pediatric Asthma Therapy Assessment Questionnaire (ATAQ) into Brazilian Portuguese and analyze its measurement properties. This exploratory methodological study included eight experts and 30 caregivers in the translation and cross-cultural adaptation steps. Thereafter, 118 caregivers of pediatric patients with asthma aged between 5 and 17 years were involved in the analysis of measurement properties. We analyzed the content, structural (exploratory and confirmatory factorial), construct (convergent and discriminant), and known-groups validities; floor and ceiling effects; and determined the cut-off point (receiver operator characteristic curve) to identify pediatric patients with uncontrolled asthma. Intraclass correlation coefficient (ICC) analyzed test-retest reliability with 54 caregivers, whereas Cronbach's α and composite reliability verified the internal consistency of the items. The committee of experts and caregivers found the instructions and response options relevant, understandable, and clear (K > 0.75). During the cross-cultural adaptation, three items (2, 4, and 12) were slightly modified by including terms to facilitate understanding. A two-factor structure (asthma control and patient-provider communication) was identified. Internal consistency (α > .67; composite reliability > 0.73) and test-retest reliability (ICC > 0.80) were acceptable. For construct and know-groups validities, 85.71% of the hypothesis were confirmed. A cut-off point of >3 for the control domain was considered adequate to identify pediatric patients with uncontrolled asthma (sensitivity: 86.21%; specificity: 80.90%). The Pediatric ATAQ was adequately adapted for Brazilian pediatric patients with asthma and produced valid and reliable measures for assessing asthma control. Therefore, it may be considered an adequate instrument for monitoring asthma control in the Brazilian pediatric population.

Real-world treatment patterns and clinical outcomes among patients with HR+/HER2- advanced/metastatic breast cancer receiving palbociclib in Brazil: IRIS study.

e13088 Background: Palbociclib was approved for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (aBC/mBC) in Brazil in 2018. Worldwide studies explore palbociclib's real-world use and outcomes; however, this data is not available for Brazilian patients. IRIS Brazil study aimed to describe demographic/clinical characteristics, treatment and clinical outcomes of adult female patients who have received palbociclib as first-line treatment for HR+/HER2- aBC/mBC in private healthcare institutions in Brazil. Methods: This retrospective descriptive study included females aged 18 years or older diagnosed with HR+/HER2- aBC/mBC and those who had received palbociclib as their initial line of therapy. The study analyzed variables such as demographics, clinical characteristics, treatment history, palbociclib combinations, and clinical outcomes. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier estimates at 6- and 12-month time points. Results: A total of 121 patients were included in the study. The mean age was 54.4 years, and 82 (67.7%) were menopausal at diagnosis. A total of 51 patients (42.1%) were treated with palbociclib + fulvestrant, while 67 (55.8%) were treated with palbociclib + aromatase inhibitors. The majority of patients (n = 79; 65.3%) did not require any dose adjustments. Among the 40 patients (33.1%) who required dose adjustments, the main reason was adverse events/toxicity (n = 36; 90%). The PFS rates at 6 and 12 months were 78% and 60%, respectively. The OS rates at 6 and 12 months were 86% and 70%, respectively. Conclusions: Results from this initial real-world assessment of clinical outcomes in Brazil suggest that Palbociclib combinations exhibit favorable effectiveness in treating HR+/HER2- aBC/mBC disease, as measured by PFS and OS rates.

Clinical and Genetic Characterization of a Cohort of Brazilian Patients With Congenital Ataxia.

Congenital ataxias are rare hereditary disorders characterized by hypotonia and developmental motor delay in the first few months of life, followed by cerebellar ataxia in early childhood. The course of the disease is predominantly nonprogressive, and many patients are incorrectly diagnosed with cerebral palsy. Despite significant advancements in next-generation sequencing in the past few decades, a specific genetic diagnosis is seldom obtained in cases of congenital ataxia. The aim of the study was to analyze the clinical, radiologic, and genetic features of a cohort of Brazilian patients with congenital ataxia. Thirty patients with a clinical diagnosis of congenital ataxia were enrolled in this study. Clinical and demographic features and neuroimaging studies were analyzed. Genetic testing (whole-exome sequencing) was also performed. A heterogeneous pattern of genetic variants was detected. Eighteen genes were involved: ALDH5A1, BRF1, CACNA1A CACNA1G, CC2D2A, CWF19L1, EXOSC3, ITPR1, KIF1A, MME, PEX10, SCN2A, SNX14, SPTBN2, STXBP1, TMEM240, THG1L, and TUBB4A. Pathogenic/likely pathogenic variants involving 11 genes (ALDH5A1, CACNA1A, EXOSC3, MME, ITPR1, KIF1A, STXBP1, SNX14, SPTBN2, TMEM240, and TUBB4A) were identified in 46.7% of patients. Variants of uncertain significance involving 8 genes were detected in 33.3% of patients. Congenital ataxias were characterized by a broad phenotype. A genetic diagnosis was more often obtained in patients with cerebellar-plus syndrome than in patients with a pure cerebellar syndrome. This study re-emphasizes the genetic heterogeneity of congenital ataxias and the absence of a clear phenotype-genotype relationship. A specific genetic diagnosis was established in 46.7% of patients. Autosomal dominant, associated with sporadic cases, was recognized as an important genetic inheritance. The results of this analysis highlight the value of whole-exome sequencing as an efficient screening tool in patients with congenital ataxia.

A portrait of germline pathogenic variants from a large real-world cohort of Brazilian patients with breast cancer.

10593 Background: The estimated prevalence of germline pathogenic/likely pathogenic variants (P/LP) in high and moderate penetrance (HMP) genes is around 7-10% among women with breast cancer (BC). Up to 50% of all hereditary BC cases are due to germline variants in BRCA1/2, but other HMP genes are increasing in relevance. The prevalence and spectrum of BC P/LP variants are affected by age at diagnosis, race/ethnicity, geographical region, BC molecular subtype. Methods: Retrospective cohort study to evaluate the germline profile of P/LP variants in HMP genes ( BRCA1, BRCA2, PALB2, TP53, CDH1, NF1, PTEN, STK11, CHEK2, ATM, BARD1, RAD51C and RAD51D) in women diagnosed with BC in Brazil. All patients were tested in a single reference laboratory (Oncoclinicas [OC] Precision Medicine) using multi-gene NGS panels covering from 35 to 105 genes. Primary endpoint was the prevalence of P/LP variants and VUS in BRCA1/2as well as in other HMP BC genes, in overall population and according to age and BC subtype. Clinical and pathological data were retrieved from curated Real-World Database of OC Group and used as reference for demographics comparisons. Results: This cohort involved 2,207 women with BC from 2019 to 2023. The majority of pts (79.7%) were from Southeastern Brazil, followed by Midwestern (5.6%), Southern (5.0%) and Northeastern (4.8%) Brazil. The median age at genetic testing was 47 years and most patients (59.4%) were ≤ 50 years. As reference, median age is 57 years in the overall BC population treated at OC (> 20,000 during the study period). BC subtype was available in 641 cases, 264 pts (41.2%) were HR+/HER2-, 116 (18.1%) were HER2+ and 261 (40.7%) were triple negative (TNBC). In the OC Database, TNBC represents only 15% of all new BC cases. Overall, 217 (9.8%) had a P/LP in HMP genes, including 131 (5.9%) pts who had a BRCA1/2 P/LP variant and 86 (3.9%) who had a P/LP variant in other HMP BC genes. The most frequent LP/PV variants were found in BRCA2 (31%) / BRCA1 (29%) / TP53 (13%) / PALB2 (9%) / CHEK2 (9%). A TP53founder pathogenic variant (R337H) accounted for 75% of all TP53 LP/PV. The deleterious variants were more common in pts ≤50 years (12%) than in pts > 50 (7%) as well as in patients with TNBC (14%) followed by HER2+ (9%) and HR+/HER2- (7%). The BRCA1/2 P/LP variants were higher in TNBC pts (8%) than in HR+/HER2- (4%) and HER2+ (3%). The overall VUS rate in the HMP genes was 20%. The most frequent VUS were found in ATM, BRCA2, NF1 and CHEK2genes. Conclusions: Studies involving germline profile of P/LP variants in cancer genes have provided a broader understanding of BC risk and have opened doors to new therapeutic or surveillance strategies across all subtypes. In Brazil, the prevalence of deleterious variants in HMP is comparable to published US and EU cohorts. However, in the real-world community practice, testing is still limited to populations with higher baseline risk for hereditary BC, such as young patients with TNBC.

Immune system evaluation in a cohort of Brazilian patients with head and neck squamous cell carcinoma who are non-smokers and alcoholic beverages abstainers.

e18030 Background: Smoking and alcohol abuse are the main risk factors for head and neck squamous cell carcinoma. However, some patients do not present clear risk factors. We are studying a cohort of Brazilian patients that are non-smokers and alcoholic beverage abstainers. Brazilian people have peculiar ethnic characteristics, reflecting a miscegenation of Europeans, Africans and Amerindians. There is evidence that ethnic background may influence germline and somatic mutations, as well as tumor behavior. One of the aims is to evaluate the immune system of this cohort of miscegenated head and neck squamous cell carcinoma patients who are non-smokers and alcoholic beverages abstainers. Methods: In this prospective study, until now we have included 16 patients: 10 women and 6 men, who were non-smokers and alcoholic abstainers. All patients answered a questionnaire and collected blood, saliva and tumor samples before treatment for analysis. Self-declared skin color was mainly brown (n=8,) followed by white (n=6), black (n=1) and yellow (n=1). The median age was 56.5 years. Patients were diagnosed with oral (n=10), glotic (n=1), oropharyngeal (N=1,) lip and gingiva (n=4) carcinoma; clinical stages I (n=3), II (n=6); III (n=1) and IVA (n=5). Fourteen patients were already operated on. Results: Peripheral blood analysis revealed that within the mononuclear cell population CD16+CD66b-HLA-DR- cells, possibly NK, were significantly more frequent in patients with cancer stage III and IVA, than in patients with cancer stages I and II. There was also a significant negative correlation between the frequency of CD16+ cells in the mononuclear population and age of the patients. Finally, we observed that in the granulocyte population, patients with lesion grade I and II have 20-fold more CD16+CD66b+PD-L1+ cells than patients with lesions grade III and IV. It is possible that an IFN gamma driven response may be, in part, responsible for the induction of PD-L1 expression in granulocytes. This hypothesis is corroborated by the positive correlation between PD-L1 expression level in the granulocyte population and the frequency of CD16+CD66b- population (p=0.01, Pearson correlation 0.62). No other parameter, which included lymphocytes T and B, and monocytes, displayed correlation with clinical data. Conclusions: Our results suggest NK and myeloid cell frequency may vary in our cohort according to lesion grade as a consequence of immune responses. However, these are preliminary results, and other parameters acquisition, as well as a larger sample, will be needed for definitive conclusions.

Genetic Characterization and Population Structure of Drug-Resistant Mycobacterium tuberculosis Isolated from Brazilian Patients Using Whole-Genome Sequencing.

The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug-resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensive resistance (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides the analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definitions. Sub-lineage 4.3 (52%) was the most frequent genotype, and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected twenty novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. A cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug resistance prediction, presenting the best accuracy values for five of the nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB (p = 0.03) and either phenotypic (p = 0.006) or genotypic (p = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil and the genetic and clinical data correlations and demonstrated its utility for surveillance efforts regarding the spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates.

The impact of smoking on COVID-19-related mortality: a Brazilian national cohort study

IntroductionCurrent evidence suggests the potential heightened vulnerability of smokers to severe coronavirus disease (COVID-19) outcomes. AimsThis study aimed to analyze the clinical outcomes and mortality related to tobacco use in a cohort of hospitalized Brazilian COVID-19 patients. MethodsThis retrospective cohort study analyzed adults hospitalized for COVID-19 in Brazil using the SIVEP-Gripe database (official data reported by public and private healthcare facilities for monitoring severe acute respiratory syndrome cases in Brazil). The inclusion criteria were patients over 18 years of age with a positive RT-qPCR test for SARS-CoV-2. The analysis focused on in-hospital mortality, considering smoking as an exposure variable, and included covariates such as age, gender, and comorbidities. Smoking history was collected from the self-reported field in the database. Statistical analyses included descriptive statistics, crude Odds Ratios, and multivariable binary logistic regression. ResultsThis study included 2,124,285 COVID-19 patients, among whom 44,774 (2.1 %) were smokers. The average age of the smokers was higher than that of the never-smokers (65.3 years vs. 59.7 years). The clinical outcomes revealed that smokers had higher rates of intensive care unit admission (51.6 % vs. 37.2 % for never-smokers), invasive ventilatory support (31.5 % vs. 20.2 % for never-smokers), and higher mortality (42.7 % vs. 31.8 % for never smokers). In the multivariable analysis, smokers demonstrated a heightened risk of death (aOR 1.23; 95 % CI 1.19–1.25). ConclusionsThis large populational-based cohort study confirms the current evidence and underscore the critical importance of recognizing smoking as a substantial risk factor for adverse outcomes in COVID-19 patients.

Dental Profile of Brazilian Patients with Rare Skeletal Genetic Disorders: Clinical Features and Associated Factors.

The aim of this study is to compare the dental profiles of Brazilian patients with rare genetic skeletal disorders and normotypical patients. A cross-sectional study was carried out with 210 individuals aged between 2 and 54 years old [105 with rare diseases (Mucopolysaccharidosis/MPS n = 27 and Osteogenesis Imperfecta/OI n = 78) and 105 without rare diseases] and their parents/caregivers. The parents/caregivers answered a questionnaire about individual aspects of their child and the dental profile was identified from questions related to dental history and the presence/absence of dental problems. The patients' oral cavity was also examined by three examiners for dental caries, malocclusion, gingivitis, and dental anomalies. The average age of individuals with a rare disease was 14.1 years (±12.2) and the median was 9.5 years. Participants who had already used the public health system (SUS) dental care services had a 2.24 times higher chance of belonging to the group with a rare disease (OR = 2.24; 95% CI: 1.07-4.89). Patients with rare diseases are 14.86 times more likely to have difficulty receiving dental treatment (OR = 14.86; 95% CI: 5.96-27.03) and 10.38 times more likely to have one or more dental problems (OR = 10.38; 95% CI: 1.95-35.17). Individuals with rare disorders have a greater history of difficulty in accessing dental treatment, using the SUS, and were diagnosed with more dental problems compared to normotypical individuals.

Global Cardiac Surgery in Brazil: A Call to Action.

Global Cardiac Surgery is an innovative initiative with a focus on improving health outcomes and achieving healthcare equity for individuals worldwide affected by cardiac surgical conditions or in need of cardiac surgical care. Considering the existing disparities in access to cardiac surgery and the substantial burden of cardiac conditions amenable to surgical procedures in Brazil, it is imperative to support and scale Global Cardiac Surgery initiatives and leave no Brazilian patient behind. Here, we advocate for national initiatives within this field and highlight opportunities and challenges to support their development.

Genetic profile of Brazilian patients with LAMA2-related dystrophies.

LAMA2-related dystrophies (LAMA2-RD) constitute a rare neuromuscular disorder with a broad spectrum of phenotypic severity. Our understanding of the genotype-phenotype correlations in this condition remains incomplete, and reliable clinical data for clinical trial readiness is limited. In this retrospective study, we reviewed the genetic data and medical records of 114 LAMA2-RD patients enrolled at seven research centers in Brazil. We identified 58 different pathogenic variants, including 21 novel ones. Six variants were more prevalent and were present in 81.5% of the patients. Notably, the c.1255del, c.2049_2050del, c.3976 C>T, c.5234+1G>A, and c.4739dup variants were found in patients unable to walk and without cortical malformation. In contrast, the c.2461A>C variant was present in patients who could walk unassisted. Among ambulatory patients, missense variants were more prevalent (p < 0.0001). Although no specific hotspot regions existed in the LAMA2, 51% of point mutations were in the LN domain, and 88% of the missense variants were found within this domain. Functional analysis was performed in one intronic variant (c.4960-17C>A) and revealed an out-of-frame transcript, indicating that the variant creates a cryptic splicing site (AG). Our study has shed light on crucial phenotype-genotype correlations and provided valuable insights, particularly regarding the Latin American population.

GATA genotype and FY*B(-67T&gt;C) polymorphism as a cheap and reliable tool to evaluate ethnicity in Brazilian patients submitted to autologous transplantation

Abstract Collecting high quality data on race and ethnicity is crucial for clinical research, notably in genetic association studies, to avoid confounding by different ethnic background among patients, a bias referred to as population stratification. In Brazil, to describe race we commonly use the National Institute of Geography and Statistics (IBGE) classification, so-called “self-declared color”, but it is acknowledged that defining ancestry by phenotypic characteristics, especially in countries with highly mixed population like Brazil, can be misleading. We aimed to evaluate the relationship between the GATA FY*B(-67T&gt;C) polymorphism and self-declared race in Brazilian patients undergoing autologous transplantation and verify the feasibility of using this test as a more reliable tool to evaluate ethnicity in this population. Methods: We conducted a study to evaluate the association of candidate-gene polymorphisms and toxicities after autologous stem-cell transplantation (ASCT) in adult patients with lymphoma or myeloma from 2015 to 2021 in two Brazilian transplant centers. All patients with available DNA to study genetic polymorphisms were included. In this analysis we evaluate the association between GATA polymorphism and self-declared color in this cohort. Results: A total of 217 patients were included in this analysis. Median age at transplantation was 56 years (21-79) and 130 patients (59.9%) were male. Most patients were self-declared white (n=175, 80.6%) and the most common genotype was GATA67T/T (wild type/wild type) (n=142, 65.4%). Among the self-declared white patients, 73.1% were genotyped as GATA67T/T and 4.0% as GATA-67C/C, while among the non-white patients 21.4% were genotyped as GATA-67C/C (p&lt;.001). The allele FY*B(-67T&gt;C) frequency was 0.22 in the whole population; it was identified in 26.9% of the self-declared white patients and in 66.6% of the non-white (p&lt;.001). Twelve-month overall survival was 86.6% (95% CI 79.9 - 91.2%), with no difference according to self-declared race (86.8% vs 85.5% for white and non-white patients, respectively, p=0.81) or the presence of the allele FY*B(-67T&gt;C) (85.2% vs 89.9% for non-mutated and mutated patients, respectively, p=0.27). Conclusion: GATA FY*B(-67T&gt;C) polymorphism is associated to self-declared race in Brazilian patients submitted to ASCT. Given the importance of correctly evaluating ancestry in genetic association studies in transplantation, GATA FY*B(-67T&gt;C) polymorphism can be used as a more accurate tool in populations with mixed ethnic/racial background.

Neuropsychological Profile of 25 Brazilian Patients with 22q11.2 Deletion Syndrome: Effects of Clinical and Socioeconomic Variables.

The 22q11.2 deletion syndrome (22q11.2DS) is associated with a heterogeneous neurocognitive phenotype, which includes psychiatric disorders. However, few studies have investigated the influence of socioeconomic variables on intellectual variability. The aim of this study was to investigate the cognitive profile of 25 patients, aged 7 to 32 years, with a typical ≈3 Mb 22q11.2 deletion, considering intellectual, adaptive, and neuropsychological functioning. Univariate linear regression analysis explored the influence of socioeconomic variables on intellectual quotient (IQ) and global adaptive behavior. Associations with relevant clinical conditions such as seizures, recurrent infections, and heart diseases were also considered. Results showed IQ scores ranging from 42 to 104. Communication, executive functions, attention, and visuoconstructive skills were the most impaired in the sample. The study found effects of access to quality education, family socioeconomic status (SES), and caregiver education level on IQ. Conversely, age at diagnosis and language delay were associated with outcomes in adaptive behavior. This characterization may be useful for better understanding the influence of social-environmental factors on the development of patients with 22q11.2 deletion syndrome, as well as for intervention processes aimed at improving their quality of life.