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Background:  Hereditary transthyretin amyloidosis (ATTRv) is an inherited, progressive, and fatal disease still largely underdiagnosed. Mutations in the transthyretin ( TTR ) gene cause the TTR protein to destabilize, misfold, aggregate, and deposit in body tissues, which makes ATTRv a disease with heterogeneous clinical phenotype., Objective:  To describe the long-term efficacy and safety of inotersen therapy in patients with ATTRv peripheral neuropathy (ATTRv-PN)., Methods:  Patients who completed the NEURO-TTR pivotal study and the NEURO-TTR OLE open-label extension study migrated to the present study and were followed-up for at least 18 more months to an average of 67 months and up to 76 months since day 1 of the inotersen therapy (D1-first dose of inotersen). Disease progression was evaluated by standard measures., Results:  Ten ATTRv-PN patients with Val30Met mutation were included. The mean disease duration on D1 was of 3 years, and the mean age of the patients was of 46.8 years. During an additional 18-month follow up, neurological function, based on the Neuropathy Impairment Score and the Polyneuropathy Disability Score, functionality aspects (Karnofsky Performance Status), and nutritional and cardiac aspects were maintained. No new safety signs have been noted., Conclusion:  The treatment with inotersen was effective and well tolerated for the average of 67 months and up to 76 months. Our results are consistent with those of larger phase-III trials., Competing Interests: MWC received honoraria from NHI, Prothena, FoldRx, Ionis Pharmaceuticals, Akcea Therapeutics, Pfizer, Alnylan Pharmaceuticals, PTC Therapeutics, SOBI, and Genzyme for travel expenses, as a consultant member and as principal investigator in clinical trials. No potential competing interest was reported by the other authors., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Background: Tuberculosis (TB) treatment-related adverse drug reactions (TB-ADRs) can negatively affect adherence and treatment success rates., Methods: We developed prediction models for TB-ADRs, considering participants with drug-susceptible pulmonary TB who initiated standard TB therapy. TB-ADRs were determined by the physician attending the participant, assessing causality to TB drugs, the affected organ system, and grade. Potential baseline predictors of TB-ADR included concomitant medication (CM) use, human immunodeficiency virus (HIV) status, glycated hemoglobin (HbA1c), age, body mass index (BMI), sex, substance use, and TB drug metabolism variables (NAT2 acetylator profiles). The models were developed through bootstrapped backward selection. Cox regression was used to evaluate TB-ADR risk., Results: There were 156 TB-ADRs among 102 of the 945 (11%) participants included. Most TB-ADRs were hepatic (n = 82 [53%]), of moderate severity (grade 2; n = 121 [78%]), and occurred in NAT2 slow acetylators (n = 62 [61%]). The main prediction model included CM use, HbA1c, alcohol use, HIV seropositivity, BMI, and age, with robust performance (c-statistic = 0.79 [95% confidence interval {CI}, .74-.83) and fit (optimism-corrected slope and intercept of -0.09 and 0.94, respectively). An alternative model replacing BMI with NAT2 had similar performance. HIV seropositivity (hazard ratio [HR], 2.68 [95% CI, 1.75-4.09]) and CM use (HR, 5.26 [95% CI, 2.63-10.52]) increased TB-ADR risk., Conclusions: The models, with clinical variables and with NAT2, were highly predictive of TB-ADRs., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In Brazil, data on the management of triple negative breast cancer (TNBC) as well as the burden of the disease in terms of health care resources utilization (HCRU) are scarce. To characterize the treatment patterns and HCRU associated with the management of Brazilian TNBC patients from the perspective of the private healthcare setting. Patients with at least one claim related to ICD-10 C50 from January 2012 until December 2017, and at least one claim for breast cancer treatment were assessed from a private claims database and classified as early and locally advanced, or metastatic. All patients with hormone and/or targeted therapy were excluded. Three thousand and four patients were identified, of which 82.8% were diagnosed in early and locally advanced stages. For early and locally advanced TNBC patients, 75.3% were treated in an adjuvant setting, mainly with anthracycline regimes. For mTNBC patients, bevacizumab regimens were the main treatment prescribed. More than 48% of mTNBC patients were switched to a second line of treatment. HCRU was higher for mTNBC patients when compared to early and locally advanced patients, with higher costs for metastatic disease management. The treatment setting has little influence on the HCRU pattern or the cost of disease management. The highest burden of disease was observed for metastatic management., (© 2023. Springer Nature Limited.)

Background: Successful tuberculosis (TB) treatment is necessary for disease control. The World Health Organization (WHO) has a target TB treatment success rate of ≥90%. We assessed whether the different types of unfavorable TB treatment outcome had different predictors., Methods: Using data from Regional Prospective Observational Research for Tuberculosis-Brazil, we evaluated biological and behavioral factors associated with each component of unsuccessful TB outcomes, recently updated by WHO (death, loss to follow-up [LTFU], and treatment failure). We included culture-confirmed, drug-susceptible, pulmonary TB participants receiving standard treatment in 2015-2019. Multinomial logistic regression models with inverse probability weighting were used to evaluate the distinct determinants of each unsuccessful outcome., Results: Of 915 participants included, 727 (79%) were successfully treated, 118 (13%) were LTFU, 44 (5%) had treatment failure, and 26 (3%) died. LTFU was associated with current drug-use (adjusted odds ratio [aOR] = 5.3; 95% confidence interval [CI], 3.0-9.4), current tobacco use (aOR = 2.9; 95% CI, 1.7-4.9), and being a person with HIV (PWH) (aOR = 2.0; 95% CI, 1.1-3.5). Treatment failure was associated with PWH (aOR = 2.7; 95% CI, 1.2-6.2) and having diabetes (aOR = 2.2; 95% CI, 1.1-4.4). Death was associated with anemia (aOR = 5.3; 95% CI, 1.4-19.7), diabetes (aOR = 3.1; 95% CI, 1.4-6.7), and PWH (aOR = 3.9; 95% CI, 1.3-11.4). Direct observed therapy was protective for treatment failure (aOR = 0.5; 95% CI, .3-.9) and death (aOR = 0.5; 95% CI, .2-1.0)., Conclusions: The treatment success rate was below the WHO target. Behavioral factors were most associated with LTFU, whereas clinical comorbidities were correlated with treatment failure and death. Because determinants of unsuccessful outcomes are distinct, different intervention strategies may be needed to improve TB outcomes., Competing Interests: Potential conflicts of interest. The authors do not have an association that might pose a conflict of interest. V. C. R. reports grants or contracts outside of the submitted work from TB Alliance for Drug Development (NC-008), Impacto da COVID-19 Nas Manifestações Clínicas, Diagnóstico, Desfecho Do Tratamento e Resposta Imune para Tuberculose Pulmonar (440933/2020-0 to CNPq account (not to self), Associative BRICS Research in COVID-19 and Tuberculosis (ABRICOT) (G-202105-67821 to Fiotec), RePORT International Data Harmonization (R-202108-68053 to Fiotec), Transcriptional Signature of TB in advanced HIV (DAA3-18-64313 to Fiotec), Predictors of Resistance Emergence Evaluation in Multidrug-resistant Tuberculosis patients on Treatment – PREEMPT (R01AI134430), Caribbean, Central, and South America network for HIV Epidemiology (CCASAnet) (U01AI069923 to Fiotec), and immunogenetic predictors of active and incipient TB in HIV-negative and -positive close TB contacts (R01AI147765 to Fiotec); consulting fees paid to self from ONU-OMS Country review for HIV response Myanmar; payment or honoraria paid to self from GLAXOSMITHKLINE BRASIL LTDA, Qiagen (Infecto Rio Conference), and virology education (Infecto Rio Conference); payment directly to the conference for registration for ViiV 18 European AIDS conference; and payment directly to self from NIH Data Safety Monitoring Board., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Factors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of patients with tuberculosis (TB) were investigated in a multicentre prospective cohort from highly endemic regions in Brazil., Methods: Close contacts of 1187 patients with culture-confirmed pulmonary TB were prospectively studied between 2015 and 2019, with follow-up of 6-24 months. Data on TB screening by clinical investigation, radiographic examination and interferon-gamma release assay (IGRA) were collected. Multivariable regressions were used to identify determinants of losses in the LTBI cascade., Results: Among 4145 TB contacts initially identified, 1901 were examined (54% loss). Among those examined, 933 were people living with HIV, ≤5 years old and/or had positive IGRA results, and therefore had a recommendation to start TB preventive treatment (TPT). Of those, 454 (23%) initiated treatment, and 247 (54% of those initiating; 26% of those in whom treatment was recommended) completed TPT. Multivariable regression analysis revealed that living with HIV, illiteracy and black/ pardo (brown) race were independently associated with losses in the cascade., Conclusion: There were losses at all LTBI cascade stages, but particularly at the initial screening and examination steps. Close contacts of low socioeconomic status and living with HIV were at heightened risk of not completing the LTBI cascade of care in Brazil., Competing Interests: Competing interests: The funders of the study had no role in study design, data analysis, data interpretation, or writing of the report. All authors had access to all the data in the study and had final responsibility for the decision to submit for publication., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Neutrophils have been associated with lung tissue damage in many diseases, including tuberculosis (TB). Whether neutrophil count can serve as a predictor of adverse treatment outcomes is unknown., Methods: We prospectively assessed 936 patients (172 HIV-seropositive) with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort study from different regions in Brazil, from June 2015 to June 2019, and were followed up to two years. TB patients had a baseline visit before treatment (month 0) and visits at month 2 and 6 (or at the end of TB treatment). Smear microscopy, and culture for Mycobacterium tuberculosis (MTB) were performed at TB diagnosis and during follow-up. Complete blood counts were measured at baseline. Treatment outcome was defined as either unfavorable (death, treatment failure or TB recurrence) or favorable (cure or treatment completion). We performed multivariable logistic regression, with propensity score regression adjustment, to estimate the association between neutrophil count with MTB culture result at month 2 and unfavorable treatment outcome. We used a propensity score adjustment instead of a fully adjusted regression model due to the relatively low number of outcomes., Results: Among 682 patients who had MTB culture results at month 2, 40 (5.9%) had a positive result. After regression with propensity score adjustment, no significant association between baseline neutrophil count (10 3 /mm 3 ) and positive MTB culture at month 2 was found among either HIV-seronegative (OR = 1.06, 95% CI = [0.95;1.19] or HIV-seropositive patients (OR = 0.77, 95% CI = [0.51; 1.20]). Of 691 TB patients followed up for at least 18 months and up to 24 months, 635 (91.9%) were either cured or completed treatment, and 56 (8.1%) had an unfavorable treatment outcome. A multivariable regression with propensity score adjustment found an association between higher neutrophil count (10 3 /mm 3 ) at baseline and unfavorable outcome among HIV-seronegative patients [OR= 1.17 (95% CI= [1.06;1.30]). In addition, adjusted Cox regression found that higher baseline neutrophil count (10 3 /mm 3 ) was associated with unfavorable treatment outcomes overall and among HIV-seronegative patients (HR= 1.16 (95% CI = [1.05;1.27])., Conclusion: Increased neutrophil count prior to anti-TB treatment initiation was associated with unfavorable treatment outcomes, particularly among HIV-seronegative patients. Further prospective studies evaluating neutrophil count in response to drug treatment and association with TB treatment outcomes are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Carvalho, Amorim, Melo, Silveira, Vargas, Moreira, Rocha, Souza, Arriaga, Araújo-Pereira, Figueiredo, Durovni, Lapa-e-Silva, Cavalcante, Rolla, Sterling, Cordeiro-Santos, Andrade, Silva, Kritski and the RePORT Brazil consortium.)

Background: A major goal of tuberculosis (TB) epidemiological studies is to obtain results that can be generalized to the larger population with TB. The ability to extrapolate findings on the determinants of TB treatment outcomes is also important., Methods: We compared baseline clinical and demographic characteristics and determinants of anti-TB treatment outcomes between persons enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between June 2015 and June 2019, and the registry of TB cases reported to the Brazilian National TB Program (Information System for Notifiable Diseases [SINAN]) during the same time period. Multivariable regression models adjusted for the study site were performed using second-generation p-values, a novel statistical approach. Associations with unfavorable treatment outcomes were tested for both RePORT-Brazil and SINAN cohorts., Findings: A total of 1,060 culture-confirmed TB patients were enrolled in RePORT-Brazil and 455,873 TB cases were reported to SINAN. Second-generation p-value analyses revealed that the cohorts were strikingly similar with regard to sex, age, use of antiretroviral therapy and positive initial smear sputum microscopy. However, diabetes, HIV infection, and smoking were more frequently documented in RePORT-Brazil. Illicit drug use, the presence of diabetes, and history of prior TB were associated with unfavorable TB treatment outcomes; illicit drug use was associated with such outcomes in both cohorts., Conclusions: There were important similarities in demographic characteristics and determinants of clinical outcomes between the RePORT-Brazil cohort and the Brazilian National registry of TB cases., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Characterized by fluvio-alluvial sedimentation processes, the heterogeneity in the Pantanal Basin allows its division in several sub-regions, which present natural characteristics of their own. It is possible to find in the literature different proposals to subdivide the Pantanal plain, which vary in total area and number of sub-regions. Each author uses specific criteria - mainly vegetation, soil and humidity - in his delimitation, but does not consider the tectonic aspects of the basin. In this sense, we intend to analyze three Pantanal delimitations from the literature and to relate them to the neotectonic context of the Pantanal plain by comparing the boundaries proposed in the delimitations to structural lineaments present in the basin. As a result, we observe that the comparison of the Pantanal boundaries with the lineaments shows a high compatibility between them, suggesting the influence of these structures in the development of the sub-regions.