Brazilian Thoracic Association recommendations for the management of post-tuberculosis lung disease

Historically, all efforts against tuberculosis were focused on rapid diagnosis and effective treatment to break the chain of transmission of Mycobacterium tuberculosis. However, in the last few years, more and more evidence has been found on the dramatic consequences of the condition defined as post-tuberculosis lung disease (PTLD). Approximately one third of patients surviving pulmonary tuberculosis face considerable ongoing morbidities, including respiratory impairment, psychosocial challenges, and reduced health-related quality of life after treatment completion. Given the important global and local burden of tuberculosis, as well as the estimated burden of PTLD, the development of a consensus document by a Brazilian scientific society—Sociedade Brasileira de Pneumologia e Tisiologia (SBPT)—was considered urgent for the prevention and management of this condition in order to allocate resources to and within tuberculosis services appropriately and serve as a guide for health care professionals. A team of eleven pulmonologists and one methodologist was created by the SBPT to review the current evidence on PTLD and develop recommendations adapted to the Brazilian context. The expert panel selected the topics on the basis of current evidence and international guidelines. During the first phase, three panel members drafted the recommendations, which were divided into three sections: definition and prevalence of PTLD, assessment of PTLD, and management of PTLD. In the second phase, all panel members reviewed, discussed, and revised the recommendations until a consensus was reached. The document was formally approved by the SBPT in a special session organized during the 2023 SBPT Annual Conference

Fractional Exhaled Nitric Oxide Measurements and Screening of Obstructive Sleep Apnea in a Sleep-Laboratory Setting: A Cross-Sectional Study

PURPOSE: Obstructive sleep apnea (OSA) is a common condition characterized by repetitive collapse of the upper airways and intermittent oxygen desaturation, which may lead to airway inflammation. Here, we explored whether fractional exhaled nitric oxide (FeNO) levels provide a non-invasive screening tool of OSA. METHODS: Over a 3-month period, FeNO levels were measured in consecutive non-smoking patients referred for a sleep laboratory. All patients underwent full polysomnography. OSA severity was classified based on the apnea/hypopnea index: ≥ 5.0/h as any OSA, ≥ 15.0/h as moderate/severe OSA, and ≥ 30.0/h as severe OSA. FeNO was measured by a portable device (NIOX-MINO®; Aerocrine AB, Solna, Sweden) and expressed as parts per billion (ppb). Discrimination by area under the curve (AUC) and binary logistic regression were performed. RESULTS: A total of 229 subjects were evaluated. Mean FeNO values were similar among subjects without OSA or with OSA: 16.9 ± 10.6 ppb versus 20.2 ± 14.5 ppb, p = 0.221; respectively. FeNO was not an inclusionary parameter to predict any OSA, moderate/severe OSA, and severe OSA: odds ratio (OR) 1.023 (95% confidence interval [CI]: 0.986-1.062); OR 1.012 (95% CI: 0.991-1.034); and OR 0.999 (95% CI: 0.980-1.018), respectively. The AUC values for FeNO in the diagnosis of any OSA, moderate/severe OSA, and severe OSA showed no discriminatory properties: AUC: 0.567 (95% CI: 0.464-0.670), AUC: 0.541 (95% CI: 0.465-0.618), and AUC: 0.535 (95% CI: 0.459-0.610); respectively. CONCLUSIONS: In a sleep-lab setting, our findings suggest that FeNO measurements are inconsequential in the screening of OSA in adults.info:eu-repo/semantics/publishedVersio

Transcriptome dynamics and molecular cross-talk between bovine oocyte and its companion cumulus cells

<p>Abstract</p> <p>Background</p> <p>The bi-directional communication between the oocyte and its companion cumulus cells (CCs) is crucial for development and functions of both cell types. Transcripts that are exclusively expressed either in oocytes or CCs and molecular mechanisms affected due to removal of the communication axis between the two cell types is not investigated at a larger scale. The main objectives of this study were: 1. To identify transcripts exclusively expressed either in oocyte or CCs and 2. To identify those which are differentially expressed when the oocyte is cultured with or without its companion CCs and vice versa.</p> <p>Results</p> <p>We analyzed transcriptome profile of different oocyte and CC samples using Affymetrix GeneChip Bovine Genome array containing 23000 transcripts. Out of 13162 genes detected in germinal vesicle (GV) oocytes and their companion CCs, 1516 and 2727 are exclusively expressed in oocytes and CCs, respectively, while 8919 are expressed in both. Similarly, of 13602 genes detected in metaphase II (MII) oocytes and CCs, 1423 and 3100 are exclusively expressed in oocytes and CCs, respectively, while 9079 are expressed in both. A total of 265 transcripts are differentially expressed between oocytes cultured with (OO + CCs) and without (OO - CCs) CCs, of which 217 and 48 are over expressed in the former and the later groups, respectively. Similarly, 566 transcripts are differentially expressed when CCs mature with (CCs + OO) or without (CCs - OO) their enclosed oocytes. Of these, 320 and 246 are over expressed in CCs + OO and CCs - OO, respectively.</p> <p>While oocyte specific transcripts include those involved in transcription (<it>IRF6, POU5F1, MYF5, MED18</it>), translation (<it>EIF2AK1, EIF4ENIF1</it>) and CCs specific ones include those involved in carbohydrate metabolism (<it>HYAL1, PFKL, PYGL, MPI</it>), protein metabolic processes (<it>IHH, APOA1, PLOD1</it>), steroid biosynthetic process (<it>APOA1, CYP11A1, HSD3B1, HSD3B7</it>). Similarly, while transcripts over expressed in OO + CCs are involved in carbohydrate metabolism (<it>ACO1, 2</it>), molecular transport (<it>GAPDH, GFPT1</it>) and nucleic acid metabolism (<it>CBS, NOS2</it>), those over expressed in CCs + OO are involved in cellular growth and proliferation (<it>FOS, GADD45A</it>), cell cycle (<it>HAS2, VEGFA</it>), cellular development (<it>AMD1, AURKA, DPP4</it>) and gene expression (<it>FOSB, TGFB2</it>).</p> <p>Conclusion</p> <p>In conclusion, this study has generated large scale gene expression data from different oocyte and CCs samples that would provide insights into gene functions and interactions within and across different pathways that are involved in the maturation of bovine oocytes. Moreover, the presence or absence of oocyte and CC factors during bovine oocyte maturation can have a profound effect on transcript abundance of each cell types, thereby showing the prevailing molecular cross-talk between oocytes and their corresponding CCs.</p

Risk factors for default from tuberculosis treatment in HIV-infected individuals in the state of Pernambuco, Brazil: a prospective cohort study

BACKGROUND: Concomitant treatment of Human Immunodeficiency Virus (HIV) infection and tuberculosis (TB) presents a series of challenges for treatment compliance for both providers and patients. We carried out this study to identify risk factors for default from TB treatment in people living with HIV. METHODS: We conducted a cohort study to monitor HIV/TB co-infected subjects in Pernambuco, Brazil, on a monthly basis, until completion or default of treatment for TB. Logistic regression was used to calculate crude and adjusted odds ratios, 95% confidence intervals and P-values. RESULTS: From a cohort of 2310 HIV subjects, 390 individuals (16.9%) who had started treatment after a diagnosis of TB were selected, and data on 273 individuals who completed or defaulted on treatment for TB were analyzed. The default rate was 21.7% and the following risk factors were identified: male gender, smoking and CD4 T-cell count less than 200 cells/mm3. Age over 29 years, complete or incomplete secondary or university education and the use of highly active antiretroviral therapy (HAART) were identified as protective factors for the outcome. CONCLUSION: The results point to the need for more specific actions, aiming to reduce the default from TB treatment in males, younger adults with low education, smokers and people with CD4 T-cell counts < 200 cells/mm3. Default was less likely to occur in patients under HAART, reinforcing the strategy of early initiation of HAART in individuals with TB

Long-term outcomes of the global tuberculosis and COVID-19 co-infection cohort

Background: Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19. Methods: We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both. Results: Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p&lt;0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53). Conclusions: In our global cohort, death was the outcome in &gt;10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes

Human N-acetyltransferase 2 (NAT2) gene variability in Brazilian populations from different geographical areas

Introduction: Several polymorphisms altering the NAT2 activity have already been identified. The geographical distribution of NAT2 variants has been extensively studied and has been demonstrated to vary significantly among different ethnic population. Here, we describe the genetic variability of human N-acetyltransferase 2 (NAT2) gene and the predominant genotype-deduced acetylation profiles of Brazilians.Methods: A total of 964 individuals, from five geographical different regions, were genotyped for NAT2 by sequencing the entire coding exon.Results: Twenty-three previously described NAT2 single nucleotide polymorphisms (SNPs) were identified, including the seven most common ones globally (c.191G&gt;A, c.282C&gt;T, c.341T&gt;C, c.481C&gt;T, c.590G&gt;A, c.803A&gt;G and c.857G&gt;A). The main allelic groups were NAT2*5 (36%) and NAT2*6 (18.2%), followed to the reference allele NAT2*4 (20.4%). Combined into genotypes, the most prevalent allelic groups were NAT2*5/*5 (14.6%), NAT2*5/*6 (11.9%) and NAT2*6/*6 (6.2%). The genotype deduced NAT2 slow acetylation phenotype was predominant but showed significant variability between geographical regions. The prevalence of slow acetylation phenotype was higher in the Northeast, North and Midwest (51.3%, 45.5% and 41.5%, respectively) of the country. In the Southeast, the intermediate acetylation phenotype was the most prevalent (40.3%) and, in the South, the prevalence of rapid acetylation phenotype was significantly higher (36.7%), when compared to other Brazilian states (p &lt; 0.0001). Comparison of the predicted acetylation profile among regions showed homogeneity among the North and Northeast but was significantly different when compared to the Southeast (p = 0.0396). The Southern region was significantly different from all other regions (p &lt; 0.0001).Discussion: This study contributes not only to current knowledge of the NAT2 population genetic diversity in different geographical regions of Brazil, but also to the reconstruction of a more accurate phenotypic picture of NAT2 acetylator profiles in those regions

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research