Objective: To determine whether abnormal continuous glucose monitoring (CGM) readings (hypoglycemia/hyperglycemia) can predict the onset of cystic fibrosis-related diabetes (CFRD) and/or clinical impairment (decline in BMI and/or FEV1) in pediatric patients with cystic fibrosis (CF). Methods: This was a longitudinal prospective cohort study involving CF patients without diabetes at baseline. The mean follow-up period was 3.1 years. The patients underwent 3-day CGM, performed oral glucose tolerance test (OGTT), and had FEV1 and BMI determined at baseline. OGTT, FEV1, and BMI were reassessed at the end of the follow-up period. Results: Thirty-nine CF patients (10-19 years of age) had valid CGM readings at baseline, and 34 completed the follow-up period (mean = 3.1 ± 0.5 years). None of the study variables predicted progression to CFRD or were associated with hypoglycemic events. CGM could detect glucose abnormalities not revealed by OGTT. Patients with glucose levels = 140 mg/dL, as compared with those with lower levels, on CGM showed lower BMI values and z-scores at baseline-17.30 ± 3.91 kg/m2 vs. 19.42 ± 2.07 kg/m2; p = 0.043; and -1.55 ± 1.68 vs. -0.17 ± 0.88; p = 0.02, respectively-and at the end of follow-up-17.88 ± 3.63 kg/m2 vs. 19.95 ± 2.56 kg/m2; p = 0.039; and -1.65 ± 1.55 vs. -0.42 ± 1.08; p = 0.039. When comparing patients with and without CFRD, the former were found to have worse FEV1 (in % of predicted)-22.67 ± 5.03 vs. 59.58 ± 28.92; p = 0.041-and a greater decline in FEV1 (-36.00 ± 23.52 vs. -8.13 ± 17.18; p = 0.041) at the end of follow-up. Conclusions: CGM was able to identify glucose abnormalities not detected by OGTT that were related to early-stage decreases in BMI. CGM was ineffective in predicting the onset of diabetes in this CF population. Different diagnostic criteria for diabetes may be required for individuals with CF.

Keywords: Cystic fibrosis; Glucose intolerance; Glucose tolerance test; Diabetes mellitus.

Objective: To identify factors that lead to a positive oxygenation response and predictive factors of mortality after prone positioning. Methods: This was a retrospective, multicenter, cohort study involving seven hospitals in Brazil. Inclusion criteria were being > 18 years of age with a suspected or confirmed diagnosis of COVID-19, being on invasive mechanical ventilation, having a PaO2/FIO2 ratio < 150 mmHg, and being submitted to prone positioning. After the first prone positioning session, a 20 mmHg improvement in the PaO2/FIO2 ratio was defined as a positive response. Results: The study involved 574 patients, 412 (72%) of whom responded positively to the first prone positioning session. Multiple logistic regression showed that responders had lower Simplified Acute Physiology Score III (SAPS III)/SOFA scores and lower D-dimer levels (p = 0.01; p = 0.04; and p = 0.04, respectively). It was suggested that initial SAPS III and initial PaO2/FIO2 were predictors of oxygenation response. The mortality rate was 69.3%. Increased risk of mortality was associated with age (OR = 1.04 [95 CI: 1.01-1.06]), time to first prone positioning session (OR = 1.18 [95 CI: 1.06-1.31]), number of sessions (OR = 1.31 [95% CI: 1.00-1.72]), proportion of pulmonary impairment (OR = 1.55 [95% CI: 1.02-2.35]), and immunosuppression (OR = 3.83 [95% CI: 1.35-10.86]). Conclusions: Our results show that most patients in our sample had a positive oxygenation response after the first prone positioning session. However, the mortality rate was high, probably due to the health status and the number of comorbidities of the patients, as well as the severity of their disease. Our results also suggest that SAPS III and the initial PaO2/FIO2 predict the oxygenation response; in addition, age, time to first prone positioning, number of sessions, pulmonary impairment, and immunosuppression can predict mortality.

Keywords: Respiratory distress syndrome; Coronavirus infections; Pulmonary medicine; COVID-19; Prone position; SARS-CoV-2.

Objective: To evaluate small airway disease in COVID-19 patients using the prevalence of air trapping (AT) and correlating it with clinical outcomes. The relationship between CT-based opacities in small blood vessels and ventilation in patients with SARS-CoV-2 pneumonia was also assessed. Methods: We retrospectively included 53 patients with positive RT-PCR results for SARS-CoV-2 between March and April of 2020. All subjects underwent HRCT scanning, including inspiratory and expiratory acquisitions. Subjects were divided into two groups based on visual identification of AT. Small blood vessel volumes were estimated by means of cross-sectional areas < 5 mm2 (BV5) derived from automated segmentation algorithms. Mixed-effect models were obtained to represent the BV5 as a function of CT-based lobar opacities and lobar ventilation. Results: Of the 53 participants, AT was identified in 23 (43.4%). The presence of AT was associated with increased SpO2 at admission (OR = 1.25; 95% CI, 1.07-1.45; p = 0.004) and reduced D-dimer levels (OR = 0.99; 95% CI, 0.99-0.99; p = 0.039). Patients with AT were less likely to be hospitalized (OR = 0.27; 95% CI, 0.08-0.89; p = 0.032). There was a significant but weak inverse correlation between BV5 and CT-based lobar opacities (R2 = 0.19; p = 0.03), as well as a nonsignificant and weak direct correlation between BV5 and lobar ventilation (R2 = 0.08; p = 0.54). Conclusions: AT is a common finding in patients with COVID-19 that undergo expiratory CT scanning. The presence of AT may correlate with higher SpO2 at admission, lower D-dimer levels, and fewer hospitalizations when compared with absence of AT. Also, the volume of small pulmonary vessels may negatively correlate with CT opacities but not with lobar ventilation.

Keywords: SARS-CoV-2; COVID-19; Tomography, X-ray.

Objective: To characterize the prevalence of latent tuberculosis infection (LTBI) in patients with interstitial lung diseases (ILDs) requiring immunosuppression. Only 5 to 10% of individuals infected with Mycobacterium tuberculosis develop tuberculosis, and certain groups of patients have an increased risk of illness, such as the immunocompromised. Patients with ILDs are frequently treated with immunosuppressants and, therefore, might have a higher risk of developing the disease. Methods: Prospective study conducted at the ILD reference center of the Federal University of Paraná from January 2019 to December 2020. The screening of LTBI was performed with the use of the tuberculin skin test (TST). Results: The sample consisted of 88 patients, of whom 64.8% were women, with a mean age of 61.4 years. The most frequent diagnoses were autoimmune rheumatic disease ILD (38.6%) and hypersensitivity pneumonitis (35.2%). The most common immunosuppressant in use at the time of the TST was prednisone, either in combination with mycophenolate (19.3%) or alone (17.1%). The majority of participants had fibrotic lung disease, characterized by a reticular interstitial pattern on chest computed tomography (79.5%) and moderate to severe functional impairment (mean FVC 69.2%). A prevalence of LTBI of 9.1% (CI 95%, 2.1%-15.1%) was found, with a TST median of 13. Conclusion: Patients with ILD who are treated with immunosuppressants are not commonly screened for LTBI, despite being under a greater risk of progression to active disease. This study suggests the need for a more cautious approach to these patients.

Keywords: Latent tuberculosis infection; Interstitial lung diseases; Immunosuppression; Tuberculin test.

Objectives: Pleural tuberculosis (PlTB) diagnosis is a challenge due to its paucibacillary nature and to the need of invasive procedures. This study aimed to identify easily available variables and build a predictive model for PlTB diagnosis which may allow earlier and affordable alternative strategy to be used in basic health care units. Methods: An observational cross-sectional study compared PlTB and non-TB patients followed at a tertiary Brazilian hospital between 2010 and 2018. Unconditional logistic regression analysis was performed and a Decision Tree Classifier (DTC) model was validated and applied in additional PlTB patients with empiric diagnosis. The accuracy (Acc), sensitivity (Se), specificity (Sp), positive and negative predictive values were calculated. Results: From 1,135 TB patients, 160 were considered for analysis (111 confirmed PlTB and 49 unconfirmed PlTB). Indeed, 58 non-TB patients were enrolled as controls. Hyporexia [adjusted odds ratio (aOR) 27.39 (95% CI 6.26 - 119.89)] and cellular/biochemical characteristics on pleural fluid (PF) (polimorphonuclear in two categories: 3-14% aOR 26.22, 95% CI 7.11 - 96.68 and < 3% aOR 28.67, 95% CI 5.51 - 149.25; and protein = 5g/dL aOR 7.24, 95% CI 3.07 - 17.11) were associated with higher risk for TB. The DTC constructed using these variables showed Acc=87.6%, Se=89.2%, Sp=84.5% for PlTB diagnosis and was successfully applied in unconfirmed PlTB patients. Conclusion: The DTC model showed an excellent performance for PlTB diagnosis and can be considered as an alternative diagnostic strategy by using clinical patterns in association with PF cellular/biochemical characteristics, which were affordable and easily performed in basic health care units.

Keywords: Pleural tuberculosis; Diagnosis; Decision tree classifier.

Objective: To evaluate lung function in a cohort of patients with a history of pulmonary tuberculosis in Brazil, as well as to evaluate the decline in lung function over time and compare it with that observed in similar cohorts in Mexico and Italy. Methods: The three cohorts were compared in terms of age, smoking status, pulmonary function test results, six-minute walk test results, and arterial blood gas results. In the Brazilian cohort, pulmonary function test results, six-minute walk test results, and arterial blood gas results right after the end of tuberculosis treatment were compared with those obtained at the end of the follow-up period. Results: The three cohorts were very different regarding pulmonary function test results. The most common ventilatory patterns in the Brazilian, Italian, and Mexican cohorts were an obstructive pattern, a mixed pattern, and a normal pattern (in 58 patients [50.9%], in 18 patients [41.9%], and in 26 patients [44.1%], respectively). Only 2 multidrug-resistant tuberculosis cases were included in the Brazilian cohort, whereas, in the Mexican cohort, 27 cases were included (45.8%). Mean PaO2 and mean SaO2 were lower in the Mexican cohort than in the Brazilian cohort (p < 0.0001 and p < 0.002 for PaO2 and SaO2, respectively). In the Brazilian cohort, almost all functional parameters deteriorated over time. Conclusions: This study reinforces the importance of early and effective treatment of drug-susceptible tuberculosis patients, because multidrug-resistant tuberculosis increases lung damage. When patients complete their tuberculosis treatment, they should be evaluated as early as possible, and, if post-tuberculosis lung disease is diagnosed, they should be managed and offered pulmonary rehabilitation because there is evidence that it is effective in these patients.

Keywords: Tuberculosis; Tuberculosis, multidrug-resistant; Spirometry; Rehabilitation.

The objective of this study was to describe country-specific lockdown measures and tuberculosis indicators collected during the first year of the COVID-19 pandemic. Data on lockdown/social restrictions (compulsory face masks and hand hygiene; international and local travel restrictions; restrictions to family visits, and school closures) were collected from 24 countries spanning five continents. The majority of the countries implemented multiple lockdowns with partial or full reopening. There was an overall decrease in active tuberculosis, drug-resistant tuberculosis, and latent tuberculosis cases. Although national lockdowns were effective in containing COVID-19 cases, several indicators of tuberculosis were affected during the pandemic.

Keywords: COVID-19; Tuberculosis; Physical distancing; Health policy; Global health; Communicable disease control.

Lung transplantation is the most effective modality for the treatment of patients with end-stage lung diseases. Unfortunately, many people cannot benefit from this therapy due to insufficient donor availability. In this review and update article, we discuss donation after circulatory death (DCD), which is undoubtedly essential among the strategies developed to increase the donor pool. However, there are ethical and legislative considerations in the DCD process that are different from those of donation after brain death (DBD). Among others, the critical aspects of DCD are the concept of the end of life, cessation of futile treatments, and withdrawal of life-sustaining therapy. In addition, this review describes a rationale for using lungs from DCD donors and provides some important definitions, highlighting the key differences between DCD and DBD, including physiological aspects pertinent to each category. The unique ability of lungs to maintain cell viability without circulation, assuming that oxygen is supplied to the alveoli-an essential aspect of DCD-is also discussed. Furthermore, an updated review of the clinical experience with DCD for lung transplantation across international centers, recent advances in DCD, and some ethical dilemmas that deserve attention are also reported.

Keywords: Tissue and organ procurement; Brain death; Lung transplantation; Respiratory insufficiency.

Objective: Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening infectious disease. Treatment requires multiple antimicrobial agents used for extended periods of time. The present study sought to evaluate the treatment success rate of bedaquiline-based regimens in MDR-TB patients. Methods: This was a systematic review and meta-analysis of studies published up to March 15, 2021. The pooled treatment success rates and 95% CIs were assessed with the fixed-effect model or the random-effects model. Values of p < 0.05 were considered significant for publication bias. Results: A total of 2,679 articles were retrieved by database searching. Of those, 29 met the inclusion criteria. Of those, 25 were observational studies (including a total of 3,536 patients) and 4 were experimental studies (including a total of 440 patients). The pooled treatment success rate was 74.7% (95% CI, 69.8-79.0) in the observational studies and 86.1% (95% CI, 76.8-92.1; p = 0.00; I2 = 75%) in the experimental studies. There was no evidence of publication bias (p > 0.05). Conclusions: In patients with MDR-TB receiving bedaquiline, culture conversion and treatment success rates are high even in cases of extensive resistance.

Keywords: Tuberculosis; Drug resistance; Tuberculosis, multidrug-resistant; Efficacy.