Objective: To evaluate the process of diagnosing patients with malignant pleural mesothelioma (MPM) at a tertiary care hospital. Methods: This was a retrospective study involving patients referred to a tertiary-care cancer center in Brazil between 2009 and 2020. The diagnostic process was divided into four steps: onset of symptoms, referral to a specialist visit, histopathological diagnosis, and beginning of treatment. The intervals between each phase and the factors for delays were evaluated. Data including clinical status, radiological examinations, staging, treatment modalities, and survival outcomes were collected. Results: During the study period, 66 patients (mean age = 64 years) were diagnosed with MPM and underwent treatment. Only 27 (41%) of the patients had knowledge of prior exposure to asbestos. The median number of months (IQR) between the onset of symptoms and the first specialist visit, between the specialist visit and histopathological characterization, and between definite diagnosis and beginning of treatment was, respectively, 6.5 (2.0-11.4), 1.5 (0.6-2.1), and 1.7 (1.2-3.4). The knowledge of prior asbestos exposure was associated with a shorter time to referral to a specialist (median: 214 vs. 120 days; p = 0.04). A substantial number of nondiagnostic procedures and false-negative biopsy results (the majority of which involved the use of Cope needle biopsy) were found to be decisive factors for the length of waiting time. The mean overall survival was 11.9 months. Conclusions: The unfamiliarity of health professionals with MPM and the patient's lack of knowledge of prior asbestos exposure were the major factors to cause a long time interval between the onset of symptoms and beginning of treatment. An overall survival shorter than 1 year is likely to have been due to the aforementioned delays.

Keywords: Mesothelioma; Mesothelioma, malignant; Pleural effusion, malignant; Pleural diseases.

Malignant mesothelioma (MM) is a highly aggressive form of cancer, has a long latency period, and is resistant to chemotherapy. It is extremely fatal, with a mean survival of less than one year. The development of MM is strongly correlated with exposure to asbestos and erionite, as well as to simian virus 40. Although various countries have banned the use of asbestos, MM has proven to be difficult to control and there appears to be a trend toward an increase in its incidence in the years to come. In Brazil, MM has not been widely studied from a genetic or biochemical standpoint. In addition, there have been few epidemiological studies of the disease, and the profile of its incidence has yet to be well established in the Brazilian population. The objective of this study was to review the literature regarding the processes of malignant transformation, as well as the respective mechanisms of tumorigenesis, in MM.

Keywords: Occupational diseases; Mesothelioma; Genes, tumor suppressor; Oncogenes; Signal transduction.

Objective: To evaluate the diagnostic contribution of molecular analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in patients suspected of having mild or atypical cystic fibrosis (CF). Methods: This was a cross-sectional study involving adolescents and adults aged ≥ 14 years. Volunteers underwent clinical, laboratory, and radiological evaluation, as well as spirometry, sputum microbiology, liver ultrasound, sweat tests, and molecular analysis of the CFTR gene. We then divided the patients into three groups by the number of mutations identified (none, one, and two or more) and compared those groups in terms of their characteristics. Results: We evaluated 37 patients with phenotypic findings of CF, with or without sweat test confirmation. The mean age of the patients was 32.5 ± 13.6 years, and females predominated (75.7%). The molecular analysis contributed to the definitive diagnosis of CF in 3 patients (8.1%), all of whom had at least two mutations. There were 7 patients (18.9%) with only one mutation and 26 patients (70.3%) with no mutations. None of the clinical characteristics evaluated was found to be associated with the genetic diagnosis. The most common mutation was p.F508del, which was found in 5 patients. The combination of p.V232D and p.F508del was found in 2 patients. Other mutations identified were p.A559T, p.D1152H, p.T1057A, p.I148T, p.V754M, p.P1290P, p.R1066H, and p.T351S. Conclusions: The molecular analysis of the CFTR gene coding region showed a limited contribution to the diagnostic investigation of patients suspected of having mild or atypical CF. In addition, there were no associations between the clinical characteristics and the genetic diagnosis.

Objective: To investigate the diagnostic accuracy of a chest X-ray (CXR) score and of clinical and laboratory data in predicting the clinical course of patients with SARS coronavirus 2 (SARS-CoV-2) infection. Methods: This is a pilot multicenter retrospective study including patients with SARS-CoV-2 infection admitted to the ERs in three hospitals in Italy between February and March of 2020. Two radiologists independently evaluated the baseline CXR of the patients using a semi-quantitative score to determine the severity of lung involvement: a score of 0 represented no lung involvement, whereas scores of 1 to 4 represented the first (less severe) to the fourth (more severe) quartiles regarding the severity of lung involvement. Relevant clinical and laboratory data were collected. The outcome of patients was defined as severe if noninvasive ventilation (NIV) or intubation was necessary, or if the patient died. Results: Our sample comprised 140 patients. Most of the patients were symptomatic (132/138; 95.7%), and 133/140 patients (95.0%) presented with opacities on CXR at admission. Of the 140 patients, 7 (5.0%) showed no lung involvement, whereas 58 (41.4%), 31 (22.1%), 26 (18.6%), and 18 (12.9%), respectively, scored 1, 2, 3, and 4. In our sample, 66 patients underwent NIV or intubation, 37 of whom scored 1 or 2 on baseline CXR, and 28 patients died. Conclusions: The severity score based on CXR seems to be able to predict the clinical progression in cases that scored 0, 3, or 4. However, the score alone cannot predict the clinical progression in patients with mild-to-moderate parenchymal involvement (scores 1 and 2).

Keywords: Coronavirus infections; Radiography, thoracic; Pneumonia; Respiratory insufficiency; Severe acute respiratory syndrome.

Objective: To analyze the impact that the 2009 changes in tuberculosis treatment in Brazil had on the rates of cure, tuberculosis recurrence, mortality, treatment abandonment, and multidrug-resistant tuberculosis (MDR-TB). Methods: An ordinary least squares regression model was used in order to perform an interrupted time series analysis of secondary data collected from the Brazilian Tuberculosis Case Registry Database for the period between January of 2003 and December of 2014. Results: The 2009 changes in tuberculosis treatment in Brazil were found to have no association with reductions in the total number of cases (β = 2.17; 95% CI: −3.80 to 8.14; p = 0.47) and in the number of new cases (β = −0.97; 95% CI: −5.89 to 3.94; p = 0.70), as well as having no association with treatment abandonment rates (β = 0.40; 95% CI: −1.12 to 1.93; p = 0.60). The changes in tuberculosis treatment also showed a trend toward an association with decreased cure rates (β = −4.14; 95% CI: −8.63 to 0.34; p = 0.07), as well as an association with increased mortality from pulmonary tuberculosis (β = 0.77; 95% CI: 0.16 to 1.38; p = 0.01). Although there was a significant increase in MDR-TB before and after the changes (p < 0.0001), there was no association between the intervention (i.e., the changes in tuberculosis treatment) and the increase in MDR-TB cases. Conclusions: The changes in tuberculosis treatment were unable to contain the decrease in cure rates, the increase in treatment abandonment rates, and the increase in MDR-TB rates, being associated with increased mortality from pulmonary tuberculosis during the study period.

Keywords: Tuberculosis, pulmonary/epidemiology; Tuberculosis, pulmonary/drug therapy; Tuberculosis, pulmonary/mortality; Interrupted time series analysis; Drug resistance, multiple; Drug compounding.

Objective: VEGF-D is a potential biomarker for lymphangioleiomyomatosis (LAM); however, its diagnostic performance has yet to be systematically studied. Methods: We searched PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library to identify primary studies on VEGF-D in relation to the diagnosis of LAM. The quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Summary estimates of diagnostic accuracy were pooled using a bivariate random effects model. Subgroup and sensitivity analyses were performed to explore possible heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was applied to rate the quality of evidence and indicate the strength of recommendations. Results: Ten studies involving 945 patients were of high risk in quality, as assessed using the QUADAS-2. The pooled diagnostic parameters were indicated as follows: sensitivity = 0.82 (95% CI, 0.71-0.90); specificity = 0.98 (95% CI, 0.94-0.99); and diagnostic OR = 197 (95% CI, 66-587). The AUC of summary ROC analysis was 0.98. The subgroup and sensitivity analyses revealed that the overall performance was not substantially affected by the composition of the control group, prespecified cutoff value, the country of origin, or different cutoff values (p > 0.05 for all). A strong recommendation for serum VEGF-D determination to aid in the diagnosis of LAM was made according to the GRADE. Conclusions: VEGF-D seems to have great potential implications for the diagnosis of LAM in clinical practice due to its excellent specificity and suboptimal sensitivity.

Keywords: Lymphangioleiomyomatosis/diagnosis; Vascular endothelial growth factor D; Biomarkers; Meta-analysis.

Organizing pneumonia, whether or not accompanied by bronchiolitis obliterans, is a specific anatomicopathological condition of the lungs that can present in a variety of clinical and radiographic ways. It can be either idiopathic or secondary to a number of diseases, including infection and drugs. Objectives: To describe the clinical manifestations, radiographic and spirometric data seen in patients with organizing pneumonia. Methods: Retrospective analysis of patients with a diagnosis of organizing pneumonia. Results: 38 patients were included in the analysis. Fourteen also had clinical conditions related to organizing pneumonia, and they presented more frequently with diffuse pulmonary infiltrates (three of four cases) and associated bronchiolitis obliterans (57% vs. 20%, p = 0,05). Of the 13 patients with bronchiolitis obliterans, only one was asymptomatic and two had localized lesions (15%). Of the eight asymptomatic patients with localized lesions, no one had associated bronchiolitis obliterans, and the radiographic appearance often resembled bronchial carcinoma. Spirometry was generally of little value to diagnosis, probably because of the high prevalence of smoking in the sample. Conclusion: The clinical and radiographic presentation of organizing pneumonia is variable. Factors that suggest the absence of coexisting bronchiolitis obliterans are the absence of symptoms and localized radiographic lesions, and this form of the disease has to be more often differentiated from bronchial carcinoma in clinical practice.

Objective: Thymic tumors are a rare group of anterior mediastinal tumors. Surgery is the primary treatment. Adjuvant treatment is used in select cases. The purpose of this study was to evaluate the outcomes of patients with thymic tumors, submitted or not to radiotherapy, and identify risk factors that could impact the outcomes to better support patient selection for RT. Methods: This is a single institution retrospective cohort study. Patients with histologically proven thymoma or thymic carcinoma treated from July of 2009 to November of 2020 were included. Analysis was based on the use of radiation therapy (RT). Overall survival and disease-free survival were assessed from the date of diagnosis. To minimize selection bias, propensity score matching (PSM) regression using Kernel matching was used, estimated on the population for average treatment effect. Results: Overall, 101 patients were analyzed, with mean age at diagnosis of 54.6 years (range 25-84 years). Unfavorable histology and more advanced stages predominated in the cohort. Nevertheless, most (69.3%) were treated with radical intent. RT was delivered in 52.9% of these patients. Five-year OS, local progression and distant progression free survivals were 81.0%, 95.0% and 88.1%, respectively for the radical intent cohort. PSM showed that RT reduced the chances of death by 6.3% (matched sample size was 60, p = 0.02). Conclusions: In this retrospective cohort, RT had a positive impact in OS after PSM analysis. Prospective data regarding the role of RT in this disease is needed to validate these findings.

Keywords: Thymoma; Thymus neoplasms; Radiotherapy.

Objective: To compare different levels of ablation in terms of the degree of patient satisfaction and extent of postoperative reflex sweating in sympathectomized patients. Methods: A retrospective study involving 521 patients with primary hyperhidrosis, submitted to thoracic sympathectomy at the Monte Sinai Hospital and University Hospital of the Federal University of Juiz de Fora, from January of 2001 to December 2005. All patients were submitted to thermal ablation of the sympathetic stem and were divided into three groups: up to T2 (group I, n = 162); up to T3 (group II, n = 65); and up to T4 (group III, n = 294). Results: Optimal postoperative control of palmar/axillary hyperhidrosis was achieved in, respectively, 94/82% of the patients of group I, 89/89% of those in group II and 80/80% of those in group III. Postoperative reflex sweating was observed in 67% of the patients in groups I and II, compared with 61.29% of those in group III. Severe reflex sweating occurred in 32% of the group I patients, 9% of the group II patients and 4% of the group III patients. Conclusion: Sympathectomy provided excellent patient satisfaction and a low incidence of complications. There was no significant difference between the levels of ablation in terms of reflex sweating, although the intensity of this complication decreased when lower levels of blockage, principally at the T4 level, were employed.

Keywords: Sympathectomy; Thoracoscopy; Hyperhidrosis.

Objective: To identify the determinants of tuberculosis-related variables in the various regions of Brazil and evaluate trends in those variables over the ten-year period preceding the end of the timeframe defined for the United Nations Millennium Development Goals (MDGs). Methods: This was an ecological analytical study in which we utilized eight national public databases to investigate the 716,971 new tuberculosis cases reported between 2006 and 2015. Results: Over the study period, there were slight reductions in the prevalence, incidence, and mortality associated with tuberculosis. Brazil did not reach the MDG for tuberculosis-related mortality. Among the performance indicators of tuberculosis control, there were improvements only in those related to treatment and treatment abandonment. In terms of the magnitude of tuberculosis, substantial regional differences were observed. The tuberculosis incidence rate was highest in the northern region, as were the annual mean temperature and relative air humidity. That region also had the second lowest human development index, primary health care (PHC) coverage, and number of hospitalizations for tuberculosis. The northeastern region had the highest PHC coverage, number of hospitalizations for primary care-sensitive conditions, and tuberculosis-related mortality rate. The southern region showed the smallest reductions in epidemiological indicators, together with the greatest increases in the frequency of treatment abandonment and retreatment. The central-west region showed the lowest overall magnitude of tuberculosis and better monitoring indicators. Conclusions: The situation related to tuberculosis differs among the five regions of Brazil. Those differences can make it difficult to control the disease in the country and could explain the fact that Brazil failed to reach the MDG for tuberculosis-related mortality. Tuberculosis control measures should be adapted to account for regional differences.

Keywords: Tuberculosis/epidemiology; Tuberculosis, pulmonary/epidemiology; Health status indicators; Social determinants of health; Healthcare disparities.

A significant percentage of pleural effusions remains without a diagnostic explanation. In such circumstances, the anatomical-pathological result of nonspecific chronic pleuritis should be revised. This is an important issue, not only for the pathologist, but mainly for the pneumologist, who usually makes the clinical-pathological correlation during the routine practice. Although the existence of established criteria is accepted, they are certainly subjective and make the communication by means of a common language difficult, mainly among pathologists. The authors recently studied 311 pleural biopsies with histo-pathological diagnoses of chronic nonspecific pleuritis. All specimens were reviewed and the histo-pathological parameters quantified by stereology. The patients were stratified according to the final diagnosis of their disease, including cases of chronic renal failure, vasculitis, pancreatitis, tuberculosis, cancer, and congestive cardiac failure, in this case considering the pleura as normal. This procedure allowed us to obtain a discriminating model, whose morphological subcriteria classified almost 90% of the nonspecific chronic pleuritis biopsies, according to their final clinical diagnoses, which included true nonspecific chronic pleuritis or tuberculosis pleuritis, paraneoplastic pleuritis, or even normal pleura. By adding to this model the biochemistry or differential cytology of the pleural liquid, its classificatory power reaches 99% of correctness. This study represents the result of the experience acquired over several years in the histo-pathological interpretation of pleural biopsies, based on the correlation between morphology and biochemistry and cytology of the pleural fluid.

Keywords: Biopsy, needle. Pleura/pathology. Pleura/cytology. Pleural effusion.

Objective: Various markers have shown promise as diagnostic markers and prognostic predictors in malignant mesothelioma (MM). Methods: Through morphometric and immunological studies of markers in stromal components (calretinin, CEA, Leu-M1 and thrombomodulin) and nuclear components (p53 and Ki-67), we evaluated post-diagnosis survival in 58 patients with MM. Results: The histologic pattern of the MM was typical in 50 cases and atypical in 8. Through immunohistochemistry, we confirmed 40 cases of mesothelioma and 11 cases of adenocarcinoma, although we were unable to classify 7 of the 8 cases presenting atypical histologic patterns. Cox multivariate analysis revealed that the risk factor for death was higher (476.2) among patients of advanced age, presenting the biphasic subtype and testing positive for components expressed at the nuclear level. Conclusion: The most useful immunohistochemical markers were was calretinin (for mesothelioma) and CEA (for adenocarcinoma). Immunohistochemical quantification of thrombomodulin facilitated the diagnosis of mesothelioma in patients testing positive for both calretinin and CEA. The most useful prognostic information was that provided by the routine histopathological analysis of the tumor type. It is of note that the combination of a mean age of 55 years and 30.5% immunohistochemical markers in nuclear components created a natural dividing point between patients in which survival was shorter than expected and those in which it was longer than expected. Therefore, histopathological analysis offers a powerful weapon with great potential to inform decisions regarding the use of adjuvant chemotherapy after surgical excision of a mesothelioma.

Keywords: Pleural neoplasms; Mesothelioma; Tumor markers, Biological; Carcinoembryonic antigen; Prognosis.

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.