Prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros / Smoking prevalence and lung cancer morbimortality in Brazilian states / Prevalencia del tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños

Introdução: O câncer de pulmão é uma doença grave, sendo a segunda maior causa de morte em todo o mundo, entretanto, em alguns países desenvolvidos, tornou-se já a primeira causa de morte. Cerca de 90% dos casos de neoplasia pulmonares são causados pela inalação da fumaça do cigarro. Objetivo: Correlacionar a prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, além de demonstrar a associação destes com sexo e faixa etária. Métodos: Estudo de caráter ecológico acerca da prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, nos períodos de 2013 e 2019, dividida por sexo e faixa etária. Foram utilizados bancos de coleta de dados como o Tabnet e Pesquisa Nacional de Saúde. Resultados: As maiores taxas de mortalidade e internações hospitalares foram do público masculino, em 2013, com taxa de 2,7 e 10, respectivamente, e em 2019 com 3,3 e 11,9, respectivamente. Ademais, a maior prevalência de tabagismo foi encontrada nos homens; entretanto seu índice tem caído, enquanto a quantidade de mulheres tabagistas tem aumentado. A Região Sul demonstrou maiores números de mortalidade em ambos os períodos estudados, com taxas de 4,9 e 5,8 por 100 mil habitantes, e morbidade hospitalar com 19,9 e 23,5 por 100 mil habitantes. Já a Região Norte se configurou com as menores prevalências: em 2013 apresentou taxa de óbito por câncer de pulmão de 1,0 e morbidade hospitalar de 3,5/100 mil habitantes, em 2019 apresentou taxa de mortalidade de 4,6 e internações de 1,6/100 mil habitantes. Os coeficientes de correlação de morbidade hospitalar e prevalência de tabagismo foram R2=0,0628, r=0,251 e p=0,042, enquanto os de mortalidade e prevalência de tabagismo foram R2=0,0337, r=0,183 e p=0,140. Conclusões: Na presente pesquisa, pode-se inferir que houve associação positiva na comparação entre taxa de morbidade hospitalar e prevalência de tabagismo; em contrapartida, não foi possível observar associação positiva na correlação da taxa de mortalidade por câncer de pulmão e prevalência de tabagismo.

Introduction: Lung cancer is a serious disease, being the second leading cause of death worldwide. Moreover, in some developed countries, it has already become the leading cause of death. About 90% of lung cancer cases are caused by cigarette smoking. Objective: To correlate the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states, and to demonstrate their association with sex and age group as well. Methods: An ecological study on the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states between 2013 and 2019, divided by sex and age group. The data collection databases Tabnet and National Health Survey were used. Results: The highest rates of mortality and hospital admissions were among men, in 2013 with a rate of 2.7 and 10, respectively, and in 2019 with 3.3 and 11.9, respectively. In addition, the highest prevalence of smoking was found in men, but this rate has fallen, while the number of women smokers has increased. The South region showed higher mortality rates in both periods studied, with rates of 4.9 and 5.8 per 100,000 inhabitants, and hospital morbidity with 19.9 and 23.5 per 100,000 inhabitants. The North region had the lowest prevalence, where in 2013, it had a death rate from lung cancer of 1.0 and hospital morbidity of 3.5/100 thousand inhabitants, and where in 2019, it had a mortality rate of 4.6 and hospitalizations of 1.6/100 thousand inhabitants. The correlation coefficients for hospital morbidity and smoking prevalence were R2=0.0628, r=0.251 and p=0.042, while for mortality and smoking prevalence, these were R2=0.0337, r=0.183 and p=0.140. Conclusions: In the present study, it can be inferred that there was a positive association between hospital morbidity rate and prevalence of smoking, while it was not possible to observe a correlation between lung cancer mortality rate and prevalence of smoking.

Introducción: El cáncer de pulmón es una enfermedad grave, siendo la segunda causa de muerte en todo el mundo, sin embargo, en algunos países desarrollados, ya se ha convertido en la primera causa de muerte. Alrededor del 90% de los casos de neoplasias pulmonares están causados por la inhalación del humo del cigarrillo. Objetivo: Correlacionar la prevalencia de tabaquismo y la morbimortalidad por cáncer de pulmón en los estados brasileños, además de demostrar la asociación de estos con el género y el grupo de edad. Métodos: estudio ecológico sobre la prevalencia de tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños, dentro de los períodos 2013 y 2019, divididos por sexo y grupo de edad. Se utilizaron bancos de recogida de datos como Tabnet y la Encuesta Nacional de Salud. Resultados: las mayores tasas de mortalidad e ingresos hospitalarios se dieron en el público masculino, en 2013 con una tasa de 2,7 y 10, respectivamente, y en 2019 con 3,3 y 11,9, respectivamente. Además, la mayor prevalencia del tabaquismo se encontró en los hombres, sin embargo, su tasa ha disminuido, mientras que la cantidad de mujeres fumadoras ha aumentado. La región Sur presentó cifras más altas de mortalidad en ambos periodos estudiados, con tasas de 4,9 y 5,8 por 100.000 habitantes, y de morbilidad hospitalaria con 19,9 y 23,5 por 100.000 habitantes. Mientras que la región Norte se configuró con las prevalencias más bajas, en 2013 presentó una tasa de mortalidad por cáncer de pulmón de 1,0 y una morbilidad hospitalaria de 3,5/100.000 habitantes, en 2019 presentó una tasa de mortalidad de 4,6 y hospitalizaciones de 1,6/100.000 habitantes. Los coeficientes de correlación para la morbilidad hospitalaria y la prevalencia del tabaquismo fueron R2=0,0628, r=0,251 y p=0,042, mientras que para la mortalidad y la prevalencia del tabaquismo fueron R2=0,0337, r=0,183 y p=0,140. Conclusiones: En la presente investigación se puede inferir que existe una asociación positiva en la comparación entre la tasa de morbilidad hospitalaria y la prevalencia de tabagismo, en contrapartida, no fue posible observar una asociación positiva en la correlación de la tasa de mortalidad por cáncer de pulmón y la prevalencia de tabagismo.

Edema pulmonar por reexpansión. Reporte de Caso / Pulmonary edema due to re-expansion. Case Report

Introducción. El edema pulmonar por reexpansión es una complicación poco frecuente, secundaria a una rápida reexpansión pulmonar posterior al drenaje por toracentesis o toracostomía cerrada. Al día de hoy, se ha descrito una incidencia menor al 1 % tras toracostomía cerrada, con mayor prevalencia en la segunda y tercera década de la vida. Su mecanismo fisiopatológico exacto es desconocido; se ha planteado un proceso multifactorial de daño intersticial pulmonar asociado con un desequilibrio de las fuerzas hidrostáticas. Caso clínico. Presentamos el caso de un paciente que desarrolló edema pulmonar por reexpansión posterior a toracostomía cerrada. Se hizo una revisión de la literatura sobre esta complicación. Resultados. Aunque la clínica sugiere el diagnóstico, la secuencia de imágenes desempeña un papel fundamental. En la mayoría de los casos suele ser autolimitado, por lo que su manejo es principalmente de soporte; sin embargo, se han reportado tasas de mortalidad que alcanzan hasta el 20 %, por tanto, es importante conocer los factores de riesgo y las medidas preventivas. Conclusión. El edema pulmonar de reexpansión posterior a toracostomía es una complicación rara en los casos con neumotórax, aunque es una complicación que se puede presentar en la práctica diaria, por lo cual debe tenerse en mente para poder hacer el diagnóstico y un manejo adecuado.

Introduction. Re-expansion pulmonary edema is a rare complication secondary to rapid pulmonary re-expansion after drainage by thoracentesis and/or closed thoracostomy. As of today, an incidence of less than 1% has been described after closed thoracostomy, with a higher prevalence in the second and third decades of life. Its exact pathophysiological mechanism is unknown; a multifactorial process of lung interstitial damage associated with an imbalance of hydrostatic forces has been proposed. Clinical case. We present the case of a patient who developed pulmonary edema due to re-expansion after closed thoracostomy, conducting a review of the literature on this complication. Results. Although the clinic suggests the diagnosis, the sequence of images plays a fundamental role. In most cases, it tends to be a self-limited disease, so its management is mainly supportive. However, mortality rates of up to 20% have been recorded. Therefore, it is important to identify patients with major risk factors and initiate preventive measures in these patients. Conclusions. Re-expansion pulmonary edema after thoracostomy is a rare complication in cases with pneumothorax; however, it is a complication that can occur in daily practice. Therefore, it must be kept in mind to be able to make the diagnosis and an adequate management.

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Abstract The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

The impact of hospitalization on mortality in patients with connective tissue disease-associated interstitial lung disease: a medical records review study

Abstract Background Interstitial lung disease (ILD) remains one of the most important causes of morbidity and mortality in patients with Connective Tissue Diseases (CTD). This study evaluated the impact of hospitalization on mortality in an ethnically and racially diverse cohort of CTD-ILD patients. Methods We conducted a medical records review study at Montefiore Medical Center, Bronx, NY. We included 96 patients and collected data on demographic characteristics, reasons for hospitalization, length of stay, immunosuppressant therapy use, and mortality. We stratified our patients into two cohorts: hospitalized and nonhospitalized. The hospitalized cohort was further subdivided into cardiopulmonary and non-cardiopulmonary admissions. Two-sample tests or Wilcoxon's rank sum tests for continuous variables and Chi-square or Fisher's exact tests for categorical variables were used for analyses as deemed appropriate. Results We identified 213 patients with CTD-ILD. Out of them, 96 patients met the study's inclusion criteria. The majority of patients were females (79%), and self-identified as Hispanic (54%) and Black (40%). The most common CTDs were rheumatoid arthritis (RA) (29%), inflammatory myositis (22%), and systemic sclerosis (15%). The majority (76%) of patients required at least one hospitalization. In the non-hospitalized group, no deaths were observed, however we noted significant increase of mortality risk in hospitalized group (p = 0.02). We also observed that prolonged hospital stay (> 7 days) as well as older age and male sex were associated with increased mortality. Conclusion Prolonged (> 7 days) hospital stay and hospitalization for cardiopulmonary causes, as well as older age and male sex were associated with an increased mortality risk in our cohort of CTD-ILD patients.

Relação entre a Complacência Pulmonar Estática e a Falha de Extubação em Pacientes Pós-Operatório de Cirurgia Cardíaca / Relationship between Static Lung Compliance and Extubation Failure in Postoperative Cardiac Surgery Patients

Resumo Fundamento: Pouco explorada na decisão de extubação no pós-operatório de cirurgia cardíaca, a complacência pulmonar estática seriamente afetada no procedimento cirúrgico pode levar à insuficiência respiratória e à falha na extubação. Objetivo: Avaliar a complacência pulmonar estática no pós-operatório de cirurgia cardíaca e relacionar sua possível redução aos casos de falha na extubação dos pacientes submetidos ao método fast-track de extubação. Métodos: Foram incluídos pacientes que realizaram cirurgia cardíaca com uso de circulação extracorpórea (CEC) em um hospital universitário estadual admitidos na UTI sob sedação e bloqueio residual. Tiveram sua complacência pulmonar estática avaliada no ventilador mecânico por meio do software que utiliza o least squares fitting (LSF) para a medição. No período de 48 horas após a extubação os pacientes foram observados respeito à necessidade de reintubação por insuficiência respiratória. O nível de significância adotado para os testes estatísticos foi de 5%, ou seja, p<0,05. Resultados: Obtiveram sucesso na extubação 77 pacientes (75,49%) e falharam 25 (24,51%). Os pacientes que falharam na extubação tiveram a complacência pulmonar estática mais baixa quando comparados aos que tiveram sucesso (p<0,001). Identificamos o ponto de corte para complacência por meio da análise da curva Receiver Operating Characteristic Curve (ROC) sendo o ponto de corte o valor da complacência <41ml/cmH2O associado com maior probabilidade de falha na extubação (p<0,001). Na análise de regressão múltipla, verificou-se a influência da complacência pulmonar (dividida pelo ponto de corte da curva ROC) com risco de falha 9,1 vezes maior para pacientes com complacência <41ml/cmH2O (p< 0,003). Conclusões: A complacência pulmonar estática <41ml/cmH2O é um fator que compromete o sucesso da extubação no pós-operatório de cirurgia cardíaca.

Abstract Background: Static lung compliance, which is seriously affected during surgery, can lead to respiratory failure and extubation failure, which is little explored in the decision to extubate after cardiac surgery. Objective: To evaluate static lung compliance in the postoperative period of cardiac surgery and relate its possible reduction to cases of extubation failure in patients submitted to the fast-track method of extubation. Methods: Patients undergoing cardiac surgery using cardiopulmonary bypass (CPB) at a state university hospital admitted to the ICU under sedation and residual block were included. Their static lung compliance was assessed on the mechanical ventilator using software that uses least squares fitting (LSF) for measurement. Within 48 hours of extubation, the patients were observed for the need for reintubation due to respiratory failure. The level of significance adopted for the statistical tests was 5%, i.e., p<0.05. Results: 77 patients (75.49%) achieved successful extubation and 25 (24.51%) failed extubation. Patients who failed extubation had lower static lung compliance compared to those who succeeded (p<0.001). We identified the cut-off point for compliance through analysis of the Receiver Operating Characteristic Curve (ROC), with the cut-off point being compliance <41ml/cmH2O associated with a higher probability of extubation failure (p<0.001). In the multiple regression analysis, the influence of lung compliance (divided by the ROC curve cut-off point) was found to be 9.1 times greater for patients with compliance <41ml/cmH2O (p< 0.003). Conclusions: Static lung compliance <41ml/cmH2O is a factor that compromises the success of extubation in the postoperative period of cardiac surgery.

Xuebijing improves inflammation and pyroptosis of acute lung injury by up-regulating miR-181d-5p-mediated SPP1 inactivation

Abstract Background Xuebijing (XBJ) is widely applied in the treatment of Acute Lung Injury (ALI). This study focused on the potential mechanism of XBJ in Lipopolysaccharide (LPS)-induced ALI. Methods The rat ALI model was established by injection of LPS (10 mg/kg) and pretreated with XBJ (4 mL/kg) three days before LPS injection. BEAS-2B cell line was stimulated with LPS (1 μg/mL) and ATP (5 mM) to induce pyroptosis, and XBJ (2 g/L) was pretreated 24h before induction. The improvement effects of XBJ on pulmonary edema, morphological changes, and apoptosis in ALI lung tissue were evaluated by lung wet/dry weight ratio, HE-staining, and TUNEL staining. Inflammatory cytokines in lung tissue and cell supernatant were determined by ELISA. pyroptosis was detected by flow cytometry. Meanwhile, the expressions of miR-181d-5p, SPP1, p-p65, NLRP3, ASC, caspase-1, p20, and GSDMD-N in tissues and cells were assessed by RT-qPCR and immunoblotting. The relationship between miR-181d-5p and SPP1 in experimental inflammation was reported by dual luciferase assay. Results XBJ could improve inflammation and pyroptosis of ALI by inhibiting contents of inflammatory cytokines, and levels of inflammation- and pyroptosis-related proteins. Mechanistically, XBJ could up-regulate miR-181d-5p and inhibit SPP1 in ALI. miR-181d-5p can target the regulation of SPP1. Depressing miR-181d-5p compensated for the ameliorative effect of XBJ on ALI, and overexpressing SPP1 suppressed the attenuating effect of XBJ on LPS-induced inflammation and pyroptosis. Conclusion XBJ can regulate the miR-181d-5p/SPP1 axis to improve inflammatory response and pyroptosis in ALI.

Local imaging to interpret tumor size in F18 fluorodeoxyglucose positron emission tomography/CT in lung cancers

SUMMARY OBJECTIVE: This study aimed to determine the thoracic and extra-thoracic extension of the disease in patients diagnosed with lung cancer and who had whole-body F18-fluorodeoxyglucose positron emission tomography/CT imaging and to investigate whether there is a relationship between tumor size and extrathoracic spread. METHODS: A total of 308 patients diagnosed with lung cancer were included in this study. These 308 patients were first classified as group 1 (SPN 30 mm>longest lesion diameter ≥10 mm) and group 2 (lung mass (longest lesion diameter ≥30 mm), and then the same patients were classified as group 3 (nodular diameter of ≤20 mm) and group 4 (nodular size of >20 mm). Group 1 was compared with group 2 in terms of extrathoracic metastases. Similarly, group 3 was compared with group 4 in terms of frequency of extrathoracic metastases. F18 fluorodeoxyglucose positron emission tomography/CT examination was used to detect liver, adrenal, bone, and supraclavicular lymph node metastasis, besides extrathoracic metastasis. RESULTS: Liver, bone, and extrathoracic metastasis in group 1 was statistically lower than in group 2 (p<0.001, p<0.01, and p=0.03, respectively). Liver, extrathoracic, adrenal, and bone metastasis in group 3 was statistically lower than that in group 4 (p<0.001, p=0.01, and p=0.04, p<0.01, respectively). The extrathoracic extension was observed in only one patient in group 3. In addition, liver, adrenal, and bone metastases were not observed in group 3 patients. CONCLUSION: Positron emission tomography/CT may be more appropriate for cases with a nodule diameter of ≤20 mm. Performing local imaging in patients with a nodule diameter of ≤20 mm could reduce radiation exposure and save radiopharmaceuticals used in positron emission tomography/CT imaging.

Performance Evaluation of Geometrically Different Pediatric Arterial Cannulae in a Pediatric Cardiopulmonary Bypass Model

ABSTRACT Objective: To define a reference chart comparing pressure drop vs. flow generated by a set of arterial cannulae currently utilized in cardiopulmonary bypass conditions in pediatric surgery. Methods: Cannulae from two manufacturers were selected considering their design and outer and inner diameters. Cannula performance was evaluated in terms of pressure drop vs. flow during simulated cardiopulmonary bypass conditions. The experimental circuits consisted of a Jostra HL-20 roller pump, a Quadrox-i pediatric oxygenator (Maquet Cardiopulmonary AG, Rastatt, Germany), and a custom pediatric tubing set. The circuit was primed with lactated Ringer's solution only (first condition) and with human packed red blood cells added (second condition) to achieve a hematocrit of 30%. Cannula sizes 8 to 16 Fr were inserted into the cardiopulmonary bypass circuit with a "Y" connector. The flow was adjusted in 100 ml/min increments within typical flow ranges for each cannula. Pre-cannula and post-cannula pressures were measured to calculate the pressure drop. Results: Utilizing a pressure drop limit of 100 mmHg, our results suggest a recommended flow limit of 500, 900, 1400, 2600, and 3100 mL/min for Braile arterial cannulae sizes 8, 10, 12, 14, and 16 Fr, respectively. For Medtronic DLP arterial cannulae sizes 8, 10, 12, 14, and 16 Fr, the recommended flow limit is 600, 1100, 1700, 2700, and 3300 mL/min, respectively. Conclusion: This study reinforces discrepancies in pressure drop between cannulae of the same diameter supplied by different manufacturers and the importance of independent translational research to evaluate components' performance.

Respiratory system parameters in children with low severity cystic fibrosis: is there early involvement in relation to healthy peers? / Parâmetros do sistema respiratório em crianças com fibrose cística de baixa gravidade: há acometimento precoce em relação a pares saudáveis?

ABSTRACT Objective: To compare and analyze pulmonary function and respiratory mechanics parameters between healthy children and children with cystic fibrosis. Methods: This cross-sectional analytical study included healthy children (HSG) and children with cystic fibrosis (CFG), aged 6-13 years, from teaching institutions and a reference center for cystic fibrosis in Florianópolis/SC, Brazil. The patients were paired by age and sex. Initially, an anthropometric evaluation was undertaken to pair the sample characteristics in both groups; the medical records of CFG were consulted for bacterial colonization, genotype, and disease severity (Schwachman-Doershuk Score — SDS) data. Spirometry and impulse oscillometry were used to assess pulmonary function. Results: In total, 110 children were included, 55 in each group. In the CFG group, 58.2% were classified as excellent by SDS, 49.1% showed the ΔF508 heterozygotic genotype, and 67.3% were colonized by some pathogens. Statistical analysis revealed significant differences between both groups (p<0.05) in most pulmonary function parameters and respiratory mechanics. Conclusions: Children with cystic fibrosis showed obstructive ventilatory disorders and compromised peripheral airways compared with healthy children. These findings reinforce the early changes in pulmonary function and mechanics associated with this disease.

RESUMO Objetivo: Comparar e analisar parâmetros de função pulmonar e de mecânica respiratória entre escolares saudáveis e com fibrose cística (FC). Métodos: Estudo transversal que incluiu escolares saudáveis (GES) e com FC (GFC), com idades entre seis e 13 anos, provenientes de instituições de ensino e de um centro de referência da FC em Florianópolis/SC, Brasil, pareados por idade e sexo, respectivamente. Inicialmente, conduziu-se avaliação antropométrica para pareamento e caracterização de ambos os grupos e, no GFC, consultou-se prontuário médico para registro dos dados de colonização bacteriana, genótipo e gravidade da doença (Escore de Schwachman-Doershuk — ESD). Para a avaliação da função pulmonar, realizou-se espirometria e a avaliação da mecânica respiratória foi conduzida por meio do sistema de oscilometria de impulso. Resultados: Participaram 110 escolares, 55 em cada grupo. No GFC, 58,2% foram classificados pelo ESD como excelentes, 49,1% apresentaram genótipo ∆F508 heterozigoto e 67,3% eram colonizados por alguma patógeno. Houve diferença significativa (p<0,05) na maioria dos parâmetros de função pulmonar e de mecânica respiratória entre os grupos. Conclusões: Escolares com FC apresentaram distúrbio ventilatório obstrutivo e com comprometimento de vias aéreas periféricas, em comparação aos escolares hígidos. Esse evento reforça o início precoce da alteração de função pulmonar e de mecânica respiratória nessa enfermidade, evidenciados pelos achados desta investigação.

Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells

Background Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection. Results Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimer:monomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimer:monomer ratio. These effects were prevented by combined administration of IFN-β, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimer:monomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimer:monomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimer:monomer equilibrium. Conclusions Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related biological response which partakes in the suppression of viral replication. Further studies are needed to replicate our findings in neuronal cells as well as animal models, and to ascertain the nature of such α-syn conformations.

Relative incidence of interstitial lung diseases in Brazil / Incidência relativa de doenças pulmonares intersticiais no Brasil

ABSTRACT Objective: To assess the relative frequency of incident cases of interstitial lung diseases (ILDs) in Brazil. Methods: This was a retrospective survey of new cases of ILD in six referral centers between January of 2013 and January of 2020. The diagnosis of ILD followed the criteria suggested by international bodies or was made through multidisciplinary discussion (MDD). The condition was characterized as unclassifiable ILD when there was no specific final diagnosis following MDD or when there was disagreement between clinical, radiological, or histological data. Results: The sample comprised 1,406 patients (mean age = 61 ± 14 years), and 764 (54%) were female. Of the 747 cases exposed to hypersensitivity pneumonitis (HP)-related antigens, 327 (44%) had a final diagnosis of HP. A family history of ILD was reported in 8% of cases. HRCT findings were indicative of fibrosis in 74% of cases, including honeycombing, in 21%. Relevant autoantibodies were detected in 33% of cases. Transbronchial biopsy was performed in 23% of patients, and surgical lung biopsy, in 17%. The final diagnoses were: connective tissue disease-associated ILD (in 27%), HP (in 23%), idiopathic pulmonary fibrosis (in 14%), unclassifiable ILD (in 10%), and sarcoidosis (in 6%). Diagnoses varied significantly among centers (c2 = 312.4; p < 0.001). Conclusions: Our findings show that connective tissue disease-associated ILD is the most common ILD in Brazil, followed by HP. These results highlight the need for close collaboration between pulmonologists and rheumatologists, the importance of detailed questioning of patients in regard with potential exposure to antigens, and the need for public health campaigns to stress the importance of avoiding such exposure.

RESUMO Objetivo: Avaliar a frequência relativa de casos incidentes de doenças pulmonares intersticiais (DPI) no Brasil. Métodos: Levantamento retrospectivo de casos novos de DPI em seis centros de referência entre janeiro de 2013 e janeiro de 2020. O diagnóstico de DPI seguiu os critérios sugeridos por órgãos internacionais ou foi feito por meio de discussão multidisciplinar (DMD). A condição foi caracterizada como DPI não classificável quando não houve um diagnóstico final específico após a DMD ou houve discordância entre dados clínicos, radiológicos ou histológicos. Resultados: A amostra foi composta por 1.406 pacientes (média de idade = 61 ± 14 anos), sendo 764 (54%) do sexo feminino. Dos 747 casos expostos a antígenos para pneumonite de hipersensibilidade (PH), 327 (44%) tiveram diagnóstico final de PH. Houve relato de história familiar de DPI em 8% dos casos. Os achados de TCAR foram indicativos de fibrose em 74% dos casos, incluindo faveolamento, em 21%. Autoanticorpos relevantes foram detectados em 33% dos casos. Biópsia transbrônquica foi realizada em 23% dos pacientes, e biópsia pulmonar cirúrgica, em 17%. Os diagnósticos finais foram: DPI associada à doença do tecido conjuntivo (em 27%), PH (em 23%), fibrose pulmonar idiopática (em 14%), DPI não classificável (em 10%) e sarcoidose (em 6%). Os diagnósticos variaram significativamente entre os centros (c2 = 312,4; p < 0,001). Conclusões: Nossos achados mostram que DPI associada à doença do tecido conjuntivo é a DPI mais comum no Brasil, seguida pela PH. Esses resultados destacam a necessidade de uma estreita colaboração entre pneumologistas e reumatologistas, a importância de fazer perguntas detalhadas aos pacientes a respeito da potencial exposição a antígenos e a necessidade de campanhas de saúde pública destinadas a enfatizar a importância de evitar essa exposição.

Connective tissue disease-associated interstitial lung disease / Doença pulmonar intersticial associada a doença do tecido conjuntivo

ABSTRACT Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a group of systemic autoimmune disorders characterized by immune-mediated organ dysfunction. Systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myositis, and Sjögren's syndrome are the most common CTDs that present with pulmonary involvement, as well as with interstitial pneumonia with autoimmune features. The frequency of CTD-ILD varies according to the type of CTD, but the overall incidence is 15%, causing an important impact on morbidity and mortality. The decision of which CTD patient should be investigated for ILD is unclear for many CTDs. Besides that, the clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. A significant proportion of patients will present with a more severe and progressive disease, and, for those, immunosuppression with corticosteroids and cytotoxic medications are the mainstay of pharmacological treatment. In this review, we summarized the approach to diagnosis and treatment of CTD-ILD, highlighting recent advances in therapeutics for the various forms of CTD.

RESUMO Doença pulmonar intersticial associada à doença do tecido conjuntivo (DPI-DTC) representa um grupo de distúrbios autoimunes sistêmicos caracterizados por disfunção de órgãos imunomediada. Esclerose sistêmica, artrite reumatoide, miosite inflamatória idiopática e síndrome de Sjögren são as DTC mais comuns que apresentam acometimento pulmonar, bem como pneumonia intersticial com achados autoimunes. A frequência de DPI-DTC varia de acordo com o tipo de DTC, mas a incidência total é de 15%, causando um impacto importante na morbidade e mortalidade. A decisão sobre qual paciente com DTC deve ser investigado para DPI não é clara para muitas DTC. Além disso, o espectro clínico pode variar desde achados assintomáticos em exames de imagem até insuficiência respiratória e morte. Parte significativa dos pacientes apresentará doença mais grave e progressiva, e, para esses pacientes, imunossupressão com corticosteroides e medicamentos citotóxicos são a base do tratamento farmacológico. Nesta revisão, resumimos a abordagem do diagnóstico e tratamento de DPI-DTC, destacando os recentes avanços na terapêutica para as diversas formas de DTC.

Lung cancer screening in Brazil: recommendations from the Brazilian Society of Thoracic Surgery, Brazilian Thoracic Association, and Brazilian College of Radiology and Diagnostic Imaging / Recomendações da Sociedade Brasileira de Cirurgia Torácica, Sociedade Brasileira de Pneumologia e Tisiologia e Colégio Brasileiro de Radiologia e Diagnóstico por Imagem para o rastreamento do câncer de pulmão no Brasil

ABSTRACT Although lung cancer (LC) is one of the most common and lethal tumors, only 15% of patients are diagnosed at an early stage. Smoking is still responsible for more than 85% of cases. Lung cancer screening (LCS) with low-dose CT (LDCT) reduces LC-related mortality by 20%, and that reduction reaches 38% when LCS by LDCT is combined with smoking cessation. In the last decade, a number of countries have adopted population-based LCS as a public health recommendation. Albeit still incipient, discussion on this topic in Brazil is becoming increasingly broad and necessary. With the aim of increasing knowledge and stimulating debate on LCS, the Brazilian Society of Thoracic Surgery, the Brazilian Thoracic Association, and the Brazilian College of Radiology and Diagnostic Imaging convened a panel of experts to prepare recommendations for LCS in Brazil. The recommendations presented here were based on a narrative review of the literature, with an emphasis on large population-based studies, systematic reviews, and the recommendations of international guidelines, and were developed after extensive discussion by the panel of experts. The following topics were reviewed: reasons for screening; general considerations about smoking; epidemiology of LC; eligibility criteria; incidental findings; granulomatous lesions; probabilistic models; minimum requirements for LDCT; volumetric acquisition; risks of screening; minimum structure and role of the multidisciplinary team; practice according to the Lung CT Screening Reporting and Data System; costs versus benefits of screening; and future perspectives for LCS.

RESUMO O câncer de pulmão (CP) é uma das neoplasias mais comuns e letais no Brasil, e apenas 15% dos pacientes são diagnosticados nos estágios iniciais. O tabagismo persiste como o responsável por mais de 85% de todos os casos. O rastreamento do CP (RCP) por meio da TC de baixa dosagem de radiação (TCBD) reduz a mortalidade do CP em 20%, e, quando combinado com a cessação do tabagismo, essa redução chega a 38%. Na última década, diversos países adotaram o RCP como recomendação de saúde populacional. No Brasil, embora ainda incipiente, a discussão sobre o tema é cada vez mais ampla e necessária. Com o intuito de aumentar o conhecimento e estimular o debate sobre o RCP, a Sociedade Brasileira de Cirurgia Torácica, a Sociedade Brasileira de Pneumologia e Tisiologia e o Colégio Brasileiro de Radiologia e Diagnóstico por Imagem constituíram um painel de especialistas para elaborar as recomendações para o RCP. As recomendações aqui apresentadas foram baseadas em revisão narrativa da literatura, com ênfase em grandes estudos populacionais, em revisões sistemáticas e em recomendações de diretrizes internacionais, sendo construídas após ampla discussão pelo grupo de especialistas. Os temas revisados foram os seguintes: porque rastrear, considerações gerais sobre tabagismo, epidemiologia do CP, critérios de elegibilidade, achados incidentais, lesões granulomatosas, modelos probabilísticos, requisitos mínimos da TCBD, aquisições volumétricas, riscos do rastreamento, estrutura mínima e papel da equipe multidisciplinar, conduta segundo o Lung CT Screening Reporting and Data System (Lung-RADS), custos vs. benefícios e perspectivas do rastreamento.

Research advances in thermal ablation for lung cancer / 中国胸心血管外科临床杂志

@#Although surgical resection remains to be the best treatment strategy for stageⅠnon-small cell lung cancer (NSCLC), percutaneous thermal ablation offers an important option for patients who are unable to undergo surgical resection. Currently, there are three main thermal ablation methods used in the treatment of lung cancer, including radiofrequency ablation (RFA), microwave ablation (MWA) and argon-helium cryoablation (AHC). With the improvement of technique and the accumulation of experience in the treatment of lung cancer, some limitations are disclosed in the initial application of RFA, such as heat sink effect, skin burns and rapid carbonization. These shortcomings have been overcome in the development of MWA and AHC. The feasibility and safety of thermal ablation for the treatment of lung cancer has been demonstrated and its efficacy has been significantly improved (especially for the tumour diameter≤3 cm). This article will focus on the application and recent research developments of these ablation techniques in the treatment of lung cancer.

Research progress of artificial intelligence in pathological subtypes classification and gene expression analysis of lung adenocarcinoma / 中国胸心血管外科临床杂志

@#Lung adenocarcinoma is a prevalent histological subtype of non-small cell lung cancer with different morphologic and molecular features that are critical for prognosis and treatment planning. In recent years, with the development of artificial intelligence technology, its application in the study of pathological subtypes and gene expression of lung adenocarcinoma has gained widespread attention. This paper reviews the research progress of machine learning and deep learning in pathological subtypes classification and gene expression analysis of lung adenocarcinoma, and some problems and challenges at the present stage are summarized and the future directions of artificial intelligence in lung adenocarcinoma research are foreseen.

Risk factors for postoperative pulmonary infection in lung cancer patients: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To systematically evaluate the risk factors for postoperative pulmonary infection in patients with lung cancer (PPILC), and to provide a theoretical reference for clinicians to prevent the occurrence of PPILC. Methods     The databases of CNKI, Wanfang data, VIP, CBM, PubMed, EMbase and The Cochrane Library were searched by computer to collect researches on the risk factors for PPILC. The search period was from 2012 to 2021. Two clinicians independently screened literature and extracted data and assessed studies for risk of bias, cross-checked and agreed. Meta-analysis was performed using RevMan 5.3 software. Results     A total of 25 studies were included, including 20 case-control studies, 1 cohort study, and 4 cross-sectional studies, covering 15 129 patients. Twenty case-control studies and 1 cohort study had Newcastle-Ottawa Scale (NOS) scores≥6 points, and 4 cross-sectional studies had the Agency for Health Care Quality and Research (AHRQ) scale scores≥6 points. The results of meta-analysis showed that the risk factors for PPILC included: (1) 4 patient's own factors: age≥60 years, male, smoking history, smoking index≥400; (2) 7 preoperative factors: suffering from diabetes, chronic heart failure and chronic obstructive pulmonary disease, the ratio of forced expiratory volume in 1 second to forced expiratory volume<70%, the ratio of forced expiratory volume in 1 second to the predicted value, preoperative airway colonization, non-standard use of prophylactic antibiotics before surgery; (3) 3 intraoperative factors: operation time≥3 h, thoracotomy, the number of resected lobe≥2; (4) 3 postoperative factors: postoperative pain, postoperative mechanical ventilation≥12 h, postoperative invasive operation. Large number of preoperative lymphocyte, intraoperative systematic lymph node dissection, TNM stage Ⅰ and Ⅱ, and enhanced recovery after surgery were protective factors for PPILC. Conclusion     The current research evidence shows that multiple factors are associated with the risk of PPILC. However, considering the influence of the quality and quantity of the included literature, the results of this study urgently need to be further verified by more high-quality clinical studies.

High risk factors in images for infiltrating lung adenocarcinoma manifesting as peripheral ground-glass nodules / 中国胸心血管外科临床杂志

@#Objective     To explore the correlation between the imaging features of peripheral ground-glass pulmonary nodules and the invasion degree of lung adenocarcinoma, and the high risk factors for infiltrating lung adenocarcinoma under thin-slice CT, which provides some reference for clinicians to plan the surgical methods of pulmonary nodules before operation and to better communicate with patients, and assists in building a clinical predictive model for invasive adenocarcinoma. Methods    Clinical data of the patients with peripheral ground-glass pulmonary nodules (diameter≤3 cm) in thin-slice chest CT in the First Affiliated Hospital of Soochow University from January 2019 to January 2020 were continuously collected. All patients underwent thin-slice CT scan and thoracoscopic surgery in our center. According to the pathological examination results, they were divided into two groups: an adenocarcinoma lesions before infiltration group, and an invasive lung adenocarcinoma group. The thin-slice CT imaging parameters of pulmonary nodules were collected. The nodular diameter, mean CT value, consolidation tumor ratio (CTR), nodular shape, vacuolar sign, bronchial air sign, lobulation sign, burr sign, lesion boundary, pleural depression sign, vascular cluster sign and other clinical data were collected. Univariate and multivariate analyses were conducted to analyze the independent risk factors for the infiltrating lung adenocarcinoma, and to analyze the threshold value and efficacy of each factor for the identification of infiltrating lung adenocarcinoma. Results     Finally 190 patients were enrolled. There were 110 patients in the adenocarcinoma lesions before infiltration group, including 21 males and 89 females with a mean age of 53.57±10.90 years, and 80 patients in the invasive lung adenocarcinoma group, including 31 males and 49 females with a mean age of 56.45±11.30 years. There was a statistical difference in the mean CT value, nodular diameter, CTR, gender, smoking, nodular type, nodular shape, vacuolar sign, lobulation sign, burr sign, lesion boundary, pleural depression sign, vascular cluster sign between the two groups (P<0.05). However, there was no statistical difference between the two groups in age (P=0.081), lesion site (P=0.675), and bronchial air sign (P=0.051). Multiple logistic regression analysis showed that nodular diameter, mean CT value, CTR and lobulation sign were independent risk factors for differentiating preinvasive adenocarcinoma from invasive adenocarcinoma. At the same time, the threshold value was calculated by Youden index, indicating that the CTR was 0.45, the nodal diameter was 10.5 mm and the mean CT value was –452 Hu. Conclusion     In the peripheral ground-glass pulmonary nodules, according to the patient's CT imaging features, such as mixed ground-glass nodules, irregular shapes, vacuoles, short burrs, clear boundaries, pleural indentations, and vascular clusters, have a certain reference value in the discrimination of the invasion degree of ground-glass pulmonary nodules. At the same time, it is found in this research that peripheral ground-glass pulmonary nodules with diameter greater than 10.5 mm, CT value greater than –452 Hu, CTR greater than 0.45 and lobulation sign are more likely to be infiltrating lung adenocarcinoma.

Analysis of intraoperative frozen section diagnosis of 1 263 pulmonary nodules / 中国胸心血管外科临床杂志

@#Objective    To explore the key points and difficulties of intraoperative frozen section diagnosis of pulmonary diseases. Methods    The intraoperative frozen section and postoperative paraffin section results of pulmonary nodule patients in Beijing Chaoyang Hospital, Capital Medical University from January 2021 to January 2022 were collected. The main causes of misdiagnosis in frozen section diagnosis were analyzed, and the main points of diagnosis and differential diagnosis were summarized. Results    According to the inclusion criteria, a total of 1 263 frozen section diagnosis results of 1 178 patients were included in the study, including 475 males and 703 females, with an average age of 58.7 (23-86) years. In 1 263 frozen section diagnosis results, the correct diagnosis rate was 95.65%, and the misdiagnosis rate was 4.35%. There were 55 misdiagnoses, including 18 (3.44%) invasive adenocarcinoma, 17 (5.82%) adenocarcinoma in situ, 7 (35.00%) mucinous adenocarcinoma, 4 (2.09%) minimally invasive adenocarcinoma, 3 (100.00%) IgG4 related diseases, 2 (66.67%) mucinous adenocarcinoma in situ, 1 (16.67%) atypical adenomatous hyperplasia, 1 (14.29%) sclerosing pulmonary cell tumor, 1 (33.33%) bronchiolar adenoma, and 1 (100.00%) papillary adenoma. Conclusion    Intraoperative frozen section diagnosis still has its limitations. Clinicians need to make a comprehensive judgment based on imaging examination and clinical experience.

A predictive model of lymph node metastasis after thoracoscopic surgery for lung adenocarcinoma with a diameter≤3 cm / 中国胸心血管外科临床杂志

@#Objective    To predict the probability of lymph node metastasis after thoracoscopic surgery in patients with lung adenocarcinoma based on nomogram. Methods    We analyzed the clinical data of the patients with lung adenocarcinoma treated in the department of thoracic surgery of our hospital from June 2018 to May 2021. The patients were randomly divided into a training group and a validation group. The variables that may affect the lymph node metastasis of lung adenocarcinoma were screened out by univariate logistic regression, and then the clinical prediction model was constructed by multivariate logistic regression. The nomogram was used to show the model visually, the receiver operating characteristic (ROC) curve, calibration curve and clinical decision curve to evaluate the calibration degree and practicability of the model. Results    Finally 249 patients were collected, including 117 males aged 53.15±13.95 years and 132 females aged 47.36±13.10 years. There were 180 patients in the training group, and 69 patients in the validation group. There was a significant correlation between the 6 clinicopathological characteristics and lymph node metastasis of lung adenocarcinoma in the univariate logistic regression. The area under the ROC curve in the training group was 0.863, suggesting the ability to distinguish lymph node metastasis, which was confirmed in the validation group (area under the ROC curve was 0.847). The nomogram and clinical decision curve also performed well in the follow-up analysis, which proved its potential clinical value. Conclusion    This study provides a nomogram combined with clinicopathological characteristics, which can be used to predict the risk of lymph node metastasis in patients with lung adenocarcinoma with a diameter≤3 cm.

Clinical application of Mimics software system to three-dimensional reconstruction to guide thoracoscopic anatomic pulmonary segmentectomy / 中国胸心血管外科临床杂志

@#Objective    To investigate the clinical effect of 3D computed tomography bronchial bronchography and angiography (3D-CTBA) and guidance of thoracoscopic anatomic pulmonary segmentectomy by Mimics software system. Methods    A retrospective analysis was performed on patients who underwent thoracoscopic segmentectomy in the Department of Thoracic Surgery of Affiliated People's Hospital of Jiangsu University from June 2020 to December 2022. The patients who underwent preoperative 3D-CTBA using Materiaise's interactive medical image control system (Mimics) were selected as an observation group, and the patients who did not receive 3D-CTBA were selected as a control group. The relevant clinical indicators were compared between the two groups. Results    A total of 59 patients were included, including 29 males and 30 females, aged 25-79 years. There were 37 patients in the observation group, and 22 patients in the control group. The operation time (163.0±48.7 min vs. 188.8±43.0 min, P=0.044), intraoperative blood loss [10.0 (10.0, 20.0) mL vs. 20.0 (20.0, 35.0) mL, P<0.001], and preoperative puncture localization rate (5.4% vs. 31.8%, P=0.019) in the observation group were better than those in the control group. There was no statistically significant difference in the thoracic tube placement time, thoracic fluid drainage volume, number of intraoperative closure nail bin, postoperative hospital stay, or postoperative air leakage incidence (P>0.05) between the two groups. Conclusion    For patients who need to undergo anatomical pulmonary segmentectomy, using Mimics software to produce 3D-CTBA before surgery can help accurately identify pulmonary arteriovenous anatomy, reduce surgical time and intraoperative blood loss, help to determine the location of nodules and reduce invasive localization before surgery, and alleviate patients' pain, which is worthy of clinical promotion.