Uma Apresentação Rara de COVID-19 com Embolia Pulmonar / A Rare Presentation of COVID-19 with Pulmonary Embolism

Resumo A doença de coronavírus 2019 (COVID-19) foi relatada em quase todos os países do mundo desde dezembro de 2019. A infecção por SARS-CoV-2 é frequentemente assintomática ou com sintomas leves, mas também pode levar à hipóxia, um estado hiperinflamatório e coagulopatia. Os parâmetros de coagulação anormais estão associados a complicações trombóticas, incluindo embolia pulmonar na COVID-19, mas pouco se sabe sobre os mecanismos. A semelhança dos sintomas iniciais de ambas as doenças também pode ser confusa, portanto, os médicos devem estar cientes do potencial para condições concomitantes. Apresentamos aqui um caso que não apresentava opacidades em vidro fosco nos pulmões, mas apresentava embolia pulmonar e derrame pleural em associação com infecção por COVID-19.

Abstract Coronavirus disease 2019 (COVID-19) has been reported in almost every country in the world since December 2019. Infection with SARS-CoV-2 is often asymptomatic or with mild symptoms, but it may also lead to hypoxia, a hyperinflammatory state, and coagulopathy. The abnormal coagulation parameters are associated with thrombotic complications, including pulmonary embolism in COVID-19, but little is known about the mechanisms. The similarity of initial symptoms of both diseases can also be confusing, therefore the physicians should be aware of the potential for concurrent conditions. Herein, we present a case who did not have ground-glass opacities in the lungs, yet presented with pulmonary embolism and pleural effusions in association with COVID-19 infection.

A New Inflammatory Prognostic Index, Based on C-reactive Protein, the Neutrophil to Lymphocyte Ratio and Serum Albumin is Useful for Predicting Prognosis in Non-Small Cell Lung Cancer Cases

Purpose: We aimed to establish an inflammatory prognostic index (IPI) in early and advanced non-small cell lung cancer (NSCLC) patients based on hematologic and biochemical parameters and to analyze its predictive value for NSCLC survival. Materials and Methods: A retrospective review of 685 patients with early and advanced NSCLC diagnosed between 2009 and 2014 was conducted with collection of clinical, and laboratory data. The IPI was calculated as C-reactive protein × NLR (neutrophil/ lymphocyte ratio)/serum albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors. Results: The optimal cut-off value of IPI for overall survival (OS) stratification was determined to be 15. Totals of 334 (48.8%) and 351 (51.2%) patients were assigned to high and low IPI groups, respectively. Compared with low IPI, high IPI was associated with older age, greater tumor size, high lymph node involvement, distant metastases, advanced stage and poor performance status. Median OS was worse in the high IPI group (low vs high, 8.0 vs 34.0 months; HR, 3.5; p<0.001). Progression free survival values of the patients who had high vs low IPI were determined 6 months (95% CI:5.3-6.6) and 14 months (95% CI:12.1-15.8), respectively (HR; 2.4, P<0.001). On multivariate analysis, stage, performance status, lactate dehydrogenase and IPI were independent prognostic factors for OS. Subgroup analysis showed IPI was generally a significant prognostic factor in all clinical variables. Conclusion: The described IPI may be an inexpensive, easily accessible and independent prognostic index for NSCLC patients, useful for clinical practice.

Thiol/disulfide homeostasis: A prognostic biomarker for patients with advanced non-small cell lung cancer?

BACKGROUND: The aim of this study was to investigate oxidative stress and thiol/disulfide status with a novel automated homeostasis assay in advanced non-small cell lung cancer (NSCLC). METHODS: Thirty-five patients with advanced NSCLC, who had been newly diagnosed and previously untreated, and 35 healthy subjects were chosen for the study. We measured plasma total thiol (-SH+-S-S-), native thiol (thiol) (-SH), and disulfide (-S-S-) levels in the patients with NSCLC and the healthy subjects. The thiol/disulfide (-SH/-S-S-) ratio was also calculated. RESULTS: Statistically significant differences between the patient group and the control group were detected for the thiol/disulfide parameters. The mean native thiol, total thiol, and disulfide levels were significantly lower in the group with advanced stage NSCLC. The cut-off value was 313 and 13.8 for native thiol and disulfide, respectively. Median overall survival (OS) was significantly shorter in patients with low native thiol and disulfide levels according to the cut-off value (respectively, P = 0.001; P = 0.006). Native thiol, total thiol, and disulfide levels were correlated with Karnofsky performance status (KPS), OS, and age. Additionally, hierarchical regression analyses showed gender, KPS, lung metastases, and plasma native thiol levels were the determinants of OS in the final model. CONCLUSION: These results suggest that in advanced stage NSCLC, the native thiol, total thiol, and disulfide levels decrease, while the native thiol/disulfide ratio does not change. Low levels of thiol/disulfide parameters are related to tumor aggressiveness and may predict a poor outcome for patients with NSCLC.

Claudin-1 expression in airway smooth muscle exacerbates airway remodeling in asthmatic subjects.

BACKGROUND: Increased airway smooth muscle (ASM) mass is an essential component of airway remodeling and asthma development, and there is no medication specifically against it. Tight junction (TJ) proteins, which are expressed in endothelial and epithelial cells and affect tissue integrity, might exist in other types of cells and display additional functions in the asthmatic lung. OBJECTIVE: The aim of this study was to investigate the existence, regulation, and function of TJ proteins in ASM in asthmatic patients. METHODS: The expression and function of TJ proteins in primary ASM cell lines, human bronchial biopsy specimens, and a murine model of asthma were analyzed by means of RT-PCR, multispectral imaging flow cytometry, immunohistochemistry, Western blotting, 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester staining, tritiated thymidine incorporation, wound-healing assay, and luminometric bead array. RESULTS: Increased claudin-1 expression was observed in ASM of asthmatic patients, as well as in a murine model of asthma-like airway inflammation. Whereas IL-1ß and TNF-α upregulated claudin-1 expression, it was downregulated by the T(H)2 cytokines IL-4 and IL-13 in primary human ASM cells. Claudin-1 was localized to the nucleus and cytoplasm but not to the cell surface in ASM cells. Claudin-1 played a central role in ASM cell proliferation, as demonstrated by increased ASM cell proliferation seen with overexpression and decreased proliferation seen with small interfering RNA knockdown of claudin-1. Overexpression of claudin-1 induced vascular endothelial growth factor and downregulated IL-6, IL-8, and IFN-γ-induced protein 10 production by ASM cells. Claudin-1 upregulation by IL-1ß or TNF-α was suppressed by dexamethasone but not by rapamycin, FK506, or salbutamol. CONCLUSION: These results demonstrate that claudin-1 might play a role in airway remodeling in asthmatic patients by means of regulation of ASM cell proliferation, angiogenesis, and inflammation.

Maspin, VEGF and p53 expression in small biopsies of primary advanced lung cancer and relationship with clinicopathologic parameters.

Maspin, one of the serine protease inhibitors, has been shown to inhibit tumor progression and metastasis. We aimed to investigate maspin, p53 and VEGF expression in patients with squamous cell carcinoma (SCC), adenocarcinoma (AC) and small cell lung carcinoma (SCLC). The study included 28 SCC, 18AC, 17 SCLC biopsy samples. We used the streptavidin biotin immunoperoxidase method to test for maspin, p53 and VEGF antibodies. Medical records of these patients were reviewed from archival files. Cytoplasmic maspin expression was detected in 89.3%, 77.8%, 52.9% of SCC, AC and SCLC, respectively. The rate was significantly higher in non-small cell lung cancer (NSCLC) and SCC than SCLC (p = 0.013, p = 0.021, respectively). The mean percentages of maspin expression were significantly higher in NSCLC, SCC and AC than in SCLC (p = 0.0001, p = 0.0001, p = 0.038, respectively). In ACs, maspin and p53 expressions were correlated, although this was not statistically significant (p = 0.053, r = 0.464), and maspin positive cases had a significantly higher T status compared to negative cases (p = 0.036). In SCC, the stage of disease was positively correlated with p53 (p = 0.007, r = 0.536) and negatively correlated with VEGF expression (p = 0.013, r = -0.498). Multivariate analysis demonstrated that stage of disease was a significant independent prognostic parameter in NSCLC (95% confidence interval: 1.067-3.969; p = 0.031). Although maspin expression is higher in SCC and AC, and is related with higher T status in AC, our data did not indicate its prognostic significance. Larger scale studies are needed to reveal the exact role of maspin in lung cancer pathogenesis.

The attitude toward tobacco dependence and barriers to discussing smoking cessation: a survey among Turkish general practitioners.

OBJECTIVES: To evaluate the general attitude of a sample of Turkish general practitioners (GPs) toward tobacco dependence and to assess their knowledge and behavior regarding smoking cessation (SC). METHODS: A self-administered questionnaire modified from WHO, Global Health Professional Survey was distributed to GPs, working in our district, Isparta. RESULTS: As much as 41% of GPs were current smokers. Ever smokers were generally less likely to agree with statements that would change their freedom to smoke in certain places. While 46% of GPs frequently inquired about tobacco use in their patients, 13.5% did not advise any of their patients to quit smoking during the month preceding the questionnaire. The most common barriers reported by GPs to discussing SC with their patients were as follows: considering the discussion not to be effective (57.8%), having low confidence in knowledge (48.1%), having unpleasant personal experience or considering it a thankless task (46.1%). CONCLUSIONS: It appears essential to reduce the number of GPs who smoke and to improve GP training on SC procedures for integrating SC treatment into primary care in Turkey.

Observations on environmental asbestos exposure in a high risk area.

BACKGROUND AND OBJECTIVE: Environmental asbestos exposure is causally associated with various pulmonary pathologies. In Turkey, one of the most important sources of asbestos exposure is dust originating from the walls of homes whitewashed with white stucco. The main asbestos types implicated are tremolite and, to a lesser extent, chrysotile. This study investigated the presence and effect of environmental asbestos exposure in a small village in Isparta, Turkey. METHODS: Samples of asbestos mine ore, whitewashed plaster from the interior walls of the houses and whitesoil from the outside walls of the houses were analysed. Chest radiographs of 132 villagers aged 30 years and over and living in the village during the study were obtained. Verbal histories from the relatives of people who had died from lung cancer or mesothelioma and hospital records contributed 13 cases to the study population, giving a total of 145 cases under study. RESULTS: Chrysotile fibres were found in the old asbestos mine sample, and zeolite in the whitesoil sample from the outside walls. Abnormal CXR were found in 19 subjects (14. 4%), the most common being pleural calcifications and/or pleural plaques (n = 14, 10.6%). A further five subjects with pleural calcifications and/or pleural plaques were identified from verbal autopsy and hospital records. Malignant pleural mesothelioma was present in one living subject and four of the deaths. A possible familial clustering of lung cancer and malignant mesothelioma was noted. CONCLUSION: While tremolite asbestos is the asbestos found in most white soil in Turkey, in this village chrysotile asbestos was found in the white soil. Familial clustering may indicate genetic susceptibility or increased environmental exposure in some families.

Mineral status of COPD patients under long-term inhaled corticosteroid therapy.

PURPOSE: The aim of this study was to determine the mineral status of mandibles, femurs, and spines in chronic obstructive pulmonary disease (COPD) patients under long-term inhaled corticosteroid therapy. MATERIALS AND METHODS: Pulmonary function tests were conducted on patients (n = 30) with COPD under inhaled corticosteroid therapy for at least 1 year. The results were compared to sex- and age-matched controls (n = 30). Analyses of blood gases were also carried out relative to COPD, and bone mineral densities (BMD) of the mandible, lumbar spine, femoral neck, trochanter, and Ward's triangle were also measured by dual-energy X-ray absorptiometry (DEXA). Levels of serum osteocalcin, alkaline phosphatase, calcium, phosphorus, and cortisol were also assessed. RESULTS: In accordance with the Global Initiative for Chronic Obstructive Lung Disease criteria, 8 of the COPD patients had moderate, 11 patients had severe, and 11 patients had very severe forms of the disease. All BMD measurements were lower in the COPD patients than in the control group. The serum osteocalcin levels in COPD patients were significantly lower than those in the control group (p < 0.0001). Serum calcium (p < 0.004) and cortisol levels (p < 0.026) in the COPD patients were also significantly lower than those in the control subjects. Although serum alkaline phosphatase level was higher and the phosphorus level was lower in the treatment group than in the control group, the differences were not statistically significant. CONCLUSION: Regular evaluation of the biochemical markers of bone metabolism and BMD would be helpful for detecting any detrimental changes of bone in COPD patients under long-term inhaled corticosteroid therapy. In this study, mandibular BMD was observed to be lower in COPD patients under long-term inhaled corticosteroid therapy than in healthy subjects. Thus, dental implant treatment may require preventive measures in COPD patients under long-term inhaled corticosteroid therapy.

Evaluation of the effects of toluene inhalation on alveolar epithelial permeability by 99mTc-DTPA inhalation scintigraphy in automobile painters.

BACKGROUND: The main component of paint thinner used in industry is toluene diisocyanate (TDI) which can cause occupational asthma in 5-10% of exposed workers. AIM: To investigate the effect of TDI on 99mTc clearance rate of alveolar epithelium and on pulmonary function tests (PFT) in automobile painters, and to determine the relationship between 99mTc-DTPA radioaerosol lung scintigraphy and serum levels of antioxidant enzymes and metalloproteinases (MMPs) of automobile painters. METHODS: Twenty-eight automobile painters and 13 control subjects were included in the study. 99mTc-DTPA aerosol inhalation scintigraphy and PFT were administered to all subjects. Clearance half-time (T1/2) and penetration index (PI) on the first-minute image after 99mTc-DTPA scintigraphy were calculated. Blood levels of MDA, antioxidant enzymes and metalloproteinases were measured. RESULTS: The mean T1/2 values of automobile painters were longer in both smoker and non-smoker subjects, but the difference was not significant (P>0.05). Although the PFT values decreased in automobile painters, there was no significant difference between each group. Any correlation between spirometric measurements and T1/2 or PI values in non-smoking automobile painters was not detected. Negative correlation among mean T1/2 value and FVC% and FEV1% in smoking automobile painters, and positive correlation between mean T1/2 value and MMP-9, GSH-Px levels in non-smoking automobile painters were detected. CONCLUSION: Our results suggested that the clearance of 99mTc-DTPA from the lungs of automobile painters was slower than in the control group, but the difference is not statistically significant. This data also supports the observation that TDI occasionally stimulates bronchial changes rather than alveolar changes in automobile painters.

Mediastinal tuberculous lymphadenitis with anthracosis as a cause of vocal cord paralysis.

Anthracotic pigmentation in the bronchial mucosa has been regarded as a bronchoscopic finding of pneumoconiosis or evidence of heavy atmospheric soot. Anthracotic pigmentation with bronchial narrowing or obliteration, surrounded by calcified or noncalcified lymph nodes is typical finding of anthracofibrosis. There is a potential relationship between bronchial anthracofibrosis and tuberculosis. Tuberculous lymphadenopathy of superior mediastinum presentation with hoarseness is very rare. The paper reports a case of tuberculous mediastinal lymphadenitis with anthracosis causing vocal cord paralysis. A 66-year-old woman was admitted to our clinic with the symptoms of dry cough, hoarseness, malaise, anorexia, night sweats and with the multiple mediastinal lymphadenopathy. Fiberoptic bronchoscopy revealed left vocal cord paralysis, bronchial mucosal inflammation and multiple anthracotic plaques. Bronchial lavage and mucosal biopsy were negative for malignancy and tuberculosis. The thoracotomy was performed and a mediastinal lymph node showing caseating granulomatous inflammation with anthracosis and parenchymal anthracosis were detected. The diagnosis of anthracosis and mediastinal tuberculous lymphadenitis was made and the patients put on antituberculous treatment. But she unfortunately died in the second month of the treatment because of the abdominal complication of gastric adenocarcinoma operation.

Evaluation of patients followed up in a cigarette cessation clinic.

OBJECTIVES: The aim of this study was to evaluate the demographic characteristics and factors determining success in a smoking cessation clinic in smokers who completed a 1-year follow up. METHOD: A total of 349 patients were assessed retrospectively. RESULTS: There were 238 men (mean age: 41+/-13.5 years) and 111 women (mean age: 37+/-11.9 years) (t-test P=0.004). The average age at which they began to smoke, number of years of smoking and the number of cigarettes/day were 17.5+/-5.2 years (median 17), 22.1+/-13.3 years, 23.5+/-12.0, respectively. Cigarette smoking was mostly observed in university graduates (56.8%) and a moderate negative correlation existed between education status and smoking duration (r=-0.27, P=0.000). Patients with a Fagerström Tolerance Questionnaire score of >or=6 and those exposed to cigarette smoke in childhood tended to commence and become committed smokers later in life (chi2=4.915, P=0.027). In all, 151 patients (43.26%) were successful in quitting (chi2=36.4, P=0.000). Of these, 87 (24.93%) used medication such as nicotine patches (13.5%), bupropion (7.2%), nicotine patches+bupropion (4.3%) and 64 (18.33%) refused medication, but came for professional support. CONCLUSION: Increased education level, behavioural therapy and intensive motivational support, follow-up visits and phone calls all appear to play important roles in smoking cessation. Families also play a major role.

Apoptosis and loss of adhesion of bronchial epithelial cells in asthma.

BACKGROUND: Asthma is an inflammatory airway disease associated with infiltration of T cells and eosinophils, increased levels of pro-inflammatory cytokines, and shedding of bronchial epithelial cells (EC). We have recently shown that T cells and eosinophils cooperate in inducing bronchial EC apoptosis in asthma through secretion of IFN-gamma and TNF-alpha. Since EC shedding is a histologic hallmark of asthma, the intercellular junction of EC may be a target of pro-inflammatory cytokines. METHODS: Bronchial EC, cultured and exposed to IFN-gamma and TNF-alpha, were studied for the expression of adhesion molecules and apoptosis. In addition, the epithelial layer of bronchial biopsies from asthma patients was evaluated for apoptosis, shedding, and expression of adhesion molecules. RESULTS: We demonstrate that the induction of EC apoptosis is accompanied by loss of E-cadherin. In situ examination of E-cadherin in asthma revealed a reduction in its expression on EC membranes. In contrast, the in vitro and in vivo expression of beta1-integrins and intercellular adhesion molecule-1 (ICAM-1) increased on EC during asthmatic airway inflammation. CONCLUSIONS: Loss of cadherin-mediated intercellular adhesion and apoptosis could account for fragility and shedding of EC in asthma, especially since this occurs between columnar and basal EC.

Absence of pulmonary uptake of Tc-99m methylenediphosphonate in alveolar microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is a rare disease of unknown etiology characterized by accumulation of calcific concretions in the alveolar spaces. The paper reports a case of PAM in a 56-year-old male. The patient had persistent dry cough, and gradually progressive dyspnea on exertion. The diagnosis was established on the basis of roentgenography and confirmed by the sputum and transbronchial biopsy findings. Scintigraphy revealed the absence of Tc-99m methylenediphosphonate uptake of lungs. Familial occurrence was not observed. Chest roentgenogram, pulmonary function, and clinical status of the patient have remained stable for 41 months. Radiological and clinical follow-up of the disease continues.

Asymptomatic IgE mediated food hypersensitivity in patients with nasal polyps.

The aim of this prospective study is to compare the prevalence of atopy in patients afflicted by nasal polyps with the atopy prevalence in healthy volunteers without nasal polyps, since systemic allergy and allergy in the nasal mucosa are still being debated as underlying causes for nasal polyps. Thirty-four cases with nasal polyposis without asthma and history of allergy or atopic disease were enrolled in the study and compared with 20 healthy volunteer controls in respect to asymptomatic food hypersensitivity. Hypersensitivity for 48 kinds of commonly consumed food in Turkey was investigated by an epicutaneuos prick test, Multi-Test II (Lincoln Diagnostic, Inc, USA), using a special applicator. The food allergy test was positive in 25 out of the 34 cases with nasal polyps and in 6 out of the 20 controls. The difference between the two groups was statistically significant (chi2 = 0.000, p < 0.001). The number of skin tests with positive results in patients with nasal polyps ranged from 1 to 37 (mean +/- S.D. = 10.0 +/- 7.9), whereas in the control subjects the range was 1 to 10 (mean +/- S.D. = 4.0 +/- 3.3). The difference in the number of food reactions was also statistically significant. Asymptomatic food hypersensitivity, being immunologically mediated, may be a triggering factor for the pathogenesis of nasal polyps. Therefore, treatment of asymptomatic food allergy in patients with nasal polyps may alleviate symptoms, slow the progress of nasal polyps and prolong the disease-free interval after polypectomy.

T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma.

BACKGROUND: Asthma is an inflammatory airway disease associated with an infiltration of T cells and eosinophils, increased levels of pro-inflammatory cytokines, and shedding of bronchial epithelial cells (ECs). OBJECTIVE: Shedding of bronchial ECs is characterized by loss of the normal bronchial pseudostratified epithelium and the maintenance of a few basal cells on a thickened basement membrane. The aim of this study was to investigate whether, and by which mechanism, T cells and eosinophils can cause damage to airway ECs. METHODS: Bronchial ECs, cultured and exposed to cytokines, eosinophil cationic protein, activated T cells, and eosinophils were studied for the expression of apoptosis receptors (flow cytometry, immunoblotting, and RNA expression) and for the susceptibility for undergoing apoptosis. In addition, bronchial biopsy specimens from patients with asthma were evaluated for EC apoptosis. RESULTS: We demonstrate herein that the respiratory epithelium is an essential target of the inflammatory attack by T cells and eosinophils. Bronchial ECs underwent cytokine-induced cell death with DNA fragmentation and morphologic characteristics of apoptosis mediated by activated T cells and eosinophils. T cell- and eosinophil-induced EC apoptosis was blocked by inhibition of IFN-alpha and TNF-alpha; the Fas ligand-Fas pathway appears to be less important. Recombinant eosinophil cationic protein induced mainly necrosis of ECs. Furthermore, we demonstrated in situ apoptotic features of ECs in bronchial biopsy specimens of asthmatic patients. CONCLUSION: T cell- and eosinophil-induced apoptosis represents a key pathogenic event leading to EC shedding in asthma.