Risk factors for the development of interstitial lung disease following severe COVID-19 pneumonia and outcomes of systemic corticosteroid therapy: 3-month follow-up.

BACKGROUND: We aimed to evaluate the pulmonary involvement status, its related factors, and pulmonary function test (PFT) results in the first month follow-up in patients who were discharged for severe Covid-19 pneumonia, and to assess the efficacy of corticosteroid treatment on these parameters in severe pulmonary involvement patients. METHODS: We retrospectively analyzed all consecutive patients who applied to our COVID-19 follow-up clinic at the end of the first month of hospital discharge. Functional and radiological differences were compared after 3 months of corticosteroid treatment in severe pulmonary involvement group. Results We analyzed 391 patients with "pulmonary parenchymal involvement" (PPIG) and 162 patients with "normal lung radiology" (NLRG). 122 patients in the PPIG (corticosteroid-required interstitial lung disease group (CRILD)) had severe pulmonary involvement with frequent symptoms and required corticosteroid prescription. Pulmonary involvement was more common in males and elder patients (P<0.001, for both). Being smoker and elderly were associated with a higher risk-ratio in predicting to be in PPIG (OR:2.250 and OR:1.057, respectively). Smokers, male and elderly patients, and HFNO2 support during hospitalization were risk factors for being a patient with CRILD (OR:2.737, OR:4.937, OR:4.756, and OR:2.872, respectively). After a three-months of methylprednisolone medication, a good response was achieved on radiological findings and PFT results in CRILD. CONCLUSIONS: In conclusion, after severe COVID-19 pneumonia, persistent clinical symptoms and pulmonary parenchymal involvement would be inevitable in elder and smoker patients. Moreover, corticosteroid treatment in patients with severe parenchymal involvement was found to be effective in the improvement of radiological and functional parameters.

Can serum progranulin level be used as a prognostic biomarker in non-small cell lung cancer?

Progranulin has been considered to be a poor prognostic biomarker for some types of malignancies. However, the clinical significance of serum progranulin level and the prognostic value are still not explored in advanced stages of lung cancer.  The current study investigates the prognostic significance of progranulin serum levels in advanced-stage non-small cell lung cancer (NSCLC) patients. This study involved 94 subjects (70 advanced-stage NSCLC patients and 24 healthy controls). Serum progranulin level was measured by enzyme-linked immunosorbent assay (ELISA) and was correlated with patient outcome. The association between circulating progranulin level and clinicopathological parameters was detected. Serum progranulin cut-off level predicting six-month survival was determined. Serum progranulin level was found significantly elevated in NSCLC patients than in the control group (p<0.001). We did not determine a significant difference between stage IIIB and stage IV NSCLC patients for serum progranulin levels (p=0.166). When we evaluated the laboratory parameters, only serum LDH level was found significantly correlated with serum progranulin level (p=0.043), also bone and liver metastasis showed a significant correlation with progranulin level (p=0.008 and p = 0.024, respectively). The cut-off level of serum progranulin in predicting six months of survival was determined as 16.03 ng/ml (AUC = 0.973, 95%Cl: 0.903-0.997, p<0.001) with 97.06% sensitivity and 88.89% specificity. Overall survival was determined shorter in patients with progranulin level ≥16 ng/ml than those with <16 ng/ml (p<0.001). Also, in the multivariate analysis using the Cox regression model serum progranulin level was found as an independent prognostic factor for NSCLC (p=0.001). Serum progranulin level may be a useful biomarker for predicting poor survival in advanced-stage NSCLC patients.

Effect of chronic lung diseases on mortality of prevariant COVID-19 pneumonia patients.

Background: The aim of the study is to assess the effect of chronic lung disease on mortality in patients hospitalized with the diagnosis of prevariant COVID-19 Pneumonia compared to patients without chronic lung disease. Research design and methods: A cohort of 1,549 patients admitted to the pandemic clinic with a COVID-19 Pneumonia diagnosis was analyzed. Group 1 and Group 2 were compared in terms of the treatment they received, admission to intensive care, mortality and follow-up parameters. Results: The patient group with COVID-19 and lung disease consisted of 231 participants (14.91%) (Group 1). The patient group with COVID-19 but without lung disease had 1,318 participants (85.19%). Group 1 cases were found to receive more oxygen therapy and mechanical ventilation than Group 2 cases (p ≤ 0.001), Following univariate and multiple logistic regression analyses, it was determined that patients with chronic lung disease had a 25.76% higher mortality risk [OR: 25.763, 95% CI (Lower-Upper) (2.445-271.465), p = 0.007]. Conclusion: It was found that chronic lung disease contributed significantly to mortality in this study. Among chronic lung diseases, Chronic Obstructive Pulmonary Disease (COPD), lung cancer and interstitial lung diseases (ILDs) were shown to be more effective than other chronic lung diseases in patients with prevariant COVID-19 population.

FDG PET/CT Findings of Recurrent Respiratory Papillomatosis With Malignant Degeneration in the Lung.

Recurrent respiratory papillomatosis is a rare benign disease caused by HPV-6 or HPV-11. The tumors may rarely undergo malignant degeneration. We performed FDG PET/CT in a patient experiencing recurrent respiratory papillomatosis who had pulmonary involvement. Although squamous cell carcinoma was detected in one of the pulmonary masses, squamous metaplasia with dysplasia were detected in the other one. Intensity modulated radiation therapy was performed to treat the malignancy. Second FDG PET/CT was performed 15 months after radiotherapy.

Factors associated with treatment outcome in 64 HIV negative patients with multidrug resistant tuberculosis.

OBJECTIVES: In this study we aimed to determine the factors associated with treatment outcome in HIV negative patients with multidrug resistant tuberculosis (MDR TB). MATERIALS AND METHODS: The study comprised 64 (43 female and 21 male) patients in whom second line TB drugs were administered in directly observed treatment (DOT) programme. Achievement of sputum AFB (acid fast bacilli) negativity in the 3rd month of the treatment was accepted as the bacteriologic response. Treatment outcome of the patients and the factors influencing the bacteriologic response were evaluated. RESULTS: The mean time of sputum smear negativity was determined as 3±2.2 months. Bacteriologic response was determined in 73.4% of the patients. The mean duration time of the treatment was 16.4±8.2 months. Treatment outcome of the patients was determined as cure in 34 (53.1%), default in 18 (28.1%), treatment failure in 1 (1.6%) and exitus in 3 (4.7%) patients. Also, in 8 (12.5%) patients treatment was incomplete and continued. Adverse effects of the drugs were seen in 39 (60.9%) patients with the most frequency of gastrointestinal disturbance (51.5%), psychiatric disorders (15.6%), dermatological effects (12.5%). In logistic regression analysis only presence of cavity and the extensive disease were found to be associated with poor bacteriologic response (OR=1.5, 95% CI: 1.23-1.82, P=0.01 and OR=2, 95% CI: 1.42-2.79, P=0.00, respectively). CONCLUSIONS: Although radiological findings might affect the bacteriologic response, MDR TB is a treatable disease if regular and appropriate treatment regimen is administered.

Cytopathologic differential diagnosis of malignant mesothelioma, adenocarcinoma and reactive mesothelial cells: A logistic regression analysis.

Distinguishing malignant mesothelioma, adenocarcinoma and reactive mesothelial proliferation in both cytologic and surgical pathologic specimens is often a diagnostic challenge. Conventional cytomorphologic assessment is an important step in the differential diagnosis of these entities.The pleural effusion cytologies from 40 cases of malignant mesothelioma, 40 cases of adenocarcinoma and 30 cases of reactive mesothelial proliferation diagnosed between 1997 and 2007 were reviewed. Twenty-seven cytologic features which are regarded as useful in the differential diagnosis of mesothelioma, adenocarcinoma and benign mesothelial proliferation were assessed. These cytologic features were subjected to a stepwise logistic regression analysis. Three features were selected to distinguish malignant mesothelioma from adenocarcinoma: giant atypical mesothelial cell (P = 0.0001), nuclear pleomorphism (P = 0.0001) and acinar structures (P = 0.0001), the latter two being characteristics of adenocarcinoma. The variables selected to differentiate malignant mesothelioma from reactive mesothelial cells were: cell ball formation (P = 0.0001), cell in cell engulfment (P = 0.0001) and monolayer cell groups (P = 0.0001), the latter being a feature of benign mesothelial proliferation. When these selected variables were subjected to a stepwise logistic regression analysis, the logistic model correctly predicted 90% of cases of benign mesothelial proliferation versus 97.5% of malignant mesothelioma and 92.5% of malignant mesothelioma versus 92.5% of adenocarcinoma.Conventional cytomorphologic assessment is the first step to establish an accurate diagnosis in pleural effusions. Several cytologic features have predictive value to separate malignant mesothelioma from adenocarcinoma and reactive mesothelial proliferation.

Vascular endothelial growth factor immunostaining correlates with postoperative relapse and survival in non-small cell lung cancer.

BACKGROUND: Angiogenesis is an early step in tumor progression, and vascular endothelial growth factor (VEGF) is an important angiogenic factor. In this study, we investigated the prognostic significance of VEGF immunostaining in tumor tissues of non-small cell lung cancer (NSCLC) patients during a 5-year follow-up period. METHODS: The study comprised 50 male patients diagnosed with NSCLC with a mean age of 57.26 +/- 8.64 years (range: 40-74 years). All patients had early stage NSCLC and none of the patients received chemo- or radiation therapy before surgery. VEGF immunostaining was performed in tumor tissues and immunoreactivity was graded as negative (0-10%), weak (10-50%), and strong (>50% tumors are stained). RESULTS: VEGF staining was weak in 20 (40%) specimens and strong in 13 (26%) specimens, whereas VEGF staining was negative in 17 (34%) specimens. Strong VEGF staining showed a significant correlation with both short time of relapse (p = 0.0001) and short survival (p = 0.0005). Multivariate analysis using Cox regression model was performed to determine the independent prognostic factors. Age (p = 0.029, OR: 1.05), tumor stage (p = 0.001, OR: 14.89), and VEGF staining (p = 0.006, OR: 4.65) were all found as independent prognostic factors in NSCLC. CONCLUSIONS: Strong VEGF immunostaining in tumor tissues was found to be an important prognostic factor for time to relapse and survival in patients with early stage disease.

The effects of shock waves on lung tissue in acute period: an in vivo study.

The acute effects of extracorporeal shock waves on lung morphology were studied by light microscopy in 30 New Zealand rabbits. The left kidneys of the ten animals were exposed to 2,000 shockwaves at 18 kV under anesthesia (ESWL group). Ten rabbits were in the control group; an intramuscular anesthetic agent (ketamine) and intravenous contrast media were administered to ten animals in the sham group. Localization of the left kidneys was achieved following contrast medium injection through an ear vein under fluoroscopic control. The animals were killed after the ESWL procedures and the lungs were removed. Edema, emphysema, hemorrhage, congestion, inflammation, loss of normal structure, and epithelial desquamation were determined and graded between 0 and 3 in all areas of both lungs. In order to determine whether proximity has any effect on the histopathological changes, left and right lungs were evaluated separately as well as upper and lower lobes. We found that ESWL exposed to kidney also affects all areas of the lungs in a rabbit model.

Biphasic malignant mesothelioma cases with osseous differentiation and long survival: a review of the literature.

This report describes two cases of diffuse biphasic malignant mesothelioma with osseous differentiation and long survival. Two male patients aged 66 and 54 years presented with chest pain, bloody pleural effusions, and diffuse and nodular pleural thickening. They both had a history of prolonged asbestos exposure. Sarcomatoid and epithelioid areas were identified on histopathological examination. In addition, there were foci of ossification. Epithelioid tumor cells as well as benign osteoclasts within the ossification reacted positively for cytokeratin 5/6, whereas sarcomatoid areas were negative. Both patients survived 39 and 69 months, respectively. To our knowledge, these two cases with biphasic malignant mesothelioma and osseous differentiation with long survival are the first to be described from Central Anatolia.

Correlation between survivin expression and prognosis in non-small cell lung cancer.

AIMS AND BACKGROUND: Survivin is a recently identified protein as an inhibitor of apoptosis, which supresses programmed cell death and regulates cell division. In this study, we investigated the prognostic significance of both nuclear and cytoplasmic survivin expression in non-small cell lung cancer (NSCLC) and examined the association with clinicopathological parameters. METHODS: The study comprised 58 male patients diagnosed NSCLC with a mean age of 57.29+/-8.82 years; range 40-76 years. Patients underwent lobectomy (64%) or pneumonectomy (36%) with hilar and mediastinal lymph node sampling. Paraffin embedded tumor sections were retrieved for evaluation of nuclear and cytoplasmic staining of survivin. Clinicopathological data, stage and survival of patients were all determined. RESULTS: Cytoplasmic staining was found significantly increased in squamous cell carcinoma (P=0.003), whereas there was no association between nuclear staining and histopathological type (P=0.837). Also, both nuclear and cytoplasmic staining did not show any association with tumor stage (P>0.05). In univariate analysis there was significant correlation between nuclear survivin and short survival (P=0.0002). In multivariate survival analysis using Cox regression, only nuclear staining of survivin was determined as an independent prognostic factor (P=0.004). CONCLUSIONS: Localization of survivin expression might have an important regulatory mechanism in carcinogenesis and tumor progression. Nuclear survivin expression in tumor tissues might predict the prognosis in NSCLC, whereas cytoplasmic survivin has no prognostic significance.

The value of serum interferon-gamma level in the differential diagnosis of active and inactive pulmonary tuberculosis.

Interferon (IFN)-gamma plays a pivotal role in protective immunity against Mycobacterium tuberculosis. Elevations of IFN-gamma have been found in the affected lung and bloodstream of patients with pulmonary tuberculosis. In the present study, we aimed to investigate the role of serum IFN-gamma level in the differential diagnosis of active and inactive pulmonary tuberculosis. Fourty seven patients with newly diagnosed active pulmonary tuberculosis, 21 patients with inactive pulmonary tuberculosis, and 20 healthy volunteers were enrolled in the study. Serum samples were collected from each subject and stored at - 70 degrees C until the analysis of IFN-gamma. The mean value of IFN-gamma levels were 9.3 +/- 4.6 pg/mL in patients with newly diagnosed pulmonary tuberculosis, 9.8 +/- 3.8 pg/mL in patients with inactive tuberculosis, and 10.2 +/- 3.4 pg/mL in healthy controls. The comparison of IFN-gamma levels of the three groups was not found statistically significant (p= 0.4). Serum IFN-gamma level was not found to be valuable in the differential diagnosis of active and inactive pulmonary tuberculosis.

Analysis of patients with hemoptysis in a reference hospital for chest diseases.

Chest physicians frequently come across with the symptom hemoptysis, an alerting symptom which may result from a wide variety of disorders. In this study, we aimed to determine the main causes of hemoptysis in a reference hospital for chest diseases. All the patients who admitted to our emergency clinic with hemoptysis during three months of study period were included in the study. The mean age of 143 patients (106 males, 37 females) who were included in this study was 48 +/- 17 years. Medical history, physical examination and chest radiography were performed for each patient. Sputum examination for acid fast bacilli, computed tomography of thorax, fiberoptic bronchoscopy, ventilation-perfusion scintigraphy, echocardiography, ear-nose-throat examination and upper gastrointestinal system endoscopy were the further diagnostic investigations for selected patients. Bronchiectasis was the most common cause of hemoptysis (22.4%), followed by lung cancer (18.9%), active tuberculosis (11.2%), and inactive tuberculosis (10.5%). Sputum smear for acid fast bacilli was performed in 102 patients and were positive in 15.6% of them. Computed tomography of thorax was performed in 102 patients and was pathologic in 81.3% of them. Fiberoptic bronchoscopy was performed in 46 patients and localized the bleeding site in 67.4% of them. In conclusion, the most common causes of hemoptysis were bronchiectasis, lung cancer and tuberculosis in our hospital. Based on this finding, we suggest that, the diagnostic approach to the patients presenting with hemoptysis should include first a detailed medical history, physical examination, and chest radiography; second sputum smear for acid fast bacilli; third computed tomography of thorax and lastly fiberoptic bronchoscopy.

[The role of serum neopterin level in the evaluation of activation and response to treatment in the patients with pulmonary tuberculosis]. / Akciger tüberkülozlu hastalarda aktivasyon ve tedaviye yanitin degerlendirilmesinde serum neopterin düzeyinin yeri.

Neopterin is an important parameter showing cell mediated immunity activation. In this study we aimed to determine whether serum neopterin level could be used as a marker in the evaluation of tuberculosis activation and response to treatment. The study comprised 40 new case smear positive pulmonary tuberculosis patients and 40 healthy control. Serum neopterin levels were measured both before the treatment and 2nd month of the treatment in the patient group. The association between serum neopterin level and clinical, radiological and bacteriological parameters were also investigated. In patients with pulmonary tuberculosis the mean levels of serum neopterin were 35.1+/-13.4 nmol/L before the treatment and 21.2+/-10.4 nmol/L in the 2nd month of the treatment. In the control group, serum neopterin level was 19+/-10.4 nmol/L. The serum neopterin levels of the patients were significantly higher than the control group (p=0.001). Also, there was significant difference between serum neopterin levels before the treatment and the 2nd month of the treatment (p=0.000). Serum neopterin level was higher in the group with extensive disease than the cases with limited disease (p=0.02). In conclusion, we think that serum neopterin level might be used as a reliable immunological marker in the evaluation of tuberculosis activation and response to treatment.

Prognostic significance of vascular endothelial growth factor, tumor necrosis, and mitotic activity index in malignant pleural mesothelioma.

OBJECTIVES: Tumor growth and metastasis are angiogenesis-dependent events, and several prognostic factors have been determined in malignant mesothelioma. In this study, we investigated the prognostic significance of vascular endothelial growth factor (VEGF), tumor necrosis (TN), and mitotic activity index (MAI) in malignant mesothelioma. For the first time (to our knowledge), we also demonstrated the association between VEGF staining, TN, and MAI in malignant mesothelioma. METHODS: Decortication and VATS materials of 40 patients were investigated. The routinely processed formalin-fixed, paraffin-embedded, hematoxylin-eosin-stained tumor sections that had been used for the original diagnostic purposes were retrieved. Hematoxylin-eosin sections were selected for VEGF immunostaining, TN, and mitotic count. Clinicopathologic data, stage of disease, and survival of patients were all determined. The correlations between variables were evaluated by Spearman rank correlation test. Both univariate analysis using the log-rank test and multivariate analysis using Cox regression model were performed for survival analysis. RESULTS: There was a significant correlation between VEGF staining and TN (r = 0.42, p = 0.006). In univariate analysis, both VEGF staining (p = 0.0002) and TN (p = 0.0055) showed significant correlation with short survival. Also, there was a positive correlation between VEGF and tumor stage (p = 0.046). In multivariate analysis, only VEGF was determined as an independent prognostic factor in malignant mesothelioma (p = 0.001). There was no association between MAI and survival (p = 0.504). CONCLUSIONS: VEGF, known as an important angiogenic peptide, is an independent prognostic factor in malignant pleural mesothelioma. TN stimulates angiogenesis, and we observed a significant correlation between VEGF and TN. However, further studies are needed to evaluate the prognostic significance of angiogenic properties in malignant mesothelioma.

Analysis of insulin like growth factor 1 and insulin like growth factor binding protein 3 levels in bronchoalveolar lavage fluid and serum of patients with lung cancer.

OBJECTIVE: Insulin like growth factor 1 (IGF-1) is recognized as a potent mitogen for many cancer cell lines and there is good evidence that lung cancer cells produce both IGF-1 and insulin like growth factor binding protein 3 (IGFBP-3). The aim of this study was to investigate the clinical significance of IGF-1 and IGFBP-3 levels in serum and in bronchoalveolar lavage (BAL) fluid by comparing lung cancer patients with healthy controls. METHODS: BAL fluid and serum samples were obtained from 24 lung cancer patients and 12 healthy controls, and were analyzed for IGF-1 and IGFBP-3 levels by a two site immunoradiometric assay. The recovered BAL fluid was standardized by albumin to remove the variable of dilution and the data was expressed in epithelial lining fluid (ELF). RESULTS: Serum IGF-1 and IGFBP-3 levels were lower in lung cancer patients, but the difference between the groups did not reach a statistical significance. IGF-1/IGFBP-3 ratio in ELF was significantly lower in lung cancer patients (P=0.035). Mean IGF-1 level in ELF was determined to be significantly lower in patients with distant metastasis (P=0.04). Serum IGF-1/IGFBP-3 ratio was found to be significantly lower in patients with distant (P=0.04) and nodal metastasis (P=0.03). Tumor stage was negatively correlated with IGF-1 level in ELF (P=0.05, r=-0.4) and serum IGF-1/IGFBP-3 ratio (P=0.04, r=-0.4). CONCLUSION: IGF-1 and IGFBP-3 levels both in serum and ELF might serve a clinical significance in patients with lung cancer. However, further studies comprising more cases are needed to investigate the clinical significance of IGF-1 and IGFBP-3 in lung cancer.

Prognostic significance of hemostatic parameters in patients with lung cancer.

There is a subclinical activation of coagulation and fibrinolysis system in lung cancer. Alterations in hemostatic system are seen frequently in lung cancer correlated with the prognosis of disease. In this prospective study, our purpose was to investigate the prognostic significance of hemostatic markers in patients with lung cancer. The study comprised 58 patients (22 squamous cell carcinoma, 16 adenocarcinoma, 20 small cell carcinoma). There were 55 men (95%)and 3 women (5%) with a mean age of 61 years range (36-74). Plasma level of platelets (PLT), prothrombin time (PT), active partial thromboplastin time (aPTT), antithrombin III (AT III), fibrinogen (F) and D-dimer level were measured before the initiation of any therapy. Patients were followed up for 17 (12-20) months. The median survival was determined as 6.4 months. Three histopathologic groups; squamous cell carcinoma, adenocarcinoma and small cell carcinoma were compared for the hemostatic parameters. There were no statistically significant differences among the histopathologic types for any of the parameters (P > 0.05). Patients were divided into two groups as patients without distant metastasis (stages I,II,III) and with distant metastasis (stage IV). The group with distant metastasis had higher level of D-dimer than the other group (P < 0.05). However, there were no statistically significant differences for D-dimer level between stages IIIB and IV (P > 0.05). Patients having high D-dimer and low AT III level had poor survival in our study. Thus, high level of D-dimer and low AT III level were determined as correlated with short survival (P < 0.05). These results suggest that elevated plasma level of D-dimer and low AT III level might be a sign of poor prognosis in patients with lung cancer.