Nesrin Mogulkoc

Intracardiac thrombus in Behçet's disease : A systematic review

BACKGROUND Intracardiac thrombus formation is a rare but serious complication of Behçets disease. We aimed to review the clinical and pathologic correlates of cardiac thrombus formation in the context of Behçets disease. METHODS AND RESULTS A comprehensive search of the medical literature was conducted using MEDLINE including bibliographies of all selected articles. Although the disease has a unique geographic distribution, being most common in the population of the ancient Silk Route, cases complicated by intracardiac thrombus have mostly originated from the Mediterranean basin and the Middle East. Young men appear to be most at risk, with the right heart the most frequent site of involvement. The first symptoms and signs of the disease frequently precede systemic organ manifestations. In those cases in which intracardiac thrombus occurs, it is apparent in more than half of cases on first recognition of the disease. CONCLUSION A diagnosis of Behçets disease should be considered if a patient presents with a mass in the right-sided cardiac chambers, even in the absence of the characteristic clinical features of the condition. This is particularly applicable if the patient is a young man from the Mediterranean basin or the Middle East.

Macitentan for the treatment of idiopathic pulmonary fibrosis: the randomised controlled MUSIC trial

Idiopathic pulmonary fibrosis is a progressive, fatal disease. This prospective, randomised, double-blind, multicentre, parallel-group, placebo-controlled phase II trial (NCT00903331) investigated the efficacy and safety of the endothelin receptor antagonist macitentan in idiopathic pulmonary fibrosis. Eligible subjects were adults with idiopathic pulmonary fibrosis of <3 years duration and a histological pattern of usual interstitial pneumonia on surgical lung biopsy. The primary objective was to demonstrate that macitentan (10 mg once daily) positively affected forced vital capacity versus placebo. Using a centralised system, 178 subjects were randomised (2:1) to macitentan (n=119) or placebo (n=59). The median change from baseline up to month 12 in forced vital capacity was -0.20 L in the macitentan arm and -0.20 L in the placebo arm. Overall, no differences between treatments were observed in pulmonary function tests or time to disease worsening or death. Median exposures to macitentan and placebo were 14.5 months and 15.0 months, respectively. Alanine and/or aspartate aminotransferase elevations over three times upper limit of normal arose in 3.4% of macitentan-treated subjects and 5.1% of placebo recipients. In conclusion, the primary objective was not met. Long-term exposure to macitentan was well tolerated with a similar, low incidence of elevated hepatic aminotransferases in each treatment group. Long-term exposure to macitentan was well tolerated in IPF in a trial that did not meet its primary end-point http://ow.ly/p0RDL

Evaluation of CMV viral load using taqman CMV quantitative PCR and comparison with CMV antigenemia in heart and lung transplant recipients

BACKGROUND Quantitative assessment of cytomegalovirus (CMV) infection using the antigenemia test has been used to monitor CMV infection in heart and lung transplant patients enabling a preemptive treatment strategy. However, the method is labour intensive, samples have to be processed within a few hours and requires skilled interpretation. A comparative prospective evaluation of a real-time TaqMan CMV quantitative PCR (QPCR) with the CMV antigenemia was undertaken. METHODS A real-time quantitative TaqMan CMV PCR from EDTA bloods was developed. In this study 25 heart transplant and single-lung transplant patients were monitored posttransplantation by antigenemia and TaqMan CMV QPCR. CMV DNA extracted from EDTA blood was amplified by TaqMan QPCR using primers and probe designed from the CMV glycoprotein B (gB) gene. Quantification of the genome copies is extrapolated from a standard curve generated from amplification of quantified standards. RESULTS Antigenaemia levels and TaqMan CMV QPCR genome copies showed a linear correlation between the two assays (R=0.843, P=0.001). A clinically significant threshold of 50 CMV pp65 antigen positive polymorphonuclear leucocytes (PMNLs) per 200 000 cells previously reported was used to extrapolate an equivalent value of 40 000 (log 4.6) genome copies per ml of blood for the TaqMan CMV QPCR. CONCLUSIONS The TaqMan system enables a rapid high-throughput of samples. The TaqMan CMV QPCR can be used as an accurate and robust alternative to the antigenemia test to predict CMV disease and to monitor effectiveness of treatment.

High dose rate endobronchial brachytherapy in the management of lung cancer: Response and toxicity evaluation in 158 patients

The aim of this study was to evaluate the symptomatic and endoscopic responses as well as the toxicities in 158 patients with endobronchial lung cancer treated with high dose rate endobronchial brachytherapy (HDR-EB). Forty-three patients with stage III NSCLC were treated with 60Gy external beam radiotherapy (ERT) and three applications of 5Gy each of HDR-EB (group A). Seventy-four patients who did not receive previous RT were treated with 30Gy ERT and two applications of 7.5Gy HDR-EB with palliative intent (group B). Forty-one patients with recurrent tumor who were irradiated previously were treated with three applications of 7.5Gy HDR-EB, with palliative intent (group C). In group A, bronchoscopic complete (CR) and overall response rates (ORR) were 67% and 86%, respectively. Symptomatic improvement was obtained in 58% of patients with cough, 77% of patients with dyspnea and 100% of patients with hemoptysis. Two and 5-year survival rates were 25.5% and 9.5%, respectively and the median survival time (MST) was 11 months. In group B, the bronchoscopic CR and ORR were 39% and 77%, respectively and 28% and 72% in group C. The symptomatic response rates were 57% and 55% for cough, 90% and 78% for dyspnea and 94% and 77% for hemoptysis, with a MST of 7 and 6 months in Groups B and C, respectively. Eighteen patients (11%) died of fatal hemoptysis (FH) with the median time to this event of 7 months. Treatment intent (p<0.001), total BED (p<0.001) and the number of HDR-EB fractions (p<0.001) were significant prognostic factors for FH. HDR-EB provides effective palliation in relieving the symptoms of patients with endobronchial lung cancer, however, there is a risk of developing FH that is associated with a high BED and multiple HDR-EB applications.

High dose rate endobronchial brachytherapy in combination with external beam radiotherapy for stage III non-small cell lung cancer.

INTRODUCTION A phase-II study was planned to test the effect of external beam radiotherapy in combination with endobronchial brachytherapy on the local control and survival of stage-III non-small cell lung cancer patients. MATERIALS AND METHODS Thirty patients with stage-III non-small cell lung cancer have been treated with 60 Gy external beam radiotherapy and 3 x 5 Gy HDR endobronchial brachytherapy to control tumor and to prolong survival. RESULTS Therapy regimen was found to be very effective for the palliation of major symptoms, palliation rates were 42.8% for cough, 95.2% for hemoptysis, 88.2% for chest pain and 80.0% for dyspnea. There was a 76.7% tumor response (53.3% complete, 23.3% partial) verified by chest CT scans and bronchoscopy. However, median locoregional disease free survival was 9+/-4 months (95% CI: 1-17) and it was only 9.6% at 5 years. Major side effects were radiation bronchitis (70.0%), esophagitis (6.6%) in the acute period and bronchial fibrosis (25%), esophagial fibrosis (12.5%) and fatal hemoptysis (10.5%) in the late period. Median survival was 11+/-4 months (95% CI: 4-18),and 5-year actuarial survival was 10%. Locoregional disease free survival (P=0.008) and the overall survival was longer (P<0.001) in the patients younger than 60, survival was also improved in the patients with complete response (P=0.019). There were no major complications during catheterisation; early side effects were quite tolerable but severe late complications were around 10%. CONCLUSIONS It is concluded that endobronchial brachytherapy in combination with external irradiation provides a good rate of response, however does not eradicate locoregional disease and does not prolong survival except for some subgroups such as younger patients.

Bronchiolitis obliterans syndrome in single lung transplant recipients—patients with emphysema versus patients with idiopathic pulmonary fibrosis

Bronchiolitis obliterans syndrome (BOS) after lung transplantation is a disease of small airways that is currently graded according to a decline in forced expiratory volume in 1 second (FEV(1)) even in single lung transplant recipients in whom native diseased lung may influence lung physiology. The aim of this study was to evaluate the comparative changes in lung function and survival following the onset of BOS in patients with emphysema and patients with idiopathic pulmonary fibrosis (IPF) who have undergone single lung transplantation. We analyzed data from 31 single lung transplant recipients with emphysema and 25 with IPF who were at risk of BOS. There was no difference in the incidence of BOS between the 2 groups (10 patients with emphysema and 6 patients with IPF), but after the onset of BOS the patients with emphysema had a significantly greater median survival (18 months vs 8 months) despite a poorer mean FEV(1) (1.26 liter, 45% predicted vs 2.11 liter, 67% predicted) compared with the IPF group (p < 0.05) and this difference in lung function persisted at death (0.8 liter, 30% predicted vs 1.65 liter, 51% predicted) (p < 0.05). In summary the native lung physiology appears to influence lung function and therefore survival, and this may indicate that the classification of BOS should include disease-specific characteristics.

Intracardiac Thrombus in Behçet's Disease

BACKGROUND Intracardiac thrombus formation is a rare but serious complication of Behçets disease. We aimed to review the clinical and pathologic correlates of cardiac thrombus formation in the context of Behçets disease. METHODS AND RESULTS A comprehensive search of the medical literature was conducted using MEDLINE including bibliographies of all selected articles. Although the disease has a unique geographic distribution, being most common in the population of the ancient Silk Route, cases complicated by intracardiac thrombus have mostly originated from the Mediterranean basin and the Middle East. Young men appear to be most at risk, with the right heart the most frequent site of involvement. The first symptoms and signs of the disease frequently precede systemic organ manifestations. In those cases in which intracardiac thrombus occurs, it is apparent in more than half of cases on first recognition of the disease. CONCLUSION A diagnosis of Behçets disease should be considered if a patient presents with a mass in the right-sided cardiac chambers, even in the absence of the characteristic clinical features of the condition. This is particularly applicable if the patient is a young man from the Mediterranean basin or the Middle East.

Antacid therapy in idiopathic pulmonary fibrosis: more questions than answers?

Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of complex cause. Gastro-oesophageal reflux (GER) and microaspiration have been proposed as risk factors for the development and progression of IPF, but robust definitive data are few. A recent international guideline conditionally recommended the use of antacid therapy (proton pump inhibitors or histamine-2-receptor antagonists) for patients with IPF, in the absence of oesophageal reflux or symptoms. In this Position Paper, we summarise the literature addressing the association between GER and IPF, and also identify future research priorities that could clarify this issue. We shed light on the process through which the guideline recommendation was achieved and aim to contextualise the recommendation for providers caring for patients with IPF.

Dynamic computed tomography in solitary pulmonary nodules.

Objective: To evaluate the utility of dynamic computed tomography (CT) imaging in the management of solitary pulmonary nodules. Methods: We examined solitary pulmonary nodules in 45 patients. The nodules included in the study were solid, homogenous, and spherical or oval-shaped in precontrast images. Nodules that had calcification or fat density were excluded from the study. We were not able to obtain clinical or pathological diagnosis of the nodules in 23 patients, and we excluded these patients from statistical analysis. Patients were examined with 2-mm collimation and 1-mm reconstruction interval. Computed tomography examinations were done before and after injection of contrast material. Computed tomography scans of the nodule were obtained in the first, second, third, fourth, and fifth minutes after contrast injection. Results: The malignancy prevalence was 40%. The mean enhancement of malignant nodules were significantly higher than the benign ones. Also, the peak attenuation value obtained after the administration of contrast material was 82.44 ± 19.56 HU in malignant lesions and 54 ± 23.10 HU in benign ones, with statistical significance (P = 0.006). Using enhancement values greater than 15 HU as a threshold for malignancy, the calculated sensitivity, specificity, positive and negative predictive values, and accuracy of the dynamic CT examination were 100%, 69.2%, 69.2%, 100%, and 81%, respectively. Conclusion: Dynamic CT imaging demonstrates significantly greater enhancement in malignant nodules than in benign ones. Lung nodule enhancement of 15 HU or less strongly indicates benignity.

Combination and comparison of two models in prognosis of pulmonary embolism: Results from TUrkey Pulmonary Embolism Group (TUPEG) study☆

BACKGROUND Clinical parameters, biomarkers and imaging-based risk stratification are widely accepted in pulmonary embolism(PE). The present study has investigated the prognostic role of simplified Pulmonary Embolism Severity Index (sPESI) score and the European Society of Cardiology (ESC) model. METHODS This prospective cohort study included a total of 1078 patients from a multi-center registry, with objectively confirmed acute symptomatic PE. The primary endpoint was all-cause mortality during the first 30days, and the secondary endpoint included all-cause mortality, nonfatal symptomatic recurrent PE, or nonfatal major bleeding. RESULTS Of the 1078 study patients, 95 (8.8%) died within 30days of diagnosis. There was no significant difference between non-low-risk patients ESC [12.2% (103 of 754;)] and high-risk patients as per the sPESI [11.6% (103 of 796)] for 30-day mortality. The nonfatal secondary endpoint occurred in 2.8% of patients in the the sPESI low-risk and 1.9% in the ESC low-risk group. Thirty-day mortality occurred in 2.2% of patients the sPESI low-risk and in 2.2% the ESC low-risk group (P=NS). In the present study, in the combination of the sPESI low-risk and ESC model low-risk mortality rate was 0%. CONCLUSIONS The sPESI and the ESC model showed a similar performance regarding 30-day mortality and secondary outcomes in the present study. However, the combination of these two models appears to be particularly valuable in PE.