Meral Gülhan

Incidence of pulmonary embolism during COPD exacerbation

OBJECTIVE: Because pulmonary embolism (PE) and COPD exacerbation have similar presentations and symptoms, PE can be overlooked in COPD patients. Our objective was to determine the prevalence of PE during COPD exacerbation and to describe the clinical aspects in COPD patients diagnosed with PE. METHODS: This was a prospective study conducted at a university hospital in the city of Ankara, Turkey. We included all COPD patients who were hospitalized due to acute exacerbation of COPD between May of 2011 and May of 2013. All patients underwent clinical risk assessment, arterial blood gas analysis, chest CT angiography, and Doppler ultrasonography of the lower extremities. In addition, we measured D-dimer levels and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels. RESULTS: We included 172 patients with COPD. The prevalence of PE was 29.1%. The patients with pleuritic chest pain, lower limb asymmetry, and high NT-pro-BNP levels were more likely to develop PE, as were those who were obese or immobile. Obesity and lower limb asymmetry were independent predictors of PE during COPD exacerbation (OR = 4.97; 95% CI, 1.775-13.931 and OR = 2.329; 95% CI, 1.127-7.105, respectively). CONCLUSIONS: The prevalence of PE in patients with COPD exacerbation was higher than expected. The association between PE and COPD exacerbation should be considered, especially in patients who are immobile or obese.

Does thromboprophylaxis prevent venous thromboembolism after major orthopedic surgery

OBJECTIVE: Pulmonary embolism (PE) is an important complication of major orthopedic surgery. The aim of this study was to evaluate the incidence of venous thromboembolism (VTE) and factors influencing the development of VTE in patients undergoing major orthopedic surgery in a university hospital. METHODS: Patients who underwent major orthopedic surgery (hip arthroplasty, knee arthroplasty, or femur fracture repair) between February of 2006 and June of 2012 were retrospectively included in the study. The incidences of PE and deep vein thrombosis (DVT) were evaluated, as were the factors influencing their development, such as type of operation, age, and comorbidities. RESULTS: We reviewed the medical records of 1,306 patients. The proportions of knee arthroplasty, hip arthroplasty, and femur fracture repair were 63.4%, 29.9%, and 6.7%, respectively. The cumulative incidence of PE and DVT in patients undergoing major orthopedic surgery was 1.99% and 2.22%, respectively. Most of the patients presented with PE and DVT (61.5% and 72.4%, respectively) within the first 72 h after surgery. Patients undergoing femur fracture repair, those aged ≥ 65 years, and bedridden patients were at a higher risk for developing VTE. CONCLUSIONS: Our results show that VTE was a significant complication of major orthopedic surgery, despite the use of thromboprophylaxis. Clinicians should be aware of VTE, especially during the perioperative period and in bedridden, elderly patients (≥ 65 years of age).

Association between Glutathione S-Transferase Omega 1 A140D Polymorphism in the Turkish Population and Susceptibility to Non-Small Cell Lung Cancer

Recent years have seen a growing evidence of ethnic differences in the frequency of glutathione S-transferase omega 1 (GSTO1) A140D gene polymorphism, which is associated with various cancers such as breast and liver. Until now however, no association has been investigated between the GSTO1 A140D polymorphism and lung cancer. The aim of our study was to see if there was one in the Turkish population. To do that, we identified GSTO1 A140D polymorphism in 214 unrelated healthy individuals and 172 patients with non-small cell lung cancer (NSCLC) using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. The frequencies of A/A (wild type), A/D (heterozygous mutant), and D/D (homozygous mutant) GSTO1 A140D genotypes in healthy subjects were 48 %, 41 %, and 11 %, respectively. In NSCLC patients they were 48 %, 45 %, and 7 %, respectively. We found no significant association between the GSTO1 A140D gene polymorphism and NSCLC or its histological subtypes, namely squamous cell carcinoma or adenocarcinoma. Furthermore, this polymorphism did not correlate with smoking. Our study is the first to show that the frequency of GSTO1 A140D gene polymorphism in the Turkish population is similar to other Caucasian populations and that this polymorphism is not associated with susceptibility to NSCLC. Sažetak Posljednjih godina sve više rezultata ispitivanja upozorava na rasne razlike u učestalosti polimorfizma A140D gena glutation S-transferaze omega 1 (GSTO1) koji je povezan s više oblika karcinoma, poput raka dojke i jetara. Dosada međutim nije ispitana povezanost GSTO1 A140D i raka pluća. Mi smo u ovom ispitivanju pokušali utvrditi postoji li takva povezanost u turskog stanovništva. Izdvojili smo 214 zdravih ispitanika koji nisu bili u rodu te 172 bolesnika s rakom pluća ne-malih stranica, u kojih je polimorfizam GSTO1 A140D utvrđen pomoću lančane reakcije polimerazom - cijepanjem restrikcijskim enzimima (PCR/RFLP). Učestalost GSTO1 A140D genotipova - divljeg tipa (A/A), heterozigotnog mutanta (A/D) odnosno homozigotnog mutanta (D/D) - u zdravih ispitanika iznosila je 48 %, 41 %, odnosno 11 %, a u bolesnika s rakom pluća ne-malih stanica 48 %, 45 % odnosno 7 %. Rezultati ispitivanja nisu pokazali značajne povezanosti između genskog polimorfizma GSTO1 A140D i raka pluća ne-malih stanica odnosno njegovih histoloških podtipova raka pločastih stanica ili adenokarcinoma. Također nisu pokazali povezanost između ovog polimorfizma i pušenja. Međutim, ovo je prvo ispitivanje koje je potvrdilo da učestalost GSTO1 A140D u turske populacije odgovara učestalosti pripadnika bijele (kavkaske) rase te da nije povezan s osjetljivosti na rak pluća ne-malih stanica.

Should the cut-off value of D-dimer be elevated to exclude pulmonary embolism in acute exacerbation of COPD?

OBJECTIVE The aim of this study was to evaluate the D-dimer levels in patients with chronic obstructive pulmonary disease (COPD) exacerbation with and without pulmonary embolism (PE) and to attempt to define a new cut-off value for D-dimer to exclude the diagnosis of PE in patients with COPD exacerbation. METHODS This cross-sectional study was performed between the June 2012 and January 2013. The COPD patients who were admitted to the emergency department with acute exacerbation were consecutively included. D-dimer levels were measured upon admission. All patients underwent computed tomography angiography (CTA) and Doppler ultrasonography (US) of the lower extremities. RESULTS A total of 148 patients were enrolled. Fifty-three patients (36%) who did not have PE had higher than normal (>0.5 pg/mL) D-dimer levels. The D-dimer levels of the COPD patients with PE were significantly higher than those of the patients without PE (2.38±2.80 vs. 1.06±1.51 pg/mL) (P<0.001). The cut-off value for D-dimer in diagnosing PE in the COPD patients was 0.95 pg/mL. The area under the receiver operating characteristic (ROC) curve was 0.752±0.040 (95% CI: 0.672-0.831) (P<0.001). CONCLUSIONS This study showed that the D-dimer concentrations of COPD patients who are in the exacerbation period may be higher than normal, even without PE. The cut-off level for D-dimer was 0.95 pg/mL (sensitivity 70%, spesificity 71%) for the exclusion of PE in the patients with COPD exacerbation. The D-dimer cut-off value that is used to exclude PE in patients with acute exacerbation of COPD should be reevaluated to prevent the excessive use of further diagnostic procedures.

Patient and physician delay in the diagnosis and treatment of non-small cell lung cancer in Turkey.

AIM The early diagnosis and treatment of lung cancer are important for the prognosis of patients with lung cancer. This study was undertaken to investigate patient and doctor delays in the diagnosis and treatment of NSCLC and the factors affecting these delays. MATERIALS AND METHODS A total of 1016 patients, including 926 (91.1%) males and 90 (8.9%) females with a mean age of 61.5±10.1 years, were enrolled prospectively in this study between May 2010 and May 2011 from 17 sites in various Turkish provinces. RESULTS The patient delay was found to be 49.9±96.9 days, doctor delay was found to be 87.7±99.6 days, and total delay was found to be 131.3±135.2 days. The referral delay was found to be 61.6±127.2 days, diagnostic delay was found to be 20.4±44.5 days, and treatment delay was found to be 24.4±54.9 days. When the major factors responsible for these delays were examined, patient delay was found to be more frequent in workers, while referral delay was found to be more frequent in patients living in villages (p<0.05). We determined that referral delay, doctor delay, and total delay increased as the number of doctors who were consulted by patients increased (p<0.05). Additionally, we determined that diagnostic and treatment delays were more frequent at the early tumour stages in NSCLC patients (p<0.05). DISCUSSION The extended length of patient delay underscores the necessity of educating people about lung cancer. To decrease doctor delay, education is a crucial first step. Additionally, to further reduce the diagnostic and treatment delays of chest specialists, multidisciplinary management and algorithms must be used regularly.

Xenobiotic/drug metabolizing enzyme and TP53 polymorphisms and clinical outcome in advanced nonsmall cell lung cancer patients

BACKGROUND/AIM The association between polymorphisms of xenobiotic/drug metabolizing enzymes and TP53 and response to chemotherapy and survival of patients with nonsmall cell lung cancer (NSCLC) are limited and inconclusive. In this study, CYP2E1*5B, CYP2E1*6, CYP2E1*7B, GSTO1 (A140D), and TP53 (Arg72Pro) polymorphisms and response to platinum-based chemotherapy and survival in 137 advanced stage NSCLC patients were investigated. MATERIALS AND METHODS Genetic polymorphism analyses were determined by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). RESULTS The patients with TP53 Pro/Pro variant were more likely to be resistant to chemotherapy than those with Arg/Arg variants with marginal significance (P = 0.066). We also analyzed these gene variants in combination with CYP1A1 (Ile462Val), CYP1B1 (Asn453Ser), GSTM1, GSTP1 exon 5 (Ile105Val), and GSTP1 exon 6 (Ala114Val) and GSTT1 polymorphic genes that we have previously genotyped in the same patients (Ada et al., Neoplasma, 57, 512-527, 2010). The multivariate analysis revealed that adjusted hazard ratio (HR) of death of the combined variant genotypes of TP53 (Arg72Pro, Pro72Pro) and CYP1A1 (Ile462Val, Val462Val) increased significantly as compared to wild-type genotypes (HR, 6.03; 95% CI, 1.39-26.04, P = 0.016). CONCLUSION These results show that combined variant genotypes of TP53 (Arg72Pro, Pro72Pro) and CYP1A1 (Ile/Val, Val/Val) are associated with worsening of survival in NSCLC patients.

Association between the TP53 and CYP2E1*5B gene polymorphisms and non-small cell lung cancer.

Abstract Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Genetic polymorphisms in tumour suppressor genes and genes encoding xenobiotic metabolising enzymes alter the activity of their corresponding enzymes and are important individual susceptibility factors for NSCLC. Because of the lack of information in literature, the aim of our study was to investigate the role of the tumour suppressor gene TP53 (Arg72Pro) and the xenobiotic metabolising CYP2E1*5B gene polymorphisms on the risk of NSCLC development. The study population consisted of 172 patients and 172 controls (156 men and 16 women in each group). Genetic polymorphisms were determined with real-time polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP). Multivariate analysis showed a significant association with NSCLC for the combination between the TP53 codon72 Arg/Pro and the Pro/Pro genotypes (OR 2.21, 95 % CI 1.390-3.51; p=0.001). We also analysed whether combinations of these gene variants with GSTM1, GSTT1, GSTP1 exon 5 (Ile105Val), and GSTP1 exon 6 (Ala114Val) gene polymorphisms were associated with the NSCLC risk. A significant increase in the risk was observed for the following combinations: TP53 codon72 variant with GSTM1 null (OR 2.22, 95 % CI 1.23-4.04; p=0.009), GSTT1 null (OR 2.98, 95 % CI 1.49-5.94; p=0.002), and GSTP1 (Ala114Val) variant genotypes (OR 3.38, 95 % CI 1.54-7.41; p=0.002). Further studies with larger samples are needed to verify these findings.