František Salajka

Skinfold Anthropometry –The Accurate Method for Fat Free Mass Measurement in COPD

Abstract Purpose: Fat free mass index (FFMI) is an independent predictor of metabolic and functional consequences in COPD. For its measurement dual energy X-ray absorptiometry (DEXA), skin-fold anthropometry (SFA), bioelectrical impedance analysis (BIA) and bioimpedance spectroscopy (BIS) are used in clinical practice. The aim of our pilot study was to analyse precisely and critically which method is most accurate and available for common use in clinical practice for measurement of FFM by assessment against relevant DEXA in patients with COPD. Methods: This was an observational cross-sectional study of consecutive COPD subjects. FFM by methods of SFA, two versions of BIA, and BIS was compared with that from clinically relevant DEXA in 41 outpatients (mean age 66.5 ± 7.7 yrs) with stable COPD, 34 men and 7 women, with mean BMI 28.2 ± 6.1 kg.m−2. Results: All methods underestimate FFM in comparison with DEXA. In the general evaluation non-significant differences with the smallest mean bias were demonstrated for SFA (1.2 kg) and BIA (3.8 kg), but there was a difference of more than 9 kg using BIS and BIA COPD methods (p < 0.0001). The best agreement between DEXA and SFA was demonstrated via Lins concordance coefficient and Bland–Altman test. Conclusions: SFA has been demonstrated as an accurate, available and cheap method for determination of FFM and FM with application of the Durnin Womersley equation for body density and with the Siri equation for FM in patients with COPD. SFA can be easily applied in routine clinical practice.

Erlotinib in the treatment of advanced squamous cell NSCLC

Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor. Clinical trials have shown its efficacy in advanced non-small cell lung cancer (NSCLC). We conducted a large retrospective study based on clinical experience aiming to prove erlotinibs efficacy and safety in patients with advanced-stage squamous cell NSCLC. Totally 375 patients with advanced-stage (IIIB, IV) squamous cell NSCLC were treated with erlotinib. Erlotinib was continued until disease progression or intolerable toxicity. 1 (0.3%) complete response (CR), 28 (7.5%) partial responses (PR) and 198 (52.8%) stable diseases (SD) were achieved. Overall response rate (ORR) and disease control rate (DCR) were 7.8% and 60.5%, respectively. Median progression-free survival (PFS) was 3.0 months and median overall survival (OS) was 7.6 months. PFS of patients with CR/PR, SD and PD were 7.6, 3.9 and 1.0 months, respectively (P<0.001). OS of patients with CR/PR, SD and PD were 13.3, 10.9 and 3.8 months, respectively (P<0.001).The most common adverse effects were rash and diarrhoea. In conclusion ertlotinib is effective and well-tolerated in patients with advanced-stage squamous cell NSCLC.

Thyroid transcription factor 1 expression is associated with outcome of patients with non-squamous non-small cell lung cancer treated with pemetrexed-based chemotherapy

Pemetrexed is an antifolate cytostatic agent targeting several folate-dependent enzymatic pathways, widely used in the treatment of locally advanced or metastatic stage non-small cell lung cancer. Aside from the non-squamous histology, there is still no available molecular biomarker predicting treatment efficacy of pemetrexed-based chemotherapy. The aim of our retrospective study was to evaluate the association of thyroid transcription factor 1 expression with outcome of a large cohort of patients with non-squamous non-small cell lung cancer treated with pemetrexed. We retrospectively analysed clinical data of 463 patients with advanced-stage non-small cell lung cancer (IIIB or IV) treated with pemetrexed-based chemotherapy. Thyroid transcription factor 1 expression was assessed using indirect immunohistochemical detection in formalin-fixed paraffin-embedded tumour tissue at the time of diagnosis. Thyroid transcription factor 1 expression was detected in the tumour tissue from 76.0% of patients, and tumours from 24.0% of patients were thyroid transcription factor 1 negative. The median progression-free survival and overall survival for patients with thyroid transcription factor 1 positive tumours were 4.8 and 11.8 months compared to 2.8 and 8.3 months for those with thyroid transcription factor 1 negative tumours (p = 0.001 and p < 0.001). The multivariable Cox proportional hazards model revealed that thyroid transcription factor 1 expression was significantly associated with progression-free survival (hazard ratio = 1.57, p < 0.001) and also with overall survival (hazard ratio = 1.73, p < 0.001). In conclusion, the results of the conducted retrospective study suggest that the thyroid transcription factor 1 expression was independently associated with progression-free survival and overall survival in patients with advanced-stage non-squamous non-small cell lung cancer treated with pemetrexed-based chemotherapy.

A pilot data analysis of a metabolomic HPLC-MS/MS study of patients with COPD

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with multiple clinical faces. Metabolomic profiling studies small molecules present in biological samples by combined use of chromatography with mass spectrometry. OBJECTIVES The goal of our work was to perform a high performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS) metabolomic study to compare the concentrations of metabolites in COPD patients and in controls. MATERIAL AND METHODS Participants were recruited at the University Hospital, Hradec Králové, Czech Republic, with the approval of the ethics committee. The analysis of blood samples was performed at Health Sciences Center (HSC) in Kuwait. The blood samples were analyzed for concentrations of acylcarnitines and amino acids by high performance liquid chromatography (Waters 2690 HPLC; Waters, Milford, USA) and a triple-quadruple tandem mass spectrometer (Quattro LC, Micromass, Manchester, United Kingdom). RESULTS Groups of 10 subjects with COPD and 10 healthy controls were analyzed. Carnitine analysis showed that the free carnitine to acylcarnitine ratio (C0/AC ratio) was significantly lower in COPD (0.58 μM/L) compared to the controls (0.73 μM/L; p = 0.002). The mean C8/C2 ratio in the COPD group was significantly higher (0.03 μM/L) - in the control group it was 0 μM/L (p = 0.03). Amino acid analysis showed lower levels of phenylalanine in the COPD group (22.05 μM/L) compared to the controls (30.05 μM/L; p = 0.008). The alanine concentrations were significantly lower in the COPD group (173 μM/L) than in the control group (253 μM/L; p = 0.001). The pyroglutamate levels were higher in COPD (1.58 μM/L) than in the controls (1 μM/L; p = 0.040). CONCLUSIONS The carnitine and acylcarnitine levels in COPD subjects in this study possibly indicate a predisposition to atherosclerosis as a result of inadequate β-oxidation of fatty acids and show the presence of oxidative stress. Furthermore, the high sensitivity to changes in circulating amino acid levels may allow us to detect subclinical malnutrition and take early preventative interventions such as nutritional supplementation and patient education.

Pemetrexed in the Second Line Chemotherapy of Non-small Cell Lung Cancer. A Multicentre Prospective Analysis of Data From Clinical Practice

Non small cell lung cancer (NSCLC) is one of the most aggressive tumours with unsatisfactory prognosis and extremely high mortality. Pemetrexed became one of the standard chemotherapeutic options in advanced NSCLC. It is recommended both in the 1st line and in the 2nd line.