Miroslav Kovarik

Clinically relevant determinants of body composition, function and nutritional status as mortality predictors in lung cancer patients

Lung cancer belongs to the type of tumors with a relatively high frequency of malnutrition, sarcopenia and cachexia, severe metabolic syndromes related to impairment of physical function and quality of life, resistance to therapy and short survival. Inexpensive and accessible methods of evaluating changes in body composition, physical function and nutrition status are for this reason of great importance for clinical practice to enable the early identification, monitoring, preventing and treatment of these nutritional deficiencies. This could lead to improved outcomes in the quality of life, physical performance and survival of patients with lung cancer. The aim of this article is to summarize the recent knowledge for the use of such methods, their predictability for patient outcomes and an association with other clinically relevant parameters, specifically with lung cancer patients, because such an article collectively describing their practical application in clinical practice is lacking. The interest of this article is in the use of anthropometry, handgrip dynamometry, bioelectrical impedance analysis derived phase angle and nutritional screening questionnaires in lung cancer patients.

Protein metabolism in slow- and fast-twitch skeletal muscle during turpentine-induced inflammation

The aim of our study was to evaluate the differences in protein and amino acid metabolism after subcutaneous turpentine administration in the soleus muscle (SOL), predominantly composed of red fibres, and the extensor digitorum longus muscle (EDL) composed of white fibres. Young rats (40–60 g) were injected subcutaneously with 0.2 ml of turpentine oil/100 g body weight (inflammation) or with the same volume of saline solution (control). Twenty‐four hours later SOL and EDL were dissected and incubated in modified Krebs–Heinseleit buffer to estimate total and myofibrillar proteolysis, chymotrypsin‐like activity of proteasome (CHTLA), leucine oxidation, protein synthesis and amino acid release into the medium. The data obtained demonstrate that in intact rats, all parameters measured except protein synthesis are significantly higher in SOL than in EDL. In turpentine treated animals, CHTLA increased and protein synthesis decreased significantly more in EDL. Release of leucine was inhibited significantly more in SOL. We conclude that turpentine‐induced inflammation affects more CHTLA, protein synthesis and leucine release in EDL compared to SOL.

Alterations in protein metabolism and amino acid concentrations in rats fed by a high-protein (casein-enriched) diet - effect of starvation.

Rats were fed with a standard laboratory diet (SLD) or a high-protein diet (HPD). After three months changes in amino acid concentration and protein metabolism were examined in fed and 24h-fasted animals. In the blood of the HPD animals sacrificed in fed state were found higher concentrations of urea, aspartate, taurine, proline, valine, isoleucine, and leucine, and lower concentrations of glycine and cysteine. The main alterations in tissues were decreased concentrations of glycine and increased concentrations of valine, isoleucine, and leucine. Differences in weight, protein concentration, protein synthesis, and proteolysis in tissues were insignificant. The exception was soleus muscle in which higher values of protein synthesis and proteolysis were found in HPD animals. The response to starvation of HPD and SLD fed animals was different. In animals fed before starvation by HPD was found more pronounced decrease in a number of individual amino acids in plasma and tissues and more pronounced decrease in protein synthesis in muscle, spleen, jejunum, and colon. It is concluded that chronic intake of HPD has not positive effect on protein balance in any tissue, results in the imbalance in aminoacidemia in extracellular and intracellular fluid, and alters the response of the organism to starvation.

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.

The effect of new proteasome inhibitors, belactosin A and C, on protein metabolism in isolated rat skeletal muscle

The proteasome inhibitors are used as research tools to study of the ATP-dependent ubiquitin-proteasome system. Some of them are at present undergoing clinical trials to be used as therapeutic agents for cancer or inflammation. These diseases are often accompanied by muscle wasting. We herein demonstrate findings about new proteasome inhibitors, belactosin A and C, and their direct effect on protein metabolism in rat skeletal muscle. M. soleus (SOL) and m. extensor digitorum longus (EDL) were dissected from both legs of male rats (40–60g) and incubated in a buffer containing belactosin A or C (30 μM) or no inhibitor. The release of amino acids into the medium was estimated using high performance liquid chromatography to calculate total and myofibrillar proteolysis. Chymotrypsin-like activity (CTLA) of proteasome and cathepsin B, L activity were determined by fluorometric assay. Protein synthesis and leucine oxidation were detected using specific activity of L-[1-14C] leucine added to medium. Inhibited and control muscles from the same rat were compared using paired t-test. The results indicate that after incubation with both belactosin A and C total proteolysis and CTLA of proteasome decreased while cathepsin B, L activity did not change in both SOL and EDL. Leucine oxidation was significantly enhanced in SOL, protein synthesis decreased in EDL. Myofibrillar proteolysis was reduced in both muscles in the presence of belactosin A only. In summary, belactosin A and C affected basic parameters of protein metabolism in rat skeletal muscle. The response was both muscle- and belactosin-type-dependent.

Hand grip endurance test relates to clinical state and prognosis in COPD patients better than 6-minute walk test distance

Purpose Patients with COPD present peripheral muscle dysfunction and atrophy, expressed as muscle strength and endurance reduction. The goal of this study was direct dynamometric assessment of hand grip endurance and strength in relation to the stage of disease, multidimensional predictors of mortality, and 6-minute walk test (6MWT). To the best of our knowledge, there has been no previous study determining these parameters. Patients and methods In this observational study, 58 consecutive outpatients with stable COPD and 25 volunteers without respiratory problems were compared. All COPD subjects underwent a comprehensive examination to determine COPD severity, prognostic scales, and 6MWT. Body composition, basic spirometric parameters, and hand grip strength and endurance were determined in all study participants. Results Patients in the COPD group had a 15% decrease in maximum strength (P=0.012) and a 28% decrease in area under the force/time curve (AUC) of the endurance test (P<0.001) compared to the control group. Dynamometric parameters were significantly negatively associated with the stage of disease and values of multivariable prediction indexes, and positively associated with the results of 6MWT. In most cases, closer associations were found with AUC than with 6MWT and in the gender-specific groups. Conclusion Both hand grip strength and endurance are impaired in COPD patients in comparison with the control group. In particular, AUC could be considered as an attractive option not only to assess exercise capacity but also as a predictive marker with a better prognostic value than 6MWT in COPD patients. This is the first study to observe the dependence of hand grip endurance on combined COPD assessment.

Energy, Protein, Carbohydrate, and Lipid Intakes and Their Effects on Morbidity and Mortality in Critically Ill Adult Patients: A Systematic Review

The guidelines for nutritional support in critically ill adult patients differ in various aspects. The optimal amount of energy and nutritional substrates supplied is important for reducing morbidity and mortality, but unfortunately this is not well known, because the topic is complex and every patient is individual. The aim of this review was to gather recent pertinent information concerning the nutritional support of critically ill patients in the intensive care unit (ICU) with respect to the energy, protein, carbohydrate, and lipid intakes and the effect of their specific utilization on morbidity and mortality. Enteral nutrition (EN) is generally recommended over parenteral nutrition (PN) and is beneficial when administered within 24-48 h after ICU admission. In contrast, early PN does not provide substantial advantages in terms of morbidity and mortality, and the time when it is safe and beneficial remains unclear. The most advantageous recommendation seems to be administration of a hypocaloric (<20 kcal · kg-1 · d-1), high-protein diet (amino acids at doses of ≥2 g · kg-1 · d-1), at least during the first week of critical illness. Another important factor for reducing morbidity is the maintenance of blood glucose concentrations at 120-150 mg/dL, which is accomplished with the use of insulin and lower doses of glucose of 1-2 g · kg-1 · d-1, because this prevents the risk of hypoglycemia and is associated with a better prognosis according to recent studies. A fat emulsion is used as a source of required calories because of insulin resistance in the majority of patients. In addition, lipid oxidation in these patients is ∼25% higher than in healthy subjects.

Prognostic value of respiratory quotients in severe polytrauma patients with nutritional support

OBJECTIVE The association between energy metabolism and prognosis in polytrauma patients has not yet been defined. The aim of this study was to describe energy metabolism and analyze the prognostic value of respiratory quotient (RQ) and nonprotein respiratory quotient (npRQ) in fasting polytrauma patients (fPP) and polytrauma patients with nutritional support (nsPP). METHODS Twenty-two polytrauma patients (before and after parenteral nutrition administration) and 22 healthy controls (after overnight fasting) were examined on day 4 (median) after admission to the intensive care unit. To evaluate energy expenditure in nsPP and resting energy expenditure in fPP and controls with RQ and npRQ in all groups, we used indirect calorimetry. With regression analysis, the descriptive models of intensive care unit (ICU) length of stay (LOS) and mechanical ventilation time (VT) were derived. RESULTS RQ and npRQ were significantly lower in fPP than in controls (P < 0.05 and P < 0.01, respectively) and in nsPP (P < 0.05). In nsPP, relationships between RQ or npRQ and the ICU LOS or mechanical VT were demonstrated (P < 0.0001, r = -0.78 for RQ and VT; P < 0.0001, r = -0.78 for npRQ and VT; P < 0.001, r = -0.69 for RQ and LOS; P < 0.001, r = -0.72 for npRQ and LOS). CONCLUSIONS RQ and npRQ parameters measured by indirect calorimetry in polytrauma patients with parenteral nutrition on the fourth day of ICU stay related to clinical outcomes such as duration of mechanical ventilation and ICU LOS.