A multi-center prospective study of plant-based nutritional support in adult community-based patients at risk of disease-related malnutrition.

Introduction: There is an emerging need for plant-based, vegan options for patients requiring nutritional support. Methods: Twenty-four adults at risk of malnutrition (age: 59 years (SD 18); Sex: 18 female, 6 male; BMI: 19.0 kg/m2 (SD 3.3); multiple diagnoses) requiring plant-based nutritional support participated in a multi-center, prospective study of a (vegan suitable) multi-nutrient, ready-to-drink, oral nutritional supplement (ONS) [1.5 kcal/mL; 300 kcal, 12 g protein/200 mL bottle, mean prescription 275 mL/day (SD 115)] alongside dietary advice for 28 days. Compliance, anthropometry, malnutrition risk, dietary intake, appetite, acceptability, gastrointestinal (GI) tolerance, nutritional goal(s), and safety were assessed. Results: Patients required a plant-based ONS due to personal preference/variety (33%), religious/cultural reasons (28%), veganism/reduce animal-derived consumption (17%), environmental/sustainability reasons (17%), and health reasons (5%). Compliance was 94% (SD 16). High risk of malnutrition ('MUST' score ≥ 2) reduced from 20 to 16 patients (p = 0.046). Body weight (+0.6 kg (SD 1.2), p = 0.02), BMI (+0.2 kg/m2 (SD 0.5), p = 0.03), total mean energy (+387 kcal/day (SD 416), p < 0.0001) and protein intake (+14 g/day (SD 39), p = 0.03), and the number of micronutrients meeting the UK reference nutrient intake (RNI) (7 vs. 14, p = 0.008) significantly increased. Appetite (Simplified Nutritional Appetite Questionnaire (SNAQ) score; p = 0.13) was maintained. Most GI symptoms were stable throughout the study (p > 0.06) with no serious adverse events related. Discussion: This study highlights that plant-based nutrition support using a vegan-suitable plant-based ONS is highly complied with, improving the nutritional outcomes of patients at risk of malnutrition.

Evaluation of a New Glycomacropeptide-Based Protein Substitute in Powdered and Liquid Format in Patients with PKU.

(1) Background: Good adherence to a Phe-restricted diet supplemented with an adequate amount of a protein substitute (PS) is important for good clinical outcomes in PKU. Glycomacropeptide (cGMP)-PSs are innovative, palatable alternatives to amino acid-based PSs (AA-PS). This study aimed to evaluate a new cGMP-PS in liquid and powder formats in PKU. (2) Methods: Children and adults with PKU recruited from eight centres were prescribed at least one serving/day of cGMP-PS for 7-28 days. Adherence, acceptability, and gastrointestinal tolerance were recorded at baseline and the end of the intervention. The blood Phe levels reported as part of routine care during the intervention were recorded. (3) Results: In total, 23 patients (powder group, n = 13; liquid group, n = 10) completed the study. The majority assessed the products to be palatable (77% of powder group; 100% of liquid group) and well tolerated; the adherence to the product prescription was good. A total of 14 patients provided blood Phe results during the intervention, which were within the target therapeutic range for most patients (n = 11) at baseline and during the intervention. (4) Conclusions: These new cGMP-PSs were well accepted and tolerated, and their use did not adversely affect blood Phe control.

Evaluation of a New 'Mix-In' Style Glycomacropeptide-Based Protein Substitute for Food and Drinks in Patients with Phenylketonuria and Tyrosinemia.

(1) Background: Poor palatability, large volume, and lack of variety of some liquid and powdered protein substitutes (PSs) for patients with phenylketonuria (PKU) and tyrosinemia (TYR) can result in poor adherence. This study aimed to evaluate a new unflavoured, powdered GMP-based PS designed to be mixed into drinks, foods, or with other PSs, in patients with PKU and TYR. (2) Methods: Paediatric and adult community-based patients were recruited from eight metabolic centres and prescribed ≥1 sachet/day (10 g protein equivalent (PE)) of the Mix-In-style PS over 28 days. Adherence, palatability, GI tolerance, and metabolic control were recorded at baseline and follow-up. Patients who completed at least 7 days of intervention were included in the final analysis. (3) Results: Eighteen patients (3-45 years, nine males) with PKU (n = 12) and TYR (n = 6) used the Mix-In-style PS for ≥7 days (mean 26.4 days (SD 4.6), range 11-28 days) alongside their previous PS, with a mean intake of 16.7 g (SD 7.7) PE/day. Adherence was 86% (SD 25), and GI tolerance was stable, with n = 14 experiencing no/no new symptoms and n = 3 showing improved symptoms compared to baseline. Overall palatability was rated satisfactory by 78% of patients, who successfully used the Mix-In-style PS in various foods and drinks, including smoothies, squash, and milk alternatives, as a top-up to meet their protein needs. There was no concern regarding safety/metabolic control during the intervention. (4) Conclusions: The 'Mix-In'-style PS was well adhered to, accepted, and tolerated. Collectively, these data show that providing a flexible, convenient, and novel format of PS can help with adherence and meet patients' protein needs.

Clinical evaluation of the new indirect calorimeter in canopy and face mask mode for energy expenditure measurement in spontaneously breathing patients.

BACKGROUND & AIMS: The new indirect calorimeter developed in the framework of the ICALIC project was first evaluated in ventilation mode. This second phase aimed to compare its ease of use and precision with another commonly used device in spontaneously breathing adult patients using a canopy hood or a face mask. METHODS: The time required to measure resting energy expenditure (REE) with Q-NRG® in canopy and face mask mode was compared with Quark RMR® in canopy mode by sequential measurements in 45 and 40 spontaneously breathing adult patients, respectively. Their precision was assessed at different time intervals, using coefficients of variation (CV%) and repeated measures one-way ANOVA. Agreement between the two devices was evaluated by correlation coefficients, Bland-Altman plots, and paired t-test. Patients' characteristics potentially affecting the measurement were assessed using linear regression analysis. RESULTS: REE measurement with Q-NRG® was faster than Quark RMR® (19.7 ± 2.9 min vs 24.5 ± 4.3 min, P < 0.001). In canopy mode, Q-NRG® gave values similar to Quark RMR®, with 73% of patients achieving a steady state (CV% <10%) within the 5-15 min interval. In face mask mode, Q-NRG® was less stable than Quark RMR® in canopy mode, and steady state was achieved in only 40% of the patients within the 5-15 min interval. Correlation between the two devices was stronger when Q-NRG® was used in canopy than in face mask mode, with Pearson coefficients of 0.96 and 0.86, respectively. Compared to Quark RMR® in canopy mode, systematic bias±1.96∗SD with Q-NRG® was -14 ± 236 kcal/day in canopy and 73 ± 484 kcal/day in face mask mode. Q-NRG® in face mask mode overestimated REE by 150 ± 51 kcal/day in men compared to Quark RMR® in canopy mode. CONCLUSIONS: Q-NRG® in canopy mode made it possible to save at least 5 min compared to Quark RMR® while maintaining the same measurement precision. However, its use in face mask mode could lead to REE overestimation in men and, therefore, should not be recommended in the clinical setting. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT03947294.

Indirect calorimetry: The 6 main issues.

BACKGROUND AND AIMS: Optimal nutritional therapy, including the individually adapted provision of energy, is associated with better clinical outcomes. Indirect calorimetry is the best tool to measure and monitor energy expenditure and hence optimize the energy prescription. Similarly to other medical techniques, indications and contra-indications must be acknowledged to optimise the use of indirect calorimetry in clinical routine. Measurements should be repeated to enable adaptation to the clinical evolution, as energy expenditure may change substantially. This review aims at providing clinicians with the knowledge to routinely use indirect calorimetry and interpret the results. METHOD: We performed a bibliographic research of publications referenced in PubMed using the following terms: "indirect calorimetry", "energy expenditure", "resting energy expenditure", "VCO2", "VO2", "nutritional therapy". We included mainly studies published in the last ten years, related to indirect calorimetry principles, innovations, patient's benefits, clinical use in practice and medico-economic aspects. RESULTS: We have gathered the knowledge required for routine use of indirect calorimetry in clinical practice and interpretation of the results. A few clinical cases illustrate the decision-making process around its application for prescription, and individual optimisation of nutritional therapy. We also describe the latest technical innovations and the results of tailoring nutrition therapy according to the measured energy expenditure in medico-economic benefits. CONCLUSION: The routine use of indirect calorimetry should be encouraged as a strategy to optimize nutrition care.

How to choose the best route of feeding during critical illness.

Increased and specific nutritional requirements occurring during critical illness need to be covered by appropriate administration of energy, nitrogen and micronutrients, especially in case of pre-existing malnutrition, chronic insufficient oral intakes or expected delay before recovery of eating. The use of artificial nutrition (enteral or parenteral) is recommended whenever the oral intakes are insufficient, in order to avoid the detrimental consequences of malnutrition and promote the best possible outcome of severely ill patients. This paper aims to provide an overview and practical recommendations of artificial nutrition therapy in the ICU setting.

Association of phase angle and running performance.

BACKGROUND: A high phase angle derived from bioelectrical impedance analysis has been linked to a high level of physical activity. However, it is unknown whether a high phase angle is related to running performance. METHODS: We included all subjects who participated for the first time to the Course de l'Escalade between 1999 and 2016, a yearly city run occurring in Geneva. The subjects underwent a measurement by 50-kHz tetrapolar bioelectrical impedance analysis (Nutriguard®). Running time was converted to running speed in km/h. Results are shown as mean (SD) and as frequencies. We performed sex-specific univariate and multivariate regressions, adjusted for age, body mass index, categories of running distance and year of measurement, to evaluate whether the phase angle is associated with running speed. RESULTS: We analyzed 2264 subjects (1025 women and 1239 men). In univariate regressions, phase angle was significantly related to running speed in women (coeff 0.52, 95% CI 0.35-0.67, p < 0.001, adjusted R2 0.037) and men (coeff 0.57, 95% CI 0.42-0.73, p < 0.001, adjusted R2 0.039). Multivariate regressions showed that the phase angle was still significantly associated with running speed in women and men (p < 0.001 for both models), with an adjusted R2 of 0.262 and 0.282, respectively. CONCLUSIONS: The phase angle is positively associated with running performance in men and women. It remains to be demonstrated if this association reflects the benefit of regular training and whether the phase angle might be suitable to monitor improvements in running performance. CLINICAL TRIAL REGISTRY: clinicaltrials.gov, identifier: NCT03400761.

The clinical evaluation of the new indirect calorimeter developed by the ICALIC project.

BACKGROUND & AIMS: The ICALIC project was initiated for developing an accurate, reliable and user friendly indirect calorimeter (IC) and aimed at evaluating its ease of use and the feasibility of the EE measurements in intensive care unit (ICU). METHODS: This was a prospective unblinded, observational, multi-center study. Simultaneous IC measurements in mechanically ventilated ICU patients were performed using the new IC (Q-NRG®) and currently used devices. Time required to obtain EE was recorded to evaluate the ease of use of Q-NRG® versus currently used ICs and EE measurements were compared. Conventional descriptive statistics were used: data as mean ± SD. RESULTS: Six centers out of nine completed the required number of patients for the primary analysis. Mean differences in the time needed by Q-NRG® against currently used ICs were -32.3 ± 2.5 min in Geneva (vs. Deltatrac®; p < 0.01), -32.3 ± 3.1 in Lausanne (vs. Quark RMR®; p < 0.05), -33.7 ± 1.4 in Brussels (vs. V-Max Encore®; p < 0.05), -26.4 ± 7.8 in Tel Aviv (vs. Deltatrac®; p < 0.05), -28.5 ± 3.5 in Vienna (vs. Deltatrac®; p < 0.05), and 0.3 ± 1.2 in Chiba (vs. E-COVX®; p = 0.17). EE (kcal/day) measurements by the Q-NRG® were similar to the Deltatrac® in Geneva and Vienna (mean differences±SD: -63.1 ± 157.8 (p = 0.462) and -22.9 ± 328.2 (=0.650)), but significantly different in Tel Aviv (307.4 ± 324.5, p < 0.001). Significant differences were observed in Lausanne (Quark RMR®: -224.4 ± 514.9, p = 0.038) and in Brussels (V-max®: -449.6 ± 667.4, p < 0.001), but none was found in Chiba (E-COVX®; 55.0 ± 204.1, p = 0.165). CONCLUSION: The Q-NRG® required a much shorter time than most other ICs to determine EE in mechanically ventilated ICU patients. The Q-NRG® is the only commercially available IC tested against mass spectrometry to ensure gas accuracy, while being very easy-to use.

Evaluation of the accuracy and precision of a new generation indirect calorimeter in canopy dilution mode.

BACKGROUND & AIMS: Indirect calorimetry (IC) is the only way to measure in real time energy expenditure (EE) and to optimize nutrition support in acutely and chronically ill patients. Unfortunately, most of the commercially available indirect calorimeters are rather complex to use, expensive and poorly accurate and precise. Therefore, an innovative device (Q-NRG®, COSMED, Rome, Italy) that matches clinicians' needs has been developed as part of the multicenter ICALIC study supported by the two academic societies ESPEN and ESICM. The aim of this study was to evaluate the accuracy and intra- and inter-unit precision of this new device in canopy dilution mode in vitro and in spontaneously breathing adults. METHODS: Accuracy and precision of oxygen consumption (VO2) and carbon dioxide production (VCO2) measurements were evaluated in vitro and in 15 spontaneously breathing healthy adults by interchanging three Q-NRG® units in a random order. In vitro validation was performed by gas exchange simulation using high-precision gas mixture and mass flow controller. Accuracy was calculated as error of measured values against expected ones based on volume of gas infused. Respiratory coefficient (RQ) accuracy was furthermore assessed using the ethanol-burning test. To evaluate the intra- and inter-unit precisions, the coefficient of variation (CV% = SD/Mean*100) was calculated, respectively, from the mean ± SD or the mean ± SD of the three mean values of VO2, VCO2, RQ and EE measured by each Q-NRG® units. In vivo accuracy measurement of the Q-NRG® was assessed by simultaneous comparison with mass spectrometry (MS) gas analysis, using Bland-Altman plot, Pearson correlation and paired t-test (significance level of p = 0.05). RESULTS: In vitro evaluation of the Q-NRG® accuracy showed measurement errors <1% for VO2, VCO2 and EE and <1.5% for RQ. Evaluation of the intra- and inter-unit precision showed CV% ≤1% for VO2 and EE and CV% ≤1.5% for VCO2 and RQ measurements, except for one Q-NRG® unit where CV% was 2.3% for VO2 and 3% for RQ. Very good inter-unit precision was confirmed in vivo with CV% equal to 2.4%, 3%, 2.8% and 2.3% for VO2, VCCO2, RQ and EE, respectively. Comparison with MS showed correlation of 0.997, 0.987, 0.913 and 0.997 for VO2, VCO2, RQ and EE respectively (p ≤ 0.05). Mean deviation of paired differences was 1.6 ± 1.4% for VO2, -1.5 ± 2.5% for VCO2, -3.1 ± 2.6% for RQ and 0.9 ± 1.4% for EE. CONCLUSION: Both in vitro and in vivo measurements of VO2, VCO2, RQ and EE on three Q-NRG® units showed minimal differences compared to expected values and MS and very low intra- and inter-unit variability. These results confirm the very good accuracy and precision of the Q-NRG® indirect calorimeter in canopy dilution mode in spontaneously breathing adults.

Indirect Calorimetry in Clinical Practice.

Indirect calorimetry (IC) is considered as the gold standard to determine energy expenditure, by measuring pulmonary gas exchanges. It is a non-invasive technique that allows clinicians to personalize the prescription of nutrition support to the metabolic needs and promote a better clinical outcome. Recent technical developments allow accurate and easy IC measurements in spontaneously breathing patients as well as in those on mechanical ventilation. The implementation of IC in clinical routine should be promoted in order to optimize the cost-benefit balance of nutrition therapy. This review aims at summarizing the latest innovations of IC as well as the clinical indications, benefits, and limitations.

In vitro validation of indirect calorimetry device developed for the ICALIC project against mass spectrometry.

RATIONALE: Accurate evaluation of the energy needs is required to optimize nutrition support of critically ill patients. Recent evaluations of indirect calorimeters revealed significant differences among the devices available on the market. A new indirect calorimeter (Q-NRG®, Cosmed, Roma, Italy) has been developed by a group of investigators supporting the international calorimetry study initiative (ICALIC) to achieve ultimate accuracy for measuring energy expenditure while being easy to use, and affordable. This study aims to validate the precision and the accuracy of the Q-NRG® in the in-vitro setting, within the clinically relevant range for adults on mechanical ventilation in the ICU. Mass spectrometry is the reference method for the gas composition analysis to evaluate the analytic performances of the Q-NRG®. METHODS: The accuracy and precision of the O2 and CO2 measurements by the Q-NRG were evaluated by comparing the measurements of known O2 and CO2 gas mixtures with the measurements by the mass spectrometer (Extrel, USA). The accuracy and precision of the Q-NRG® for measurements of VO2 (oxygen consumption) and VCO2 (CO2 production) at clinically relevant ranges (150, 250 and 400 ml/min STPD) were evaluated by measuring simulated gas exchange under mechanically ventilated setting at different FiO2 settings (21-80%), in comparison to the reference measurements by the mass spectrometer-based mixing chamber system. RESULTS: The measurements of gas mixtures of predefined O2 and CO2 concentrations by the Q-NRG® were within 2% accuracy versus the mass spectrometer measurements in Passing Bablok regression analysis. In a mechanically ventilated setting of FiO2 from 21 up to 70%, the Q-NRG® measurements of simulated VO2 and VCO2 were within 5% difference of the reference mass spectrometer measurements. CONCLUSION: In vitro evaluation confirms that the accuracy of the Q-NRG® indirect calorimeter is within 5% at oxygen enrichment to 70%; i.e. maximum expected for clinical use. Further recommendations for the clinical use of the Q-NRG® by will be released once the ongoing multi-center study is completed.

An Increase in Fat Mass Index Predicts a Deterioration of Running Speed.

A low fat mass is associated with a good running performance. This study explores whether modifications in body composition predicted changes in running speed. We included people who underwent several measurements of body composition by bioelectrical impedance analysis between 1999 and 2016, at the "Course de l'Escalade", taking place yearly in Geneva. Body composition was reported as a fat-free mass index (FFMI) and fat mass index (FMI). Running distances (men: 7.2 km; women: 4.8 km) and running times were used to calculate speed in km/h. We performed multivariate linear mixed regression models to determine whether modifications of body mass index, FFMI, FMI or the combination of FFMI and FMI predicted changes in running speed. The study population included 377 women (1419 observations) and 509 men (2161 observations). Changes in running speed were best predicted by the combination of FFMI and FMI. Running speed improved with a reduction of FMI in both sexes (women: ß -0.31; 95% CI -0.35 to -0.27, p < 0.001. men: ß -0.43; 95% CI -0.48 to -0.39, p < 0.001) and a reduction of FFMI in men (ß -0.20; 95% CI -0.26 to -0.15, p < 0.001). Adjusted for body composition, the decline in running performance occurred from 50 years onward, but appeared earlier with a body mass, FFMI or FMI above the median value at baseline. Changes of running speed are determined mostly by changes in FMI. The decline in running performance occurs from 50 years onward but appears earlier in people with a high body mass index, FFMI or FMI at baseline.

Running performance in a timed city run and body composition: A cross-sectional study in more than 3000 runners.

OBJECTIVE: The importance of body composition for running performance is unclear in the general population. The aim of this study was to evaluate whether body composition influences running speed and whether it is a better predictor of running speed than body mass index (BMI). METHODS: The study included 1353 women (38.2 ± 12.1 y of age) and 1771 men (39.6 ± 12.1 y of age) who underwent, for the first time, a measurement of body composition by bioelectrical impedance analysis between 1999 and 2016, before a timed run occurring annually in Geneva. The running distances and times were converted to average speed (km/h). Body composition was expressed as sex-specific quartiles, where quartile 1 (lowest values) was the reference quartile. The relationships between speed and BMI or body composition were analyzed by multivariate linear regressions. RESULTS: Multivariate regressions showed that the higher the fat mass index (FMI) quartile, the lower the running speed in women and men (all P < 0.001). In men, a fat-free mass index (FFMI) in quartile 4 (>20 kg/m2) was associated with a poor running performance (r = -0.50, P < 0.001), whereas in women, an FFMI in quartile 2 or 3 (15-16.4 kg/m2) was associated with a higher running speed (r = 0.23, P = 0.04; r = 0.28, P = 0.01, respectively). Body composition predicted speed better than BMI in women (R2 = 26.8% versus 14.4%) and men (R2 = 29.8% versus 25.4%). CONCLUSIONS: Running speed is negatively associated with BMI and FMI in both sexes. Body composition is a better predictor of running performance than BMI.

Plant Polyphenols Stimulate Adhesion to Intestinal Mucosa and Induce Proteome Changes in the Probiotic Lactobacillus acidophilus NCFM.

SCOPE: Plant phenolics, known to exert beneficial effects on human health, were supplemented to cultures of the probiotic bacterium Lactobacillus acidophilus NCFM (NCFM) to assess their effect on its adhesive capacity and the abundancy of individual proteins. METHODS AND RESULTS: The presence of resveratrol and ferulic acid during bacterial growth stimulated adhesion of NCFM to mucin and human intestinal HT-29 cells, while tannic acid improved adhesion only to HT-29 cells and caffeic acid had very modest effect overall. Some dosage dependence was found for the four phenolics supplemented at 100, 250, and 500 µg mL-1 to the cultures. Notably, 500 µg mL-1 ferulic acid only stimulated adhesion to mucin. Analyses of differential whole-cell as well as surface proteomes revealed relative abundancy changes for a total of 27 and 22 NCFM proteins, respectively. These changes include enzymes acting in metabolic pathways, such as glycolysis, nucleotide metabolism, and stress response, as well as known moonlighting or surface-associated proteins. CONCLUSION: The five plant phenolics found in various foods stimulate the adhesive capacity of NCFM in diverse ways and elicit relative abundancy changes of specific proteins, providing molecular level insight into the mechanism of the putative beneficial effects of the polyphenols.

Association of GSTT1 null, XPD 751 CC and XPC 939 CC genotypes with increased levels of genomic damage among hospital pathologists.

CONTEXT: Hospital workers are at risk for genotoxic damage following occupationally exposure to xenobiotics. Pathologists are exposed to chemicals during their use in health care environments, particularly throughout inhalation of airborne agents, absorption through skin or contact with the patient's body fluids. OBJECTIVE: We evaluated the level of genomic damage in a sample of 61 hospital pathologists (occupationally exposed to antineoplastic drugs and sterilizing agents) and 60 control subjects. MATERIALS AND METHODS: Lymphocytes were analyzed by SCEs and CAs assays and genotyped for GSTT1, GSTM1, CYP1A1 Ile/Val, XPD (A751C) and XPC (A939C) gene polymorphisms. RESULTS: Pathologists showed significantly higher frequencies of SCEs and CAs with respect to control subjects. GSTT1 null genotype was found to be associated with higher SCEs and CAs frequencies, whereas XPD 751 CC and XPC 939 CC genotypes only with a higher level of SCEs. DISCUSSION AND CONCLUSIONS: The SCEs and CAs results are consistent with other published data, placing hospital workers as a category at risk for genotoxic damage caused by chronic exposure to xenobiotics. The higher levels of cytogenetic damage observed among GSTT1 null, XPD 751 and XPC 939 CC homozygote subjects confirm the importance of the genetic polymorphisms analysis associated to genotoxicological studies.

Relationships between cytokine (IL-6 and TGF-ß1) gene polymorphisms and chromosomal damage in hospital workers.

Cytokine gene polymorphisms have been found to be associated with a pre-disposition to a variety of diseases, including inflammatory and cancer diseases. The present study evaluated the influence of six cytokine gene polymorphisms on the level of genomic damage observed in peripheral blood lymphocytes from hospital pathologists chronically exposed to low doses of different xenobiotics. Lymphocytes from 50 pathologists and 50 control subjects were recruited and analyzed in Sister Chromatid Exchange (SCE) and Chromosomal Aberrations (CA) assays. The frequencies of six cytokine gene polymorphisms and their relationships with the cytogenetic damage levels were also evaluated. The results indicated that significant differences were found between pathologists and controls in terms of SCE frequency (p < 0.001) and RI values (p < 0.001), as well as in terms of CA and cells with aberrations (p < 0.001). No associations were found between all analyzed cytokine gene polymorphisms and CA frequency in both pathologists and control groups. Vice versa, among pathologists, homozygote individuals for the IL-6 G allele showed a significantly (p = 0.017) lower frequency of SCE with respect to heterozygote subjects. Similarly, for TGFß1 codon 10 locus, homozygote for T allele and heterozygote TC subjects showed a significantly (p = 0.021) lower frequency of SCE with respect to homozygote CC individuals. Among controls, no significant differences were found in the frequency of SCE between genotypes at all loci. Based on these results, we speculate that high circulating levels of a pro-inflammatory cytokine like IL-6 and lower levels of the immunosuppressant cytokine TGFß1 could be associated directly with a longer duration and/or greater intensity of inflammatory processes, and indirectly with significantly higher levels of genomic damage.