Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America.

BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

Sympathetic nervous activation, mitochondrial dysfunction and outcome in acutely decompensated cirrhosis: the metabolomic prognostic models (CLIF-C MET).

BACKGROUND AND AIMS: Current prognostic scores of patients with acutely decompensated cirrhosis (AD), particularly those with acute-on-chronic liver failure (ACLF), underestimate the risk of mortality. This is probably because systemic inflammation (SI), the major driver of AD/ACLF, is not reflected in the scores. SI induces metabolic changes, which impair delivery of the necessary energy for the immune reaction. This investigation aimed to identify metabolites associated with short-term (28-day) death and to design metabolomic prognostic models. METHODS: Two prospective multicentre large cohorts from Europe for investigating ACLF and development of ACLF, CANONIC (discovery, n=831) and PREDICT (validation, n=851), were explored by untargeted serum metabolomics to identify and validate metabolites which could allow improved prognostic modelling. RESULTS: Three prognostic metabolites strongly associated with death were selected to build the models. 4-Hydroxy-3-methoxyphenylglycol sulfate is a norepinephrine derivative, which may be derived from the brainstem response to SI. Additionally, galacturonic acid and hexanoylcarnitine are associated with mitochondrial dysfunction. Model 1 included only these three prognostic metabolites and age. Model 2 was built around 4-hydroxy-3-methoxyphenylglycol sulfate, hexanoylcarnitine, bilirubin, international normalised ratio (INR) and age. In the discovery cohort, both models were more accurate in predicting death within 7, 14 and 28 days after admission compared with MELDNa score (C-index: 0.9267, 0.9002 and 0.8424, and 0.9369, 0.9206 and 0.8529, with model 1 and model 2, respectively). Similar results were found in the validation cohort (C-index: 0.940, 0.834 and 0.791, and 0.947, 0.857 and 0.810, with model 1 and model 2, respectively). Also, in ACLF, model 1 and model 2 outperformed MELDNa 7, 14 and 28 days after admission for prediction of mortality. CONCLUSIONS: Models including metabolites (CLIF-C MET) reflecting SI, mitochondrial dysfunction and sympathetic system activation are better predictors of short-term mortality than scores based only on organ dysfunction (eg, MELDNa), especially in patients with ACLF.

Post-transplant diabetes mellitus and renal cell cancer after renal transplantation.

BACKGROUND: Diabetes is a risk factor for cancer in the general population. However, few data are available on the association between post-transplant diabetes mellitus (PTDM) and cancer after transplantation. METHODS: We analyzed this issue in a Spanish cohort of patients without diabetes before transplantation. PTDM was diagnosed with consensus criteria at 12 months after transplantation and 12 months before the diagnosis of cancer. The association between PTDM and cancer (overall and specific types) was evaluated with regression analysis. RESULTS: During a follow-up of 12 years (interquartile range 8-14), 85 cases of 603 developed cancer (829/100 000/year) and 164 (27%) PTDM. The most frequent cancers were renal cell cancer (RCC) n = 15, 146/cases/100 000/year), lung (n = 12, 117/cases/100 000/year), colon (n = 9, 88/cases/100 000/year) and prostate (n = 9, 88/cases/100 000/year). In logistic regression, PTDM was not associated with cancer. Eight of the 164 patients with PTDM (4.9%) vs 7 of the 439 without PTDM developed RCC (1.6%) (P = .027). In multivariate analysis, PTDM was independently associated with RCC [odds ratio (OR) 2.92, confidence interval (CI) 1.03-8.27], adjusting for smoking (OR 4.020, 95% CI 1.34-12.02) and other covariates. PTDM was not associated with other types of cancer. CONCLUSIONS: Patients with PTDM must be considered a population at risk for RCC and accordingly, the subject of active surveillance.

Cross-cultural adaptation and validation of the Nine Item ARFID Screen (NIAS) in Mexican youths.

Avoidant/Restrictive Food Intake Disorder (ARFID) is defined by limited volume or variety of food intake motivated by the sensory properties of food, fear of aversive consequences, or lack of interest in food or eating associated with medical, nutritional, and psychosocial impairment. Currently, two of the most widely validated measures are The Eating Disturbances in Youth-Questionnaire (EDY-Q) and the Nine Item ARFID Screen (NIAS). The latter has proven valid and reliable for assessing this disorder. OBJECTIVE: To validate a culturally sensitive adaptation of the NIAS instrument and evaluate its psychometric properties in Mexican youths. METHOD: The sample consisted of 800 participants aged 12-30 (M = 18.56, SD = 3.52) from Mexico City and Hidalgo public educational institutions. RESULTS: The S-NIAS obtained a Cronbach's alpha of 0.84, adequate construct validity adjustment rates: CMIN = 1.88; GFI = 0.97; AGFI = 0.94; CFI = 0.98; RMR = 0.050; and RMSEA = 0.047. Measurement invariance by gender, age, and survey administration which show that construct is understood in the same way across both groups and despite the change from paper-and-pencil to online survey administration. CONCLUSION: The psychometric properties of the Spanish Nine Item ARFID Screen (S-NIAS) indicate that it is a valid and reliable instrument for evaluating symptoms associated with ARFID in this sample of youths. PUBLIC SIGNIFICANCE: Although there are advances in studying ARFID, their epidemiological data comes mainly from a few countries. Furthermore, these data are scarcer due to the lack of validated screening and assessment instruments available in a variety of world languages; having instruments for the evaluation of ARFID symptoms is essential because it could function as an auxiliary means for the detection and prevention of people at risk.

Transdiagnostic factors in symptoms of depression and post-traumatic stress: a systematic review.

The current systematic review sought to identify quantitative empirical studies that focused on the transdiagnostic factors of intolerance of uncertainty, emotional dysregulation and rumination, and their relation with depression and post-traumatic stress disorder (PTSD). The overall research aim was to examine the relationship between these transdiagnostic factors and their relation with depression and PTSD symptoms. The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Out of the 768 articles initially identified, 55 met the inclusion criteria for the current review. The results determined that intolerance of uncertainty is indirectly related to depression and PTSD symptoms, mainly through other factors including emotion dysregulation and rumination. Additionally, emotional dysregulation is a significant predictor of both depression and PTSD symptoms. Rumination is a robust factor related to depression and PTSD symptoms, this relationship was significant in cross-sectional and longitudinal studies. This review provides evidence on the transdiagnostic factors of intolerance of uncertainty, emotional dysregulation and rumination in the relationship with depression and PTSD symptoms.

The Serine Protease Autotransporters TagB, TagC, and Sha from Extraintestinal Pathogenic Escherichia coli Are Internalized by Human Bladder Epithelial Cells and Cause Actin Cytoskeletal Disruption.

TagB, TagC (tandem autotransporter genes B and C), and Sha (Serine-protease hemagglutinin autotransporter) are recently described members of the SPATE (serine protease autotransporters of Enterobacteriaceae) family. These SPATEs can cause cytopathic effects on bladder cells and contribute to urinary tract infection in a mouse model. Bladder epithelial cells form an important barrier in the urinary tract. Some SPATEs produced by pathogenic E. coli are known to breach the bladder epithelium. The capacity of these newly described SPATEs to alter bladder epithelial cells and the role of the serine protease active site were investigated. All three SPATE proteins were internalized by bladder epithelial cells and altered the distribution of actin cytoskeleton. Sha and TagC were also shown to degrade mucin and gelatin respectively. Inactivation of the serine catalytic site in each of these SPATEs did not affect secretion of the SPATEs from bacterial cells, but abrogated entry into epithelial cells, cytotoxicity, and proteolytic activity. Thus, our results show that the serine catalytic triad of these proteins is required for internalization in host cells, actin disruption, and degradation of host substrates such as mucin and gelatin.

Prediabetes is a risk factor for cardiovascular disease following renal transplantation.

Prediabetes and post-transplant diabetes mellitus affect about 20-30% of renal transplant patients. The latter is a risk factor for cardiovascular disease. However, no clear evidence linking prediabetes and cardiovascular disease is available. To study this we analyzed the impact of prediabetes on cardiovascular disease in 603 renal transplant patients followed with repeated oral glucose tests for up to five years and a long term survival evaluation. Prediabetes and post-transplant diabetes mellitus were defined at 12 months after transplantation to avoid their high reversibility rate before this period. 73 cardiovascular events were observed. The incidence of events was significantly higher in patients with either prediabetes, (17%; 0.023 person/year) or post-transplant diabetes mellitus (20%; 0.028 person/year) than in normal individuals, (7%; 0.0095 person/year). The incidence of events was comparable between prediabetes and post-transplant diabetes mellitus. Prediabetes at 12 months was a risk factor for cardiovascular events in univariate and multivariate Cox survival analyses (hazard ratio 2.24, 95% confidence interval 1.11-4.52). Prediabetes at three months and hemoglobin A1c at 12 months were not significantly associated with cardiovascular disease. Thus, prediabetes is a risk factor for cardiovascular disease in renal transplantation, a population at high risk for cardiovascular events. Since prediabetes is potentially a reversible condition, there is an opportunity to prevent cardiovascular disease in this population.

Mean platelet volume as a prognostic factor for venous thromboembolic disease.

BACKGROUND: Mean platelet volume (MPV) is a risk factor for cardiovascular and inflammatory diseases. AIM: To evaluate the association between high MPV and 90-day mortality after an episode of venous thromboembolism (VTE). MATERIAL AND METHODS: Retrospective cohort of 594 patients with a median age of 73 years (58% women) with a first episode VTE, included in an institutional Thromboembolic Disease registry between 2014 and 2015. MPV values were obtained from the automated blood cell count measured at the moment of VTE diagnosis. Volumes ≥ 11 fL were classified as high. All patients were followed for 90 days to assess survival. RESULTS: The main comorbidities were cancer in 221 patients (37%), sepsis in 172 (29%) and coronary artery disease in 107 (18%). Median MPV was 8 fl (8-9), brain natriuretic peptide 2,000 pg/ml (1,025-3,900) and troponin 40 pg/ml (19.5-75). Overall mortality was 20% (121/594) during the 90 days of follow-up. Thirty three deaths occurred within 7 days and 43 within the first month. The loss of patients from follow-up was 5% (28/594) at 90 days. Mortality among patients with high MP was 36% (23/63). The crude mortality hazard ratio (HR) for high MPV was 2.2 (95% confidence intervals (CI) 1.4-3.5). When adjusted for sepsis, oncological disease, heart disease, kidney failure and surgery, the mortality HR of high MPV was 2.4 (CI95% 1.5-3.9) in the VTE group, 2.3 (CI95% 1.5-4.4) in the deep venous thrombosis group, and 2.9 (CI95% 1.6 -5.6) in the pulmonary embolism group. CONCLUSIONS: High MPV is an independent risk factor for mortality following an episode of VTE.

Cognitive remediation therapy in Mexico as a treatment for Anorexia Nervosa: A case study.

The purpose of this study was to conduct a preliminary evaluation of cognitive remediation therapy (CRT) as part of the treatment of a patient with anorexia nervosa (AN) from Mexico. The participant was a 21-year-old woman with a body mass index (BMI) of 14.7, who had suffered from the disorder for 10 years. Using a pre-post treatment design, changes were evaluated using four neuropsychological tests, two tests to measure the AN symptoms and two to measure psychological distress (depression and anxiety). BMI was also evaluated before and after the intervention. The results of the present study were similar to those reported for patients from English-speaking countries. The average percentage of favorable change in the different measures was higher than 30%, except for BMI, which increased by only 21%. The results suggest that the inclusion of CRT in AN treatment programs in Mexico is a potentially viable option.

Children with obesity: peer influence as a predictor of body dissatisfaction.

PURPOSE: To analyze self-esteem, as well as the different peer influence components (messages, interactions and likability) as predictors of body dissatisfaction in children with obesity. METHOD: A total of 123 children aged between 10 and 12 years were divided into two groups according to their body mass index. The group with obesity was comprised of 36 boys and 21 girls and the group with normal weight of 32 boys and 34 girls. All of the participants answered the Body Shape Questionnaire-16, the Inventory of Peer Influence on Eating Concerns, and the Rosenberg Self-Esteem Scale. RESULTS: The hierarchical multiple regression analysis for each group showed that likability and peer messages explain 67% of the body dissatisfaction variance in children with obesity and 54% in children with normal weight. CONCLUSION: Peer influence predicted body dissatisfaction in children; however, children with obesity assimilate messages from their peers differently compared with children with normal weight.

Towards End-to-End Acoustic Localization Using Deep Learning: From Audio Signals to Source Position Coordinates.

This paper presents a novel approach for indoor acoustic source localization using microphone arrays, based on a Convolutional Neural Network (CNN). In the proposed solution, the CNN is designed to directly estimate the three-dimensional position of a single acoustic source using the raw audio signal as the input information and avoiding the use of hand-crafted audio features. Given the limited amount of available localization data, we propose, in this paper, a training strategy based on two steps. We first train our network using semi-synthetic data generated from close talk speech recordings. We simulate the time delays and distortion suffered in the signal that propagate from the source to the array of microphones. We then fine tune this network using a small amount of real data. Our experimental results, evaluated on a publicly available dataset recorded in a real room, show that this approach is able to produce networks that significantly improve existing localization methods based on SRP-PHAT strategies and also those presented in very recent proposals based on Convolutional Recurrent Neural Networks (CRNN). In addition, our experiments show that the performance of our CNN method does not show a relevant dependency on the speaker's gender, nor on the size of the signal window being used.

Genetic damage in patients moving from hemodialysis to online hemodiafiltration.

End-stage renal failure patients exhibit a high incidence of genetic damage and genomic instability. Part of this genetic damage is assumed to be caused by the hemodialysis (HD) procedure. To reduce these effects, different alternative HD procedures have been proposed, such as the use of high efficiency convective therapies to improve the reactive oxygen species/antioxidant ratio. To determine the efficiency of online hemodiafiltration (HDF) technique on the levels of DNA damage, we have measured the frequency of micronucleus in peripheral blood lymphocytes of 33 individuals moving from low-flux HD to post-dilution online HDF. In addition to basal levels of genetic damage, potential changes in radiosensitivity were measured as indicators of genomic instability. Plasma antioxidant capacity was also determined. Second samples were obtained after 6 months on the HDF protocol. Results indicate that moving to online HDF therapy produce a significant reduction of the basal levels of genetic damage, but does not affect the genomic instability status. In addition, a greater increase in plasma antioxidant capacity was observed. In spite of the lack of correlation between these parameters, our results confirm the usefulness of the online HDF technique as a way to reduce DNA damage in HD patients.

Cytomegalovirus prevention strategies in seropositive kidney transplant recipients: an insight into current clinical practice.

There is notable heterogeneity in the implementation of cytomegalovirus (CMV) prevention practices among CMV-seropositive (R+) kidney transplant (KT) recipients. In this prospective observational study, we included 387 CMV R+ KT recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis or preemptive therapy) were applied according to institutional protocols at each site. The impact on the 12-month incidence of CMV disease was assessed by Cox regression. Asymptomatic CMV infection, acute rejection, graft function, non-CMV infection, graft loss, and all-cause mortality were also analyzed (secondary outcomes). Models were adjusted for a propensity score (PS) analysis for receiving antiviral prophylaxis. Overall, 190 patients (49.1%) received preemptive therapy, 185 (47.8%) antiviral prophylaxis, and 12 (3.1%) no specific intervention. Twelve-month cumulative incidences of CMV disease and asymptomatic infection were 3.6% and 39.3%, respectively. Patients on prophylaxis had lower incidence of CMV disease [PS-adjusted HR (aHR): 0.10; 95% confidence interval (CI): 0.01-0.79] and asymptomatic infection (aHR: 0.46; 95% CI: 0.29-0.72) than those managed preemptively, with no significant differences according to the duration of prophylaxis. All cases of CMV disease in the prophylaxis group occurred after prophylaxis discontinuation. There were no differences in any of the secondary outcomes. In conclusion, antiviral prophylaxis was associated with a lower occurrence of CMV disease in CMV R+ KT recipients, although such benefit should be balanced with the risk of late-onset disease.

Mechanisms of NFATc3 activation by increased superoxide and reduced hydrogen peroxide in pulmonary arterial smooth muscle.

We recently demonstrated increased superoxide (O2(·-)) and decreased H2O2 levels in pulmonary arteries of chronic hypoxia-exposed wild-type and normoxic superoxide dismutase 1 (SOD1) knockout mice. We also showed that this reciprocal change in O2(·-) and H2O2 is associated with elevated activity of nuclear factor of activated T cells isoform c3 (NFATc3) in pulmonary arterial smooth muscle cells (PASMC). This suggests that an imbalance in reactive oxygen species levels is required for NFATc3 activation. However, how such imbalance activates NFATc3 is unknown. This study evaluated the importance of O2(·-) and H2O2 in the regulation of NFATc3 activity. We tested the hypothesis that an increase in O2(·-) enhances actin cytoskeleton dynamics and a decrease in H2O2 enhances intracellular Ca(2+) concentration, contributing to NFATc3 nuclear import and activation in PASMC. We demonstrate that, in PASMC, endothelin-1 increases O2(·-) while decreasing H2O2 production through the decrease in SOD1 activity without affecting SOD protein levels. We further demonstrate that O2(·-) promotes, while H2O2 inhibits, NFATc3 activation in PASMC. Additionally, increased O2(·-)-to-H2O2 ratio activates NFATc3, even in the absence of a Gq protein-coupled receptor agonist. Furthermore, O2(·-)-dependent actin polymerization and low intracellular H2O2 concentration-dependent increases in intracellular Ca(2+) concentration contribute to NFATc3 activation. Together, these studies define important and novel regulatory mechanisms of NFATc3 activation in PASMC by reactive oxygen species.

Cinacalcet for hypercalcaemic secondary hyperparathyroidism after renal transplantation: a multicentre, retrospective, 3-year study.

AIMS: Our aim was to evaluate the long-term effect of cinacalcet in patients with hypercalcaemic secondary hyperparathyroidism (SHPT) after renal transplantation (RT) in order to expand real-world data in this population. METHODS: We performed a multicentre, observational, retrospective study in 17 renal transplant units from Spain. We collected data from renal recipients with hypercalcaemic (calcium >10.2 mg/dL) SHPT (intact parathyroid hormone (iPTH) > 120 pg/mL) who initiated cinacalcet in the clinical practice. RESULTS: We included 193 patients with a mean (standard deviation (SD)) age of 52 (12) years, 58% men. Cinacalcet treatment was initiated at a median of 20 months after RT (median dose 30 mg/day). Mean calcium levels decreased from a mean (SD) of 11.1 (0.6) at baseline to 10.1 (0.8) at 6 months (9.0% reduction, P < 0.0001). Median iPTH was reduced by 23.0% at 6 months (P = 0.0005) and mean phosphorus levels increased by 11.1% (P < 0.0001). The effects were maintained up to 3-years. No changes were observed in renal function or anticalcineurin drug levels. Only 4.1% of patients discontinued cinacalcet due to intolerance and 1.0% due to lack of efficacy. CONCLUSIONS: In renal transplant patients with hypercalcaemic SHPT, cinacalcet controlled serum calcium, iPTH and phosphorus levels up to 3 years. Tolerability was good.

Obesity hypoventilation syndrome, literature review.

Obesity is a global health concern that has been increasing over the years, and it is associated with several pathophysiological changes affecting the respiratory system, including alveolar hypoventilation. Obesity hypoventilation syndrome (OHS) is one of the six subtypes of sleep-hypoventilation disorders. It is defined as the presence of obesity, chronic alveolar hypoventilation leading to daytime hypercapnia and hypoxia, and sleep-disordered breathing. The existence of a sleep disorder is one of the characteristics that patients with OHS present. Among them, 90% of patients have obstructive sleep apnea (OSA), and the remaining 10% of patients with OHS have non-obstructive sleep hypoventilation without OSA or with mild OSA. This review aims to provide a comprehensive understanding of the epidemiological and pathophysiological impact of OHS and to highlight its clinical features, prognosis, and severity, as well as the available treatment options.

Usual interstitial pneumopathy in a patient with hypersensitivity pneumonitis and microscopic polyangiitis. Case report.

One of the most frequent diffuse interstitial lung diseases is hypersensitivity pneumonitis. It is related to exposure to diverse antigens, causing fibrosis in advanced stages, making the differential diagnosis with interstitial pulmonary fibrosis difficult as it overlaps with the usual interstitial pneumonia pattern. On the other hand, there are interstitial lung diseases associated with ANCA, such as microscopic polyangiitis, which is also related to the usual interstitial pneumonia pattern. We present the case of a 74-year-old male patient with chronic dyspnea, history of smoking and exposure to organic particles, in addition to a pattern suggestive of moderately severe restriction. The diagnosis was confirmed by histology of hypersensitivity pneumonitis by presenting granules, however, anti MPO and p-ANCA positivity was found, integrating the simultaneous diagnosis of microscopic polyangiitis. This is a case of difficult diagnosis since these pathologies have not been previously reported to coexist.

NFAT is required for spontaneous pulmonary hypertension in superoxide dismutase 1 knockout mice.

Elevated reactive oxygen species are implicated in pulmonary hypertension (PH). Superoxide dismutase (SOD) limits superoxide bioavailability, and decreased SOD activity is associated with PH. A decrease in SOD activity is expected to increase superoxide and reduce hydrogen peroxide levels. Such an imbalance of superoxide/hydrogen peroxide has been implicated as a mediator of nuclear factor of activated T cells (NFAT) activation in epidermal cells. We have shown that NFATc3 is required for chronic hypoxia-induced PH. However, it is unknown whether NFATc3 is activated in the pulmonary circulation in a mouse model of decreased SOD1 activity and whether this leads to PH. Therefore, we hypothesized that an elevated pulmonary arterial superoxide/hydrogen peroxide ratio activates NFATc3, leading to PH. We found that SOD1 knockout (KO) mice have elevated pulmonary arterial wall superoxide and decreased hydrogen peroxide levels compared with wild-type (WT) littermates. Right ventricular systolic pressure (RVSP) was elevated in SOD1 KO and was associated with pulmonary arterial remodeling. Vasoreactivity to endothelin-1 was also greater in SOD1 KO vs. WT mice. NFAT activity and NFATc3 nuclear localization were increased in pulmonary arteries from SOD1 KO vs. WT mice. Administration of A-285222 (selective NFAT inhibitor) decreased RVSP, arterial wall thickness, vasoreactivity, and NFAT activity in SOD1 KO mice to WT levels. The SOD mimetic, tempol, also reduced NFAT activity, NFATc3 nuclear localization, and RVSP to WT levels. These findings suggest that an elevated superoxide/hydrogen peroxide ratio activates NFAT in pulmonary arteries, which induces vascular remodeling and increases vascular reactivity leading to PH.

Genomic damage as an independent predictor marker of mortality in hemodialysis patients.

AIM: Hemodialysis (HD) patients present an enhanced mortality. Since oxidative DNA damage can be considered a biomarker of genomic instability our aim was to evaluate the influence of this genetic biomarker in all-cause mortality in a group of HD patients followed for 4 years. MATERIAL AND METHODS: 123 chronic HD patients were included. Overall genomic damage was analyzed using the Comet assay. Oxidative DNA damage was measured using the Comet assay complemented with the use of Endo-III and FPG enzymes. Follow-up was carried out from January 2007 to July 2011. RESULTS: Selected HD patients had a mean age of 62 ± 15 years. During the follow-up 36% of patients died (48% due to cardiovascular disease) and 23% were transplanted. Older patients, with high CRP levels, low levels of cholesterol-HDL and albumin, and higher genetic damage at the beginning of the study showed an increased risk for mortality. Multivariate analysis showed that only genomic damage, age and CRP were independently associated with mortality. CONCLUSIONS: Our study shows for the first time that, in HD patients, the presence of high levels of genomic damage is a strong predictor of all-cause mortality. This association remains significant after adjustment for relevant covariates.