Comparison of oxidative stress markers in HIV-infected patients on efavirenz or atazanavir/ritonavir-based therapy

INTRODUCTION: Chronic low-grade inflammation and immune activation may persist in HIV patients despite effective antiretroviral therapy (ART). These abnormalities are associated with increased oxidative stress (OS). Bilirubin (BR) may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UGT1A1, thus increasing unconjugated BR levels, a distinctive feature of this drug. We compared changes in OS markers in HIV patients on ATV/r versus efavirenz (EFV)-based first-line therapies. MATERIALS AND METHODS: Cohort of the Spanish Research Network (CoRIS) is a multicentre, open, prospective cohort of HIV-infected patients naïve to ART at entry and linked to a biobank. We identified hepatitis C virus/hepatitis B virus (HCV/HBV) negative patients who started first-line ART with either ATV/r or EFV, had a baseline biobank sample and a follow-up sample after at least nine months of ART while maintaining initial regimen and being virologically suppressed. Lipoprotein-associated Phospholipase A2 (Lp-PLA2), Myeloperoxidase (MPO) and Oxidized LDL (OxLDL) were measured in paired samples. Marker values at one year were interpolated from available data. Multiple imputations using chained equations were used to deal with missing values. Change in the OS markers was modelled using multiple linear regressions adjusting for baseline marker values and baseline confounders. Correlations between continuous variables were explored using Pearson's correlation tests. RESULTS: 145 patients (97 EFV; 48 ATV/r) were studied. Mean (SD) baseline values for OS markers in EFV and ATV/r groups were: Lp-PLA2 [142.2 (72.8) and 150.1 (92.8) ng/mL], MPO [74.3 (48.2) and 93.9 (64.3) µg/L] and OxLDL [76.3 (52.3) and 82.2 (54.4) µg/L]. After adjustment for baseline variables patients on ATV/r had a significant decrease in Lp-PLA2 (estimated difference -16.3 [CI 95%: -31.4, -1.25; p=0.03]) and a significantly lower increase in OxLDL (estimated difference -21.8 [-38.0, -5.6; p<0.01] relative to those on EFV, whereas no differences in MPO were found. Adjusted changes in BR were significantly higher for the ATV/r group (estimated difference 1.33 [1.03, 1.52; p<0.01]). Changes in BR and changes in OS markers were significantly correlated. CONCLUSIONS: In virologically suppressed patients on stable ART, OS was lower in ATV/r-based regimens compared to EFV. We hypothesize these changes could be in part attributable to increased BR plasma levels.S

Late gadolinium enhancement‐MRI determines definite lesion formation most accurately at 3 months post ablation compared to later time points

Aims: Neither the long-term development of ablation lesions nor the capability of late gadolinium enhancement (LGE)-MRI to detect ablation-induced fibrosis at late stages of scar formation have been defined. We sought to assess the development of atrial ablation lesions over time using LGE-MRI and invasive electroanatomical mapping (EAM). Methods and results: Ablation lesions and total atrial fibrosis were assessed in serial LGE-MRI scans 3 months and >12 months post pulmonary vein (PV) isolation. High-density EAM performed in subsequent repeat ablation procedures served as a reference. Serial LGE-MRI of 22 patients were analyzed retrospectively. The PV encircling ablation lines displayed an average LGE, indicative of ablation-induced fibrosis, of 91.7% ± 7.0% of the circumference at 3 months, but only 62.8% ± 25.0% at a median of 28 months post ablation (p 12 months post ablation. Accordingly, the agreement with EAM regarding detection of ablation-induced fibrosis and functional gaps was good for the LGE-MRI at 3 months (κ .74; p < .0001), but only weak for the LGE-MRI at 28 months post-ablation (κ .29; p < .0001). Conclusion: While non-invasive lesion assessment with LGE-MRI 3 months post ablation provides accurate guidance for future redo-procedures, detectability of atrial ablation lesions appears to decrease over time. Thus, it should be considered to perform LGE-MRI 3 months post-ablation rather than at later time-points > 12 months post ablation, like for example, prior to a planned redo-ablation procedure

Ventricular tachycardia burden reduction after substrate ablation: predictors of recurrence.

BACKGROUND Substrate-based ventricular tachycardia (VT) ablation is a first-line treatment in patients with structural cardiac disease and sustained VT refractory to medical therapy. Despite technological improvements and increased knowledge of VT substrate, recurrence still is frequent. Published data are lacking on the possible reduction in VT burden after ablation despite recurrence. OBJECTIVE The purpose of this study was to assess VT burden reduction during long-term follow-up after substrate ablation and identify predictors of VT recurrence. METHODS We analyzed 234 consecutive VT ablation procedures in 207 patients (age 63 6 14.9 years; 92% male; ischemic heart disease in 65%) who underwent substrate ablation in a single center from 2013 to 2018. RESULTS After follow-up of 3.14 6 1.8 years, the VT recurrence rate was 41.4%. Overall, a 99.6% reduction in VT burden (median VT episodes per year: preprocedural 3.546 [1.347-13.951] vs postprocedural 0.001 [0-0.689]; P 5 .001) and a 96.3% decrease in implantable cardioverter-defibrillator (ICD) shocks (preprocedural 1.145 [0.118-4.467] vs postprocedural 0.042 [0-0.111] per year; P 5 .017) were observed. In the subgroup of patients who experienced VT recurrences, VT burden decreased by 69.2% (median VT episodes per year: preprocedural 2.876 [1.105-8.801] vs postprocedural 0.882 [0.505-2.283]; P ,.001). Multivariable analysis showed persistence of late potentials (67% vs 19%; hazard ratio 3.18 [2.18- 6.65]; P ,.001) and lower left ventricular ejection fraction (EF) (30 [25-40] vs 39 [30-50]; P 5 .022) as predictors of VT recurrence. CONCLUSION Despite a high recurrence rate during long-term follow-up, substrate-based VT ablation is related to a large reduction in VT burden and a decrease in ICD therapies. Lower EF and persistence of late potentials are predictors of recurrence. KEYWORDS Arrhythmic burden reduction; Implantable cardioverter-defibrillator shock prevention; Ventricular tachycardia ablation; Ventricular tachycardia recurrence predictors; Ventricular tachycardia storm; Ventricular tachycardia substrate ablatio

Orthogonal high-density mapping with ventricular tachycardia isthmus analysis vs. pure substrate ventricular tachycardia ablation: A case–control study

Substrate-based ablation has become a successful technique for ventricular tachycardia (VT) ablation. High-density (HD) mapping catheters provide high-resolution electroanatomical maps and better discrimination of local abnormal electrograms. The HD Grid Mapping Catheter is an HD catheter with the ability to map orthogonal signals on top of conventional bipolar signals, which could provide better discrimination of the arrhythmic substrate. On the other hand, conventional mapping techniques, such as activation mapping, when possible, help to identify the isthmus of the tachycardia.The purpose of this study was to compare clinical outcomes after using two different VT ablation strategies: one based on extensive mapping with the HD Grid Mapping Catheter, including VT isthmus analysis, and the other based on pure substrate ablation.Forty consecutive patients undergoing VT ablation with extensive HD mapping method in the hospital clinic (November 2018-November 2019) were included. Clinical outcomes were compared with a historical cohort of 26 consecutive patients who underwent ablation using a scar dechanneling technique before 2018.The density of mapping points was higher in the extensive mapping group (2370.24 ± 920.78 vs. 576.45 ± 294.46; p < 0.001). After 1 year of follow-up, VT recurred in 18.4% of patients in the extensive mapping group vs. 34.6% of patients in the historical control group (p = 0.14), with a significantly greater reduction of VT burden: VT episodes (81.7 ± 7.79 vs. 43.4 ± 19.9%, p < 0.05), antitachycardia pacing (99.45 ± 2.29 vs. 33.9 ± 102.5%, p < 0.001), and implantable cardioverter defibrillator (ICD) shocks (99 ± 4.5 vs. 64.7 ± 59.9%, p = 0.02).The use of a method based on extensive mapping with the HD Grid Mapping Catheter and VT isthmus analysis allows better discrimination of the arrhythmic substrate and could be associated with a greater decrease in VT burden.Copyright © 2022 Vázquez-Calvo, Garre, Sanchez-Somonte, Borras, Quinto, Caixal, Pujol-Lopez, Althoff, Guasch, Arbelo, Tolosana, Brugada, Mont and Roca-Luque

Scar channels in cardiac magnetic resonance to predict appropriate therapies in primary prevention.

Background Scar characteristics analyzed by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) are related with ventricular arrhythmias. Current guidelines are based only on the left ventricular ejection fraction to recommend an implantable cardioverter-defibrillator (ICD) in primary prevention. Objectives Our study aims to analyze the role of imaging to stratify arrhythmogenic risk in patients with ICD for primary prevention. Methods From 2006 to 2017, we included 200 patients with LGE-CMR before ICD implantation for primary prevention. The scar, border zone, core, and conducting channels (CCs) were automatically measured by a dedicated software. Results The mean age was 60.9 ± 10.9 years; 81.5% (163) were men; 52% (104) had ischemic cardiomyopathy. The mean left ventricular ejection fraction was 29% ± 10.1%. After a follow-up of 4.6 ± 2 years, 46 patients (22%) reached the primary end point (appropriate ICD therapy). Scar mass (36.2 ± 19 g vs 21.7 ± 10 g; P 10 g (25.31% vs 5.26%; hazard ratio 4.74; P = .034) and the presence of CCs (34.75% vs 8.93%; hazard ratio 4.07; P = .003) were also strongly associated with the primary end point. However, patients without channels and with scar mass < 10 g had a very low rate of appropriate therapies (2.8%). Conclusion Scar characteristics analyzed by LGE-CMR are strong predictors of appropriate therapies in patients with ICD in primary prevention. The absence of channels and scar mass < 10 g can identify patients at a very low risk of ventricular arrhythmias in this population

Progressive and Simultaneous Right and Left Atrial Remodeling Uncovered by a Comprehensive Magnetic Resonance Assessment in Atrial Fibrillation

Background Left atrial structural remodeling contributes to the arrhythmogenic substrate of atrial fibrillation (AF), but the role of the right atrium (RA) remains unknown. Our aims were to comprehensively characterize right atrial structural remodeling in AF and identify right atrial parameters predicting recurrences after ablation. Methods and Results A 3.0 T late gadolinium enhanced-cardiac magnetic resonance was obtained in 109 individuals (9 healthy volunteers, 100 patients with AF undergoing ablation). Right and left atrial volume, surface, and sphericity were quantified. Right atrial global and regional fibrosis burden was assessed with validated thresholds. Patients with AF were systematically followed after ablation for recurrences. Progressive right atrial dilation and an increase in sphericity were observed from healthy volunteers to patients with paroxysmal and persistent AF; fibrosis was similar among the groups. The correlation between parameters recapitulating right atrial remodeling was mild. Subsequently, remodeling in both atria was compared. The RA was larger than the left atrium (LA) in all groups. Fibrosis burden was higher in the LA than in the RA of patients with AF, whereas sphericity was higher in the LA of patients with persistent AF only. Fibrosis, volume, and surface of the RA and LA, but not sphericity, were strongly correlated. Tricuspid regurgitation predicted right atrial volume and shape, whereas diabetes was associated with right atrial fibrosis burden; sex and persistent AF also predicted right atrial volume. Fibrosis in the RA was mostly located in the inferior vena cava-RA junction. Only right atrial sphericity is significantly associated with AF recurrences after ablation (hazard ratio, 1.12 [95% CI, 1.01-1.25]). Conclusions AF progression associates with right atrial remodeling in parallel with the LA. Right atrial sphericity yields prognostic significance after ablation

Non-motor symptom burden in patients with Parkinson's disease with impulse control disorders and compulsive behaviours : results from the COPPADIS cohort

The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Mortality Risk Factors for Individuals Experiencing Homelessness in Catalonia (Spain): A 10-Year Retrospective Cohort Study

Persones sense sostre; Mortalitat: Factors de riscPersonas sin techo; Mortalidad; Factores de riesgoHomelessness; Mortality; Risk factorsCurrent evidence suggests that mortality is considerably higher in individuals experiencing homelessness. The aim of this study was to analyze the mortality rate and the mortality risk factors in a sample of individuals experiencing homelessness in the city of Girona over a ten-year period. (2) Methods: We retrospectively examined the outcomes of 475 people experiencing homelessness with the available clinical and social data. Our sample was comprised of 84.4% men and 51.8% foreign-born people. Cox's proportional hazard models were used to identify mortality risk factors between origin groups. (3) Results: 60 people died during the ten-year period. The average age of death was 49.1 years. After adjusting for demographic characteristics and the duration of homelessness, the risk factors for mortality were origin (people born in Spain) (HR = 4.34; 95% CI = 1.89-10.0), type 2 diabetes (HR = 2.9; 95% CI = 1.62-5.30), alcohol use disorder (HR = 1.9; 95% CI = 1.12-3.29), and infectious diseases (HR = 1.6; 95% CI = 1.09-2.39). Our results show a high prevalence of infectious and chronic diseases. Type 2 diabetes emerges as an important risk factor in homelessness. The average age of death of individuals experiencing homelessness was significantly lower than the average age of death in the general population (which is greater than 80 years). Foreign-born homeless people were generally younger and healthier than Spanish-born homeless people. Chronic diseases were controlled better in Spanish-born people, but this group showed an increased risk of mortality

Gut microbiota profiles in feces and paired tumor and non-tumor tissues from Colorectal Cancer patients. Relationship to the Body Mass Index.

Colorectal Cancer (CRC) and Obesity constitute two of the most common malignancies in the western world, and previously have been associated with intestinal microbial composition alterations. Our main aim in this study is to provide molecular data on intestinal microbiota patterns in subjects with CRC, as well as to establish possible associations with their Body Mass Index (BMI). A total of 113 samples from 45 subjects were collected and submitted to metagenomics analysis for gut microbiota. This study was performed by 16S ribosomal RNA bacterial gene amplification and sequencing using the Ion Torrent™ technology. The same dominant phyla were observed in feces and colorectal tissues, although a greater proportion of Fusobacteriota was found in tumor samples. Moreover, at the genus level, LEfSe analysis allowed us to detect a significant increase in Fusobacterium and Streptococcus in colorectal tissues with respect to fecal samples, with a significant preponderance of Fusobacterium in tumor tissues. Also, our data revealed relevant associations between gut microbiota composition and tumor location. When comparing bacterial profiles between right and left colon cancers, those from the left-sided colon showed a significant preponderance, among others, of the order Staphylococcales. Moreover, phyla Firmicutes and Spirochaetota were more abundant in the group of right-sided CRCs and phylum Proteobacteria was increased in rectal cancers. In relation to BMI of patients, we detected significant differences in beta diversity between the normal weight and the obese groups of cases. Microbiota from obese patients was significantly enriched, among others, in Bacteroidales. Therefore, our results are useful in the molecular characterization of CRC in obese and non-obese patients, with a clear impact on the establishment of diagnostic and prognosis of CRC