Nevin Manimala

J Lipid Res. 2023 May 19:100391. doi: 10.1016/j.jlr.2023.100391. Online ahead of print.

ABSTRACT

Immunoglobulin M (IgM) autoantibodies to oxidation-specific epitopes (OSE) can be present at birth and protect against atherosclerosis in experimental models. This study sought to determine whether high titers of IgM titers to OSE (IgM OSE) are associated with lower risk of acute myocardial infarction (AMI) in humans. IgM to malondialdehyde-low density lipoprotein (MDA-LDL), phosphocholine-modified bovine serum albumin (PC-BSA), IgM apolipoprotein B100-immune complexes (ApoB-IC) and a peptide mimotope of malondialdehyde (MDA) were measured within 24 hours of first AMI in 4559 patients and 4617 age and sex-matched controls in the Pakistan Risk of Myocardial Infarction Study. Adjustment was made for sex, age, smoking, hypertension, diabetes, LDL-C, HDL-C, and triglycerides. Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (95% CI) for AMI. All four IgM OSE were lower in AMI versus controls (p<0.001 for all). Males, smokers and individuals with hypertension and diabetes had lower levels of all 4 IgM OSE compared to unaffected individuals (p<0.001 for all). Compared to the lowest quintile, the highest quintiles of IgM MDA-LDL, PC-BSA, ApoB-IC, and MDA mimotope P1 had lower OR of AMI: OR (95% (CI)] of 0.67 (0.58-0.77), 0.64 (0.56-0.73), 0.70 (0.61-0.80) and 0.72 (0.62-0.82) (p<0.001 for all], respectively. Upon addition of IgM OSE to conventional risk factors, the C-statistic improved by 0.0062 (0.0028-0.0095) and net reclassification by 15.5% (11.4-19.6). These findings demonstrate that IgM OSE provide clinically meaningful information and support the hypothesis that higher levels of IgM OSE may be protective against AMI.

PMID:37211249 | DOI:10.1016/j.jlr.2023.100391

J Cardiol. 2023 May 19:S0914-5087(23)00112-0. doi: 10.1016/j.jjcc.2023.05.006. Online ahead of print.

ABSTRACT

BACKGROUND: Despite optimal treatment, a residual inflammatory risk often remains in patients with atherosclerotic cardiovascular disease. In a US-based phase 2 trial, ziltivekimab, a fully human monoclonal antibody targeting the interleukin-6 ligand, significantly reduced biomarkers of inflammation compared with placebo in patients at high atherosclerotic risk. Here, we report the efficacy and safety of ziltivekimab in Japanese patients.

METHODS: RESCUE-2 was a randomized, double-blind, 12-week, phase 2 trial. Participants aged ≥20 years with stage 3-5 non-dialysis-dependent chronic kidney disease and high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L were randomized to receive placebo (n = 13) or subcutaneous ziltivekimab 15 mg (n = 11) or 30 mg (n = 12) at Weeks 0, 4, and 8. The primary endpoint was percentage change in hsCRP levels from baseline to end of treatment (EOT; mean of Week 10 and Week 12 values).

RESULTS: At EOT, median hsCRP levels were reduced by 96.2 % in the 15 mg group (p < 0.0001 versus placebo), by 93.4 % in the 30 mg group (p = 0.002 versus placebo), and by 27.0 % in the placebo group. Serum amyloid A and fibrinogen levels were also reduced significantly. Ziltivekimab was well tolerated and did not affect total cholesterol to high-density lipoprotein cholesterol ratios. There was a small, but statistically significant increase in triglyceride levels with ziltivekimab 15 mg and 30 mg compared with placebo.

CONCLUSIONS: The efficacy and safety results support the development of ziltivekimab for secondary prevention and the treatment of patients at high atherosclerotic risk.

CLINICALTRIALS: gov identifier, NCT04626505.

PMID:37211246 | DOI:10.1016/j.jjcc.2023.05.006

Resuscitation. 2023 May 19:109847. doi: 10.1016/j.resuscitation.2023.109847. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of this study was to develop a risk adjustment strategy, including effect modifiers, for benchmarking emergency medical service (EMS) performance for out-of-hospital cardiac arrest (OHCA) in Australia and New Zealand.

METHOD: Using 2017-2019 data from the Australasian Resuscitation Outcomes Consortium (Aus-ROC) OHCA Epistry, we included adults who received an EMS attempted resuscitation for a presumed medical OHCA. Logistic regression was applied to develop risk adjustment models for event survival (return of spontaneous circulation at hospital handover) and survival to hospital discharge/30 days. We examined potential effect modifiers, and assessed model discrimination and validity.

RESULTS: Both OHCA survival outcome models included EMS agency and the Utstein variables (age, sex, location of arrest, witnessed arrest, initial rhythm, bystander cardiopulmonary resuscitation, defibrillation prior to EMS arrival, and EMS response time). The model for event survival had good discrimination according to the concordance statistic (0.77) and explained 28% of the variation in survival. The corresponding figures for survival to hospital discharge/30 days were 0.87 and 49%. The addition of effect modifiers did little to improve the performance of either model.

CONCLUSION: The development of risk adjustment models with good discrimination is an important step in benchmarking EMS performance for OHCA. The Utstein variables are important in risk-adjustment, but only explain a small proportion of the variation in survival. Further research is required to understand what factors contribute to the variation in survival between EMS.

PMID:37211232 | DOI:10.1016/j.resuscitation.2023.109847

Environ Pollut. 2023 May 19:121855. doi: 10.1016/j.envpol.2023.121855. Online ahead of print.

ABSTRACT

Coke oven emissions (COEs) exposure leads to oxidative stress, an imbalance between oxidant production and antioxidant defence in the body, which then leads to shortened relative telomere length (RTL) and reduced mitochondrial DNA copy number (mtDNAcn), ultimately leading to ageing and disease. By analysing the relationship among COEs, oxidative stress, RTL and mtDNAcn, we investigated the chain-mediating effects of oxidative stress and telomeres on mitochondrial damage and mitochondria on telomere damage in coke oven workers. A total of 779 subjects were included in the study. Cumulative COEs exposure concentrations were estimated, and the RTL and mtDNAcn of peripheral blood leukocytes were measured using real-time fluorescence quantitative PCR. Total antioxidant capacity (T-AOC) was measured to reflect the level of oxidative stress. The data were statistically analysed using SPSS 21.0 software and discussed using mediation effect analysis. After adjusting for age, sex, smoking, drinking and BMI, generalised linear model revealed dose-response associations between COEs and T-AOC, RTL and mtDNAcn, respectively. (P_trend < 0.05). The results of chain-mediating effect showed that the proportion of the chain-mediating effect of “CED-COEs→T-AOC→ RTL→mtDNAcn” was 0.82% (β = -0.0005, 95% CI = [-0.0012, -0.0001]), and the proportion of the chain-mediating effect of “CED-COEs→T-AOC→ mtDNAcn → RTL ″ was 2.64% (β = -0.0013, 95% CI = [-0.0025, -0.0004]). After oxidative stress is induced by COEs, mitochondria and telomeres may interact with each other while leading further to potential bodily damage. This study provides clues to explore the association between mitochondria and telomeres.

PMID:37211230 | DOI:10.1016/j.envpol.2023.121855

Anaesth Crit Care Pain Med. 2023 May 19:101247. doi: 10.1016/j.accpm.2023.101247. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Brachiocephalic vein is a novel site for central venous cannulation in infants. It becomes useful in patients where the internal jugular vein lumen is small (e.g., volume deficient patient), patients with a history of multiple cannulations, and in whom subclavian puncture is contraindicated.

METHODS: In this randomized double-blinded study, 100 patients, aged between 0 and 1 year scheduled for elective central venous cannulation were recruited. The patients were allocated into two groups (50 patients in each). Group I patients had ultrasound (US) guided cannulation of the left brachiocephalic vein (BCV) by inserting a needle in-plane to the US probe from lateral to the medial direction, whereas Group II patients underwent cannulation of the BCV via an out-of-plane approach.

RESULTS: The first-attempt success rate was significantly higher in Group I (74%) than in Group II (36%) (p < 0.001). The total success rate was higher in group I (98%) than in group II (88%) however the difference was statistically insignificant (p > 0.05). The mean BCV cannulation time was significantly shorter in group I (35.46 ± 25.10) than in group II (65.24 ± 40.26) (p < 0.001). The rate of unsuccessful BCV cannulation (12%) and hematoma development (12%) was significantly higher in group II than in group I (2%).

CONCLUSION: Compared to the out-of-plane approach of left BCV cannulation, US-guided in-plane cannulation of the left BCV increased the first-attempt success rate, decreased the number of puncture attempts, and decreased the time required for cannulation.

PMID:37211216 | DOI:10.1016/j.accpm.2023.101247

Prog Cardiovasc Dis. 2023 May 19:S0033-0620(23)00053-1. doi: 10.1016/j.pcad.2023.05.005. Online ahead of print.

ABSTRACT

BACKGROUND: Dyspnea and fatigue are characteristics of long SARS-CoV-2 (COVID)-19. Cardiopulmonary exercise testing (CPET) can be used to better evaluate such patients.

RESEARCH QUESTION: How significantly and by what mechanisms is exercise capacity impaired in patients with long COVID who are coming to a specialized clinic for evaluation?

STUDY DESIGN AND METHODS: We performed a cohort study using the Mayo Clinic exercise testing database. Subjects included consecutive long COVID patients without prior history of heart or lung disease sent from the Post-COVID Care Clinic for CPET. They were compared to a historical group of non-COVID patients with undifferentiated dyspnea also without known cardiac or pulmonary disease. Statistical comparisons were performed by t-test or Pearson’s chi² test controlling for age, sex, and beta blocker use where appropriate.

RESULTS: We found 77 patients with long COVID and 766 control patients. Long COVID patients were younger (47 ± 15 vs 50 ± 10 years, P < .01) and more likely female (70% vs 58%, P < .01). The most prominent difference on CPETs was lower percent predicted peak V̇O₂ (73 ± 18 vs 85 ± 23%, p < .0001). Autonomic abnormalities (resting tachycardia, CNS changes, low systolic blood pressure) were seen during CPET more commonly in long COVID patients (34 vs 23%, P < .04), while mild pulmonary abnormalities (mild desaturation, limited breathing reserve, elevated V̇_E/V̇CO₂) during CPET were similar (19% in both groups) with only 1 long COVID patient showing severe impairment.

INTERPRETATION: We identified severe exercise limitation among long COVID patients. Young women may be at higher risk for these complications. Though mild pulmonary and autonomic impairment were common in long COVID patients, marked limitations were uncommon. We hope our observations help to untangle the physiologic abnormalities responsible for the symptomatology of long COVID.

PMID:37211198 | DOI:10.1016/j.pcad.2023.05.005

Environ Res. 2023 May 19:116191. doi: 10.1016/j.envres.2023.116191. Online ahead of print.

ABSTRACT

Polycyclic aromatic hydrocharbons (PAHs) are a class of highly toxic pollutants that are highly detrimental to the ecosystem. Landfill leechate emanated from municipal solid waste are reported to constitute significant PAHs. In the present investigation, three Fenton proceses, namely conventional Fenton, photo-fenton and electro-fenton methods have been employed to treat landfill leehcate for removing PAHs from a waste dumpig yard. Response surface methodology (RSM) and artificial neural network (ANN) methodologies were adopted to optimize and validate the conditions for optimum oxidative removal of COD and PAHs. The statistical analysis results showed that all independent variables chosen in the study are reported to have significant influence of the removal effects with P-values <0.05. Sensitivity analysis by the developed ANN model showed that the pH had the highest significance of 1.89 in PAH removal when compared to the other parameters. However for COD removal, H₂O₂ had the highest relative importance of 1.15, followed by Fe²⁺ and pH. Under optimal treatment conditions, the photo-fenton and electro-fenton processes showed better removal of COD and PAH compared to the Fenton process. The photo-fenton and electro-fenton treatment processes removed 85.32% and 74.64% of COD and 93.25% and 81.65% of PAHs, respectively. Also the investigations revelaed the presence of 16 distinct PAH compunds and the removal percentage of each of these PAHs are also reported. The PAH treatment research studies are generally limited to the assay of removal of PAH and COD levels. In the present investigation, in addition to the treatment of landfill leachate, particle size distribution analysis and elemental characterization of the resultant iron sludge by FESEM and EDX are reported. It was revealed that elemental oxygen is present in highest percentage, followed by iron, sulphur, sodium, chlorine, carbon and potassium. However, iron percentage can be reduced by treating the Fenton-treated sample with NaOH.

PMID:37211185 | DOI:10.1016/j.envres.2023.116191

Environ Res. 2023 May 19:116202. doi: 10.1016/j.envres.2023.116202. Online ahead of print.

ABSTRACT

Understanding the community assembly process is a central issue in microbial ecology. In this study, we analyzed the community assembly of particle-associated (PA) and free-living (FL) surface water microbiomes in 54 sites from the headstream to the river mouth of an urban river in Japan, the river basin of which has the highest human population density in the country. Analyses were conducted from two perspectives: (1) analysis of deterministic processes considering only environmental factors using a geo-multi-omics dataset and (2) analysis of deterministic and stochastic processes to estimate the contributions of heterogeneous selection (HeS), homogeneous selection (HoS), dispersal limitation (DL), homogenizing dispersal (HD), and drift (DR) as community assembly processes using a phylogenetic bin-based null model. The variation in microbiomes was successfully explained from a deterministic perspective by environmental factors, such as organic matter-related, nitrogen metabolism, and salinity-related parameters, using multivariate statistical analysis, network analysis, and habitat prediction. In addition, we demonstrated the dominance of stochastic processes (DL, HD, and DR) over deterministic processes (HeS and HoS) in community assembly from both deterministic and stochastic perspectives. Our analysis revealed that as the distance between two sites increased, the effect of HoS sharply decreased while the effect of HeS increased, particularly between upstream and estuary sites, indicating that the salinity gradient could potentially enhance the contribution of HeS to community assembly. Our study highlights the importance of both stochastic and deterministic processes in community assembly of PA and FL surface water microbiomes in urban riverine ecosystems.

PMID:37211183 | DOI:10.1016/j.envres.2023.116202

J Vasc Surg. 2023 May 19:S0741-5214(23)01251-X. doi: 10.1016/j.jvs.2023.05.023. Online ahead of print.

ABSTRACT

OBJECTIVES: The outcomes of patients with premature cerebrovascular disease (age ≤ 55 years) who undergo carotid artery stenting are not well defined. Our study objective was to analyze the outcomes of younger patients undergoing carotid stenting.

METHODS: The SVS VQI was queried for transfemoral carotid artery stenting (TF-CAS) and transcarotid artery revascularization (TCAR) between 2016-2020. Patients were stratified based on age ≤ 55 or > 55 years. Primary endpoints were periprocedural stroke, death, myocardial infarction (MI), and composite outcomes. Secondary endpoints included procedural failure (defined as ipsilateral restenosis ≥80% or occlusion) and reintervention rates.

RESULTS: Of the 35,802 patients who underwent either TF-CAS or TCAR, 2912 (6.1%) were ≤ 55 years. Younger patients were less likely than older patients to have coronary disease (30.5% vs 50.2%, p <.001), diabetes (31.5% vs 37.9%, p < .001) and hypertension (71.8% vs 89.8%, p <.001), but were more likely to be female (45% vs 35.4%, p <.001) and active smokers (50.9% vs 24.0%, p< .001) Younger patients were also more likely to have had a prior transient ischemic attack (TIA) or stroke than older patients (70.7% vs 56.9%, p <.001). TF-CAS was more frequently performed in younger patients (79.7% vs 55.4%, p <.001). In the periprocedural period, younger patients were less likely to have a MI than older patients (0.3% vs, 0.7%, p<.001), but there was no significant difference in the rates of periprocedural stroke (1.5% vs. 2.0%, p = .173) and composite outcomes of stroke/death (2.6% vs 2.7%, p =.686) and stroke/death/MI (2.9% vs 3.2%, p = .353) between our two cohorts. The mean follow-up was 12 months regardless of age. During follow up, younger patients were significantly more likely to experience significant (≥ 80%) restenosis or occlusion (4.7% vs. 2.3%, p= .001) and to undergo reintervention (3.3% vs. 1.7%, p< .001). However, there was no statistical difference in the frequency of late strokes between younger and older patients (3.8% vs. 3.2%, p = .129).

CONCLUSIONS: Patients with premature cerebrovascular disease undergoing carotid artery stenting are more likely to be African American, female, and active smokers than their older counterparts. Young patients are also more likely to present symptomatically. Although periprocedural outcomes are similar, younger patients have higher rates of procedural failure (significant restenosis or occlusion) and reintervention at 1 year follow-up. However, the clinical implication of late procedural failure is unknown given that we found no significant difference in the rate of stroke at follow-up. Until further longitudinal studies are completed, clinicians should carefully consider the indications for carotid stenting in patients with premature cerebrovascular disease, and those who do undergo stenting may require close follow-up given.

PMID:37211144 | DOI:10.1016/j.jvs.2023.05.023

Am J Ophthalmol. 2023 May 19:S0002-9394(23)00206-4. doi: 10.1016/j.ajo.2023.05.014. Online ahead of print.

ABSTRACT

PURPOSE: To systematically assess the ability-to-detect-change and retest-reliability for a panel of visual function assessments in ABCA4-retinopathy DESIGN: Prospective natural-history study (NCT01736293) METHODS: ss SETTING: Tertiary referral center STUDY POPULATION: Patients with at least one documented pathogenic ABCA4 variant and a clinical phenotype consistent with ABCA4-retinopathy OBSERVATION PROCEDURES: Participants underwent longitudinal, multifaceted functional testing, including measures of function at fixation (best-corrected visual acuity, low-vision Cambridge Color Test [LvCCT]), macular function (microperimetry), and retina-wide function (full-field electroretinography (ERG)).

MAIN OUTCOME MEASURES: Two- and five-year ability-to-detect-change based on the Eta-squared statistic RESULTS: A total of 134 eyes from 67 participants with a mean follow-up of 3.65 years were included. In the two-year interval, the microperimetry-derived peri-lesional sensitivity (η² of 0.73 [0.53, 0.83]; -1.79 dB/yr [-2.2, -1.37]) and mean sensitivity (η² of 0.62 [0.38, 0.76]; -1.28 dB/yr [-1.67, -0.89]) showed most change over time, but could only be recorded in 71.6 % of the participants. In the five-year interval, the dark-adapted ERG a- and b-wave amplitude showed marked change-over-time as well (e.g., DA 30 a-wave amplitude with an η² of 0.54 [0.34, 0.68]; -0.02 Log10(µV)/yr [-0.02, -0.01]). The genotype explained a large fraction of variability in the ERG-based age-of-disease-initiation (adj. R² of 0.73) CONCLUSIONS AND RELEVANCE: Microperimetry-based clinical outcome assessments were most sensitive to change but could only be acquired in a subset of participants. Across a 5-year interval, the ERG DA 30 a-wave amplitude was sensitive to disease progression, potentially allowing for more inclusive clinical trial designs encompassing the whole ABCA4-retinopathy spectrum.

PMID:37211138 | DOI:10.1016/j.ajo.2023.05.014