Does quantification of [11C]meta-hydroxyephedrine and [13N]ammonia kinetics improve risk stratification in ischemic cardiomyopathy.

BACKGROUND: In ischemic cardiomyopathy patients, cardiac sympathetic nervous system dysfunction is a predictor of sudden cardiac arrest (SCA). This study compared abnormal innervation and perfusion measured by [11C]meta-hydroxyephedrine (HED) vs [13N]ammonia (NH3), conventional uptake vs parametric tracer analysis, and their SCA risk discrimination. METHODS: This is a sub-study analysis of the prospective PAREPET trial, which followed ischemic cardiomyopathy patients with reduced left ventricular ejection fraction (LVEF ≤ 35%) for events of SCA. Using n = 174 paired dynamic HED and NH3 positron emission tomography (PET) scans, regional defect scores (%LV extent × severity) were calculated using HED and NH3 uptake, as well as HED distribution volume and NH3 myocardial blood flow by kinetic modeling. RESULTS: During 4.1 years follow-up, there were 27 SCA events. HED defects were larger than NH3, especially in the lowest tertile of perfusion abnormality (P < .001). Parametric defects were larger than their respective tracer uptake defects (P < .001). SCA risk discrimination was not significantly improved with parametric or uptake mismatch (AUC = 0.73 or 0.70) compared to HED uptake defect scores (AUC = 0.67). CONCLUSION: Quantification of HED distribution volume and NH3 myocardial blood flow produced larger defects than their respective measures of tracer uptake, but did not lead to improved SCA risk stratification vs HED uptake alone.

Reproducible Quantification of Regional Sympathetic Denervation with [11C]meta-Hydroxyephedrine PET Imaging.

BACKGROUND: Regional cardiac sympathetic denervation is predictive of sudden cardiac arrest in patients with ischemic cardiomyopathy. The reproducibility of denervation scores between automated software programs has not been evaluated. This study seeks to (1) compare the inter-rater reliability of regional denervation measurements using two analysis programs: FlowQuant® and Corridor4DM®; (2) evaluate test-retest repeatability of regional denervation scores. METHODS: N = 190 dynamic [11C]meta-hydroxyephedrine (HED) PET scans were reviewed from the PAREPET trial in ischemic cardiomyopathy patients with reduced left ventricular ejection fraction(LVEF ≤ 35%). N = 12 scans were excluded due to non-diagnostic quality. N = 178 scans were analyzed using FlowQuant and Corridor4DM software, each by two observers. Test-retest scans from N = 20 patients with stable heart failure were utilized for test-retest analysis. Denervation scores were defined as extent × severity of relative uptake defects in LV regions with < 75% of maximal uptake. Results were evaluated using intraclass correlation coefficient (ICC) and Bland-Altman coefficient of repeatability (RPC). RESULTS: Inter-observer, inter-software, and test-retest ICC values were excellent (ICC = 94% to 99%) and measurement variability was small (RPC < 11%). Mean differences between observers ranged .2% to 1.1% for Corridor4DM (P = .28), FlowQuant (P < .001), and between software programs (P < .001). Kaplan-Meier analysis demonstrated HED scores from both programs were predictive of SCA. CONCLUSION: Inter-rater reliability for both analysis programs was excellent and test-retest repeatability was consistent. The minimal difference in scores between FlowQuant and Corridor4DM supports their use in future trials.

Race-Based Pulmonary Function Testing Correction in COPD Inhaler Therapy Trials: A Systematic Review.

Purpose: Race-based correction is widely utilized in clinical practice, but may contribute to overestimation of lung function, underdiagnoses in minority groups, and exclusion of minority groups from research trials. The aim of this systematic review is to examine the usage of race-based correction in pulmonary function testing (PFT) within chronic obstructive lung disease (COPD) research and its impact on the exclusion of minority groups from research trials. Methods: We systematically searched Medline from 2010 to 2022 to identify randomized controlled trials (RCTs) that examine inhaler therapy for COPD. Article screening, critical appraisal, and data extraction were completed in duplicate by independent reviewers. Data regarding study design, inclusion criteria, demographics, and race-based correction were extracted and synthesized narratively. Results: Of the 774 screened articles, we included 21 RCTs in the review, which were multinational trials involving 70696 study participants. All studies had an inclusion criteria of an FEV1 cutoff of 50% to 80%. Racial minorities remained underrepresented in the trials, with the proportion of black participants ranging from <1% to 4.7%. Four studies directly mentioned race-based correction, while the remainder of the studies did not provide any explicit details. After obtaining additional information by contacting authors and reviewing the citations, 15 were estimated to utilize race-based correction. Conclusion: Race-based correction may be frequently utilized in major COPD RCTs, but there remains inconsistent reporting regarding the usage of race-based correction. This may contribute to the exclusion of racialized populations from research trials as there remains significant underrepresentation of racialized populations from research.

An approach for the evaluation of synergy between antimicrobials.

Synergy can be assessed by a variety of microbiological techniques. Mathematical modelling of synergy data can accomplish similar results and may provide more information than currently available techniques. In this study a combination of 1/4 MIC of aztreonam (AZTR) and 1 MIC of ciprofloxacin (CIPX) showed synergy against Pseudomonas aeruginosa in killing curve studies (based on the two log different criteria) at the end of 24 h. However, re-growth was always observed even when bactericidal concentrations of antibiotics were present. The surviving organisms showed a two-fold increase of MIC to CIPX after the studies and this resistance was not reversible. A mathematical model to quantitatively describe this observation is proposed.