Correlates of urinary excretion of catechols in humans

An endogenous system involving renal uptake of dihydroxyphenylalanine (DOPA) and conversion to the natriuretic catecholamine,:dopamine (DA), may participate in sodium homeostasis. Normal values for and correlates of urinary excretion of free (unconjugated) catechols in humans are incompletely understood. Daily excretion rates of DOPA, DA, the DA metabolite dihydroxyphenylacetic acid (DOPAC), the sympathetic neurotransmitter norepinephrine (NE), the NE metabolite dihydroxyphenylglycol (DHPG), and the adrenomedullary hormone epinephrine (EPI) were measured in 70 American normotensive volunteers of different ages, sex, and race, and 35 Israeli Caucasian males in their sixth decade, with no dietary or activity restrictions. In both groups, the excretion rate of DOPAC (overall mean 12.53 ± 1.08 (SEM) μmoles/day) exceeded by far those of all other catechols combined. Catechol excretion rates were positively inter-correlated in both subject groups - especially DA with DOPA (r=0.71 across all subjects, p\u3c0.001). Excretion rates of catechols were also positively correlated with the excretion rate of sodium in both groups (for DOPA r=0.70 across all subjects, p\u3c0.001; for DA r=0.54, p\u3c0.001; for DOPAC r=0.46, p\u3c0.001; for NE r=0.47, p\u3c0.001; and for EPI r=0.29, p\u3c0.01), but not with urine volume. DA and DOPA excretion rates were higher in Black Americans than in Caucasian Americans (2.50 ± (SEM) 0.19 vs 1.86 ± 0.10 μmoles/d, p\u3c0.01; 0.21 ± 0.02 vs 0.16 ± 0.01 μmoles/d. p\u3c0.01); DA excretion decreased with increasing subject age (r=-0.24); and excretion rates of DOPA were negatively correlated with MAP (r=-0.33, p\u3c0.01). The high rate of urinary excretion of DOPAC probably mainly reflects glomerular filtration or tubular secretion of plasma DOPAC. The multiple positive correlations among excretion rates of catechols indicate a common source, such as coupled synthesis and turnover of catecholamines in the sympathoadrenal system. Positive correlations of excretion rates of DOPA, DA, and DOPAC with ad libitum dietary salt intake are consistent with salt-induced activation of a renal DOPA-DA natnuretic system

A Five-Decade Text Mining Analysis of Cochlear Implant Research: Where We Started and Where We Are Heading

Background and Objectives: Since its invention in the 1970s, the cochlear implant (CI) has been substantially developed. We aimed to assess the trends in the published literature to characterize CI. Materials and Methods: We queried PubMed for all CI-related entries published during 1970–2022. The following data were extracted: year of publication, publishing journal, title, keywords, and abstract text. Search terms belonged to the patient’s age group, etiology for hearing loss, indications for CI, and surgical methodological advancement. Annual trends of publications were plotted. The slopes of publication trends were calculated by fitting regression lines to the yearly number of publications. Results: Overall, 19,428 CIs articles were identified. Pediatric-related CI was the most dominant sub-population among the age groups, with the highest rate and slope during the years (slope 5.2 ± 0.3, p p p Conclusions: Publications regarding CI among pediatrics outnumbered all other indications, supporting the rising, pivotal role of CI in the rehabilitation of children with sensorineural hearing loss. Hearing-preservation publications have recently rapidly risen, identified as the primary trend of the current era, followed by a sharp rise of robotic surgery that is evolving and could define the next revolution

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Background: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402