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Background Illicit drug use may accelerate coronary disease and cardiac hypertrophy or stimulate arrhythmias. Rates of illicit drug use in young sudden cardiac death (SCD) patients are uncertain. Purpose To identify rates of illicit drug use in young SCD patients in Australia. Methods A prospective multi-centre registry identified out of hospital cardiac arrest (OHCA) patients aged 1–50 years between April 2019 and April 2020. Clinical characteristics were compared between patients with and without illicit drug use (defined by toxicological results or reported regular use). Illicit drugs included stimulants such as amphetamine-type substances and cocaine, or non-stimulants such as heroin, cannabis and novel psychoactive substances (cathinones and synthetic cannabinoids). Results 770 OHCAs occurred, with 555 patients undergoing forensic assessment. 287 patients had confirmed cardiac cause of OHCA, with 274 undergoing toxicological assessment and 79 (28.8%) having positive toxicology for illicit drugs (n=60) or reported regular drug use (n=19). An additional 121 patients experienced non-cardiac SCD due to illicit drug toxicity, resulting in a total of 200 patients (36.0% of OHCAs) with illicit drug use. Patients with SCD and illicit drug use were more commonly male (86.1% vs 72.3%, p=0.015), regular smokers (36.7% vs 21.5%, p=0.009), had cardiomegaly (76.5% vs 57.5%, p=0.007), and higher rates of coronary disease and cardiomyopathy (coronary disease 44.3% vs 33.3%, cardiomyopathy 30.4% vs 18.5%, p=0.003). Methamphetamines (n=42, 53.1%) were the most common illicit drug identified and polysubstance abuse occurred frequently (n=15, 19.0%). Conclusion Approximately one-third of young SCD patients use illicit drugs, with high rates of polysubstance abuse. Illicit drug use in SCD patients is associated with coronary disease and cardiomyopathy. Funding Acknowledgement Type of funding sources: None.

Methamphetamines are illicit drugs of the amphetamine-type stimulant class that have been increasing in popularity, availability, and purity in recent decades. As a result, rates of methamphetamine-associated cardiomyopathy (MAC) are rising globally. MAC is associated with high rates of sudden cardiac arrest, late presentation, and poor outcomes. This review discusses the medical management of MAC, including anticipated challenges specific to methamphetamine users. Not only are patients with MAC more likely to present at a younger age and with multisystem disease than patients with cardiomyopathy of other etiologies, but there may also be significant behavioral, psychosocial, financial, and system-based challenges to providing the best medical care. An individualized treatment plan that emphasizes methamphetamine abstinence as the foundation of therapy, as well as introducing optimal heart failure therapy and providing multidisciplinary support is likely to result in optimal outcomes. Given the potential reversibility of MAC, institution of guideline-directed heart failure therapy and patient support for adherence to therapy and abstinence from methamphetamines should be energetically pursued.

SUMMARYNutrient copper supply is critical for cell growth and differentiation, and its disturbance is associated with major pathologies including cancer and neurodegeneration. Although increasing copper bioavailability in late Precambrian facilitated emergence of novel cuproproteins, their intricate regulation by this essential trace element remains largely cryptic. We found that subtle rises in cellular copper strikingly increase polyubiquitination and accelerate protein degradation within 30 minutes in numerous mammalian cell lines. We track this surprising observation to allostery induced in the UBE2D ubiquitin conjugase clade through a conserved CXXXC sub-femtomolar-affinity Cu+ binding motif. Thus, physiologic fluctuation in cytoplasmic Cu+ is coupled to the prompt degradation of UBE2D protein targets, including p53. In Drosophila harboring a larval-lethal knockdown of the nearly identical fly orthologue UbcD1, complementation with human UBE2D2 restored near-normal development, but mutation of its CXXXC Cu+ binding motif profoundly disrupted organogenesis. Nutrient Cu+ emerges as a trophic allosteric modulator of UBE2D activity through a structural motif whose evolution coincides with animal multicellularity.One Sentence SummaryModulation of nutrient copper impacts protein turnover and animal morphogenesis through conserved allostery of ubiquitin E2D conjugases.HilightsNutrient copper supply is critical for cell growth and differentiationThe E2D clade of ubiquitin conjugases contains a sub-femtomolar-affinity Cu+ binding motifAllosteric activation by Cu+ markedly accelerates protein polyubiquitinationThis sensor couples physiologic fluctuations in cytoplasmic Cu+ with the degradation rate of E2D targets, including p53This metazoan signaling mechanism is critical for drosophila morphogenesisIn BriefConserved allostery of ubiquitin E2D conjugases links nutrient copper signaling to protein degradation and animal morphogenesis.Abstract FigureGraphical Abstract

Infective endocarditis is an uncommon microbial infection of the endocardial surface of the heart. Patients with structural heart disease, such as a ventricular septal defect, are at higher risk for infective endocarditis and clinicians must have a high index of suspicion in such patients presenting with recurrent fevers. We present a patient with a known ventricular septal defect presenting with recurrent fevers associated with migratory lung nodules following a “low‐risk” dental procedure without antibiotic prophylaxis. The unusual presentation delayed the diagnosis of the migratory lung lesions as septic pulmonary emboli and consequentially the diagnosis of ventricular septal defect related infective endocarditis. The patient made an uneventful recovery following antibiotic therapy and surgical intervention.

The objective of this study is to describe the extent, nature, age distribution and external causes of older-worker fatalities and to provide baseline data for future studies. The methods included retrospective descriptive cohort study using existing population-based mortality data. The study examined work-related fatalities aged 55 years and older, 2000–2009, in Australia following coronial investigation. Of the 336 fatalities identified, almost all (96.3%) were male. The industry with most deaths was agriculture, forestry and fishing (37.8%), followed by transport, postal and warehousing (19.3%) and construction (16.6%). The most frequent injury mechanism was transport-related (40.4%). With predicted workforce ageing, older-worker deaths will become a significant public health issue. Employers and authorities will need to understand older-workers characteristics and vulnerabilities to enable appropriate injury prevention strategy implementation.