Assessing atrial myopathy with cardiac magnetic resonance imaging in embolic stroke of undetermined source.

BACKGROUND: Left atrial myopathy has been implicated in atrial fibrillation (AF)-related stroke and embolic stroke of undetermined source (ESUS). OBJECTIVE: To use advanced cardiac magnetic resonance (CMR) imaging techniques, including left atrial (LA) strain and 4D flow CMR, to identify atrial myopathy in patients with ESUS. METHODS: 20 patients with ESUS and no AF or other cause for stroke, and 20 age and sex-matched controls underwent CMR with 4D flow analysis. Markers of LA myopathy were assessed including LA size, volume, ejection fraction, and strain. 4D flow CMR was performed to measure novel markers of LA stasis such as LA velocities and the LA residence time distribution time constant (RTDtc). These markers of LA myopathy were compared between the two groups. RESULTS: There was no significant difference in: CMR-calculated LA velocities or LA total, passive or active ejection fractions between the groups. There was no significant difference in CMR-derived reservoir, conduit or contractile average longitudinal strain between the ESUS and control groups (22.9 vs 22.6%, p=0.379, 11.2 ± 3.5 vs 12.4 ± 2.6% p=0.224, 10.8 ± 3.2 vs 10.4 ± 2.3%, p=0.625 respectively). Similarly, RTDtc was not significantly longer in ESUS patients compared to controls (1.3 ± 0.2 vs 1.2 ± 0.2, p=0.1). CONCLUSIONS: There were no significant differences in any CMR marker of atrial myopathy in ESUS patients compared to healthy controls, likely reflecting the multiple possible aetiologies of ESUS suggesting that the role LA myopathy plays in ESUS is smaller than previously thought.

GHR disruption in mature adult mice alters xenobiotic metabolism gene expression in the liver.

BACKGROUND: Lifelong reduction of growth hormone (GH) action extends lifespan and improves healthspan in mice. Moreover, congenital inactivating mutations of GH receptor (GHR) in mice and humans impart resistance to age-associated cancer, diabetes, and cognitive decline. To investigate the consequences of GHR disruption at an adult age, we recently ablated the GHR at 6-months of age in mature adult (6mGHRKO) mice. We found that both, male and female 6mGHRKO mice have reduced oxidative damage, with males 6mGHRKO showing improved insulin sensitivity and cancer resistance. Importantly, 6mGHRKO females have an extended lifespan compared to controls. OBJECTIVE AND METHODS: To investigate the possible mechanisms leading to health improvements, we performed RNA sequencing using livers from male and female 6mGHRKO mice and controls. RESULTS: We found that disrupting GH action at an adult age reduced the gap in liver gene expression between males and females, making gene expression between sexes more similar. However, there was still a 6-fold increase in the number of differentially expressed genes when comparing male 6mGHRKO mice vs controls than in 6mGHRKO female vs controls, suggesting that GHR ablation affects liver gene expression more in males than in females. Finally, we found that lipid metabolism and xenobiotic metabolism pathways are activated in the liver of 6mGHRKO mice. CONCLUSION: The present study shows for the first time the specific hepatic gene expression profile, cellular pathways, biological processes and molecular mechanisms that are driven by ablating GH action at a mature adult age in males and females. Importantly, these results and future studies on xenobiotic metabolism may help explain the lifespan extension seen in 6mGHRKO mice.

The impact of the COVID-19 pandemic on global GDP growth.

This paper describes one of the first attempts to gauge the effect of the COVID-19 pandemic on the global trajectory of real GDP over the course of 2020 and 2021. It is also among the first efforts to distinguish between the role of domestic variables and global trade in transmitting the economic effects of COVID-19. We estimate panel data regressions of the quarterly growth in real GDP on pandemic variables for 90 countries over the period 2020 Q1 through 2021 Q4. We find that readings on the number of COVID-19 deaths had a very small effect in our aggregate sample. On the other hand, changes in the stringency of the lockdown measures taken by governments to restrict the spread of the virus were an important influence on GDP. The economic effects of the pandemic differed between rich and poor countries: COVID-19 deaths exerted a somewhat greater drag on GDP in advanced economies, although this difference was not statistically significant, whereas lockdown restrictions were more injurious to economic activity in emerging and developing economies. In addition to these domestic pandemic effects, global trade represented a significant channel through which the economic effects of the pandemic spilled across national borders. This finding underscores how globalization makes each country vulnerable not only to medical contagion from the COVID-19 pandemic, but to economic contagion as well.

Caring for Australians and New Zealanders With Kidney Impairment Guidelines: Rapid Development of Urate Lowering Therapy Guidelines for People With CKD.

Introduction: The slow transformation of new research findings into clinical guidelines is a barrier to providing evidence-based care. The Caring for Australians and New Zealanders with Kidney Impairment (CARI) guidelines are developing models to improve guideline production, one methodology involves more functional concordance between trial groups, such as the Australian Kidney Trials Network (AKTN) and CARI. The objective of this project was to rapidly produce an evidence-based guideline on urate-lowering therapy in patients with chronic kidney disease (CKD), in response to new clinical trial publications on the topic by the AKTN. Methods: To produce a guideline as rapidly as possible, an existing systematic review was utilized as the evidence base, and then updated with the inclusion of clinical trials that had been published subsequently. A Work Group was convened to review the evidence and compose an appropriate guideline using CARI/GRADE methodology. The group met 3 times over 45 days to formulate the guideline. Results: The result was a strong recommendation against the use urate-lowering therapies in individuals with CKD (not receiving dialysis) and asymptomatic hyperuricemia. The process of identifying an appropriate existing systematic review, updating the literature search, and synthesizing the evidence, was done by 2 individuals over 15 days. The Work Group was formulated and composed the guideline over 45 days. In all, a new guideline incorporating the most up-to-date evidence was formulated in 60 days. Conclusion: This method of guideline development represents a potentially new way of releasing guidelines that encapsulates all available evidence in a time-efficient manner.

"Remembrance": A Self-Care Tool for Clinicians.

Despite increasing attention in the medical and nursing literature about the importance of self-care for clinicians and the prevention of burnout, coping with the deaths of patients is an often-neglected component of clinical training. In this article, we describe the development of "Remembrance," an interdisciplinary approach to acknowledge and process the deaths of patients on our inpatient palliative care service, paying particular attention to how patients and their families affect us as clinicians. We believe that such a practice is an important component of both quality end-of-life care and clinician self-care, which should be routinely taught and incorporated into clinical services. We provide a template that summarizes our approach, which can be easily adapted by other hospitals to use.