North American lower-extremity revascularization and amputation during COVID-19: Observations from the Vascular Quality Initiative.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic's impact on vascular procedural volumes and outcomes has not been fully characterized. METHODS: Volume and outcome data before (1/2019 - 2/2020), during (3/2020 - 4/2020), and following (5/2020 - 6/2020) the initial pandemic surge were obtained from the Vascular Quality Initiative (VQI). Volume changes were determined using interrupted Poisson time series regression. Adjusted mortality was estimated using multivariable logistic regression. RESULTS: The final cohort comprised 57,181 patients from 147 US and Canadian sites. Overall procedure volumes fell 35.2% (95% CI 31.9%, 38.4%, p < 0.001) during and 19.8% (95% CI 16.8%, 22.9%, p < 0.001) following the surge, compared with presurge months. Procedure volumes fell 71.1% for claudication (95% CI 55.6%, 86.4%, p < 0.001) and 15.9% for chronic limb-threatening ischemia (CLTI) (95% CI 11.9%, 19.8%, p < 0.001) but remained unchanged for acute limb ischemia (ALI) when comparing surge to presurge months. Adjusted mortality was significantly higher among those with claudication (0.5% vs 0.1%; OR 4.38 [95% CI 1.42, 13.5], p = 0.01) and ALI (6.4% vs 4.4%; OR 2.63 [95% CI 1.39, 4.98], p = 0.003) when comparing postsurge with presurge periods. CONCLUSION: The first North American COVID-19 pandemic surge was associated with a significant and sustained decline in both elective and nonelective lower-extremity vascular procedural volumes. When compared with presurge patients, in-hospital mortality increased for those with claudication and ALI following the surge.

Protected from torsades de pointes? What psychiatrists need to know about pacemakers and defibrillators.

BACKGROUND: Consultation-liaison (C-L) psychiatrists are frequently asked to initiate and manage psychotropic drugs, some of which can delay cardiac repolarization, prolong the QT interval, and increase the risk of torsades de pointes (TdP). This task is complicated by the growing number of patients with cardiovascular implantable electronic devices (CIED) [i.e., permanent pacemakers (PPM), implantable cardioverter defibrillators (ICD), and cardiac resynchronization therapy devices (CRT)]. The precise protective role of CIEDs in the prevention and treatment of TdP is not well-defined. METHODS: We review practical tips for assessment of the QT interval in patients with paced rhythms, as well as the basic operative principles of CIEDs. We examine the available clinical evidence for the use of CIEDs in patients at risk for TdP. RESULTS: Most CIEDs have a pacing function that, when utilized appropriately, can offer partial protection against TdP by prevention of bradycardia. Defibrillators deliver shocks and are reasonably effective at terminating TdP; however, recurrent shocks are common and are associated with significant physical and psychological morbidity. CONCLUSIONS: CIEDs are important tools in the management of drug-induced ventricular arrhythmias in spite of significant limitations. The C-L psychiatrist should remain vigilant in recognizing and managing patients at risk for TdP, and refrain from over-reliance on CIEDs regardless of type or settings. Ultimately, the presence of a CIED should serve as a marker of increased risk of TdP.

The FGF14(F145S) mutation disrupts the interaction of FGF14 with voltage-gated Na+ channels and impairs neuronal excitability.

Fibroblast growth factor 14 (FGF14) belongs to the intracellular FGF homologous factor subfamily of FGF proteins (iFGFs) that are not secreted and do not activate tyrosine kinase receptors. The iFGFs, however, have been shown to interact with the pore-forming (alpha) subunits of voltage-gated Na+ (Na(v)) channels. The neurological phenotypes seen in Fgf14-/- mice and the identification of an FGF14 missense mutation (FGF14(F145S)) in a Dutch family presenting with cognitive impairment and spinocerebellar ataxia suggest links between FGF14 and neuronal functioning. Here, we demonstrate that the expression of FGF14(F145S) reduces Na(v) alpha subunit expression at the axon initial segment, attenuates Na(v) channel currents, and reduces the excitability of hippocampal neurons. In addition, and in contrast with wild-type FGF14, FGF14(F145S) does not interact directly with Na(v) channel alpha subunits. Rather, FGF14(F145S) associates with wild-type FGF14 and disrupts the interaction between wild-type FGF14 and Na(v) alpha subunits, suggesting that the mutant FGF14(F145S) protein acts as a dominant negative, interfering with the interaction between wild-type FGF14 and Na(v) channel alpha subunits and altering neuronal excitability.

Fibroblast growth factor 14 is an intracellular modulator of voltage-gated sodium channels.

Genetic ablation of the fibroblast growth factor (Fgf) 14 gene in mice or a missense mutation in Fgf14 in humans causes ataxia and cognitive deficits. These phenotypes suggest that the neuronally expressed Fgf14 gene is essential for regulating normal neuronal activity. Here, we demonstrate that FGF14 interacts directly with multiple voltage-gated Na(+) (Nav) channel alpha subunits heterologously expressed in non-neuronal cells or natively expressed in a murine neuroblastoma cell line. Functional studies reveal that these interactions result in the potent inhibition of Nav channel currents (I(Na)) and in changes in the voltage dependence of channel activation and inactivation. Deletion of the unique amino terminus of the splice variant of Fgf14, Fgf14-1b, or expression of the splice variant Fgf14-1a modifies the modulatory effects on I(Na), suggesting an important role for the amino terminus domain of FGF14 in the regulation of Na(v) channels. To investigate the function of FGF14 in neurones, we directly expressed Fgf14 in freshly isolated primary rat hippocampal neurones. In these cells, the addition of FGF14-1a-GFP or FGF14-1b-GFP increased I(Na) density and shifted the voltage dependence of channel activation and inactivation. In fully differentiated neurones, FGF14-1a-GFP or FGF14-1b-GFP preferentially colocalized with endogenous Nav channels at the axonal initial segment, a critical region for action potential generation. Together, these findings implicate FGF14 as a unique modulator of Nav channel activity in the CNS and provide a possible mechanism to explain the neurological phenotypes observed in mice and humans with mutations in Fgf14.