Reshaping care in the aftermath of the pandemic. Implications for cardiology health systems

In the last two years, the COVID-19 pandemic has undeniably changed everyday life and significantly reshaped the healthcare systems. Besides the direct effect on daily care leading to significant excess mortality, several collateral damages have been observed during the pandemic. The impact of the pandemic led to staff shortages, disrupted education, worse healthcare professional well-being, and a lack of proper clinical training and research. In this review we highlight the results of these important changes and how can the healthcare systems can adapt to prevent unprecedented events in case of future catastrophes

Correction: Diuretic dose trajectories in dilated cardiomyopathy: prognostic implications

Within the abstract, the following phrase in the ‘Methods’ section “According to FED trajectory, patients were classified as (i) dose (FED increase by ≥ 50% or newly initiated);” was corrected to read “According to FED trajectory, patients were classified as (i) dose ↑ (FED increase by ≥ 50% or newly initiated);”. In the ‘Results’ section of the abstract, the sentence “Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04–1.22, p = 0.003].” was corrected to “Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04–1.22], p = 0.003).” Finally, in Table 1, the LVEF, % for Dose↓ patients was given incorrectly whenit should have been “28 (22-34)” and the N value has been corrected from “263” to “282”. The original article has been corrected

Single Shot Amplitude and Phase Characterization of Optical Arbitrary Waveforms

Using a time-gated dual quadrature spectral interferometry technique, for the first time we demonstrate single-shot characterization of both spectral amplitude and phase of ~1THz bandwidth optical arbitrary waveforms generated from a 10 GHz frequency comb. Our measurements provide a temporal resolution of 1ps over a record length of 100ps. Singleshot characterization becomes particularly relevant when waveform synthesis operations are updated at the repetition rate of the comb allowing creation of potentially infinite record length waveforms. We first demonstrate unambiguous single shot retrieval using rapidly updating waveforms. We then perform additional single-shot measurements of static user-defined waveforms generated via line-by-line pulse shaping.Comment: 10 pages, 6 figures. Added new references and minor changes to tex

Current treatment and immunomodulation strategies in Acute Myocarditis

Myocarditis is an inflammatory disease of the myocardium characterized by a great heterogeneity of presentation and evolution. Treatment of myocarditis is often supportive and the evidence for immunosuppression is scarce and debated. Conventional treatment is based on clinical presentation, ranging from conservative to advanced mechanical assist devices. In this setting, immunosuppression and immunomodulation therapies are mostly reserved for patients presenting with major clinical syndromes. In this review, we will summarise the current evidence and strategies for conventional and immunosuppressive treatments for patients presenting with acute myocarditis

A nationwide, population‐based study on specialized care for acute heart failure throughout the COVID‐19 pandemic

Aims - The COVID-19 pandemic disrupted the delivery of care for patients with heart failure (HF), leading to fewer HF hospitalizations and increased mortality. However, nationwide data on quality of care and long-term outcomes across the pandemic are scarce.Methods and results - We used data from the National Heart Failure Audit (NHFA) linked to national records for hospitalization and deaths. We compared pre-COVID (2018–2019), COVID (2020), and late/post-COVID (2021–2022) periods. Data for 227 250 patients admitted to hospital with HF were analysed and grouped according to the admission year and the presence of HF with (HFrEF) or without reduced ejection fraction (non-HFrEF). The median age at admission was 81 years (interquartile range 72–88), 55% were men (n = 125 975), 87% were of white ethnicity (n = 102 805), and 51% had HFrEF (n = 116 990). In-hospital management and specialized cardiology care were maintained throughout the pandemic with an increasing percentage of patients discharged on disease-modifying medications over time (p &lt; 0.001). Long-term outcomes improved over time (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.90–0.95, p &lt; 0.001), mainly driven by a reduction in cardiovascular death. Receiving specialized cardiology care was associated with better long-term outcomes both for those who had HFrEF (HR 0.79, 95% CI 0.77–0.82, p &lt; 0.001) and for those who had non-HFrEF (HR 0.87, 95% CI 0.85–0.90, p &lt; 0.001).Conclusions - Despite the disruption of healthcare systems, the clinical characteristics of patients admitted with HF were similar and the overall standard of care was maintained throughout the pandemic. Long-term survival of patients hospitalized with HF continued to improve after COVID-19, especially for HFrEF.<br/

EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer

Transport of macromolecules through the nuclear pore by importins and exportins plays a critical role in the spatial regulation of protein activity. How cancer cells co-opt this process to promote tumorigenesis remains unclear. The epidermal growth factor receptor (EGFR) plays a critical role in normal development and in human cancer. Here we describe a mechanism of EGFR regulation through the importin β family member RAN-binding protein 6 (RanBP6), a protein of hitherto unknown functions. We show that RanBP6 silencing impairs nuclear translocation of signal transducer and activator of transcription 3 (STAT3), reduces STAT3 binding to the EGFR promoter, results in transcriptional derepression of EGFR, and increased EGFR pathway output. Focal deletions of the RanBP6 locus on chromosome 9p were found in a subset of glioblastoma (GBM) and silencing of RanBP6 promoted glioma growth in vivo. Our results provide an example of EGFR deregulation in cancer through silencing of components of the nuclear import pathway.This research was supported by the National Brain Tumor Society (I.K.M.), the National Institutes of Health grants 1R01NS080944-01 (I.K.M.), 1 R35 NS105109 01 (I.K.M.), and P30CA008748 (MSKCC Core Grant), the Geoffrey Beene Cancer Research Foundation (I.K.M.), the Cycle of Survival (I.K.M.), and the Seve Ballesteros Foundation (M.S.). B.O. was supported by an American–Italian Cancer Foundation fellowship and a MSKCC Brain Tumor Center grant. W.-Y.H. is the recipient of a FY15 Horizon Award from the U.S. Department of Defense (W81XWH-15-PRCRP-HA). A.C.-G. is the recipient of the Severo-Ochoa PhD fellowship. Further support was provided by the Sontag Foundation (B.S.T.). We thank all members of the Mellinghoff laboratory for helpful suggestions. We thank Dr. Fiona Ginty (Diagnostic Imaging and Biomedical Technologies, GE Global Research Center, Niskayuna, New York, USA) for assistance with multiplexed immunofluorescence. We thank A.J. Schuhmacher and C.S. Clemente-Troncone for assistance with the in vivo experiments, M. Kaufmann for assistance in the luciferase assays and N. Yannuzzi for assistance in cloning.S

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p129(ctn)

Cadherin cell-cell adhesion molecules form membrane-spanning molecular complexes that couple homophilic binding by the cadherin ectodomain to the actin cytoskeleton. A fundamental issue in cadherin biology is how this complex converts the weak intrinsic binding activity of the ectodomain into strong adhesion. Recently we demonstrated that cellular cadherins cluster in a ligand-dependent fashion when cells attached to substrata coated with the adhesive ectodomain of Xenopus C-cadherin (CEC1-5). Moreover, forced clustering of the ectodomain alone significantly strengthened adhesiveness (Yap, A.S., W.M. Brieher, M. Pruschy, and B.M. Gumbiner. Curr. Biol. 7:308-315). In this study we sought to identify the determinants of the cadherin cytoplasmic tail responsible for clustering activity. A deletion mutant of C-cadherin (CT669) that retained the juxtamembrane 94-amino acid region of the cytoplasmic tail, but not the beta-catenin-binding domain, clustered upon attachment to substrata coated with CEC1-5. Like wild-type C-cadherin, this clustering was Ligand dependent. In contrast, mutant molecules lacking either the complete cytoplasmic tail or just the juxtamembrane region did not cluster. The juxtamembrane region was itself sufficient to induce clustering when fused to a heterologous membrane-anchored protein, albeit in a ligand-independent fashion. The CT669 cadherin mutant also displayed significant adhesive activity when tested in laminar flow detachment assays and aggregation assays. Purification of proteins binding to the juxtamembrane region revealed that the major associated protein is p120(ctn). These findings identify the juxtamembrane region of the cadherin cytoplasmic tail as a functionally active region supporting cadherin clustering and adhesive strength and raise the possibility that p120(ctn) is involved in clustering and cell adhesion