Uptake of SGLT2i and Outcomes in Patients with Diabetes and Heart Failure: A Population-Based Cohort and a Specialized Clinic Cohort.

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are effective in adults with diabetes mellitus (DM) and heart failure (HF) based on randomized clinical trials. We compared SGLT2 inhibitor uptake and outcomes in two cohorts: a population-based cohort of all adults with DM and HF in Alberta, Canada and a specialized heart function clinic (HFC) cohort. METHODS: The population-based cohort was derived from linked provincial healthcare datasets. The specialized clinic cohort was created by chart review of consecutive patients prospectively enrolled in the HFC between February 2018 and August 2022. We examined the association between SGLT2 inhibitor use (modeled as a time-varying covariate) and all-cause mortality or deaths/cardiovascular hospitalizations. RESULTS: Of the 4,885 individuals from the population-based cohort, 64.2% met the eligibility criteria of the trials proving the effectiveness of SGLT2 inhibitors. Utilization of SGLT2 inhibitors increased from 1.2% in 2017 to 26.4% by January 2022. In comparison, of the 530 patients followed in the HFC, SGLT2 inhibitor use increased from 9.8% in 2019 to 49.1 % by March 2022. SGLT2 inhibitor use in the population-based cohort was associated with fewer all-cause mortality (aHR 0.51, 95%CI 0.41-0.63) and deaths/cardiovascular hospitalizations (aHR 0.65, 95%CI 0.54-0.77). However, SGLT2 inhibitor usage rates were far lower in HF patients without DM (3.5% by March 2022 in the HFC cohort). CONCLUSIONS: Despite robust randomized trial evidence of clinical benefit, the uptake of SGLT2 inhibitors in patients with HF and DM remains low, even in the specialized HFC. Clinical care strategies are needed to enhance the use of SGLT2 inhibitors and improve implementation.

Cardiac manifestations and clinical management of X-linked Emery-Dreifuss muscular dystrophy: a case series.

Background: Heart disease is an under-recognized cause of morbidity and mortality in patients with Emery-Dreifuss muscular dystrophy (EDMD). Arrhythmias and conduction delays are highly prevalent and given the rarity of this disease the patient care process remains poorly defined. Case summary: This study closely followed four adult patients from the Neuromuscular Multidisciplinary Clinic (Alberta, Canada) that presented with X-linked recessive EDMD. Patients were assessed and managed on a case-by-case basis. Clinical status and cardiac function were assessed through clinical history, physical examination, and investigations (12-lead electrocardiogram, 24 hour Holter monitor, transthoracic echocardiogram, and plasma biomarkers). Conduction disease, requiring permanent pacemaker, was prevalent in all patients. With appropriate medical therapy over a median follow-up period five years the cardiac status was shown to have stabilized in all these patients. Discussion: We demonstrate the presentation of arrhythmias, conduction abnormalities, and chamber dilation in adult patients with X-linked EDMD. Cardiac medications and pacemaker therapy are shown to prevent adverse outcomes from these complications. Patients with EDMD are expected to develop heart disease early and prior to the development of an overt neuromuscular phenotype. These patients should be closely monitored in a multidisciplinary setting for effective management to improve their clinical outcomes.

Review of Hydroxychloroquine Cardiotoxicity: Lessons From the COVID-19 Pandemic.

PURPOSE OF REVIEW: The coronavirus disease 2019 (COVID-19) pandemic has popularized the usage of hydroxychloroquine and chloroquine (HCQ/CQ) as treatments for COVID-19. Previously used as anti-malarial and now commonly used in rheumatologic conditions, preliminary in vitro studies have demonstrated these medications also have anti-viral properties. Retinopathy and neuromyopathy are well recognized complications of using these treatments; however, cardiotoxicity is under-recognized. This review will discuss the implications and cardiotoxicity of HCQ/CQ, their mechanisms of action, and their utility in COVID-19. RECENT FINDINGS: Early clinical trials demonstrated a modest benefit of HCQ in COVID-19, causing a push for the usage of it. However, further large multi-center randomized control centers, demonstrated no benefit, and even a trend towards worse outcomes. The predominant cardiac complication observed with HCQ in COVID-19 was cardiac arrhythmias and prolonging of the QT interval. However, with chronic usage of HCQ/CQ, the development of heart failure (HF) and cardiomyopathy (CM) can occur. Although, most adverse cardiac events related to HCQ/CQ usage in COVID-19 were secondary to conduction disorders given the short duration of treatment, HCQ/CQ can cause CM and HF, with chronic usage. Given the insufficient evidence, HCQ/CQ usage in COVID-19 is not routinely recommended, especially with novel therapies now being developed and used. Additionally, usage of HCQ/CQ should prompt initial cardiac evaluation with ECG, and yearly monitoring, with consideration for advanced imaging if clinically warranted. The diagnosis of HCQ/CQ cardiomyopathy is important, as prompt cessation can allow for recovery when these changes are still reversible.

Kounis Syndrome: A Case of Vancomycin-Associated Coronary Artery Vasospasm Resulting in Myocardial Infarction.

We describe a case of Kounis syndrome, an allergic reaction causing coronary artery vasospasm, triggered by a vancomycin infusion, in a healthy 32-year-old man. The patient initially presented with an inguinal abscess requiring intravenous vancomycin. During his third infusion, he developed typical chest pain that resolved with cessation of the infusion. Troponin was elevated, and electrocardiogram showed ST elevation, prompting emergent cardiac catheterization that demonstrated normal coronary arteries. The cause of the myocardial infarction was consistent with Kounis syndrome. Diagnosis of Kounis syndrome is important, as prompt cessation of the offending agent is a priority to reduce further cardiac injury.

Nous décrivons un cas de syndrome de Kounis, une réaction allergique causant un angiospasme coronarien, déclenchée par une perfusion de vancomycine, chez un homme en bonne santé de 32 ans. Le patient a d'abord présenté un abcès inguinal nécessitant l'administration intraveineuse de vancomycine. Au cours de sa troisième perfusion, il a ressenti une douleur type à la poitrine, qui s'est résorbée après l'interruption de la perfusion. Le taux de troponine était élevé, et l'électrocardiogramme montrait une élévation du segment ST, ce qui a mené à un cathétérisme cardiaque d'urgence qui a révélé des artères coronaires normales. La cause de l'infarctus du myocarde cadrait avec le syndrome de Kounis. Le diagnostic de ce syndrome est important, car l'interruption rapide de l'administration de l'agent concerné est prioritaire pour limiter les lésions cardiaques.

Cardiac Complications of Common Drugs of Abuse: Pharmacology, Toxicology, and Management.

Cardiovascular complications from drugs of abuse are becoming more apparent because of increased usage worldwide. Substance abuse can cause acute and chronic cardiovascular complications and is increasing in prevalence especially in young adults. These substances contribute to the development of acute coronary syndrome, type 2 myocardial injury, arrhythmias, and cardiomyopathies, and have numerous other cardiovascular complications. Although no screening guidelines exist, clinical awareness of these potential complications and their prevention, clinical presentation, diagnosis, and treatment are critically important. Management of cardiovascular disease should be coupled with appropriate social and mental health interventions to provide sustained clinical benefit. The higher the number of substances used recreationally, the greater the risk of premature heart disease. Epidemiological studies showed that 1 in 5 young adults misuse several substances and often start using at younger ages with a greater risk for adverse health outcomes over the long term. The aim of this review is to highlight the basic epidemiology, cardiac complications, and disease-specific treatment options of commonly abused substances including methamphetamine, cocaine, alcohol, anabolic-androgenic steroids, cannabis, and tobacco.

Barriers to reporting guideline adherence in point-of-care ultrasound research: a cross-sectional survey of authors and journal editors.

OBJECTIVE: Although the literature supporting the use of point-of-care ultrasound (POCUS) continues to grow, incomplete reporting of primary diagnostic accuracy studies has previously been identified as a barrier to translating research into practice and to performing unbiased systematic reviews. This study assesses POCUS investigator and journal editor attitudes towards barriers to adhering to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015 guidelines. DESIGN, SETTING, PARTICIPANTS: Two separate surveys using a 5-point Likert scale were sent to POCUS study investigators and journal editors to assess for knowledge, attitude and behavioural barriers to the complete reporting of POCUS research. Respondents were identified based on a previous study assessing STARD 2015 adherence for POCUS studies published in emergency medicine, anaesthesia and critical care journals. Responses were anonymously linked to STARD 2015 adherence data from the previous study. Written responses were thematically grouped into the following categories: knowledge, attitude and behavioural barriers to quality reporting, or other. Likert response items are reported as median with IQRs. MAIN OUTCOME MEASURES: The primary outcome was the median Likert score for the investigator and editor surveys assessing knowledge, attitude and behavioural beliefs about barriers to adhering to the STARD 2015 guidelines. RESULTS: The investigator survey response rate was 18/69 (26%) and the editor response rate was 5/21 (24%). Most investigator respondents were emergency medicine practitioners (13/21, 62%). Two-thirds of investigators were aware of the STARD 2015 guidelines (12/18, 67%) and overall agreed that incomplete reporting limits generalisability and the ability to detect risk of bias (median 4 (4, 5)). Investigators felt that the STARD 2015 guidelines were useful, easy to find and easy to use (median 4 (4, 4.25); median 4 (4, 4.25) and median 4 (3, 4), respectively). There was a shared opinion held by investigators and editors that the peer review process be primarily responsible for ensuring complete research reporting (median 4 (3, 4) and median 4 (3.75, 4), respectively). Three of 18 authors (17%) felt that the English publication language of STARD 2015 was a barrier to adherence. CONCLUSIONS: Although investigators and editors recognise the importance of completely reported research, reporting quality is still a core issue for POCUS research. The shared opinion held by investigators and editors that the peer review process be primarily responsible for reporting quality is potentially problematic; we view completely reported research as an integral part of the research process that investigators are responsible for, with the peer review process serving as another additional layer of quality control. Endorsement of reporting guidelines by journals, auditing reporting guideline adherence during the peer review process and translation of STARD 2015 guidelines into additional languages may improve reporting completeness for the acute POCUS literature. TRIAL REGISTRATION NUMBER: Open Science Framework Registry (https://osf.io/5pzxs/).

Pseudomonas aeruginosa Biofilm Antibiotic Resistance Gene ndvB Expression Requires the RpoS Stationary-Phase Sigma Factor.

Chronic, biofilm-based bacterial infections are exceptionally difficult to eradicate due to the high degree of antibiotic recalcitrance exhibited by cells in biofilm communities. In the opportunistic pathogen Pseudomonas aeruginosa, biofilm recalcitrance is multifactorial and arises in part from the preferential expression of resistance genes in biofilms compared to exponential-phase planktonic cells. One such mechanism involves ndvB, which we have previously shown to be expressed specifically in biofilms. In this study, we investigated the regulatory basis of this lifestyle-specific expression by developing an unstable green fluorescent protein (GFP) transcriptional reporter to observe the expression pattern of ndvB We found that in addition to its expression in biofilms, ndvB was upregulated in planktonic cells as they enter stationary phase. The transcription of ndvB in both growth phases was shown to be dependent on the stationary-phase sigma factor RpoS, and mutation of a putative RpoS binding site in the ndvB promoter abolished the activity of the promoter in stationary-phase cells. Overall, we have expanded our understanding of the temporal expression of ndvB in P. aeruginosa and have uncovered a regulatory basis for its growth phase-dependent expression.IMPORTANCE Bacterial biofilms are more resistant to antibiotics than free-living planktonic cells, and understanding the mechanistic basis of this resistance can inform treatments of biofilm-based infections. In addition to chemical and structural barriers that can inhibit antibiotic entry, the upregulation of specific genes in biofilms contributes to the resistance. We investigated this biofilm-specific gene induction by examining expression patterns of ndvB, a gene involved in biofilm resistance of the opportunistic pathogen Pseudomonas aeruginosa We characterized ndvB expression in planktonic and biofilm growth conditions with an unstable green fluorescent protein (GFP) reporter and found that the expression of ndvB in biofilms is dependent on the stationary-phase sigma factor RpoS. Overall, our results support the physiological similarity between biofilms and stationary-phase cells and suggest that the induction of some stationary-phase genes in biofilms may contribute to their increased antibiotic resistance.

Targeting the alternative sigma factor RpoN to combat virulence in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that infects immunocompromised and cystic fibrosis patients. Treatment is difficult due to antibiotic resistance, and new antimicrobials are needed to treat infections. The alternative sigma factor 54 (σ54, RpoN), regulates many virulence-associated genes. Thus, we evaluated inhibition of virulence in P. aeruginosa by a designed peptide (RpoN molecular roadblock, RpoN*) which binds specifically to RpoN consensus promoters. We expected that RpoN* binding to its consensus promoter sites would repress gene expression and thus virulence by blocking RpoN and/or other transcription factors. RpoN* reduced transcription of approximately 700 genes as determined by microarray analysis, including genes related to virulence. RpoN* expression significantly reduced motility, protease secretion, pyocyanin and pyoverdine production, rhamnolipid production, and biofilm formation. Given the effectiveness of RpoN* in vitro, we explored its effects in a Caenorhabditis elegans-P. aeruginosa infection model. Expression of RpoN* protected C. elegans in a paralytic killing assay, whereas worms succumbed to paralysis and death in its absence. In a slow killing assay, which mimics establishment and proliferation of an infection, C. elegans survival was prolonged when RpoN* was expressed. Thus, blocking RpoN consensus promoter sites is an effective strategy for abrogation of P. aeruginosa virulence.

Electrochemical regeneration of a reduced graphene oxide/magnetite composite adsorbent loaded with methylene blue.

In this work, two different reduced graphene oxide/iron oxide (rGO-IO) nanocomposites with different iron oxide loadings were fabricated using a one-step solvothermal method. The structure, properties and applications of the synthesized nanocomposites were evaluated with Raman spectroscopy, attenuated total reflectance Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, electron microscopy, and energy-dispersive X-ray spectroscopy. The iron oxide is in the form of magnetite (Fe3O4), so that the resultant adsorbent can readily be separated from the treated water using a magnetic field. The ability of the nanocomposites to remove methylene blue (MB) from water by adsorption was investigated. The highest adsorptive capacity observed was 39 mg g-1, for the composite containing 60 wt% iron oxide. The adsorptive capacity of the rGO-IO decreased to 26 mg g-1 when the mass fraction of iron oxide was increased to 75 wt%. Electrochemical regeneration of MB loaded rGO-IO was also investigated. The electrochemical regeneration was found to be rapid and with low electrical energy consumption relative to conventional adsorbents, due to the high electrical conductivity and nonporous surface of the rGO. A regeneration efficiency of 100% was obtained after 30 min of electrochemical treatment using a 2 mm thick bed of rGO-IO loaded with 39 mg g-1 MB, using a current density of 10 mA cm-2. Multiple adsorption-electrochemical regeneration cycles demonstrated that the surface of the rGO was modified leading to increase in the adsorptive capacity to around 80 mg g-1 after the second regeneration cycle. The morphology of the rGO was observed to change significantly after electrochemical regeneration, suggesting that the rGO based adsorbent materials could only be used for a few cycles.

Safety and efficacy of composite collagen-silver nanoparticle hydrogels as tissue engineering scaffolds.

The increasing number of multidrug resistant bacteria has revitalized interest in seeking alternative sources for controlling bacterial infection. Silver nanoparticles (AgNPs), are amongst the most promising candidates due to their wide microbial spectrum of action. In this work, we report on the safety and efficacy of the incorporation of collagen coated AgNPs into collagen hydrogels for tissue engineering. The resulting hybrid materials at [AgNPs] < 0.4 µM retained the mechanical properties and biocompatibility for primary human skin fibroblasts and keratinocytes of collagen hydrogels; they also displayed remarkable anti-infective properties against S. aureus, S. epidermidis, E. coli and P. aeruginosa at considerably lower concentrations than silver nitrate. Further, subcutaneous implants of materials containing 0.2 µM AgNPs in mice showed a reduction in the levels of IL-6 and other inflammation markers (CCL24, sTNFR-2, and TIMP1). Finally, an analysis of silver contents in implanted mice showed that silver accumulation primarily occurred within the tissue surrounding the implant.

Photochemical synthesis of biocompatible and antibacterial silver nanoparticles embedded within polyurethane polymers.

In situ light initiated synthesis of silver nanoparticles (AgNP) was employed for AgNP incorporation within the polymeric matrices of medical grade polyurethane. The resulting materials showed improved antibacterial and antibiofilm activity against Pseudomonas aeruginosa with negligible toxicity for human primary skin cells and erythrocytes.