Atherosclerosis in Systemic Lupus Erythematosus.

PURPOSE OF THE REVIEW: Systemic lupus erythematosus (SLE) patients are at increased risk of cardiovascular disease (CVD) compared to the general population, despite most patients being young females, who are not classically considered to be at high risk for cardiovascular disease using traditional risk assessment tools. The purpose of this review is to discuss the pathophysiology of atherosclerosis in SLE and raise awareness of the relationship between SLE and CVD. RECENT FINDINGS: The increased risk of CVD in SLE patients is multifactorial, due to proatherogenic lipid profiles, immune dysregulation and inflammation, side effects of lupus treatment, and microvascular dysfunction. Conventional CV risk models often underperform in the identification of SLE patients at high risk of atherosclerosis. The use of non-invasive imaging serves as a strategy to identify patients with evidence of subclinical CVD and in the evaluation of symptomatic patients. Identification of subclinical atherosclerosis allows for aggressive management of CV risk factors. SLE patients experience an increased risk of atherosclerotic CVD, which is not solely explained by traditional CV risk factors. It is imperative that clinicians are aware of this association to implement prompt detection and treatment of atherosclerotic CVD in SLE patients.

Physical Functioning in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent, yet interventions and therapies to improve outcomes remain limited. There has been increasing attention towards the impact of comorbidities and physical functioning (PF) on poor clinical outcomes within this population. In this review, we summarize and discuss the literature on PF in HFpEF, its association with clinical and patient-centered outcomes, and future advances in the care of HFpEF with respect to PF. Multiple PF metrics have been demonstrated to provide prognostic value within HFpEF, yet the data are less robust compared with other patient populations, highlighting the need for further investigation. The evaluation and detection of poor PF provides a potential strategy to improve care in HFpEF, and future studies are needed to understand if modulating PF improves clinical and/or patient-reported outcomes. LAY SUMMARY: • Patients with heart failure with preserved ejection fraction (HFpEF) commonly have impaired physical functioning (PF) demonstrated by limitations across a wide range of common PF metrics.• Impaired PF metrics demonstrate prognostic value for both clinical and patient-reported outcomes in HFpEF, making them plausible therapeutic targets to improve outcomes.• Clinical trials are ongoing to investigate novel methods of detecting, monitoring, and improving impaired PF to enhance HFpEF care.Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent, yet interventions and therapies to improve outcomes remain limited. As such, there has been increasing focus on the impact of physical performance (PF) on clinical and patient-centered outcomes. In this review, we discuss the state of PF in patients with HFpEF by examining the multitude of PF metrics available, their respective strengths and limitations, and their associations with outcomes in HFpEF. We highlight future advances in the care of HFpEF with respect to PF, particularly regarding the evaluation and detection of poor PF.

Clinical outcomes in patients co-infected with COVID-19 and Staphylococcus aureus: a scoping review.

BACKGROUND: Endemic to the hospital environment, Staphylococcus aureus (S. aureus) is a leading bacterial pathogen that causes deadly infections such as bacteremia and endocarditis. In past viral pandemics, it has been the principal cause of secondary bacterial infections, significantly increasing patient mortality rates. Our world now combats the rapid spread of COVID-19, leading to a pandemic with a death toll greatly surpassing those of many past pandemics. However, the impact of co-infection with S. aureus remains unclear. Therefore, we aimed to perform a high-quality scoping review of the literature to synthesize the existing evidence on the clinical outcomes of COVID-19 and S. aureus co-infection. METHODS: A scoping review of the literature was conducted in PubMed, Scopus, Ovid MEDLINE, CINAHL, ScienceDirect, medRxiv, and the WHO COVID-19 database using a combination of terms. Articles that were in English, included patients infected with both COVID-19 and S. aureus, and provided a description of clinical outcomes for patients were eligible. From these articles, the following data were extracted: type of staphylococcal species, onset of co-infection, patient sex, age, symptoms, hospital interventions, and clinical outcomes. Quality assessments of final studies were also conducted using the Joanna Briggs Institute's critical appraisal tools. RESULTS: Searches generated a total of 1922 publications, and 28 articles were eligible for the final analysis. Of the 115 co-infected patients, there were a total of 71 deaths (61.7%) and 41 discharges (35.7%), with 62 patients (53.9%) requiring ICU admission. Patients were infected with methicillin-sensitive and methicillin-resistant strains of S. aureus, with the majority (76.5%) acquiring co-infection with S. aureus following hospital admission for COVID-19. Aside from antibiotics, the most commonly reported hospital interventions were intubation with mechanical ventilation (74.8 %), central venous catheter (19.1 %), and corticosteroids (13.0 %). CONCLUSIONS: Given the mortality rates reported thus far for patients co-infected with S. aureus and COVID-19, COVID-19 vaccination and outpatient treatment may be key initiatives for reducing hospital admission and S. aureus co-infection risk. Physician vigilance is recommended during COVID-19 interventions that may increase the risk of bacterial co-infection with pathogens, such as S. aureus, as the medical community's understanding of these infection processes continues to evolve.

Surfactant protein C dampens inflammation by decreasing JAK/STAT activation during lung repair.

Surfactant protein C (SPC), a key component of pulmonary surfactant, also plays a role in regulating inflammation. SPC deficiency in patients and mouse models is associated with increased inflammation and delayed repair, but the key drivers of SPC-regulated inflammation in response to injury are largely unknown. This study focuses on a new mechanism of SPC as an anti-inflammatory molecule using SPC-TK/SPC-KO (surfactant protein C-thymidine kinase/surfactant protein C knockout) mice, which represent a novel sterile injury model that mimics clinical acute respiratory distress syndrome (ARDS). SPC-TK mice express the inducible suicide gene thymidine kinase from by the SPC promoter, which targets alveolar type 2 (AT2) cells for depletion in response to ganciclovir (GCV). We compared GCV-induced injury and repair in SPC-TK mice that have normal endogenous SPC expression with SPC-TK/SPC-KO mice lacking SPC expression. In contrast to SPC-TK mice, SPC-TK/SPC-KO mice treated with GCV exhibited more severe inflammation, resulting in over 90% mortality; there was only 8% mortality of SPC-TK animals. SPC-TK/SPC-KO mice had highly elevated inflammatory cytokines and granulocyte infiltration in the bronchoalveolar lavage (BAL) fluid. Consistent with a proinflammatory phenotype, immunofluorescence revealed increased phosphorylated signal transduction and activation of transcription 3 (pSTAT3), suggesting enhanced Janus kinase (JAK)/STAT activation in inflammatory and AT2 cells of SPC-TK/SPC-KO mice. The level of suppressor of cytokine signaling 3, an anti-inflammatory mediator that decreases pSTAT3 signaling, was significantly decreased in the BAL fluid of SPC-TK/SPC-KO mice. Hyperactivation of pSTAT3 and inflammation were rescued by AZD1480, a JAK1/2 inhibitor. Our findings showing a novel role for SPC in regulating inflammation via JAK/STAT may have clinical applications.

Improving Upper Arm Skin Laxity Using a Tripollar Radiofrequency Device.

BACKGROUND: Non-ablative treatments for excess subcutaneous fat have been increasingly integrated into dermatologic practice. OBJECTIVE: The objective of this study was to determine the safety and efficacy of a tripolar radiofrequency device on tightening skin and reducing the circumference of the upper arms. METHODS & MATERIALS: Twelve females received eight weekly non-ablative treatments using a tripolar radiofrequency device on the anterior and posterior upper arms. Evaluations included body weight, photographs, and circumference measurements at baseline and each subsequent week throughout the 8-week time period. The subjects and the investigator completed evaluations of clinical improvement using a 5-point assessment scale. RESULTS: A significant circumference reduction was achieved in each arm of all twelve patients. A mean reduction of 1.99 ± 0.94 cm (P=0.001) was observed between the initial and final measurements after the 8-week treatment period. At the 4-week follow up, the average circumferential reductions of the posterior and anterior upper arms were sustained. Patient evaluations indicated moderate to good improvement of size, tightness, and overall appearance. The procedure was well tolerated without pain. CONCLUSION: Tripolar radiofrequency devices offer a safe and effective non-invasive technology with beneficial effects on the circumferential reduction and overall appearance of the posterior and anterior upper arms.

Spirituality in Patients With Heart Failure.

With advances in heart failure (HF) treatment, patients are living longer, putting further emphasis on quality of life (QOL) and the role of palliative care principles in their care. Spirituality is a core domain of palliative care, best defined as a dynamic, multidimensional aspect of oneself for which 1 dimension is that of finding meaning and purpose. There are substantial data describing the role of spirituality in patients with cancer but a relative paucity of studies in HF. In this review article, we explore the current knowledge of spirituality in patients with HF; describe associations among spirituality, QOL, and HF outcomes; and propose clinical applications and future directions regarding spiritual care in this population. Studies suggest that spirituality serves as a potential target for palliative care interventions to improve QOL, caregiver support, and patient outcomes including rehospitalization and mortality. We suggest the development of a spirituality-screening tool, similar to the Patient Health Questionnaire-2 used to screen for depression, to identify patients with HF at risk for spiritual distress. Novel tools are soon to be validated by members of our group. Given spirituality in HF remains less well studied compared with other patient populations, further controlled trials and uniform measures of spirituality are needed to understand its impact better.

Race Differences in Quality of Life following a Palliative Care Intervention in Patients with Advanced Heart Failure: Insights from the Palliative Care in Heart Failure Trial.

Introduction: Black patients have a higher incidence of heart failure (HF) and worse outcomes than white patients. Guidelines recommend palliative care for patients with advanced HF, but no studies have examined outcomes in a black patient cohort. Methods: This is a post hoc analysis of the Palliative Care in Heart Failure trial, which randomized patients to usual care plus a palliative care intervention (UC+PAL) or usual care (UC). Quality of life (QoL) was measured using Kansas City Cardiomyopathy Questionnaire (KCCQ) and Functional Assessment of Chronic Illness Therapy-Palliative Care scale (FACIT-Pal). Results: Black patients represented 41% of the 148 patients. At six months, QoL improved more in UC+PAL than UC for both racial subgroups. The difference was greater for black than white patients (difference: KCCQ 10.8 vs. 2.5; FACIT-Pal: 14.8 vs. 3.9). However, the findings were not statistically significant. Conclusions: Larger studies are needed to assess the benefits of palliative care for black patients with HF. ClinicalTrials.gov Identifier: NCT01589601.

The Irish organic food market: shortfalls, opportunities and the need for research.

In 2009 the Irish organic food market was forecasted to grow from €120 m to €239 m by 2013; however, recent figures set its value at just €90 m. An estimated 70% of this market is imported. Surveys of Irish consumers reveal that 66% of consumers prefer to buy local produce and most organic consumers are buying organic at supermarkets. This evidence reveals that Irish producers must trade at supermarkets, and promote 'local produce' to ensure their produce reach the majority of buyers. Seventy-eight % of organic rejecters state price and 21% state unawareness of the benefits as reasons for not buying organic. Many Irish consumers are buying organic food on the perceived belief that it is healthier, safer and tastes better; however, a review of studies on organic versus conventional foods in terms of health benefits, safety and sensory quality has shown that existing data is limited in scope and fails to show a clear trend. The review concludes with the need for a comprehensive study of a range of organic and conventional foods available to the Irish consumer in order to determine if differences in organic cultivation result in statistically significant differences in health linked compounds and sensory quality.

Exosome-Mediated Benefits of Cell Therapy in Mouse and Human Models of Duchenne Muscular Dystrophy.

Genetic deficiency of dystrophin leads to disability and premature death in Duchenne muscular dystrophy (DMD), affecting the heart as well as skeletal muscle. Here, we report that clinical-stage cardiac progenitor cells, known as cardiosphere-derived cells (CDCs), improve cardiac and skeletal myopathy in the mdx mouse model of DMD. Injection of CDCs into the hearts of mdx mice augments cardiac function, ambulatory capacity, and survival. Exosomes secreted by human CDCs reproduce the benefits of CDCs in mdx mice and in human induced pluripotent stem cell-derived Duchenne cardiomyocytes. Surprisingly, CDCs and their exosomes also transiently restored partial expression of full-length dystrophin in mdx mice. The findings further motivate the testing of CDCs in Duchenne patients, while identifying exosomes as next-generation therapeutic candidates.

FAK activation is required for IGF1R-mediated regulation of EMT, migration, and invasion in mesenchymal triple negative breast cancer cells.

Triple negative breast cancer (TNBC) is a highly metastatic disease that currently lacks effective prevention and treatment strategies. The insulin-like growth factor 1 receptor (IGF1R) and focal adhesion kinase (FAK) signaling pathways function in numerous developmental processes, and alterations in both are linked with a number of common pathological diseases. Overexpression of IGF1R and FAK are closely associated with metastatic breast tumors. The present study investigated the interrelationship between IGF1R and FAK signaling in regulating the malignant properties of TNBC cells. Using small hairpin RNA (shRNA)-mediated IGF1R silencing methods, we showed that IGF1R is essential for sustaining mesenchymal morphologies of TNBC cells and modulates the expression of EMT-related markers. We further showed that IGF1R overexpression promotes migratory and invasive behaviors of TNBC cell lines. Most importantly, IGF1R-driven migration and invasion is predominantly mediated by FAK activation and can be suppressed using pharmacological inhibitors of FAK. Our findings in TNBC cells demonstrate a novel role of the IGF1R/FAK signaling pathway in regulating critical processes involved in the metastatic cascade. These results may improve the current understanding of the basic molecular mechanisms of TNBC metastasis and provide a strong rationale for co-targeting of IGF1R and FAK as therapy for mesenchymal TNBCs.