Optimal treatment of asymptomatic patients with severe aortic stenosis: protocol of a prospective, multicentre, registry study.

INTRODUCTION: Decisions regarding the optimal timing of intervention for asymptomatic aortic stenosis (AS) are controversial. The study aims to identify potential risk factors for asymptomatic patients with severe AS that are associated with worse prognosis and to evaluate the benefits of early interventions for asymptomatic patients presenting with one or more additional risk factors. METHODS AND ANALYSIS: This is a non-interventional, prospective, open-label, multicentre registry study across China. A total of 1000 patients will be enrolled and categorised as symptomatic or asymptomatic. The primary endpoint is the occurrence of all-cause mortality, stroke, acute myocardial infarction and heart failure-related hospitalisation at 1-year follow-up. In asymptomatic severe AS patients presenting with one or more risk factors, the occurrence rate of the primary endpoint between those who undergo transcatheter aortic valve replacement (TAVR) and those who do not will be compared. We will also compare the occurrence rate of the primary endpoint for asymptomatic severe AS patients with additional risk factors who undergo TAVR with those presenting with symptoms. This study is believed to provide additional evidence to help clinicians identify and refer severe AS patients who are asymptomatic but present with additional risk factors for early intervention of TAVR. ETHICS AND DISSEMINATION: The study protocol has been approved by the local ethics committee of each participating site: West China Hospital, Sichuan University; Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Second Hospital of Hebei Medical University; Tianjin Chest Hospital; and First Affiliated Hospital of Nanchang University. All participants will provide written informed consent. Study results will be published through academic conferences and peer-reviewed journals. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry (https:// www.chictr.org.cn), with the registration number ChiCTR2200064853.

Patients with Limited Life Expectancy Are Biopsied for Keratinocyte Cancers at Similar Frequency to Healthy Patients.

BACKGROUND: In many fields of medicine, guidelines recommend reduced cancer screening in patients of advanced age with limited life expectancy (LLE). In dermatology, there are currently no guidelines for adjusted evaluation and management practices of keratinocyte cancer (KC) in patients with LLE. Little is known regarding evaluation and management patterns and frequency of biopsies in these patients. OBJECTIVE: We sought to determine if dermatology providers biopsy LLE patients with similar frequency to their age-matched peers and quantify frequency of associated complications. METHODS: This was a retrospective cohort study of evaluations for skin cancer quantified by skin biopsy frequency at the North Texas Veterans Affairs Health System dermatology clinic for 3,062 patients between 2005 and 2009, including a 5-year follow-up period. Life expectancy was quantified by the validated Charlson Comorbidity Index (CCI) with a Deyo adaptation. RESULTS: There was no significant difference in biopsy frequency of KC in LLE versus non-LLE patients in most age-controlled groups, with increased biopsy frequency in LLE patients in the 65-74 age category (p = 0.02). There was also an increased risk of complications from biopsy in the 75-84 (many comorbidities subgroup: RR = 3.27, p = 0.002; some comorbidities subgroup: RR = 2.26, p = 0.048) and 65-74 (many comorbidities subgroup: RR = 1.52, p = 0.004) age groups when compared to age-matched healthy controls. CONCLUSION: Biopsy frequency is similar or increased in patients with LLE compared with age-matched controls, with increased frequency of complications. Further studies are needed to understand the underlying factors driving these practice patterns.

mRNA based vaccines provide broad protection against different SARS-CoV-2 variants of concern.

In order to overcome the pandemic of COVID-19, messenger RNA (mRNA)-based vaccine has been extensively researched as a rapid and versatile strategy. Herein, we described the immunogenicity of mRNA-based vaccines for Beta and the most recent Omicron variants. The homologous mRNA-Beta and mRNA-Omicron and heterologous Ad5-nCoV plus mRNA vaccine exhibited high-level cross-reactive neutralization for Beta, original, Delta, and Omicron variants. It indicated that the COVID-19 mRNA vaccines have great potential in the clinical use against different SARS-CoV-2 variants.

The nano delivery systems and applications of mRNA.

The current COVID-19 epidemic has greatly accelerated the application of mRNA technology to our real world, and during this battle mRNA has proven it's unique advantages compared to traditional biopharmaceutical and vaccine technology. In order to overcome mRNA instability in human physiological environments, mRNA chemical modifications and nano delivery systems are two key factors for their in vivo applications. In this review, we would like to summarize the challenges for clinical translation of mRNA-based therapeutics, with an emphasis on recent advances in innovative materials and delivery strategies. The nano delivery systems include lipid delivery systems (lipid nanoparticles and liposomes), polymer complexes, micelles, cationic peptides and so on. The similarities and differences of lipid nanoparticles and liposomes are also discussed. In addition, this review also present the applications of mRNA to other areas than COVID-19 vaccine, such as infectious diseases, tumors, and cardiovascular disease, for which a variety of candidate vaccines or drugs have entered clinical trials. Furthermore, mRNA was found that it might be used to treat some genetic disease, overcome the immaturity of the immune system due to the small fetal size in utero, treat some neurological diseases that are difficult to be treated surgically, even be used in advancing the translation of iPSC technology et al. In short, mRNA has a wide range of applications, and its era has just begun.

A C-terminally truncated mouse Best3 splice variant targets and alters the ion balance in lysosome-endosome hybrids and the endoplasmic reticulum.

The Bestrophin family has been characterized as Cl(-) channels in mammals and Na(+) channels in bacteria, but their exact physiological roles remian unknown. In this study, a natural C-terminally truncated variant of mouse Bestrophin 3 (Best3V2) expression in myoblasts and muscles is demonstrated. Unlike full-length Best3, Best3V2 targets the two important intracellular Ca stores: the lysosome and the ER. Heterologous overexpression leads to lysosome swelling and renders it less acidic. Best3V2 overexpression also results in compromised Ca(2+) release from the ER. Knocking down endogenous Best3 expression in myoblasts makes these cells more excitable in response to Ca(2+) mobilizing reagents, such as caffeine. We propose that Best3V2 in myoblasts may work as a tuner to control Ca(2+) release from intracellular Ca(2+) stores.

Acquired protein energy malnutrition in glutaric acidemia.

We report a case of acquired protein energy malnutrition with associated zinc deficiency in an 18-month-old boy with type 1 glutaric acidemia. Physical examination findings included generalized nonpitting edema, widespread desquamative plaques, and sparse hair with a reddish tinge. Laboratory abnormalities included low levels of zinc, albumin, alkaline phosphatase, and iron. A review of skin manifestations of nutritional deficiencies, specifically kwashiorkor, is presented, as well as the relatively new entity called acrodermatitis dysmetabolica.

The biocompatibility of titanium cardiovascular devices seeded with autologous blood-derived endothelial progenitor cells: EPC-seeded antithrombotic Ti implants.

Implantable and extracorporeal cardiovascular devices are commonly made from titanium (Ti) (e.g. Ti-coated Nitinol stents and mechanical circulatory assist devices). Endothelializing the blood-contacting Ti surfaces of these devices would provide them with an antithrombogenic coating that mimics the native lining of blood vessels and the heart. We evaluated the viability and adherence of peripheral blood-derived porcine endothelial progenitor cells (EPCs), seeded onto thin Ti layers on glass slides under static conditions and after exposure to fluid shear stresses. EPCs attached and grew to confluence on Ti in serum-free medium, without preadsorption of proteins. After attachment to Ti for 15 min, less than 5% of the cells detached at a shear stress of 100 dyne / cm(2). Confluent monolayers of EPCs on smooth Ti surfaces (Rq of 10 nm), exposed to 15 or 100 dyne/cm(2) for 48 h, aligned and elongated in the direction of flow and produced nitric oxide dependent on the level of shear stress. EPC-coated Ti surfaces had dramatically reduced platelet adhesion when compared to uncoated Ti surfaces. These results indicate that peripheral blood-derived EPCs adhere and function normally on Ti surfaces. Therefore EPCs may be used to seed cardiovascular devices prior to implantation to ameliorate platelet activation and thrombus formation.

Application of energy-based technologies and topical hemostatic agents in the management of surgical hemostasis.

Achieving intraoperative hemostasis is essential for excellent surgical outcomes. A variety of methods, ranging from mechanical tools and energy-based technologies to topical hemostatic agents, are available to the modern surgeon. Given that bleeding develops from different origins, from small discrete bleeding or venous oozing to arterial hemorrhage, different tools and agents have different efficacy in specific situations. In this article, we review the mechanism by which currently available hemostatic tools and agents stop bleeding and give recommendations for their use during surgery. Furthermore, the costs of the various methods are presented, allowing the provider to choose not only the most potent but also the most cost-effective treatment modality in each situation.