Recommendations on the use of innovative medical technologies in cardiology and cardiac surgery and solutions leading to increased availability for Polish patients

There is a great need for innovative technologies that will improve the health and quality of life (QoL) of Polish patients with cardiac problems. It is important that the safety and effectiveness of the technology are confirmed by scientific evidence on which guidelines and clinical recommendations are based. Scientific evidence for medical devices is also increasingly important for decision-making in finance approval from public funds. New technologies in cardiology and cardiac surgery contribute to improved patient QoL, increased treatment effectiveness and facilitated diagnosis. Hence, it is necessary to increase accessibility to such technologies, primarily through the development of clinical recommendations, and education of medical personnel in conjunction with public funding. The aim of this publication is to present the recommendations of leading experts in the field of cardiology and cardiosurgery, supported by clinical research results, regarding the use of the cited innovative medical technologies and solutions leading to their increased availability for Polish patients.

Heart failure in Poland: Left ventricular assist device destination therapy and other challenges of interventional cardiology and cardiac surgery

Patients with severe heart failure (HF), who are not eligible for cardiac transplantation and receive optimal medical management, based mainly on the use of pharmacological treatment and devices such as resynchronization therapy (implantable cardioverter-defibrillator), achieve poor clinical outcomes and constitute a group with extremely poor prognosis. Currently, the technology used in the latest generation left ventricular assist devices (LVADs), such as the HeartMate 3, makes it possible to achieve patient survival at the level obtained by patients after heart transplantation, and they can be used not only in patients eligible for heart transplantation as a bridge to transplant, but also in those with significantly worse prognosis, who are ineligible for heart transplantation as destination therapy. The objective of this publication is to present recommendations from experts in cardiology and cardiac surgery, supported by clinical trial results, on the use of LVADs as a destination therapy in HF patients who are not eligible for cardiac transplantation. The paper also presents the issue of cardiac transplantation and extracorporeal membrane oxygenation therapy in Poland, as well as current challenges faced by interventional cardiology and cardiac surgery in Poland

A novel Rac-dependent checkpoint in B cell development controls entry into the splenic white pulp and cell survival

Rac1 and Rac2 GTPases transduce signals from multiple receptors leading to cell migration, adhesion, proliferation, and survival. In the absence of Rac1 and Rac2, B cell development is arrested at an IgD− transitional B cell stage that we term transitional type 0 (T0). We show that T0 cells cannot enter the white pulp of the spleen until they mature into the T1 and T2 stages, and that this entry into the white pulp requires integrin and chemokine receptor signaling and is required for cell survival. In the absence of Rac1 and Rac2, transitional B cells are unable to migrate in response to chemokines and cannot enter the splenic white pulp. We propose that loss of Rac1 and Rac2 causes arrest at the T0 stage at least in part because transitional B cells need to migrate into the white pulp to receive survival signals. Finally, we show that in the absence of Syk, a kinase that transduces B cell antigen receptor signals required for positive selection, development is arrested at the same T0 stage, with transitional B cells excluded from the white pulp. Thus, these studies identify a novel developmental checkpoint that coincides with B cell positive selection

Upregulation of MMP12 and Its Activity by UVA1 in Human Skin:Potential Implications for Photoaging

UVA1 constitutes around 75% of the terrestrial UV radiation, and most of the output of artificial tanning sources. However, the molecular effects of UVA1 in human skin in vivo are surprisingly poorly understood. We have examined time-dependent whole-genome expression, along with mRNA and protein changes in the skin after one minimal erythema dose of spectrally pure UVA1 (50Jcm−2) and 300nm UVB (30mJcm−2). After 24hours, the genes induced to the greatest extent were those involved in extracellular matrix remodeling with both UVA1 (P=5.5e-7) and UVB (P=2.9e-22). UVA1 and UVB caused different effects on matrix metalloproteinase (MMP) expression: UVB induced MMP1, MMP3, and MMP10 mRNA at 24hours to a much greater extent than UVA1. MMP12 induction by UVA1 at 6hours is marked and much greater than that by UVB. We have found that MMP12 mRNA induction by UVA1 resulted in expression of MMP12 protein, which is functional as an elastase. This induction of elastase activity did not occur with UVB. We hypothesize that the UVA1 induction of MMP12 mediates some of its photoaging effects, particularly by contributing to elastin degeneration in late solar elastosis. MMP12 is a good marker of UVA1 exposure

Characterization of Innate Lymphoid Cells in Human Skin and Blood Demonstrates Increase of NKp44+ILC3 in Psoriasis

Innate lymphoid cells (ILCs) are increasingly appreciated as key regulators of tissue immunity. However, their role in human tissue homeostasis and disease remains to be fully elucidated. Here we characterize the ILCs in human skin from healthy individuals and from the inflammatory skin disease psoriasis. We show that a substantial proportion of IL-17A and IL-22 producing cells in the skin and blood of normal individuals and psoriasis patients are CD3-negative innate lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically significant increase in the frequency of circulating NKp44+ ILC3 in the blood of psoriasis patients compared with healthy individuals or atopic dermatitis patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte–associated antigen, indicating their potential for skin homing. Analysis of skin tissue revealed a significantly increased frequency of total ILCs in the skin compared with blood. Moreover, the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared with normal skin. A detailed time course of a psoriasis patient treated with anti–tumor necrosis factor showed a close association between therapeutic response, decrease in inflammatory skin lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial observational study suggest a potential role for NKp44+ ILC3 in psoriasis pathogenesis