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Urokinase type plasminogen activator, or urokinase (uPA), is a multifunctional protein which plays special regulatory role in the vascular wall and can actuate the proteolytic and signal cascades. The authors' results and literature data concerning the role of urokinase in remodeling blood vessels and angiogenesis are summarized in the paper. At the present stage urokinase may be considered as a promising target for the effects directed to prophylaxis of restenoses, to preventing of negative remodeling of arteries, stimulation of vessels growth under the ischemic diseases and suppression of angiogenesis under oncologic diseases. [ABSTRACT FROM AUTHOR]

The aim of this study was to present the diagnostic and outcome characteristics of infants with germline status of KMT2A gene (KMT2A-g) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treated consistently according to the MLL-Baby protocol, a moderate-intensity protocol. Of the 139 patients enrolled in the MLL-Baby study, 100 (71.9%) carried different types of rearranged KMT2A (KMT2A-r), while the remaining 39 infants (28.1%) had KMT2A-g. KMT2A-g patients were generally older (77% older than 6 months), less likely to have a very high white blood cell count (greater than 100 × 10 9 /L), less likely to be central nervous system (CNS)-positive, and more likely to be CD10-positive. The 6-year event-free survival and overall survival rates for all 39 patients were 0.74 (standard error [SE] 0.07) and 0.80 (SE 0.07), respectively. Relapse was the most common adverse event (n = 5), with a cumulative incidence of relapse (CIR) of 0.13 (SE 0.06), while the incidence of a second malignancy (n = 1) and death in remission (n = 3) was 0.03 (SE 0.04) and 0.08 (SE 0.04), respectively. None of the initial parameters, including genetics and the presence of recently described fusions of NUTM1 and PAX5 genes, was able to distinguish patients with different outcomes. Only rapidity of response, measured as minimal residual disease (MRD) by flow cytometry, showed a statistically significant impact. Moderate-intensity therapy, as used in the MLL-Baby protocol in infants with KMT2A-g BCP-ALL, yields results comparable to other infant studies. Patients with a slow multicolor flow cytometry (MFC)-MRD response should be subjected to advanced therapies, such as targeted or immunotherapies., (© 2023 Wiley Periodicals LLC.)

Objectives: Although laboratory result presentation may lead to information overload and subsequent missed or delayed diagnosis, little has been done in the past to improve this post-analytical issue. We aimed to investigate the efficiency, efficacy and user satisfaction of alternative report formats., Methods: We redesigned cumulative (sparkline format) and single reports (improved tabular and z-log format) and tested these on 46 physicians, nurses and medical students in comparison to the classical tabular formats, by asking standardized questions on general items on the reports as well as on suspected diagnosis and follow-up treatment or diagnostics., Results: Efficacy remained at a very high level both in the new formats as well as in the classical formats. We found no significant difference in any of the groups. Efficiency improved in all groups when using the sparkline cumulative format and marginally when showing the improved tabular format. When asking medical questions, efficiency and efficacy remained similar between report formats and groups. All alternative reports were subjectively more attractive to the majority of participants., Conclusions: Showing cumulative reports as a graphical display led to faster detection of general information on the report with the same level of correctness. Considering the familiarity bias of the classical single report formats, the borderline-significant improvement of the alternative tabular format and the non-inferiority of the z-log format, suggests that single reports might benefit from some improvements derived from basic information design., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Endothelial cells (ECs) degrade the extracellular matrix of vessel walls and contact surrounding cells to facilitate migration during angiogenesis, leading to formation of an EC-tubular network (ETN). Mesenchymal stromal cells (MSC) support ETN formation when co-cultured with ECs, but the mechanism is incompletely understood. We examined the role of the urokinase-type plasminogen activator (uPA) system, i.e. the serine protease uPA, its inhibitor PAI-1, receptor uPAR/CD87, clearance by the low-density lipoprotein receptor-related protein (LRP1) and their molecular partners, in the formation of ETNs supported by adipose tissue-derived MSC. Co-culture of human umbilical vein ECs (HUVEC) with MSC increased mRNA expression levels of uPAR, MMP14, VEGFR2, TGFβ1, integrin β 3 and Notch pathway components (Notch1 receptor and ligands: Dll1, Dll4, Jag1) in HUVECs and uPA, uPAR, TGFβ1, integrin β 3 , Jag1, Notch3 receptor in MSC. Inhibition at several steps in the activation process indicates that uPA, uPAR and LRP1 cross-talk with α v -integrins, VEGFR2 and Notch receptors/ligands to mediate ETN formation in HUVEC-MSC co-culture. The urokinase system mediates ETN formation through the coordinated action of uPAR, uPA's catalytic activity, its binding to uPAR and its nuclear translocation. These studies identify potential targets to help control aberrant angiogenesis with minimal impact on healthy vasculature., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In laboratory medicine, much effort has been put into analytical quality in the past decades, making this medical profession one of the most standardized with the lowest rates of error. However, even the best analytical quality cannot compensate for errors or low quality in the pre or postanalytical phase of the total testing process. Guidelines for data reporting focus solely on defined data elements, which have to be provided alongside the analytical test results. No guidelines on how to format laboratory reports exist. The habit of reporting as much diagnostic data as possible, including supplemental information, may lead to an information overload. Considering the multiple tasks physicians have to do simultaneously, unfiltered data presentation may contribute to patient risk, as important information may be overlooked, or juxtaposition errors may occur. As laboratories should aim to answer clinical questions, rather than providing sole analytical results, optimizing formatting options may help improve the effectiveness and efficiency of medical decision-making. In this narrative review, we focus on the underappreciated topic of laboratory result reporting. We present published literature, focusing on the impact of laboratory result report formatting on medical decisions as well as approaches, potential benefits, and limitations for alternative report formats. We discuss influencing variables such as, for example, the type of patient (e.g. acute versus chronic), the medical specialty of the recipient of the report, the display of reference intervals, the medium or platform on which the laboratory report is presented (printed paper, within electronic health record systems, on handheld devices, etc.), the context in which the report is viewed in, and difficulties in formatting single versus cumulative reports. Evidence on this topic, especially experimental studies, is scarce. When considering the medical impact, it is of utmost importance that laboratories focus not only on the analytical aspects but on the total testing process. The achievement of high analytical quality may be of minor value if essential results get lost in overload or scattering of information by using a non-formatted tabular design. More experimental studies to define guidelines and to standardize effective and efficient reporting are most definitely needed.

Chromosomal rearrangements of the human KMT2A / MLL gene are associated with acute leukemias, especially in infants. KMT2A is rearranged with a big variety of partner genes and in multiple breakpoint locations. Detection of all types of KMT2A rearrangements is an essential part of acute leukemia initial diagnostics and follow-up, as it has a strong impact on the patients' outcome. Due to their high heterogeneity, KMT2A rearrangements are most effectively uncovered by next-generation sequencing (NGS), which, however, requires a thorough prescreening by cytogenetics. Here, we aimed to characterize uncommon KMT2A rearrangements in childhood acute leukemia by conventional karyotyping, FISH, and targeted NGS on both DNA and RNA level with subsequent validation. As a result of this comprehensive approach, three novel KMT2A rearrangements were discovered: ins(X;11)(q26;q13q25)/ KMT2A-BTK , t(10;11)(q22;q23.3)/ KMT2A-NUTM2A , and inv(11)(q12.2q23.3)/ KMT2A-PRPF19 . These novel KMT2A -chimeric genes expand our knowledge of the mechanisms of KMT2A -associated leukemogenesis and allow tracing the dynamics of minimal residual disease in the given patients.

Introduction: Kidney cancer (mostly renal cell carcinoma) is one of the ten most commonly diagnosed malignant tumors among men and women. Due to the widespread use of computer tomography and magnetic resonance imaging, the proportion of early-stage kidney cancers has increased. Currently, treatment options for stage 1 kidney cancer are radical nephrectomy, partial nephrectomy, and active surveillance. Among organ-preserving intervention, three main techniques can be distinguished: open surgery, minimally invasive surgery and ablation methods. To date, robotic-assisted procedures have occupied their place among minimally invasive interventions., Aim: To carry out a comparative analysis of two methods of organ-preserving treatment of kidney tumors, namely robot-assisted and laparoscopic partial nephrectomy., Materials and Methods: A retrospective comparative analysis of two groups of patients with kidney tumors who underwent robotic-assisted or laparoscopic partial nephrectomy during the period from 2012 to 2019 was performed., Results: There were no differences between two groups in age, mean score on the RENAL nephrometry scale, preoperative creatinine levels, tumor size, and duration of warm ischemia. However, duration of surgery, the volume of blood loss, serum creatinine after surgery, the length of stay, the use of the technique of early unclamping of the renal artery, the use of technique "off-clamp" and the proportion of exophytic tumors with growth were significantly different between patients of two groups., Conclusion: We believe that the robotic system is intuitively convenient for performing partial nephrectomy, allowing the treatment of potentially more complex cases and expanding the indications for organ-preserving procedures.

Currently, partial nephrectomy as a nephron-sparing surgery is the standard treatment method of malignant kidney tumors stage T1 in the absence of contraindications. Robotic system is an intuitively convenient platform for performing partial nephrectomy of various degrees of complexity. The technique of robot-assisted laparoscopic partial nephrectomy continues to improve but is still not standardized. A description of surgical technique, results and complications of robot-assisted laparoscopic partial nephrectomy are presented in the article.