Cardiac Surgery-Associated Acute Kidney Injury.

AKI is a common and serious complication of cardiac surgery that has a significant impact on patient morbidity and mortality. The Kidney Disease Improving Global Outcomes definition of AKI is widely used to classify and identify AKI associated with cardiac surgery (cardiac surgery-associated AKI [CSA-AKI]) on the basis of changes in serum creatinine and/or urine output. There are various preoperative, intraoperative, and postoperative risk factors for the development of CSA-AKI which should be recognized and addressed as early as possible to expedite its diagnosis, reduce its occurrence, and prevent or ameliorate its devastating complications. Crucial issues are the inaccuracy of serum creatinine as a surrogate parameter of kidney function in the perioperative setting of cardiothoracic surgery and the necessity to discover more representative markers of the pathophysiology of AKI. However, except for the tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 ratio, other diagnostic biomarkers with an acceptable sensitivity and specificity are still lacking. This article provides a comprehensive review of various aspects of CSA-AKI, including pathogenesis, risk factors, diagnosis, biomarkers, classification, prevention, and treatment management.

Association of metabolic syndrome and chronic kidney disease.

The prevalence of kidney disease is increasing rapidly worldwide, reflecting rising rates of obesity, diabetes, and associated metabolic syndrome (MetS). Chronic kidney disease and related comorbidities such as obesity, diabetes, and hypertension place a significant financial burden on healthcare systems. Despite the widespread use of RAAS inhibitors, intensive blood pressure and glycemic control, and newer therapeutic options consisting of sodium/glucose cotransporter-2 (SGLT-2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists, a significant risk of progression to end-stage renal disease remains in the high-risk obese and diabetic population. The MetS is a cluster of cardiovascular risk factors that adversely affect the development and progression of chronic kidney failure. According to the criteria of the World Health Organization, it is defined by visceral adiposity, impaired glucose tolerance or insulin resistance, atherogenic dyslipidemia, raised blood pressure, and microalbuminuria with a albumin-to-creatinine ratio ≥30 mg/g. At molecular level MetS is marked by a proinflammatory state and increased oxidative stress leading to various pathophysiological changes causing endothelial dysfunction and a hypercoagulable state. Because the kidney is a highly vascularized organ, it is especially susceptible for those microvascular changes. Therefore, the MetS and its individual components are associated with the premature development, acceleration, and progression of chronic kidney disease. Therefore, it is becoming increasingly important to elucidate the underlying mechanisms of MetS-associated chronic kidney disease in order to develop new strategies for preventing and slowing the progression of renal disease. In this review, we will elucidate (i) the renal structural, hemodynamic, and metabolic changes that occur in obesity and obesity-related kidney injury; (ii) the clinicopathological characteristics of obesity-related kidney injury, primarily focusing on obesity-associated glomerulopathy; (iii) the potential additional factors or predisposing factors that may turn patients more susceptible to renal structural or functional compensatory failure and subsequent injury.

Effectiveness of multi-professional educational interventions to train Comprehensive Geriatric Assessment (CGA) - a Systematic Review.

Introduction: As the world population ages, health and social care professionals are increasingly confronted with patients with chronic long-term conditions and multimorbidity, requiring an extensive assessment and integrated care management strategy. The aim of this paper was to systematically collect and assess evidence of interprofessional education and training strategies for Comprehensive Geriatric Assessment (CGA) to build a competent health workforce. Methods: A systematic review was conducted according to PRISMA guidelines and the databases Medline, CINAHL, Cochrane and Embase were searched for studies illustrating effectiveness of educational interventions for teaching and training CGA in an interprofessional context. Results: Based on 21 identified studies, a great variability and heterogeneity in duration, setting and design of the interventions was identified. Promising results were found in the domains analysed, ranging from knowledge and skills; practices and behaviour; patient health outcomes; attitudes and perceptions to collaboration and quality of care. Discussion: Education and training of transversal skills within a continuous learning approach is key to equip the health care workforce for successful CGA performance in an interprofessional environment. Conclusion: Further research in this field is recommended to strengthen the evidence-base towards development of a resilient and integrated health care workforce for an ageing population.

Chefs in Future Integrated Healthcare - Current State and Innovation Needs: A First Overview of the NECTAR Project (aN Eu Curriculum for Chef gasTro-Engineering in Primary Food Care).

People in need of care, chronic or acute, often present problematic food intake and special nutritional needs. Integrated, person-centred and pro-active food and nutritional care delivery has been proven effective for people in health care. However, skills mismatches have been reported in different professions involved, which also applies to the role of chefs in healthcare. The EU funded project NECTAR aims at closing this gap by creating a new job profile, called Chef Gastro-Engineering (CGE). The current publication summarizes the status quo in hospitals and gives a perspective on the future role of chefs in integrated healthcare delivery.

Clinical Interventions to Improve Nutritional Care in Older Adults and Patients in Primary Healthcare - A Scoping Review of Current Practices of Health Care Practitioners.

In light of the increasing life expectancy of Europe's population and the rising significance of active and healthy ageing relating thereto, an integrated approach of nutritional care within primary health care is gaining importance. The aim of the review was to summarize evidence on the effectiveness of nutritional interventions in primary health care. The scoping review is based upon a comprehensive literature search of relevant literature published between January 2010 and August 2021 in PubMed, CINAHL, Cochrane Database of Systematic Reviews, Embase and Medline databases. Overall, 15 studies were included for evidence synthesis and interventions were basically clustered according to their type, into 1) eHealth and tele-medical interventions; 2) targeted single interventions; and 3) comprehensive, multi-faceted interventions. The review presents diverging evidence regarding the efficacy and effectiveness of interventions for nutritional care in primary health care, however, demonstrates encouraging outcomes. eHealth and tele-medical interventions partly show a careful positive tendency. Likewise, manifold single interventions on patient level present significant improvements in patient health outcomes. Multifaceted and comprehensive interventions found in the literature also partly demonstrate significant changes in intervention groups. Primary health care represents a critical setting for the care of older citizens and patients with complex health needs. This scoping review provides an overview of current nutrition care practices in primary health care and results reinforce the need to strengthen implementation of multi-faceted interventions carried out by the inter-disciplinary primary care team for advanced nutritional care.

Splicing factor YBX1 mediates persistence of JAK2-mutated neoplasms.

Janus kinases (JAKs) mediate responses to cytokines, hormones and growth factors in haematopoietic cells1,2. The JAK gene JAK2 is frequently mutated in the ageing haematopoietic system3,4 and in haematopoietic cancers5. JAK2 mutations constitutively activate downstream signalling and are drivers of myeloproliferative neoplasm (MPN). In clinical use, JAK inhibitors have mixed effects on the overall disease burden of JAK2-mutated clones6,7, prompting us to investigate the mechanism underlying disease persistence. Here, by in-depth phosphoproteome profiling, we identify proteins involved in mRNA processing as targets of mutant JAK2. We found that inactivation of YBX1, a post-translationally modified target of JAK2, sensitizes cells that persist despite treatment with JAK inhibitors to apoptosis and results in RNA mis-splicing, enrichment for retained introns and disruption of the transcriptional control of extracellular signal-regulated kinase (ERK) signalling. In combination with pharmacological JAK inhibition, YBX1 inactivation induces apoptosis in JAK2-dependent mouse and primary human cells, causing regression of the malignant clones in vivo, and inducing molecular remission. This identifies and validates a cell-intrinsic mechanism whereby differential protein phosphorylation causes splicing-dependent alterations of JAK2-ERK signalling and the maintenance of JAK2V617F malignant clones. Therapeutic targeting of YBX1-dependent ERK signalling in combination with JAK2 inhibition could thus eradicate cells harbouring mutations in JAK2.

Massive open online courses (MOOCs) for long-distance education in geriatric medicine across Europe : A pilot project launched by the consortium of the project "Screening for Chronic Kidney Disease among Older People": SCOPE project.

PURPOSE: To cover the increasing need for professional knowledge, skills and competences in the care of older people, new learning techniques have been developed. Using the Internet to provide educational material has come into focus of many academic institutions as the learning content can easily be transferred to a larger audience. Since the first launch of a "massive open online course" (MOOC) in 2008, this educational format has raised increasing interest among education experts. The current publication provides insight into the new format of MOOCs in general and specifically describes a MOOC developed by a Pan-European Consortium "Screening for Chronic Kidney Disease (CKD) among Older People across Europe" (SCOPE), a project funded by the European Commission under the umbrella of the Horizon 2020 program. METHODS: Technical background, learning theories and content of the MOOC of the SCOPE project are presented in this overview. RESULTS: The MOOC of the SCOPE project is provided on the MOOC ICT platform iMoox. The courses are built up of video clips, textual descriptions, graphics, animations and audio designed with a clear structure and learning goals. The concise video clips with a maximum length of 15-20 min are equipped with additional learning material such as documents, links and asynchronous communication opportunities. CONCLUSION: MOOCs are recognized as a contemporary approach to transfer required knowledge and skills not only in general but also in geriatric medicine, as the health and social care environment is ever-changing and becoming more complex.

Diverging impact of cell fate determinants Scrib and Llgl1 on adhesion and migration of hematopoietic stem cells.

PURPOSE: Cell fate determinants Scrib and Llgl1 influence self-renewal capacity of hematopoietic stem cells (HSCs). Scrib-deficient HSCs are functionally impaired and lack sufficient repopulation capacity during serial transplantation and stress. In contrast, loss of Llgl1 leads to increased HSC fitness, gain of self-renewal capacity and expansion of the stem cell pool. Here, we sought to assess for shared and unique molecular functions of Llgl1 and Scrib by analyzing their interactome in hematopoietic cells. METHODS: Interactome analysis was performed by affinity purification followed by mass spectrometry. Motility, migration and adhesion were assessed on primary murine HSCs, which were isolated by FACS sorting following conditional deletion of Scrib or Llgl1, respectively. Imaging of Scrib-deficient HSCs was performed by intravital 2-photon microscopy. RESULTS: Comparison of Scrib and Llgl1 interactome analyses revealed involvement in common and unique cellular functions. Migration and adhesion were among the cellular functions connected to Scrib but not to Llgl1. Functional validation of these findings confirmed alterations in cell adhesion and migration of Scrib-deficient HSCs in vitro and in vivo. In contrast, genetic inactivation of Llgl1 did not affect adhesion or migratory capacity of hematopoietic stem cells. CONCLUSION: Our data provide first evidence for an evolutionarily conserved role of the cell fate determinant Scrib in HSC adhesion and migration in vitro and in vivo, a unique function that is not shared with its putative complex partner Llgl1.

The cell fate determinant Scribble is required for maintenance of hematopoietic stem cell function.

Cell fate determinants influence self-renewal potential of hematopoietic stem cells. Scribble and Llgl1 belong to the Scribble polarity complex and reveal tumor-suppressor function in drosophila. In hematopoietic cells, genetic inactivation of Llgl1 leads to expansion of the stem cell pool and increases self-renewal capacity without conferring malignant transformation. Here we show that genetic inactivation of its putative complex partner Scribble results in functional impairment of hematopoietic stem cells (HSC) over serial transplantation and during stress. Although loss of Scribble deregulates transcriptional downstream effectors involved in stem cell proliferation, cell signaling, and cell motility, these effectors do not overlap with transcriptional targets of Llgl1. Binding partner analysis of Scribble in hematopoietic cells using affinity purification followed by mass spectometry confirms its role in cell signaling and motility but not for binding to polarity modules described in drosophila. Finally, requirement of Scribble for self-renewal capacity also affects leukemia stem cell function. Thus, Scribble is a regulator of adult HSCs, essential for maintenance of HSCs during phases of cell stress.