Redefining primary hyperaldosteronism as "The Syndrome of Inappropriate Aldosterone Secretion (SIALDS)": A common but unrecognized cause of hypertension.

The current screening and diagnostic recommendations for detecting Primary Hyperaldosteronism (PHA) focus on diagnosing the more severe and overt instances of renin-independent aldosterone production. However, milder forms of autonomous aldosterone secretion have been demonstrated to exist below the diagnostic thresholds of current PHA guidelines, and associate with clinically relevant cardiovascular risk. PHAencompasses a spectrum of renin independent aldosterone production, progressing from a subclinical state in normotensives to a full-blown clinical syndrome representing the resistant hypertension population. The authors propose the Syndrome of Inappropriately Elevated Aldosterone Secretion (SIALDS) concept as a potential new paradigm for understanding and diagnosing PHA and expanded diagnostic approach to improve early detection even in well-controlled hypertension. The authors also delve into the impact of treatments, including mineralocorticoid receptor antagonists and emerging aldosterone synthase inhibitors. Furthermore, The authors outline future research directions, proposing clinical trials to investigate the long-term identification and treatment outcomes of SIALDS.

Hypertension in the Kidney Transplant Recipient: Overview of Pathogenesis, Clinical Assessment, and Treatment.

Cardiovascular disease is the leading cause of death in patients with chronic renal disease and the most common cause of death and allograft loss among kidney transplant recipients. Transplant patients often have multiple cardiovascular risk factors antedating transplantation. Among the most prominent is hypertension (HTN), which affects at least 90% of transplant patients. Uncontrolled HTN is an independent risk factor for allograft loss. The etiology of HTN in transplant recipients is complex and multifactorial, including the use of essential immunosuppressive medications. Post-transplant HTN management requires a systematic and individualized approach with nonpharmacologic and pharmacologic therapies. There is no single ideal agent or treatment algorithm. Patients should regularly monitor and record their blood pressure at home. Often, multiple antihypertensive drugs are needed to achieve a goal blood pressure of 120-140/70-90 mm Hg. As transplant recipients commonly must take 8 to 12 different medications daily, adherence must be continually encouraged and monitored. Special attention must be paid to potential drug side effects and drug interactions with immunosuppressive medications.

The Secretome of Hydrogel-Coembedded Endothelial Progenitor Cells and Mesenchymal Stem Cells Instructs Macrophage Polarization in Endotoxemia.

UNLABELLED: : We previously reported the delivery of endothelial progenitor cells (EPCs) embedded in hyaluronic acid-based (HA)-hydrogels protects renal function during acute kidney injury (AKI) and promotes angiogenesis. We attempted to further ameliorate renal dysfunction by coembedding EPCs with renal mesenchymal stem cells (MSCs), while examining their paracrine influence on cytokine/chemokine release and proinflammatory macrophages. A live/dead assay determined whether EPC-MSC coculturing improved viability during lipopolysaccharide (LPS) treatment, and HA-hydrogel-embedded delivery of cells to LPS-induced AKI mice was assessed for effects on mean arterial pressure (MAP), renal blood flow (RBF), circulating cytokines/chemokines, serum creatinine, proteinuria, and angiogenesis (femoral ligation). Cytokine/chemokine release from embedded stem cells was examined, including effects on macrophage polarization and release of proinflammatory molecules. EPC-MSC coculturing improved stem cell viability during LPS exposure, an effect augmented by MSC hypoxic preconditioning. The delivery of coembedded EPCs with hypoxic preconditioned MSCs to AKI mice demonstrated additive improvement (compared with EPC delivery alone) in medullary RBF and proteinuria, with comparable effects on serum creatinine, MAP, and angiogenesis. Exposure of proinflammatory M1 macrophages to EPC-MSC conditioned medium changed their polarization to anti-inflammatory M2. Incubation of coembedded EPCs-MSCs with macrophages altered their release of cytokines/chemokines, including enhanced release of anti-inflammatory interleukin (IL)-4 and IL-10. EPC-MSC delivery to endotoxemic mice elevated the levels of circulating M2 macrophages and reduced the circulating cytokines/chemokines. In conclusion, coembedding EPCs-MSCs improved their resistance to stress, impelled macrophage polarization from M1 to M2 while altering their cytokine/chemokines release, reduced circulating cytokines/chemokines, and improved renal and vascular function when MSCs were hypoxically preconditioned. SIGNIFICANCE: This report provides insight into a new therapeutic approach for treatment of sepsis and provides a new and improved strategy using hydrogels for the delivery of stem cells to treat sepsis and, potentially, other injuries and/or diseases. The delivery of two different stem cell lines (endothelial progenitor cells and mesenchymal stem cells; delivered alone and together) embedded in a protective bioengineered scaffolding (hydrogel) offers many therapeutic benefits for the treatment of sepsis. This study shows how hydrogel-delivered stem cells elicit their effects and how hydrogel embedding enhances the therapeutic efficacy of delivered stem cells. Hydrogel-delivered stem cells influence the components of the overactive immune system during sepsis and work to counterbalance the release of many proinflammatory and prodamage substances from immune cells, thereby improving the associated vascular and kidney damage.

Improving resident morning sign-out by use of daily events reports.

OBJECTIVES: The clinician arriving at the hospital in the morning may not yet be aware of key overnight clinical activity. To address this situation at our facility, we modified our handoff software to permit continuous updating of clinical information and the automatic relay of important overnight clinical updates to relevant providers each morning. METHODS: Cross-covering residents electronically entered safety concerns and clinical issues within the reporting module of the handoff software between 5 PM and 7 AM. This updated their handoff-information at shift change and permitted the generation of reports that were emailed to primary providers and reviewed before 7 AM prerounds. At 7:30 sign-out, if a resident was already aware of an issue being signed out, he/she indicated this so that sign-out could quickly proceed to the next patient. Study sign-out duration was recorded, and residents were surveyed regarding the new communication system. RESULTS: Morning sign-out duration decreased from 25.5 to 22.7 minutes (P = 0.0338). All respondents agreed strongly (12/14, 86%) or somewhat (2/14, 14%) that daily morning events reports prevented "loss of key information between shifts" and enhanced safety greatly (10/14, 71%) or moderately (4/14, 29%).All agreed either strongly (10/14, 71%) or somewhat (4/14, 29%) that the daily report improved the quality of handoff information and strongly (12/14, 86%) or somewhat (2/14, 14%) that the report was convenient. CONCLUSIONS: The collection of key clinical handoff information and its automatic forwarding to incoming providers reduced the average duration of resident morning sign-out and significantly enhanced provider perceptions regarding patient safety and the quality of handoff information.