Publications by authors named "Sasa Vukelic"

Type II heparin-induced thrombocytopenia and thrombosis (type II HITT) is a rare but serious complication in patients receiving heparin for anticoagulation. In type II HITT, an immune-mediated reaction against platelet factor four-heparin complexes results in thrombocytopenia and an elevated risk of thrombosis. This poses significant challenges for patients with advanced heart failure requiring urgent left-ventricular assist device (LVAD) implantation.

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Microvascular dysfunction (MVD) is considered a form of cardiac allograft vasculopathy (CAV), independently associated with poor prognosis after heart transplantation (HTX). It is unknown whether traditional risk factors for CAV are also applicable to MVD. We retrospectively analyzed factors associated with MVD in 94 HTX recipients who completed a PET scan after a normal baseline left heart catheterization excluding epicardial CAV.

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We introduce the innovative use of technetium-99m-labeled macroaggregated albumin to diagnose high-output heart failure in a patient with multiple myeloma with persistent congestion symptoms. Symptom resolution occurred with lenalidomide and steroids. This marks the first clinical use of technetium-99m-labeled macroaggregated albumin for clarifying high-output heart failure etiology.

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Primary graft dysfunction (PGD) after cardiac transplantation is a devastating complication with increasing frequency lately in the setting of donation after circulatory death (DCD). Severe PGD is commonly treated with extracorporeal membrane oxygenation (ECMO) using central or peripheral cannulation. We retrospectively reviewed the outcomes of PGD after cardiac transplantation requiring ECMO support at our center from 2015 to 2020, focused on our now preferential approach using peripheral cannulation without a priori venting.

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The use of intra-aortic balloon pump (IABP) has decreased in recent years due to negative outcome studies in cardiogenic shock complicating acute myocardial infarction, despite its favorable adverse-event profile. Acute hemodynamic response studies have identified potential super-responders with immediate improvements in cardiac index (CI) in heart failure patients. This single-center retrospective study aimed to predict CI and mean arterial pressure (MAP) changes throughout the entire duration of IABP support.

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Background: Although infections are a significant potential complication among patients undergoing left ventricular assist device (LVAD) implantation, standardized surgical infection prophylaxis (SIP) regimens are not well defined. At Montefiore Medical Center, a 4-drug SIP regimen containing fluconazole, ciprofloxacin, rifampin, and vancomycin was previously utilized. In January 2020, the antimicrobial stewardship program implemented a 2-drug SIP regimen of vancomycin and cefazolin to limit exposure to broad-spectrum antibiotics.

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Article Synopsis
  • The study looked at how heart failure (HF) affects COVID-19 patients admitted to the hospital.
  • It found that patients with HF were more likely to die from COVID-19 compared to those without HF, with a death rate of 49% versus 27%.
  • The researchers concluded that having HF makes COVID-19 patients more at risk for serious outcomes and higher chances of dying in the hospital.
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The clinical spectrum of COVID-19 in heart transplant recipients has not been fully defined, because asymptomatic and sub-clinical cases are difficult to capture. Seroprevalence surveys are an important tool to identify not just cases that have come to clinical attention, but all previously infected recipients. We performed a seroprevalence survey of the adult heart transplant program at a large New York City Hospital System.

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Background Severe coronavirus disease 2019 (COVID-19) is characterized by a proinflammatory state with high mortality. Statins have anti-inflammatory effects and may attenuate the severity of COVID-19. Methods and Results An observational study of all consecutive adult patients with COVID-19 admitted to a single center located in Bronx, New York, was conducted from March 1, 2020, to May 2, 2020.

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Background: Hepatitis C virus (HCV) donors should be categorized as HCV-viremic (antibody [Ab] negative or positive/Nucleic Acid testing [NAT] positive) or HCV Abnonviremic (Ab/NAT). Whereas recipients of hearts from HCV-viremic donors will develop viremia but can be cured of HCV shortly after transplant with direct-acting antivirals (DAAs), recipients of hearts from HCV Ab nonviremic donors are highly unlikely to become viremic or require DAAs. Given this important difference in risk, we assessed the utilization trends and post-heart-transplantation outcomes of HCV-naive (Ab/NAT), HCV-viremic, and HCV Ab nonviremic donor hearts.

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Background: Hemolysis, even at low levels, activates platelets to create a prothrombotic state and is common during mechanical circulatory support. We examined the association of low-level hemolysis (LLH) and nonhemorrhagic stroke during venoarterial extracorporeal membrane oxygenation (VA ECMO) support.

Methods: A single-center retrospective review of all adult patients placed on VA ECMO from January 2012 to September 2017 was conducted.

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Background: Continuous-flow left ventricular assist devices have revolutionized the management of advanced heart failure. Device complications continue to limit survival, but enhanced management strategies have shown promise. This study compared outcomes for HeartMate II recipients before and after implementation of a multidisciplinary continuous support heart team (HTMCS) strategy.

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Background: Gastrointestinal bleeding (GIB) is one of the principal adverse events affecting patients with continuous-flow left ventricular assist devices (CF-LVADs). Despite the early recognition that GIB is commonly because of gastrointestinal angiodysplasia (GIAD), the exact pathophysiology of this process remains elusive. It has been postulated that the abnormal hemodynamic profile in CF-LVAD patients may activate the angiogenesis signaling cascade via the HIF (hypoxia-inducible factor)-1α/angiopoietin-2 pathway leading to formation of GIADs.

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Objective- Actin cytoskeleton assembly and organization, as a result of focal adhesion (FA) formation during cell adhesion, are dependent on reactive oxygen species and the cellular redox environment. Poldip2 (polymerase δ-interacting protein 2), a novel regulator of NOX4 (NADPH oxidase 4), plays a significant role in reactive oxygen species production and cytoskeletal remodeling. Thus, we hypothesized that endogenous reactive oxygen species derived from Poldip2/NOX4 contribute to redox regulation of actin and cytoskeleton assembly during integrin-mediated cell adhesion.

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Background: Hepatitis C (HCV) donors are rarely used for cardiac transplantation due to historically poor outcomes. In 2015, nucleic acid testing (NAT) for viral load was added to the routine work-up of organ donors, allowing for the distinction between subjects who remain viremic (HCV Ab/NAT) and those who have cleared HCV and are no longer viremic (HCV Ab/NAT). The American Society of Transplantation recently recommended that HCV Ab/NAT donors be considered non-infectious and safe for transplantation.

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Glucocorticoids (GCs), key mediators of stress signals, are also potent wound healing inhibitors. To understand how stress signals inhibit wound healing, we investigated the role of membranous glucocorticoid receptor (mbGR) by using cell-impermeable BSA-conjugated dexamethasone. We found that mbGR inhibits keratinocyte migration and wound closure by activating a Wnt-like phospholipase (PLC)/ protein kinase C (PKC) signaling cascade.

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Article Synopsis
  • Skin produces cholesterol and various metabolites, including farnesyl pyrophosphate (FPP), which influences epidermal differentiation and signaling pathways when accumulated due to a squalene synthase inhibitor (ZGA).
  • Elevated FPP levels have immunosuppressive effects, reducing immune signaling and downregulating genes for keratinocyte differentiation, while also inducing protective factors like Nrf2.
  • FPP acts as a ligand for the glucocorticoid receptor (GR) and shows a broad transcriptional influence, suggesting clinical implications for lipid metabolism and responses to medications like statins and glucocorticoids.
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Polymerase-δ-interacting protein 2 (Poldip2) interacts with NADPH oxidase 4 (Nox4) and regulates migration; however, the precise underlying mechanisms are unclear. Here, we investigated the role of Poldip2 in focal adhesion turnover, as well as traction force generation and polarization. Poldip2 overexpression (AdPoldip2) in vascular smooth muscle cells (VSMCs) impairs PDGF-induced migration and induces a characteristic phenotype of long cytoplasmic extensions.

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The epidermis is maintained by epidermal stem cells (ESCs) that reside in distinct niches and contribute to homeostasis and wound closure. Keratinocytes at the nonhealing edges of venous ulcers (VUs) are healing-incompetent, hyperproliferative, and nonmigratory, suggesting deregulation of ESCs. To date, genes which regulate ESC niches have been studied in mice only.

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Angiotensin II (Ang II) is today considered as one of the essential factors in the pathophysiology of cardiovascular disease, producing acute, hemodynamic and chronic, pleiotropic effects. Although now it is widely accepted that these chronic effects are important, Ang II was initially considered only a short-acting, vasoactive hormone. This view was modified a quarter of a century ago when Dr.

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An 82-year-old woman who presented to her primary care physician for preoperative evaluation was incidentally found to have severe hyponatremia (sodium = 118 mmol/L). The patient was then admitted for workup and treatment of hyponatremia. On day 2 of the admission, the patient was found to have new T-wave inversions on a telemetry monitor.

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Glucocorticoids (GCs) are known inhibitors of wound healing. In this study we report the novel finding that both keratinocytes in vitro and epidermis in vivo synthesize cortisol and how this synthesis regulates wound healing. We show that epidermis expresses enzymes essential for cortisol synthesis, including steroid 11 β-hydroxylase (CYP11B1), and an enzyme that controls negative feedback mechanism, 11β-hydroxysteroid dehydrogenase 2 (11βHSD2).

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Farnesyl pyrophosphate (FPP), a key intermediate in the mevalonate pathway and protein farnesylation, can act as an agonist for several nuclear hormone receptors. Here we show a novel mechanism by which FPP inhibits wound healing acting as an agonist for glucocorticoid receptor (GR). Elevation of endogenous FPP by the squalene synthetase inhibitor zaragozic acid A (ZGA) or addition of FPP to the cell culture medium results in activation and nuclear translocation of the GR, a known wound healing inhibitor.

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Background: Chronic wounds, including diabetic foot ulcers (DFU), pressure ulcers (PU), and venous ulcers (VU) result from multiple physiologic impairments. Operative debridement is a mainstay of treatment to remove nonviable tissue and to stimulate wound healing. Unlike tumor resection, however, operative wound specimens are not routinely sent for pathology.

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