Economic Burden of Inpatient Care for Mitral Regurgitation in Maryland.

BACKGROUND: Mitral regurgitation (MR) is the most common valvular disease in the United States and increases the risk of death and hospitalization. The economic burden of MR in the United States is not known. METHODS AND RESULTS: We analyzed inpatient hospitalization data from the 1 221 173 Maryland residents who had any in-state admissions from October 1, 2015, to September 30, 2019. We assessed the total charges for patients without MR and for patients with MR who underwent medical management, transcatheter mitral valve repair or replacement, or surgical mitral valve repair or replacement. During the study period, 26 076 inpatients had a diagnosis of MR. Compared with patients without MR, these patients had more comorbidities and higher inpatient mortality. Patients with medically managed MR incurred average total charges of $23 575 per year; MR was associated with $10 559 more in charges per year and an incremental 3.1 more inpatient days per year as compared with patients without MR. Both surgical mitral valve repair or replacement and transcatheter mitral valve repair or replacement were associated with higher charges as compared with medical management during the year of intervention ($47 943 for surgical mitral valve repair or replacement and $63 108 for transcatheter mitral valve repair or replacement). Annual charges for both groups were significantly lower as compared with medical management in the second and third years postintervention. CONCLUSIONS: MR is associated with higher mortality and inpatient charges. Patients who undergo surgical or transcatheter intervention incur lower charges compared with medically managed MR patients in the years after the procedure.

Multicentre methodological study to create a publicly available score of hospital financial standing in the USA.

OBJECTIVES: To create a straightforward scoring procedure based on widely available, inexpensive financial data that provides an assessment of the financial health of a hospital. DESIGN: Methodological study. SETTING: Multicentre study. PARTICIPANTS: All hospitals and health systems reporting the required financial metrics in the USA in 2017 were included for a total of 1075 participants. INTERVENTIONS: We examined a list of 232 hospital financial indicators and used existing models and financial literature to select 30 metrics that sufficiently describe hospital operations. In a set of hospital financial data from 2017, we used principal coordinate analysis to assess collinearity among variables and eliminated redundant variables. We isolated 10 unique variables, each assigned a weight equal to the share of its coefficient in a regression onto Moody's Credit Rating, our predefined gold standard. The sum of weighted variables is a single composite score named the Yale Hospital Financial Score (YHFS). PRIMARY OUTCOME MEASURES: Ability to reproduce both financial trends from a 'gold-standard' metric and known associations with non-fiscal data. RESULTS: The validity of the YHFS was evaluated by: (1) cross-validating it with previously excluded data; (2) comparing it to existing models and (3) replicating known associations with non-fiscal data. Ten per cent of the initial dataset had been reserved for validation and was not used in creating the model; the YHFS predicts 96.7% of the variation in this reserved sample, demonstrating reproducibility. The YHFS predicts 90.5% and 88.8% of the variation in Moody's and Standard and Poor's bond ratings, respectively, supporting its validity. As expected, larger hospitals had higher YHFS scores whereas a greater share of Medicare discharges correlated with lower YHFS scores. CONCLUSIONS: We created a reliable and publicly available composite score of hospital financial stability.

PKCα-mediated phosphorylation of the diacylglycerol kinase ζ MARCKS domain switches cell migration modes by regulating interactions with Rac1 and RhoA.

Cells can switch between Rac1 (lamellipodia-based) and RhoA (blebbing-based) migration modes, but the molecular mechanisms regulating this shift are not fully understood. Diacylglycerol kinase ζ (DGKζ), which phosphorylates diacylglycerol to yield phosphatidic acid, forms independent complexes with Rac1 and RhoA, selectively dissociating each from their common inhibitor RhoGDI. DGKζ catalytic activity is required for Rac1 dissociation but is dispensable for RhoA dissociation; instead, DGKζ stimulates RhoA release via a kinase-independent scaffolding mechanism. The molecular determinants that mediate the selective targeting of DGKζ to Rac1 or RhoA signaling complexes are unknown. Here, we show that protein kinase Cα (PKCα)-mediated phosphorylation of the DGKζ MARCKS domain increased DGKζ association with RhoA and decreased its interaction with Rac1. The same modification also enhanced DGKζ interaction with the scaffold protein syntrophin. Expression of a phosphomimetic DGKζ mutant stimulated membrane blebbing in mouse embryonic fibroblasts and C2C12 myoblasts, which was augmented by inhibition of endogenous Rac1. DGKζ expression in differentiated C2 myotubes, which have low endogenous Rac1 levels, also induced substantial membrane blebbing via the RhoA-ROCK pathway. These events were independent of DGKζ catalytic activity, but dependent upon a functional C-terminal PDZ-binding motif. Rescue of RhoA activity in DGKζ-null cells also required the PDZ-binding motif, suggesting that syntrophin interaction is necessary for optimal RhoA activation. Collectively, our results define a switch-like mechanism whereby DGKζ phosphorylation by PKCα plays a role in the interconversion between Rac1 and RhoA signaling pathways that underlie different cellular migration modes.

Association of Graduate Medical Education With Hospital Performance and Patient Outcomes.

Importance: Graduate medical education (GME) funding consists of more than $10 billion annual subsidies awarded to academic hospitals to offset the cost of resident training. Critics have questioned the utility of these subsidies and accountability of recipient hospitals. Objective: To determine the association of GME funding with hospital performance by examining 3 domains of hospital operations: financial standing, clinical outcomes, and resident academic performance. Design, Setting, and Participants: This study is an economic evaluation of all academic centers that received GME funding in 2017. GME funding data were acquired from the Hospital Compare Database. Statistical analysis was performed from May 2016 to April 2020. Exposures: GME funding. Main Outcomes and Measures: This study assessed the association between GME funding and each aspect of hospital operations. Publicly available hospital financial data were used to calculate a financial performance score from 0 to 100 for each hospital. Clinical outcomes were defined as 30-day mortality, readmission, and complication rates for a set of predefined conditions. Resident academic performance was determined by Board Certification Examination (BCE) pass rates at 0, 2, and 5 years after GME funding was awarded. Confounder-adjusted linear regression models were used to test association between GME funding data and a hospital's financial standing, clinical outcomes, and resident academic performance. Results: The sample consisted of 1298 GME-funded hospitals, with a median (IQR) of 265 (168-415) beds and 32 (10-101) residents per training site. GME funding was negatively correlated with hospitals' financial scores (ß = -7.9; 95% CI, -10.9 to -4.8, P = .001). Each additional $1 million in GME funding was associated with lower 30-day mortality from myocardial infarction (-2.34%; 95% CI, -3.59% to -1.08%, P < .001), heart failure (-2.59%; 95% CI, -3.93% to -1.24%, P < .001), pneumonia (-2.20%; 95% CI, -3.99% to -0.40%, P = .02), chronic obstructive pulmonary disease ( -1.20%; 95% CI, -2.35% to -0.05%, P = .04), and stroke (-3.40%; 95% CI, -5.46% to -1.33%, P = .001). There was no association between GME funding and readmission rates. There was an association between higher GME funding and higher internal medicine BCE pass rates (0.066% [95% CI, 0.033% to 0.099%] per $1 million in GME funding; P < .001). Conclusions and Relevance: This study found a negative linear correlation between GME funding and patient mortality and a positive correlation between GME funding and resident BCE pass rates in adjusted regression models. The findings also suggest that hospitals that receive more GME funding are not more financially stable.

In Full Flow: Left Ventricular Assist Device Infections in the Modern Era.

With the rising prevalence of heart disease in the United States, there is increasing reliance on durable mechanical circulatory support (MCS) to treat patients with end-stage heart failure. Left ventricular assist devices (LVADs), the most common form of durable MCS, are implanted mechanical pumps that connect to an external power source through a transcutaneous driveline. First-generation LVADs were bulky, pulsatile pumps that were frequently complicated by infection. Second-generation LVADs have an improved design, though infection remains a common and serious complication due to the inherent nature of implanted MCS. Infections can affect any component of the LVAD, with driveline infections being the most common. LVAD infections carry significant morbidity and mortality for LVAD patients. Therefore, it is paramount for the multidisciplinary team of clinicians caring for these patients to be familiar with this complication. We review the epidemiology, prevention, diagnosis, treatment, and outcomes of LVAD infections.

Risk of left ventricular assist device driveline infection: A systematic literature review.

BACKGROUND: Left ventricular assist devices (LVADs) improve quality of life in end-stage heart failure but can cause serious complications such as infections with driveline infection causing significant morbidity and mortality. OBJECTIVES: The purpose of this systematic literature review is to synthesize the literature to determine variables associated with driveline infection and seek opportunities to improve nursing management of LVAD drivelines. METHODS: A systematic literature review was performed. The evidence was synthesized using the Johns Hopkins Nursing Evidence-Based Practice tools and the Chain of Infection epidemiological framework. RESULTS: Thirty-four studies focused on vulnerable host, portal of entry, and causative organism aspects of the Chain of Infection. Increased BMI, younger age, exposed driveline velour showed increased risk of infection and driveline dressing protocol change showed lower risk of infection. CONCLUSIONS: Although some risk factors for infection were identified, evidence is still limited. Nurses are uniquely positioned to improve driveline management, disrupting the chain of infection.

Profound Vasoplegia During Sacubitril/Valsartan Treatment After Heart Transplantation.

Vasoplegia occurs in up to 16% of patients who undergo heart transplantation (HT) and is associated with significant morbidity and mortality. We present a case of a 61-year-old man with ischemic cardiomyopathy receiving sacubitril/valsartan (Entresto; Novartis, Cambridge, MA) who developed profound hypotension after HT. He was treated with intravenous methylene blue and high-dose vasopressors, but developed acute kidney injury requiring dialysis and a prolonged stay in the intensive care unit. This case supports a potent vasodilatory effect of sacubitril/valsartan, and if confirmed by other studies, might warrant consideration for withholding treatment while awaiting HT, particularly in patients with risk factors for vasoplegia.

A truncated Wnt7a retains full biological activity in skeletal muscle.

Wnt signaling has essential roles during embryonic development and tissue homoeostasis. Wnt proteins are post-translationally modified and the attachment of a palmitate moiety at two conserved residues is believed to be a prerequisite for the secretion and function of Wnt proteins. Here we demonstrate that a mammalian Wnt protein can be fully functional without palmitoylation. We generate a truncated Wnt7a variant, consisting of the C-terminal 137 amino acids lacking the conserved palmitoylation sites and show that it retains full biological activity in skeletal muscle. This includes binding to and signaling through its receptor Fzd7 to stimulate symmetric expansion of satellite stem cells by activating the planar-cell polarity pathway and inducing myofibre hypertrophy by signaling through the AKT/mTOR pathway. Furthermore, this truncated Wnt7a shows enhanced secretion and dispersion compared with the full-length protein. Together, these findings open important new avenues for the development of Wnt7a as a treatment for muscle-wasting diseases and have broad implications for the therapeutic use of Wnts as biologics.