A forensic analysis of spin-off and downstream revenue in an academic vascular surgery practice: Unveiling the "vascular X-factor" in a tertiary health care system.

BACKGROUND: Owing to the high level of patient and operative complexity, vascular surgery represents a major driver for elevating case mix index within health care institutions. Although several specialty services are recruited in the care of these patients, it has been difficult to quantify the financial impact of these vascular patient across the health care enterprise. This study aims to quantify all revenues attributable to the introduction of vascular surgery patients within a tertiary health care system. METHODS: Billing data from 2017 to 2020 for all new vascular surgery patients entering a tertiary health care system were captured, and segregated by encounter type--inpatient versus outpatient. Within these major categories, vascular revenue streams were analyzed according to procedural pathology types, such as aneurysm, peripheral vascular disease, cerebrovascular, and venous. Subsequent revenues for nonvascular services were also captured for both inpatient and outpatient encounters that were tied to the initial vascular surgical encounter. Revenues attributable to vascular patients were analyzed and followed with respect to other hospital service lines. RESULTS: A total of 1115 new patients were introduced to the health care system for the first time by vascular surgery. These new patients generated more than $26 million in gross revenue and more than $10 million in contribution margin to the hospital during this time interval in aggregate. From a procedural standpoint, aortic surgery generated more than $7.4 million in revenue and $2.9 million in health system contribution margin. Peripheral vascular disease contributed $7.3 million and $2.6 million in revenue and contribution margins, respectively. Aortic surgery cases generated the highest margin per encounter encompassing the total sum of contributions. Subtracting all revenue attributable to vascular billing (spin-off), new patients brought in by vascular generated $9.6 million in revenue and $4.3 million in contribution margin from other service lines. Vascular access procedures produced the greatest spin-off margin per encounter at $10,985, and ancillary inpatient/outpatient generated the greatest number of spin-off encounters (n = 597) and revenue ($8,181,708). CONCLUSIONS: Patients introduced by a tertiary care vascular surgery program produce a significant revenue/margin for the parent health care system. When considering the fiscal health of a vascular program within a tertiary health care system, spin-off and downstream revenue should be considered in terms of overall value.

Factor H interferes with the adhesion of sickle red cells to vascular endothelium: a novel disease-modulating molecule.

Sickle cell disease is an autosomal recessive genetic red cell disorder with a worldwide distribution. Growing evidence suggests a possible involvement of complement activation in the severity of clinical complications of sickle cell disease. In this study we found activation of the alternative complement pathway with microvascular deposition of C5b-9 on skin biopsies from patients with sickle cell disease. There was also deposition of C3b on sickle red cell membranes, which is promoted locally by the exposure of phosphatidylserine. In addition, we showed for the first time a peculiar "stop-and-go" motion of sickle cell red blood cells on tumor factor-α-activated vascular endothelial surfaces. Using the C3b/iC3b binding plasma protein factor Has an inhibitor of C3b cell-cell interactions, we found that factor H and its domains 19-20 prevent the adhesion of sickle red cells to the endothelium, normalizing speed transition times of red cells. We documented that factor H acts by preventing the adhesion of sickle red cells to P-selectin and/or the Mac-1 receptor (CD11b/CD18), supporting the activation of the alternative pathway of complement as an additional mechanism in the pathogenesis of acute sickle cell related vaso-occlusive crises. Our data provide a rationale for further investigation of the potential contribution of factor H and other modulators of the alternative complement pathway with potential implications for the treatment of sickle cell disease.

Improvement of maternal and fetal outcomes in women with sickle cell disease treated with early prophylactic erythrocytapheresis.

BACKGROUND: The desire for pregnancy in sickle cell disease (SCD) women has become a true challenge for hematologists, requiring a multidisciplinary approach. Erythrocytapheresis (ECP) is an important therapeutic tool in SCD, but only limited data on starting time and the effects of ECP during pregnancy are available. STUDY DESIGN AND METHODS: This is a double-center retrospective cross-sectional study on a total of 46 single pregnancies in SCD women from January 2008 to June 2017. ECP was started at 10.7 ± 5.2 weeks of gestation, and prophylactic enoxaparin (4,000 U daily) was introduced due to the reported high prevalence of thromboembolic events in pregnant SCD women. RESULTS: The alloimmunization ratio was 2.1 per 1,000 and the alloimmunization rate was 5.6%. In early ECP-treated SCD women, no severe vaso-occlusive crisis, sepsis or severe infection, or preeclampsia or eclampsia were observed. We found normal umbilical arterial impedance during pregnancy, suggesting an optimal uteroplacental function in early ECP-treated SCD women. This was also supported by the improvement in newborn birthweights compared to previous studies. In our cohort, three SCD women were started later on ECP (20-25 weeks), and gestation ended with late fetal loss. Placenta pathology documented SCD-related damage and erythroblasts in placental vessels, indicating fetal hypoxia. CONCLUSIONS: Collectively, our data generate a rationale to support a larger clinical trial of early ECP program in SCD pregnancy.

New Therapeutic Options for the Treatment of Sickle Cell Disease.

Sickle cell disease (SCD; ORPHA232; OMIM # 603903) is a chronic and invalidating disorder distributed worldwide, with high morbidity and mortality. Given the disease complexity and the multiplicity of pathophysiological targets, development of new therapeutic options is critical, despite the positive effects of hydroxyurea (HU), for many years the only approved drug for SCD. New therapeutic strategies might be divided into (1) pathophysiology-related novel therapies and (2) innovations in curative therapeutic options such as hematopoietic stem cell transplantation and gene therapy. The pathophysiology related novel therapies are: a) Agents which reduce sickling or prevent sickle red cell dehydration; b) Agents targeting SCD vasculopathy and sickle cell-endothelial adhesive events; c) Anti-oxidant agents. This review highlights new therapeutic strategies in SCD and discusses future developments, research implications, and possible innovative clinical trials.

Urinary Metabolic Signature of Primary Aldosteronism: Gender and Subtype-Specific Alterations.

PURPOSE: The current clinical investigation for primary aldosteronism (PA) diagnosis requires complex expensive tests from the initial suspicion to the final subtype classification, including invasive approaches; therefore, appropriate markers for subtype definition are greatly desirable. The present study performs a metabolomics analysis to further examine specific molecular signatures of PA urines EXPERIMENTAL DESIGN: The study considered PA subtype and gender-related differences using two orthogonal advanced UHPLC-MS metabolomics approaches. Patients with essential hypertension (n = 36) and PA (n = 50) who were referred to the outpatient hypertension clinic and matched healthy subjects (n = 10) are investigated. RESULTS: Statistically significant changes (p < 0.05 ANOVA, Fc > 1.5) of metabolites involved in central carbon, energy, and nitrogen metabolism are identified, especially purine and pyrimidine nucleosides and precursors, and free amino acids. PLS-DA interpretation provides strong evidence of a disease-specific metabolic pattern with dAMP, diiodothyronine, and 5-methoxytryptophan as leading factors, and a sex-specific metabolic pattern associated with orotidine 5-phosphate, N-acetylalanine, hydroxyproline, and cysteine. The results are verified using an independent sample set, which confirms the identification of specific signatures. CONCLUSIONS AND CLINICAL RELEVANCE: Metabolomics is used to identify low molecular weight molecular markers of PA, which paves the way for follow-up validation studies in larger cohorts.

A Late Diagnosis of Primary Aldosteronism.

We report the case of a 41-year-old male patient with juvenile onset refractory hypertension while taking four drugs including a diuretic. Fourteen years before he underwent a complete investigation for secondary hypertension (including the aldosterone to renin ratio-ARR) that was negative. Since that, hypertension control gradually worsened, hypertensive organ damage aggravated and hypokalemia developed in spite of ACE inhibitor treatment. At the re-evaluation ARR was elevated, and the further workup for primary aldosteronism demonstrated an unilateral aldosterone producing adenoma that was surgically removed, with subsequent optimal blood pressure control with two anti-hypertensive drugs. In this case, the failure of the first screening prevented a correct diagnosis of primary aldosteronism, with consequent inadequate blood pressure control in following years and end organ damage. The case suggests the need of clinical follow-up and eventual reappraisal of patients showing a condition of refractory hypertension associated with hypokalemia despite a first negative screening test.

Increased urinary excretion of the epithelial Na channel activator prostasin in patients with primary aldosteronism.

OBJECTIVES: Prostasin is a glycosylphosphatidylinositol-anchored serine protease that is released in urine and is involved in epithelial Na channel activation. A direct association between urinary prostasin (u-prostasin) concentration and activation of the aldosterone-driven pathway has been suggested; however, in previous studies on primary aldosteronism, a semiquantitative evaluation, rather than a precise quantification, of prostasin was performed. We aim to investigate if u-prostasin concentrations are higher in patients with primary aldosteronism than in patients with essential hypertension and whether u-prostasin measurements could be a useful marker for diagnosing primary aldosteronism in hypertensive patients. METHODS: A total of 62 primary aldosteronism and 56 essential hypertension patients were enrolled. Biochemical and hormonal parameters were measured by applying routine laboratory methods, and u-prostasin levels were assessed by ELISA. RESULTS: Primary aldosteronism patients had higher u-prostasin levels than did essential hypertension patients. Prostasin levels were positively correlated with the aldosterone-to-renin ratio and inversely correlated with plasma K and urinary Na levels. In the highest concentration quartile, u-prostasin levels were associated with a several-fold higher probability of primary aldosteronism diagnosis in hypertensive patients. Receiver operating characteristic curve analysis showed that prostasin was specific but poorly sensitive as a diagnostic marker for primary aldosteronism. CONCLUSIONS: The study shows that an elevated u-prostasin concentration in humans is a specific marker for primary aldosteronism, which involves the classical model of epithelial Na channel activation. There was no statistically significant difference in prostasin concentrations among patients with different primary aldosteronism subtypes. Studies with a larger series of patients are necessary to clarify the clinical usefulness of the prostasin assay.

NT-proBNP, a useful tool in hypertensive patients undergoing a diagnostic evaluation for primary aldosteronism.

Primary aldosteronism (PA) is the most frequent form of secondary hypertension, but diagnostic tools for this disease still lack optimal accuracy. The heart is one important target tissue for damage due to excess aldosterone, and the role of natriuretic peptides is well recognized in diagnosing heart failure. We hypothesized that measuring the NT-proBNP could improve the diagnostic evaluation of PA. We enrolled 132 hypertensive patients, who underwent aldosterone to renin ratio (ARR) screening, and 81 underwent an intravenous saline loading test (ivSLT) because of a high ARR. The NT-proBNP level positively correlated with the ARR and inversely correlated with the renin level. The NT-proBNP level was higher in patients with a high ARR than in those with a low ARR and higher in patients with a positive ivSLT than in those with a negative ivSLT. After logistic regression analysis, an NT-proBNP value above the median and male gender were predictors of a positive ivSLT. The proportion of patients with a positive ivSLT ranged from only 23 % in females with a low NT-proBNP to 93 % in males with a high NT-proBNP. NT-proBNP and gender are predictors of a positive PA confirmatory test. These findings highlight the possibility of using NT-proBNP to identify which patients with a high ARR should receive a complete PA diagnostic evaluation.