Incremental Utility of First-Pass Perfusion CMR for Prognostic Risk Stratification of Cancer-Associated Cardiac Masses.

BACKGROUND: Cardiac magnetic resonance (CMR) differentiates cardiac metastasis (CMET) and cardiac thrombus (CTHR) based on tissue characteristics stemming from vascularity on late gadolinium enhancement (LGE). Perfusion CMR can assess magnitude of vascularity; utility for cardiac masses (CMASS) is unknown. OBJECTIVES: This study sought to determine if perfusion CMR provides diagnostic and prognostic utility for CMASS beyond binary differentiation of CMET and CTHR. METHODS: The population comprised adult cancer patients with CMASS on CMR; CMET and CTHR were defined using LGE-CMR: CMASS+ patients were matched to CMASS- control subjects for cancer type/stage. First-pass perfusion CMR was interpreted visually and semiquantitatively for CMASS vascularity, including contrast enhancement ratio (CER) (plateau vs baseline) and contrast uptake rate (CUR) (slope). Follow-up was performed for all-cause mortality. RESULTS: A total of 462 cancer patients were studied, including patients with (CMET = 173, CTHR = 69) and without CMASS on LGE-CMR. On perfusion CMR, CER and CUR were higher within CMET vs CTHR (P < 0.001); CUR yielded better performance (AUC: 0.89-0.93) than CER (AUC: 0.66-0.72) (both P < 0.001) to differentiate LGE-CMR-evidenced CMET and CTHR, although both CUR (P = 0.10) and CER (P = 0.01) typically misclassified CMET with minimal enhancement. During follow-up, mortality among CMET patients was high but variable; 47% of patients were alive 1 year post-CMR. Patients with semiquantitative perfusion CMR-evidenced CMET had higher mortality than control subjects (HR: 1.42 [95% CI: 1.06-1.90]; P = 0.02), paralleling visual perfusion CMR (HR: 1.47 [95% CI: 1.12-1.94]; P = 0.006) and LGE-CMR (HR: 1.52 [95% CI: 1.16-2.00]; P = 0.003). Among patients with CMET on LGE-CMR, mortality was highest among patients (P = 0.002) with lesions in the bottom perfusion (CER) tertile, corresponding to low vascularity. Among CMET and cancer-matched control subjects, mortality was equivalent (P = NS) among patients with lesions in the upper CER tertile (corresponding to higher lesion vascularity). Conversely, patients with CMET in the middle (P = 0.03) and lowest (lowest vascularity) (P = 0.001) CER tertiles had increased mortality. CONCLUSIONS: Perfusion CMR yields prognostic utility that complements LGE-CMR: Among cancer patients with LGE-CMR defined CMET, mortality increases in proportion to magnitude of lesion hypoperfusion.

Cost Analysis of Health Facility Electronic Integrated Disease Surveillance and Response in One District in Sierra Leone.

Global health security depends on effective surveillance systems to prevent, detect, and respond to disease threats. Real-time surveillance initiatives aim to develop electronic systems to improve reporting and analysis of disease data. Sierra Leone, with the support of Global Health Security Agenda partners, developed an electronic Integrated Disease Surveillance and Response (eIDSR) system capable of mobile reporting from health facilities. We estimated the economic costs associated with rollout of health facility eIDSR in the Western Area Rural district in Sierra Leone and projected annual direct operational costs. Cost scenarios with increased transport costs, decreased use of partner personnel, and altered cellular data costs were modeled. Cost data associated with activities were retrospectively collected and were assessed across rollout phases. Costs were organized into cost categories: personnel, office operating, transport, and capital. We estimated costs by category and phase and calculated per health facility and per capita costs. The total economic cost to roll out eIDSR to the Western Area Rural district over the 14-week period was US$64,342, a per health facility cost of $1,021. Equipment for eIDSR was the primary cost driver (45.5%), followed by personnel (35.2%). Direct rollout costs were $38,059, or 59.2% of total economic costs. The projected annual direct operational costs were $14,091, or $224 per health facility. Although eIDSR equipment costs are a large portion of total costs, annual direct operational costs are projected to be minimal once the system is implemented. Our findings can be used to make decisions about establishing and maintaining electronic, real-time surveillance in Sierra Leone and other low-resource settings.

Hyperglycaemia, adverse outcomes and impact of intravenous insulin therapy in patients presenting with acute ST-elevation myocardial infarction in a socioeconomically disadvantaged urban setting: The Montefiore STEMI Registry.

BACKGROUND: Hyperglycaemia occurs frequently in ST-elevation myocardial infarction (STEMI) and is associated with poor outcomes, for which continuous insulin infusion therapy (CIIT) may be beneficial. Information is limited regarding hyperglycaemia in acute STEMI affecting urban minority populations, or how CIIT fares in such real-world settings. METHODS AND RESULTS: We assembled an acute STEMI registry at an inner-city health system, focusing on patients with initial blood glucose ≥180 mg/dL to determine the impact of CIIT vs usual care. Clinical and outcomes data were added through linkage to electronic records. Inverse-probability-of-treatment weighting using propensity scores (PS) was used to compare CIIT vs no CIIT. The 1067 patients included were mostly Hispanic or African American; 356 had blood glucose ≥180 mg/dL. Such pronounced hyperglycaemia was related to female sex, minority race-ethnicity and lower socioeconomic score, and associated with increased death and death or CVD readmission. CIIT was preferentially used in patients with marked hyperglycaemia and was associated with in-hospital hypoglycaemia (21% vs 11%, P = .019) and, after PS weighting, with increased in-hospital (RR 3.23, 95% CI 0.94, 11.06) and 1-year (RR 2.26, 95% CI 1.02, 4.98) mortality. No significant differences were observed for death at 30 days or throughout follow-up, or death and readmission at any time point. CONCLUSIONS: Pronounced hyperglycaemia was common and associated with adverse prognosis in this urban population. CIIT met with selective use and was associated with hypoglycaemia, together with increased mortality at specific time points. Given the burden of metabolic disease, particularly among race-ethnic minorities, assessing the benefits of CIIT is a prerogative that requires evaluation in large-scale randomized trials.

Prevalence and Predictors of Deep Vein Thrombosis in Critically Ill Medical Patients Who Underwent Diagnostic Duplex Ultrasonography.

INTRODUCTION: Deep vein thrombosis (DVT) is a recognized but preventable cause of morbidity and mortality in the medical intensive care unit (MICU). We examined the prevalence and risk factors for DVT in MICU patients who underwent diagnostic venous duplex ultrasonography (DUS) and the potential effect on clinical outcomes. METHODS: This is a retrospective study examining prevalence of DVT in 678 consecutive patients admitted to a tertiary care level academic MICU from July 2014 to 2015. Patients who underwent diagnostic DUS were included. Potential conditions of interest were mechanical ventilation, hemodialysis, sepsis, Sequential Organ Failure Assessment (SOFA) scores, central venous catheters, prior DVT, and malignancy. Primary outcomes were pulmonary embolism, ICU length of stay, and mortality. Additionally, means of thromboprophylaxis was compared between the groups. Multivariable logistic regression analysis was utilized to determine predictors of DVT occurrence. RESULTS: Of the 678 patients, 243 (36%) patients underwent DUS to evaluate for DVT. The prevalence of DVT was 16% (38) among tested patients, and a prior history of DVT was associated with DVT prevalence (P < .01). Between cases and controls, there were no significant differences in central venous catheters, mechanical ventilation, hemodialysis, sepsis, SOFA scores, malignancy, and recent surgery. Patients receiving chemical prophylaxis had fewer DVTs compared to persons with no prophylaxis (14% vs 29%; P = .01) and persons with dual chemical and mechanical prophylaxis (P = 0.1). Fourteen percent of patients tested had documented DVT while on chemoprophylaxis. There were no significant differences in ICU length of stay (P = .35) or mortality (P = .34). CONCLUSIONS: Despite the appropriate use of universal thromboprophylaxis, critically ill nonsurgical patients still demonstrated high rates of DVT. A history of DVT was the sole predictor for development of proximal DVT on DUS testing. Dual chemical and mechanical prophylaxis does not appear to be superior to single-chemical prophylaxis in DVT prevention in this population.

Dependence of brown adipose tissue function on CD36-mediated coenzyme Q uptake.

Brown adipose tissue (BAT) possesses the inherent ability to dissipate metabolic energy as heat through uncoupled mitochondrial respiration. An essential component of the mitochondrial electron transport chain is coenzyme Q (CoQ). While cells synthesize CoQ mostly endogenously, exogenous supplementation with CoQ has been successful as a therapy for patients with CoQ deficiency. However, which tissues depend on exogenous CoQ uptake as well as the mechanism by which CoQ is taken up by cells and the role of this process in BAT function are not well understood. Here, we report that the scavenger receptor CD36 drives the uptake of CoQ by BAT and is required for normal BAT function. BAT from mice lacking CD36 displays CoQ deficiency, impaired CoQ uptake, hypertrophy, altered lipid metabolism, mitochondrial dysfunction, and defective nonshivering thermogenesis. Together, these data reveal an important new role for the systemic transport of CoQ to BAT and its function in thermogenesis.

Inhibition of striatal soluble guanylyl cyclase-cGMP signaling reverses basal ganglia dysfunction and akinesia in experimental parkinsonism.

OBJECTIVE: There is clearly a necessity to identify novel non-dopaminergic mechanisms as new therapeutic targets for Parkinson's disease (PD). Among these, the soluble guanylyl cyclase (sGC)-cGMP signaling cascade is emerging as a promising candidate for second messenger-based therapies for the amelioration of PD symptoms. In the present study, we examined the utility of the selective sGC inhibitor 1H-[1], [2], [4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) for reversing basal ganglia dysfunction and akinesia in animal models of PD. METHODS: The utility of the selective sGC inhibitor ODQ for reversing biochemical, electrophysiological, histochemical, and behavioral correlates of experimental PD was performed in 6-OHDA-lesioned rats and mice chronically treated with MPTP. RESULTS: We found that one systemic administration of ODQ is sufficient to reverse the characteristic elevations in striatal cGMP levels, striatal output neuron activity, and metabolic activity in the subthalamic nucleus observed in 6-OHDA-lesioned rats. The latter outcome was reproduced after intrastriatal infusion of ODQ. Systemic administration of ODQ was also effective in improving deficits in forelimb akinesia induced by 6-OHDA and MPTP. INTERPRETATION: Pharmacological inhibition of the sGC-cGMP signaling pathway is a promising non-dopaminergic treatment strategy for restoring basal ganglia dysfunction and attenuating motor symptoms associated with PD.