Mobile Geolocation Technology to Improve Multidisciplinary Care of Patients With Ventricular Assist Devices: A Feasibility Study.

We evaluated the feasibility of a mobile phone-based geolocation technology in patients with ventricular assist devices (VAD). We prospectively enrolled VAD patients with a smartphone for 6 months. A proprietary mobile technology platform (Position Health, Reading, MA) was downloaded onto Apple or Android smartphones. When a patient entered an emergency department, the app was activated and a "ping" with patient location and contact information was sent to our VAD team pager. Fifty-four patients were approached, and 21 were enrolled. The primary reason for nonenrollment was lack of smartphone (46%). The technology was active for 3780 patient-days and activated on 4 occasions, all cases in which patients were inside a hospital but not seeking emergency care. When surveyed at 3 and 6 months, 90% and 100% of patients, respectively, reported the app remained active on their phones; 14 of 18 (78%) reported the app was helpful and gave them additional reassurance. Implementing this technology for VAD patients was feasible and accepted by patients and providers, but a larger study is needed to demonstrate an impact on care delivery.

Development of an Outpatient Guideline for Optimal Anticoagulation Bridging in Patients With Durable Mechanical Circulatory Support.

Patients with durable mechanical circulatory support are at increased risk of thromboembolic and bleeding complications. Current guidelines recommend that these patients receive chronic anticoagulation with warfarin to maintain a target international normalized ratio (INR) as specified by device manufacturers. Limited data exist regarding management of subtherapeutic INRs in this setting. To standardize clinical practice at our institution, we assembled a multidisciplinary task force including members from various specialties to develop a guideline for managing subtherapeutic INRs that incorporates published data and expert opinion. In this article, we present our clinical practice guideline as a decision support tool to aid clinicians in developing a consistent strategy for managing subtherapeutic INRs and for safely bridging anticoagulation in patients receiving mechanical circulatory support.

Left ventricular dimension decrement index early after axial flow assist device implantation: A novel risk marker for late pump thrombosis.

BACKGROUND: It is increasingly recognized that pump thrombosis most likely represents the end stage of a complex interaction between the patient-pump interface. We hypothesized that early patient/pump mismatch, as manifested by suboptimal left ventricular (LV) unloading early after left ventricular assist device (LVAD) implantation, may be a harbinger of increased risk for later LVAD thrombosis. METHODS: In 64 patients (59 ± 11 years old, 78% men, 44% destination therapy) discharged alive without thrombosis or other device malfunction after first HeartMate II LVAD implantation (between January 2011 and June 2014), LV dimensions in end diastole (LVIDd) and end systole (LVIDs) were compared between pre-implant and optimal set speed pre-discharge echocardiography. LV dimension decrement indices (pre-implant dimension - optimal set speed dimension ÷ pre-implant dimension × 100) for LVIDd [LVIDdDI] and LVIDs [LVIDsDI] were calculated. RESULTS: The incidence of pump thrombosis was 0.06 per patient year (n = 18, median time 8 [interquartile range 2, 17] months). Baseline characteristics including pre-operative LVIDd and LVIDs were similar between LVAD thrombosis and no thrombosis groups. After ventricular assist device implantation, set speed and other ramp parameters did not differ between groups. However, LVIDdDI (19 ± 13% vs 25 ± 11%, p = 0.04) and LVIDsDI (16 ± 16% vs 27 ± 13%, p = 0.008) were significantly lower in patients with later pump thrombosis. A cutoff value of ≤15% using receiver operating characteristic curve analysis was 83% sensitive for LVIDdDI and LVIDsDI for predicting pump thrombosis. Patients with LVIDdDI of >15% vs ≤15% were significantly more likely to be free of pump thrombosis over a median follow-up period of 15 (interquartile range 9, 26) months (log-rank test, p = 0.045). CONCLUSIONS: LV dimension decrement index at optimized speed setting on pre-discharge echocardiography is associated with LVAD thrombosis.

Gene expression signatures in neutrophils exposed to glucocorticoids: a new paradigm to help explain "neutrophil dysfunction" in parturient dairy cows.

Neutrophils are the first line of immunity against most pathogens that infect cattle. These normally short-lived white blood cells develop from myeloid-lineage cells in bone marrow. Upon maturation, bone marrow neutrophils are released into the circulation where they marginate on inflamed blood vessel endothelial cells and migrate through them into the area of infection. Once migrated, neutrophils do not reenter the circulation, but rather, perform their bactericidal functions and die by apoptosis in the tissue. The cytokine and hormonal milieu of the blood and extracellular tissue fluid can influence neutrophil development and immunity-related activities, but the molecular basis of these phenotypic changes and physiological benefits or drawbacks of them are poorly understood. In the current paper, we review new gene expression information that resulted from two of our functional genomics studies designed to evaluate effects of glucocorticoid hormones on bovine neutrophils. This work provides one model to describe complex changes that occur in neutrophils as the cells respond to glucocorticoids, which might act to alter the cells' functional priorities and tip the delicate balance between health and disease during stress, including at parturition. A bovine immunobiology microarray and real time RT-PCR were used to study blood neutrophils collected during the natural surge of endogenous glucocorticoid (cortisol) in parturient dairy cows and bone marrow neutrophils collected from glucocorticoid (dexamethasone)-treated dairy steers. The gene expression signatures we observed led us to perform additional phenotyping of the neutrophils and correlation analyses, which together painted a picture suggesting that glucocorticoids have key roles in modulating neutrophil development, life span, and tissue defense functions during parturition and hormone therapy. Based on these observations, we postulate that glucocorticoids orchestrate adaptive changes in the entire neutrophil system that support increased cell numbers and longevity in blood and heightened remodeling activity in tissues, while at the same time decreasing some important antimicrobial defense activities of the cells. Thus, our functional genomics studies have enabled us to elucidate multiple consequences of neutrophil exposure to glucocorticoids, highlighting a probable role for this interaction in the induction of parturition and partly explaining why some parturient dairy cows may experience heightened incidence and severity of inflammatory diseases like mastitis.

Microarray analysis of gene expression in blood neutrophils of parturient cows.

It is well documented that blood neutrophils from parturient dairy cows do not perform as well as neutrophils from nonparturient cows in laboratory assays of adhesion, migration, or phagocytosis-induced respiratory burst. However, little is known about the possible molecular basis for parturition-induced changes in neutrophils. cDNA microarray analysis was used in the current study to explore parturition-induced changes in gene expression profiles in bovine blood neutrophils. Total RNA from isolated blood neutrophils of four parturient Holstein cows was obtained before, during, and after parturition, reverse transcribed into cDNA, and sequentially labeled with Cy3 or Cy5 dyes prior to paired hybridizations to 1,056 member bovine total leukocyte (BOTL-3) microarrays in a loop design. Resulting gene expression data were LOWESS normalized by array and analyzed using a mixed model approach. Results showed that expression profiles for 302 BOTL-3 genes were influenced by parturition. BLASTn analysis and preliminary clustering of affected genes by biological function indicated that the largest proportion (14%) of changed genes encode proteins critical to regulation of apoptosis. Independent confirmation of altered expression for 16 of these genes was achieved using quantitative real-time RT-PCR (Q-RT-PCR). A predominantly survival phenotype inferred from the microarray and Q-RT-PCR results was substantiated by monitoring apoptosis status of blood neutrophils from castrated male cattle cultured in the presence of sera from parturient cows. Thus our combined gene expression and apoptosis phenotyping results suggest that bovine parturition may induce prolonged survival in normally short-lived blood neutrophils.