Right ventricular failure (RVF) increases morbidity and mortality. The RECOVER RIGHT study evaluated the safety and efficacy of a novel percutaneous right ventricular assist device, the Impella RP ...(Abiomed, Danvers, MA), in a prospective, multicenter trial.
Thirty patients with RVF refractory to medical treatment received the Impella RP device at 15 United States institutions. The study population included 2 cohorts: 18 patients with RVF after left ventricular assist device (LVAD) implantation (Cohort A) and 12 patients with RVF after cardiotomy or myocardial infarction (Cohort B). The primary end point was survival to 30 days or hospital discharge (whichever was longer). Major secondary end points included indices of safety and efficacy.
The patients (77% male) were a mean age of 59 ± 15 years, 53% had diabetes, 88.5% had a history of congestive heart failure, and 37.5% had renal dysfunction. Patients were on an average of 3.2 inotropes/pressors. Device delivery was achieved in all but 1 patient. Hemodynamics improved immediately after initiation of Impella RP support, with an increase in cardiac index from 1.8 ± 0.2 to 3.3 ± 0.23 liters/min/m(2) (p < 0.001) and a decrease in central venous pressure from 19.2 ± 4 to 12.6 ± 1 mm Hg (p < 0.001). Patients were supported for an average of 3.0 ± 1.5 days (range, 0.5-7.8 days). The overall survival at 30 days was 73.3%. All patients discharged were alive at 180 days.
In patients with life-threatening RVF, the novel percutaneous Impella RP device was safe, easy to deploy, and reliably resulted in immediate hemodynamic benefit. These data support its probable benefit in this gravely ill patient population.
Abstract
Cell based therapies are evolving as an effective new approach to treat various diseases. To understand the safety, efficacy, and mechanism of action of cell-based therapies, it is ...imperative to follow their biodistribution noninvasively. Positron-emission-tomography (PET)-based non-invasive imaging of cell trafficking offers such a potential. Herein, we evaluated and compared three different ready-to-use direct cell radiolabeling synthons,
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-SA for PET imaging-based trafficking of white blood cells (WBCs) and stem cells (SCs) up to 7 days in athymic nude mice. We compared the degree of
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Zr complexation and percentage of cell radiolabeling efficiencies with each. All three synthons,
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-SA, were successfully prepared, and used for radiolabeling of WBCs and SCs. The highest cell radiolabeling yield was found for
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-NCS, and
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-SA. In terms of biodistribution, WBCs radiolabeled with
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-NCS, were primarily accumulated in liver and spleen, whereas SCs radiolabeled with
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-NCS were found in lung, liver and spleen. A high bone uptake was observed for both WBCs and SCs radiolabeled with
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-SA synthon. This study offers an appropriate selection of ready-to-use radiolabeling synthons for noninvasive trafficking of WBCs, SCs and other cell-based therapies.
Although the literature shows rigid plate fixation has superior outcomes over wire cerclage techniques, a patient population clearly benefitting from initial sternal plating over standard closure ...has not been identified. Data on plating as primary sternal closure in the morbidly obese patient remains sparse.
A single-center retrospective study was performed on 564 consecutive patients undergoing complete median sternotomy from July 2014 to July 2017. Postoperative outcomes of patients with a body mass index of 35 kg/m2 or more were compared between sternotomies with standard wire cerclage closure and those with sternal plate reinforcement. The primary endpoint was postoperative sternal complication defined as deep sternal wound infection, acute sternal dehiscence, chronic sternal disunion, or noninfectious sternal wound complication requiring operative intervention.
In all, 32.6% of sternotomies (184 of 564) were performed on patients with a body mass index of 35 kg/m2 or greater. Of this group, 31.5% (58 of 184) underwent sternal closure with titanium plate reinforcement and 68.5% (126 of 184) underwent traditional chest closure. The overall sternal complication rate was 4.9% (9 of 184), consisting of 6 of 126 nonplated patients and 3 of 58 plated patients (4.8% vs 5.2%, P = .80).
Sternal plate reinforcement for sternotomy closure of patients with a body mass index 35 kg/m2 or greater produced no difference in postoperative sternal complication rates.
Increased shear stress conferred upon the circulation by continuous-flow pumps is associated with hemocompatibility-related adverse events, principally bleeding within the gastrointestinal system, ...and linked to the degradation of high-molecular-weight multimers (HMWMs) of von Willebrand factor (vWF). We evaluated the structure and functional characteristics of vWF HMWMs in patients with the fully magnetically levitated centrifugal-flow HeartMate 3 (HM3) and the continuous axial-flow HeartMate II (HMII) pump. Findings were correlated with bleeding events.
In a prospective, multicenter, comparative cohort study, 60 patients from the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 Continued Access Protocol (NCT02892955) with an HM3 pump were compared with 30 randomly selected HMII patients from the PREVENtion of HeartMate II Pump Thrombosis study (NCT02158403) biobank. The primary end point was the difference in the normalized vWF HMWM ratio (ratio of the HMWMs to the intermediate- and low-molecular-weight multimers, normalized to pooled plasma from healthy volunteers) between the HM3 and the HMII pump at 90 days after implantation. Assay tests for vWF activity, vWF antigen, vWF activity to antigen ratio, coagulation factor VIII activity, and ADAMTS13 activity were measured by using standard protocols. Differences in these markers were compared in the context of clinical characteristics and correlated with adjudicated bleeding events within the HM3 group.
Of 51 and 29 evaluable patients in the HM3 and HMII arms, respectively, those implanted with the HM3 pump exhibited greater preservation of the vWF HMWM ratio than those with the HMII pump at 90 days after implantation (54.1% vs 42.4%, p < 0.0001). Laboratory values for all vWF assays (antigen, activity, and coagulation factor VIII activity) remained within the normal functional range with no significant differences observed between the pumps at 90 days after implantation. At baseline, there was a decrease in the structural integrity of vWF HMWMs that correlated with increasing heart failure severity as measured by the Interagency Registry for Mechanically Assisted Circulatory Support profile. Multivariable modeling identified the HM3 pump as the only independent variable that determined post-implantation preservation of the structural integrity of vWF HMWMs.
This prospective, multicenter comparative analysis study demonstrates that the fully magnetically levitated centrifugal-flow HM3 left ventricular assist device is associated with greater preservation of the structure of vWF HMWMs than the HMII mechanical bearing axial-flow pump.
Abstract Non-invasive imaging of GSK-3 expression in the brain will help to understand the role of GSK-3 in disease pathology and progression. Herein, we report the radiosynthesis and evaluation of ...two novel isonicotinamide based 18 F labeled PET probes, 18 F 2 and 18 F 6 for noninvasive imaging of GSK3. Among the developed PET probes, the in vitro blood–brain permeability coefficient of 2 (38 ± 20 × 10 –6 cm/s, n = 3) was found to be better than 6 ( 8.75 ± 3.90 × 10 –6 cm/s, n = 5). The reference compounds 2 and 6 showed nanomolar affinity towards GSK-3α and GSK-3β. PET probe 18 F 2 showed higher stability (100%) in mouse and human serums compared to 18 F 6 (67.01 ± 4.93%, n = 3) in mouse serum and 66.20 ± 6.38%, n = 3) in human serum at 120 min post incubation. The in vivo imaging and blocking studies were performed in wild-type mice only with 18 F 2 due to its observed stability. 18 F 2 showed a SUV of 0.92 ± 0.28 ( n = 6) in mice brain as early as 5 min post-injection followed by gradual clearance over time.
An analytical model is proposed to compute the fringe capacitance between two nonoverlapping interconnects in different layers using a conformal mapping technique. With this technique, electric field ...lines are geometrically approximated to separately model the different capacitive components. These components are finally combined to obtain the equivalent fringe capacitance. Using the aforementioned technique, a model was developed to compute the capacitances of typical interconnect geometries using technology-dependent parameters. The proposed model closely matches with FASTCAP results and significantly reduces the computational complexity and time in calculating the interconnect capacitances
We present an interesting case of a patient who was discharged from the hospital on daptomycin and ertapenem in the setting of osteomyelitis. The patient did not have any respiratory symptoms during ...that hospital stay. A few weeks after discharge, the patient came back to the hospital with complaints of fever and shortness of breath. Chest X-ray showed pulmonary infiltrates. Initially, the patient was treated for acute respiratory distress syndrome (ARDS) vs pneumonia, but she did not improve. When labs showed significant eosinophilia, daptomycin-induced eosinophilic pneumonia became the working diagnosis, and the patient improved significantly when daptomycin was discontinued and steroids were started.
Clinical trials inform on average efficacy, but individualized risk assessments for outcome prediction are important in guiding treatment implementation.
The authors developed and validated a ...patient-specific risk score to predict survival at 1 and 2 years after HeartMate 3 (HM3) left ventricular assist device (LVAD) implantation.
The MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial includes 2,200 HM3 LVAD patients in the pivotal trial and Continued Access Protocol study (2014-2018). The authors randomly assigned all patients to a derivation cohort (n = 1,540) or validation cohort (n = 660). Univariate mortality predictors were screened for potential model inclusion, stepwise selection was used to build the multivariable Cox proportional hazards regression model, and performance (discrimination and calibration) was evaluated.
Age, prior cardiac surgery (coronary artery bypass grafting CABG or valve procedure), lower serum sodium, higher blood urea nitrogen (BUN), small left ventricular size, and right atrial pressure-to-pulmonary capillary wedge pressure (RAP/PCWP) ratio >0.6 were significant risk factors for mortality. Receiver-operating characteristic (ROC) analysis in the validation cohort demonstrated an area under the curve (AUC) of 0.76 (95% CI: 0.70-0.81) at 1 year and 0.71 (95% CI: 0.66-0.77) at 2 years. Calibration between predicted and observed survival of the risk quintiles was high, with Pearson correlation coefficients of 0.986 and 0.994 at 1 and 2 years, respectively. Patients were successfully stratified into tertiles with higher-than-average, average, and lower-than-average survival, and observed mortality risk increased by 2-fold from one tertile to the next.
A practical, easy-to-use HM3 Survival Risk Score with 6 components was developed to accurately predict 1- and 2-year survival after HM3 LVAD implantation. The survival risk score can be used to provide individual survival estimates to facilitate shared decision making when considering HM3 LVAD therapy. (MOMENTUM 3 Trial Portfolio; NCT02224755, NCT02892955).
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