Comparison and precision of visceral adipose tissue measurement techniques in a multisite longitudinal study using MRI.

BACKGROUND: Measurement of visceral adipose tissue (VAT) using magnetic resonance imaging (MRI) is considered accurate and safe. Single slice measurements perform similar to volumetric measurements for cross-sectional observation studies but may not perform as well for longitudinal studies. This study compared the performance of single slice to volumetric VAT measurements in a prospective longitudinal study. Consistency of results across sites and over time was also evaluated. METHODS: A total of 935 healthy participants were recruited and scanned with MRI twice, approximately six months apart as part of a randomized, controlled, parallel arm, unblinded study conducted at four clinical centers in the United States. A 3D Dixon MRI sequence was used to image the abdomen, and visceral fat volumes were quantified for the abdomen, reduced coverage volumes (11 and 25 slices), and at single slices positioned at anatomical landmarks. A traveling phantom was scanned twice at all imaging sites. RESULTS: The correlation of single slice VAT measurement to full abdomen volumetric measurements ranged from 0.78 to 0.93 for cross-sectional observation measurements and 0.30 to 0.55 for longitudinal change. Reduced coverage volumetric measurement outperformed single slice measurements but still showed improved precision with more slices with cross-sectional observation and longitudinal correlations of 0.94 and 0.66 for 11 slices and 0.94 and 0.70 for 25 slices, respectively. No significant differences were observed across sites or over time with the traveling phantom and the volume measurements had a standard deviation of 14.1 mL, 2.6% of the measured volume. CONCLUSION: Single slice VAT measurements had significantly lower correlation with abdomen VAT volume for longitudinal change than for cross-sectional observation measurements and may not be suitable for longitudinal studies. Data from multiple sites, different scanners, and over time did not show significant differences.

Automated abdominal adipose tissue segmentation and volume quantification on longitudinal MRI using 3D convolutional neural networks with multi-contrast inputs.

OBJECTIVE: Increased subcutaneous and visceral adipose tissue (SAT/VAT) volume is associated with risk for cardiometabolic diseases. This work aimed to develop and evaluate automated abdominal SAT/VAT segmentation on longitudinal MRI in adults with overweight/obesity using attention-based competitive dense (ACD) 3D U-Net and 3D nnU-Net with full field-of-view volumetric multi-contrast inputs. MATERIALS AND METHODS: 920 adults with overweight/obesity were scanned twice at multiple 3 T MRI scanners and institutions. The first scan was divided into training/validation/testing sets (n = 646/92/182). The second scan from the subjects in the testing set was used to evaluate the generalizability for longitudinal analysis. Segmentation performance was assessed by measuring Dice scores (DICE-SAT, DICE-VAT), false negatives (FN), and false positives (FP). Volume agreement was assessed using the intraclass correlation coefficient (ICC). RESULTS: ACD 3D U-Net achieved rapid (< 4.8 s/subject) segmentation with high DICE-SAT (median ≥ 0.994) and DICE-VAT (median ≥ 0.976), small FN (median ≤ 0.7%), and FP (median ≤ 1.1%). 3D nnU-Net yielded rapid (< 2.5 s/subject) segmentation with similar DICE-SAT (median ≥ 0.992), DICE-VAT (median ≥ 0.979), FN (median ≤ 1.1%) and FP (median ≤ 1.2%). Both models yielded excellent agreement in SAT/VAT volume versus reference measurements (ICC > 0.997) in longitudinal analysis. DISCUSSION: ACD 3D U-Net and 3D nnU-Net can be automated tools to quantify abdominal SAT/VAT volume rapidly, accurately, and longitudinally in adults with overweight/obesity.

Emergency department length of stay following discontinuation of routine oral contrast material.

PURPOSE: To determine the effect of discontinuing routine oral contrast material on emergency department (ED) length of stay (LOS), time from order to CT completion, and preliminary report turnaround time (TAT). METHODS: A HIPAA-compliant, IRB-waived, single-institution, retrospective cohort study was conducted on adult patients presenting with abdominal pain to the ED from October 2015 to April 2019. Routine oral contrast material was administered prior to July 2018 and discontinued thereafter. CT workflow (ED LOS, exam completion time, report TAT) data were analyzed in a univariate analysis before and after discontinuation of oral contrast. Pre- versus post-policy data were compared with 2-sided t tests. The primary outcome was ED LOS. Data were analyzed on a process control chart and confidence limits were adjusted using established criteria. RESULTS: There were 5020 included abdominopelvic CTs. After routine oral contrast material was discontinued, ED LOS (13.4 h vs 10.7 h, p < 0.001) and time from CT order to CT completion (2.7 h vs 2.1 h, p < 0.001) declined. However, control chart analysis revealed improvement in overall LOS preceded the policy change by 9 months, while improvement in time to CT completion coincided with the policy change. Preliminary report TAT increased by 4 min after the policy change (29 min vs. 33 min, p < 0.001). CONCLUSIONS: Discontinuation of routine oral contrast material in the ED accelerated time to CT completion but had a minor non-significant effect on overall ED LOS. Much of the reduction in overall LOS likely was due to unrelated process improvements.

Minimum inhibitory concentration changes in relapsed left ventricular assist device driveline infections.

Driveline infection is the most common infectious complication in patients with left ventricular assist devices. Minimum inhibitory concentration changes are not well described in relapsed driveline infections. This retrospective descriptive epidemiology study of patients with left ventricular assist device implantation between January 1, 2013, and August 1, 2017, who developed driveline infection with positive cultures aimed to describe minimum inhibitory concentration changes. Of the 330 patients underwent left ventricular assist device implantation, 30 (9%) met criteria for driveline infection. Median duration of follow-up was 26 months (interquartile range 16, 39) and time to first driveline infection was 171 days (interquartile range 83, 403). There were 74 driveline infections: 40 new and 34 relapsed. Staphylococcus aureus was most common in new and relapsed driveline infection. Thirteen patients comprised the 34 relapsed infections, 9 of which experienced a minimum inhibitory concentration change. Median time to first minimum inhibitory concentration change was 56 days (interquartile range 36-88), and type of minimum inhibitory concentration change was an increase in five cases, decrease in two cases, and both increase and decrease in two cases. Minimum inhibitory concentration changes did not result in resistance in S. aureus but did in Pseudomonas aeruginosa and Mycobacterium fortuitum relapsed driveline infection. Time to first relapse from initial infection was longer in those who received suppressive therapy, 60 days versus 83 days, p = 0.047. Relapsed driveline infections were most common with S. aureus. Minimum inhibitory concentration changes were quite variable and may not be the major contributor to relapsed infection in gram-positive driveline infection.

Anticoagulation Reversal and Risk of Thromboembolic Events Among Heart Transplant Recipients Bridged with Durable Mechanical Circulatory Support Devices.

Anticoagulation reversal agents (ARAs) can minimize bleeding complications associated with mechanical circulatory support devices (MCSDs) explantation at the time of heart transplantation (HT); data on thromboembolic (TE) risk associated with ARAs are limited in this patient population. In this single-center study, we retrospectively analyzed 118 consecutive adults who were supported with durable MCSDs and underwent HT between May 2013 and October 2016. Patients were categorized based on intraoperative use of ARAs (recombinant factor VIIa [n=23], 4-factor prothrombin complex concentrate [n=48], or factor IX complex [n=2]) at the time of HT; these agents were used at discretion of implanting surgeons for bleeding control. The primary outcome of interest was presence of venous or systemic TE events within 3 months of HT. Multivariable logistic regression analyses were used to assess association between TE events and use of ARAs. A total of 71 (60%) patients received ARAs, and a total of 32 patients (27.1%) had TE events (25 venous [median time to diagnosis: 11.5 days; interquartile range {IQR}: 9-31 days], and 10 systemic [median time to diagnosis: 5.5 days; IQR: 4-8 days]); 26 (81.2%) of those with TE events had ARAs used at the time of HT. Multivariable analysis identified use of ARAs as an independent predictor of TE events (multivariable odds ratio: 3.06; 95% CI: 1.09-8.58; p = 0.034). Unplanned intraoperative use of ARAs to control bleeding was associated with a significantly higher risk of TE events among HT recipients bridged with durable MCSD. Future studies are required to further assess safety of these agents and their impact on patient outcomes.

Pharmacotherapeutic Management of Gastrointestinal Bleeding in Patients with Continuous-Flow Left Ventricular Assist Devices.

Continuous-flow left ventricular assist devices (CF-LVADs) have become an integral component of the management in patients with advanced heart failure, serving as destination therapy or as a bridge to heart transplantation. Despite significant advances in the design and longevity of the device, the ongoing risk for bleeding remains a significant concern. The genesis of gastrointestinal bleeding (GIB) in patients with CF-LVADs is likely multifactorial and may include components of acquired von Willebrand disease, angiodysplasia, and gastrointestinal arteriovenous malformations, as well as additional risk factors such as history of GIB and increased age. Several pharmacotherapy options have been used, but the data surrounding their overall efficacy remain sparse. The necessity for larger prospective studies is essential to further advance the management of this devastating complication. Within this review, we discuss the known pathophysiologic process of CF-LVAD-related GIB and highlight the therapeutic options discussed within the literature. In addition, we discuss potential therapeutic options based on mechanisms of action as they correlate to known pathophysiologic processes of CF-LVAD-related GIB. Finally, we provide recommendations for constructing drug therapy regimens in patients with CF-LVADs who develop GIB.

Effects of vertebral-body-sparing proton craniospinal irradiation on the spine of young pediatric patients with medulloblastoma.

PURPOSE: To investigate the long-term effects of vertebral-body-sparing proton craniospinal irradiation (CSI) on the spine of young patients with medulloblastoma. METHODS AND MATERIALS: Six children between the ages of 3 and 5 years with medulloblastoma were treated with vertebral-body-sparing proton CSI after maximal safe resection. Radiation therapy was delivered in the supine position with posterior beams targeting the craniospinal axis, and the proton beam was stopped anterior to the thecal sac. Patients were treated with a dose of either 23.4 Gy or 36 Gy to the craniospinal axis followed by a boost to the posterior fossa and any metastatic lesions. Chemotherapy varied by protocol. Radiographic effects on the spine were evaluated with serial imaging, either with magnetic resonance imaging scans or plain film using Cobb angle calculations, the presence of thoracic lordosis, lumbar vertebral body-to-disc height ratios, and anterior-posterior height ratios. Clinical outcomes were evaluated by patient/family interview and medical chart review. RESULTS: Overall survival and disease free survival were 83% (5/6) at follow-up. Median clinical and radiographic follow-up were 13.6 years and 12.3 years, respectively. Two patients were clinically diagnosed with scoliosis and treated conservatively. At the time of follow-up, no patients had experienced chronic back pain or required spine surgery. No patients were identified to have thoracic lordosis. Diminished growth of the posterior portions of vertebral bodies was identified in all patients, with an average posterior to anterior ratio of 0.88, which was accompanied by compensatory hypertrophy of the posterior intervertebral discs. CONCLUSION: Vertebral-body-sparing CSI with proton beam did not appear to cause increased severe spinal abnormalities in patients treated at our institution. This approach could be considered in future clinical trials in an effort to reduce toxicity and the risk of secondary malignancy and to improve adult height.

Pharmacologic Considerations in the Management of Patients Receiving Left Ventricular Percutaneous Mechanical Circulatory Support.

Percutaneous mechanical circulatory support (MCS) devices, including the intraaortic balloon pump, Impella, and TandemHeart, are often used for hemodynamic support in the setting of refractory cardiogenic shock. The thrombotic and bleeding complications associated with these devices is well recognized, and the Impella and TandemHeart devices have unique anticoagulation considerations that may influence patient outcomes. Both devices typically require use of a heparinized purge solution in combination with intravenous unfractionated heparin, thereby providing multiple sources of heparin exposure. Each device also has specific monitoring requirements and goal ranges. This review provides an overview of percutaneous MCS devices commonly used in the acute management of left ventricular failure, with an emphasis on pharmacologic considerations. We review recent evidence and guidelines and provide recommendations for appropriate use of anticoagulation during device support. Approaches to managing heparinized purge solutions, monitoring, and the utility of nonheparin anticoagulants are also provided because high-quality evidence in the literature is limited.

Inhaled Pulmonary Vasodilator Therapy for Management of Right Ventricular Dysfunction after Left Ventricular Assist Device Placement and Cardiac Transplantation.

Right ventricular failure (RVF) after cardiac transplant (CTX) or implantation of a continuous-flow left ventricular assist device (CF-LVAD) is associated with significant postoperative morbidity and mortality. A variety of modalities have been used to treat postoperative RVF, including management of volume status, intravenous inotropes and vasodilators, and right-sided mechanical support. Inhaled vasodilator agents are a unique treatment option aimed at minimizing systemic absorption by delivering therapy directly to the pulmonary vasculature. Current LVAD and CTX guidelines endorse inhaled vasodilators for managing postoperative RVF; however, no guidance is offered regarding agent selection, dosing, or administration. A review of the current literature confirms that inhaled pulmonary vasodilator agents have been shown to decrease pulmonary artery pressure when used in the perioperative period of CF-LVAD implant or CTX. However, the literature regarding the potential impact on clinical outcomes (e.g., survival or risk of developing RVF) is lacking with these medications. Based on our assessment of the literature, we suggest that when RVF occurs in the setting of a normal pulmonary vascular resistance (PVR), traditional inotropic therapy (e.g., dobutamine) should be used. Conversely, if the PVR is elevated (> 250 dynes/sec/cm5 or 3 Wood units), or the patient has other evidence of a high right ventricular afterload (i.e., a transpulmonary gradient > 12 mm Hg), then an inhaled pulmonary vasodilator would be the preferred initial pharmacologic agent. Drug selection depends largely on the institution's capacity to safely prepare and administer the medication, along with formulary considerations, such as the high costs associated with inhaled iloprost and inhaled nitric oxide.

Phenotyping Adverse Drug Reactions: Statin-Related Myotoxicity.

It is unclear the extent to which best practices for phenotyping disease states from electronic medical records (EMRs) translate to phenotyping adverse drug events. Here we use statin-induced myotoxicity as a case study to identify best practices in this area. We compared multiple phenotyping algorithms using administrative codes, laboratory measurements, and full-text keyword matching to identify statin-related myopathy from EMRs. Manual review of 300 deidentified EMRs with exposure to at least one statin, created a gold standard set of 124 cases and 176 controls. We tested algorithms using ICD-9 billing codes, laboratory measurements of creatine kinase (CK) and keyword searches of clinical notes and allergy lists. The combined keyword algorithms produced were the most accurate (PPV=86%, NPV=91%). Unlike in most disease phenotyping algorithms, addition of ICD9 codes or laboratory data did not appreciably increase algorithm accuracy. We conclude that phenotype algorithms for adverse drug events should consider text based approaches.

Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis.

BACKGROUND: The Ras association domain family 1 (RASSF1) gene is a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor suppressor gene. However, very little is known about the function of RASSF1C both in normal and transformed cells. METHODS: Gene silencing and over-expression techniques were used to modulate RASSF1C expression in human breast cancer cells. Affymetrix-microarray analysis was performed using T47D cells over-expressing RASSF1C to identify RASSF1C target genes. RT-PCR and western blot techniques were used to validate target gene expression. Cell invasion and apoptosis assays were also performed. RESULTS: In this article, we report the effects of altering RASSF1C expression in human breast cancer cells. We found that silencing RASSF1C mRNA in breast cancer cell lines (MDA-MB231 and T47D) caused a small but significant decrease in cell proliferation. Conversely, inducible over-expression of RASSF1C in breast cancer cells (MDA-MB231 and T47D) resulted in a small increase in cell proliferation. We also report on the identification of novel RASSF1C target genes. RASSF1C down-regulates several pro-apoptotic and tumor suppressor genes and up-regulates several growth promoting genes in breast cancer cells. We further show that down-regulation of caspase 3 via overexpression of RASSF1C reduces breast cancer cells' sensitivity to the apoptosis inducing agent, etoposide. Furthermore, we found that RASSF1C over-expression enhances T47D cell invasion/migration in vitro. CONCLUSION: Together, our findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells.