Katelyn N. Brinegar

Cardiovascular Organ-on-a-Chip Platforms for Drug Discovery and Development

Cardiovascular diseases are prevalent worldwide and are the most frequent causes of death in the United States. Although spending in drug discovery/development has increased, the amount of drug approvals has seen a progressive decline. Particularly, adverse side effects to the heart and general vasculature have become common causes for preclinical project closures, and preclinical models do not fully recapitulate human in vivo dynamics. Recently, organs-on-a-chip technologies have been proposed to mimic the dynamic conditions of the cardiovascular system-in particular, heart and general vasculature. These systems pay particular attention to mimicking structural organization, shear stress, transmural pressure, mechanical stretching, and electrical stimulation. Heart- and vasculature-on-a-chip platforms have been successfully generated to study a variety of physiological phenomena, model diseases, and probe the effects of drugs. Here, we review and discuss recent breakthroughs in the development of cardiovascular organs-on-a-chip platforms, and their current and future applications in the area of drug discovery and development.

Iliac vein compression syndrome: Clinical, imaging and pathologic findings

May-Thurner syndrome (MTS) is the pathologic compression of the left common iliac vein by the right common iliac artery, resulting in left lower extremity pain, swelling, and deep venous thrombosis. Though this syndrome was first described in 1851, there are currently no standardized criteria to establish the diagnosis of MTS. Since MTS is treated by a wide array of specialties, including interventional radiology, vascular surgery, cardiology, and vascular medicine, the need for an established diagnostic criterion is imperative in order to reduce misdiagnosis and inappropriate treatment. Although MTS has historically been diagnosed by the presence of pathologic features, the use of dynamic imaging techniques has led to a more radiologic based diagnosis. Thus, imaging plays an integral part in screening patients for MTS, and the utility of a wide array of imaging modalities has been evaluated. Here, we summarize the historical aspects of the clinical features of this syndrome. We then provide a comprehensive assessment of the literature on the efficacy of imaging tools available to diagnose MTS. Lastly, we provide clinical pearls and recommendations to aid physicians in diagnosing the syndrome through the use of provocative measures.

Time-Driven Activity-Based Costing in IR

The United States spends more than 17% of its gross domestic product on health care services. Although national health care spending has recently slowed, its burden on the economy continues to be a major challenge that has caused patients, health care workers, and policy makers alike to demand reform (1,2). Current reform proposals focus on expanding access and coverage to the system but do not address the fundamental issue of how to lower actual costs without having an adverse impact on quality and patient outcomes. The most important goal for any health care organization is to provide value to patients. Value in health care delivery, as described by Kaplan and Porter (2), is measured by patient outcomes relative to the costs incurred to achieve those outcomes. Measuring value is complex because outcomes are multidimensional and include clinical, functional, and patient-reported results. Additionally, outcomes also need to be measured over different timeframes. Cost measurement is difficult because care for a medical condition is often performed in many different clinical departments, and, potentially, at multiple different locations and provider organizations. Finally, costs charged to the patient are often different from those charged to the payer or provider. Without a deep understanding of the costs incurred to provide medical care, it remains difficult to constrain

The commercialization of genome-editing technologies

Abstract The emergence of new gene-editing technologies is profoundly transforming human therapeutics, agriculture, and industrial biotechnology. Advances in clustered regularly interspaced short palindromic repeats (CRISPR) have created a fertile environment for mass-scale manufacturing of cost-effective products ranging from basic research to translational medicine. In our analyses, we evaluated the patent landscape of gene-editing technologies and found that in comparison to earlier gene-editing techniques, CRISPR has gained significant traction and this has established dominance. Although most of the gene-editing technologies originated from the industry, CRISPR has been pioneered by academic research institutions. The spinout of CRISPR biotechnology companies from academic institutions demonstrates a shift in entrepreneurship strategies that were previously led by the industry. These academic institutions, and their subsequent companies, are competing to generate comprehensive intellectual property portfolios to rapidly commercialize CRISPR products. Our analysis shows that the emergence of CRISPR has resulted in a fivefold increase in genome-editing bioenterprise investment over the last year. This entrepreneurial movement has spurred a global biotechnology revolution in the realization of novel gene-editing technologies. This global shift in bioenterprise will continue to grow as the demand for personalized medicine, genetically modified crops and environmentally sustainable biofuels increases. However, the monopolization of intellectual property, negative public perception of genetic engineering and ambiguous regulatory policies may limit the growth of these market segments.

High-throughput approaches for screening and analysis of cell behaviors

The rapid development of new biomaterials and techniques to modify them challenge our capability to characterize them using conventional methods. In response, numerous high-throughput (HT) strategies are being developed to analyze biomaterials and their interactions with cells using combinatorial approaches. Moreover, these systematic analyses have the power to uncover effects of delivered soluble bioactive molecules on cell responses. In this review, we describe the recent developments in HT approaches that help identify cellular microenvironments affecting cell behaviors and highlight HT screening of biochemical libraries for gene delivery, drug discovery, and toxicological studies. We also discuss HT techniques for the analyses of cell secreted biomolecules and provide perspectives on the future utility of HT approaches in biomedical engineering.

Aspiration thrombectomy using the penumbra catheter.

Editor: Thromboembolic diseases are among the most prevalent medical problems today and cause stroke, myocardial ischemia, acute limb ischemia, and pulmonary embolism. Various treatment modalities exist, ranging from medical therapy to endovascular techniques. In the management of a thromboembolic condition causing a threatened limb, common options for treatment include surgical thromboembolectomy, percutaneous thrombectomy, and/or thrombolysis. In recent decades, many mechanical thromboembolectomy devices have become commercially available and have proven to be useful in the treatment of acute thrombi. These devices are often limited in efficacy when treating a chronic, organized thrombus. We recently encountered two cases in which an aspiration thrombectomy device (Penumbra, Alameda, California), which is typically used in the treatment of acute stroke, was used to aspirate chronic thrombi in a patient with a cold hand and in a patient with a chronically thrombosed common iliac vein stent. A 59-year-old man with a 20-year history of poorly controlled diabetes and hypertension presented to the emergency department with left hand pain, numbness, and tingling in the dorsal and palmar surfaces of the fingers. On examination, the left hand was cold, with a weak radial pulse and a delayed capillary refill in the fingers. There was limited range of motion, particularly in the third and fourth digits, during active and passive movement. The forearm compartments were soft with no tenderness. A sensory examination had normal findings, and a Spurling test was negative. Doppler ultrasonography and left upper extremity arteriography demonstrated a focal occlusion of the radial artery at the level of the wrist and severely atherosclerotic ulnar

HHV-6 and seizure: A systematic review and meta-analysis.

Human herpesvirus‐6 (HHV‐6) is a common infection in childhood. This systematic review aims to assess the relationship between HHV‐6 infection and seizure disorders based on available literature. MEDLINE database was searched using a search strategy. We included studies that were published after 1993 in English, and described patients with HHV‐6 infection and accompanying seizure or status epilepticus. We identified 503 articles, and included 147 studies. Meta‐analysis results showed a 0.21 detection rate of HHV‐6 in febrile seizure patients. In the febrile seizure group (110 cases), 76 patients had simple and 34 had complex febrile seizures. Patients with “HHV‐6 infection and status epilepticus” had a mean age of 16.24 months. In children with febrile illnesses, a higher index of clinical suspicion for HHV‐6 infection may be required. Further studies including CSF and brain tissue may be needed to validate relationships between HHV6 infection and epilepsy. J. Med. Virol. 89:161–169, 2017.

Use of Magnetic Resonance Venography in Screening Patients With Cryptogenic Stroke for May-Thurner Syndrome

The purpose of this study was to determine the prevalence of May-Thurner syndrome (MTS) in patients with cryptogenic stroke and to determine the incidence of patent foramen ovale. Magnetic resonance venography of 214 patients with cryptogenic stroke and 50 control patients with abdominopelvic computed tomography scans were evaluated for MTS. Incidence of patent foramen ovale and MTS in the stroke group were significantly greater than the control group (P = 0.0001, P = 0.0023, respectively). In addition, there was significantly greater compression of the left common iliac vein in the stroke group (32%) compared with the control group (13%) (P < 0.00001). In conclusion, there is a significantly higher prevalence of MTS and left common iliac vein compression in patients with cryptogenic stroke. These results indicate that magnetic resonance venography of the pelvis may be appropriate in the evaluation of stroke.

Critical access hospital ED to quaternary medical center: successful implementation of an integrated Picture Archiving and Communications System for patient transfers by air and sea

PURPOSE The purpose of this study was to investigate the role of imaging in transfers between an island Critical Access Hospital (CAH) emergency department (ED) and a quaternary care hospital. METHODS Electronic medical records were reviewed to identify all patients who were transferred from an island CAH to our quaternary care hospital in 2012 and 2013. Medical history, transfer diagnosis, and the type of imaging performed at the CAH prior to transfer were reviewed. RESULTS During the study period, a total of 22075 ED visits were made to the CAH and 696 (3.2%) of these patients were transferred for higher level of care, with 424 (60.9%) of the patients transferred to our quaternary care hospital. The most common reasons for transfer were cardiac (121; 28.5%), trauma (82; 19.3%), gastrointestinal (63; 14.9%), and neurologic conditions (54; 12.7%). 349 patients (82.3%) had imaging prior to transfer (56.4% radiograph, 33.5% computed tomography, 4.7% magnetic resonance imaging, 8.0% ultrasound). Of patients that had imaging, 53.6% had positive imaging findings related to the transfer diagnosis, and patients transferred for noncardiac etiologies were significantly more likely to have imaging findings related to their transfer diagnosis compared with patients transferred for cardiac etiologies (72.9% vs 6.9%, respectively; P< .0001). CONCLUSION Approximately 3 of every 100 ED visits to the rural CAH required transfer for higher level of care, with nearly three-quarters of noncardiac transferred patients having a positive imaging finding related to the reason for transfer.

Endovascular Diagnosis of Radiographically and Intraoperatively Occult Insulinoma

internal iliac artery after EVAR, the underlying AV fistula may have contributed to the persistent retrograde aneurysmal sac filling. IIAVFs have been reported in association with penetrating trauma and iatrogenic causes (4), but spontaneous cases are rare (1). Our patient had undergone a cardiac catheterization via contralateral groin access. This procedure was not thought to have caused the fistula because the puncture site would be the expected fistula location, whereas the accessed arteries were contralateral to the site of disease. Therefore, we postulate that the patient had a preexisting CIAA that developed a spontaneous IIAVF, likely from contained rupture. In summary, our experience provides an encouraging example for endovascular management of isolated CIAA and IIAVF. Although open surgery has traditionally been performed, the present case report demonstrates the possibility of performing endovascular repair for a complex case of isolated CIAA complicated by spontaneous AV fistula with the adjacent common iliac vein.