Alice S. Ferng

Bone cancer pain

In the United States, cancer is the second most common cause of death and it is expected that about 562,340 Americans will have died of cancer in 2009. Bone cancer pain is common in patients with advanced breast, prostate, and lung cancer as these tumors have a remarkable affinity to metastasize to bone. Once tumors metastasize to bone, they are a major cause of morbidity and mortality as the tumor induces significant skeletal remodeling, fractures, pain, and anemia. Currently, the factors that drive cancer pain are poorly understood. However, several recently introduced models of bone cancer pain, which closely mirror the human condition, are providing insight into the mechanisms that drive bone cancer pain and guide the development of mechanism‐based therapies to treat the cancer pain. Several of these mechanism‐based therapies have now entered human clinical trials. If successful, these therapies have the potential to significantly enlarge the repertoire of modalities that can be used to treat bone cancer pain and improve the quality of life, functional status, and survival of patients with bone cancer.

A phenotypically restricted set of primary afferent nerve fibers innervate the bone versus skin: therapeutic opportunity for treating skeletal pain.

Although musculoskeletal pain is one of the most common causes of chronic pain and physical disability in both developing and developed countries, relatively little is known about the nerve fibers and mechanisms that drive skeletal pain. Small diameter sensory nerve fibers, most of which are C-fiber nociceptors, can be separated into two broad populations: the peptide-rich and peptide-poor nerve fibers. Peptide-rich nerve fibers express substance P (SP) and calcitonin gene-related peptide (CGRP). In contrast, the peptide-poor nerve fibers bind to isolectin B4 (IB(4)) and express the purinergic receptor P(2)X(3) and Mas-related G protein-coupled receptor member d (Mrgprd). In the present report, we used mice in which the Mrgprd(+) nerve fibers express genetically encoded axonal tracers to determine the peptide-rich and peptide-poor sensory nerve fibers that innervate the glabrous skin of the hindpaw as compared to the bone marrow, mineralized bone and periosteum of the femur. Whereas the skin is richly innervated by CGRP(+), SP(+), P(2)X(3)(+) and Mrgprd(+) sensory nerve fibers, the bone marrow, mineralized bone and periosteum receive a significant innervation by SP(+) and CGRP(+), but not Mrgprd(+) and P(2)X(3)(+) nerve fibers. This lack of redundancy in the populations of C-fibers that innervate the bone may present a unique therapeutic opportunity for targeting skeletal pain as the peptide-rich and peptide-poor sensory nerve fibers generally express a different repertoire of receptors and channels to detect noxious stimuli. Thus, therapies that target the specific types of C-nerve fibers that innervate the bone may be uniquely effective in attenuating skeletal pain as compared to skin pain.

Rapid porcine lung decellularization using a novel organ regenerative control acquisition bioreactor

To regenerate discarded lungs that would not normally be used for transplant, ex vivo reseeding after decellularization may produce organs suitable for clinical transplantation and therefore close the donor gap. Organ regenerative control acquisition (Harvard Biosciences, Holliston, MA), a novel bioreactor system that simulates physiological conditions, was used to evaluate a method of rapid decellularization. Although most current decellularization methods are 24–72 hours, we hypothesized that perfusing porcine lungs with detergents at higher pressures for less time would yield comparable bioscaffolds suitable for future experimentation. Methods involved perfusion of 1% Triton X-100 (Triton) and 0.1% sodium dodecyl sulfate at varied physiological flow rates. Architecture of native and decellularized lungs was analyzed with hematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Dry gas and liquid ventilation techniques were introduced. Our 7 hour decellularization procedure removes nuclear material while maintaining architecture. Bioscaffolds have the microarchitecture for reseeding of stem cells. Hematoxylin and eosin staining suggested removal of nuclear material, whereas SEM and TEM imaging demonstrated total removal of cells with structural architecture preserved. This process can lead to clinical implementation, thereby increasing the availability of human lungs for transplantation.

Intraoperative thermographic imaging to assess myocardial distribution of Del Nido cardioplegia

We describe the intraoperative non‐invasive use of an infrared (IR) camera to monitor Del Nido cardioplegia delivery in patients undergoing cardiac surgery. Thermal pictures were taken pre‐ and post‐cardioplegia and at timed points after arrest, and compared to readings from a transseptal temperature probe. There was good concordance between the transseptal probe and the IR camera temperature readings. This non‐invasive technique, which assesses cardioplegic distribution, may help to determine when additional doses of Del Nido cardioplegia are required during periods of cardioplegic arrest.

First in Man: Sternal Reconstruction with Autologous Stem Cells.

Sternal nonunion is associated with high morbidity and treated using rigid plate and screw fixation. This is the first reported example of successful sternal reconstruction using adipose-derived stromal vascular fraction (SVF) stem cells in addition to traditional techniques. Mesenchymal stem cells, one component of the SVF, play an important role in bone healing and were therefore used to promote remedial processes in a patient with sternal nonunion. A 3D printed model of the patients sternum was used for preoperative planning of the plating. Intraoperatively, SVF was isolated using ultrasonic cavitation and previously planned sternal plating was completed. A total of 300 million cells were delivered via both local injection and intravenously before chest closure. The patients pain dramatically decreased, commensurate with healed areas of nonunion by 3 months and maintained at 6 months postoperatively, supported by three-dimensional computed tomography imaging. Utilizing autologous stem cells from the SVF in conjunction with existing plating techniques may provide an optimal platform to stabilize the sternum and promote bone healing, although additional study is recommended.

Cardiac Regeneration in the Human Left Ventricle After CorMatrix Implantation

CorMatrix is an organic extracellular matrix (ECM) derived from porcine small intestine submucosa and is used for pericardial closure and cardiac tissue repair. During explantation of a HeartMate II (Thoratec Corp, Pleasanton, CA) left ventricular assist device (LVAD) because of infection, CorMatrix was used to repair the left ventricular apex and aorta. Three months later, a HeartWare HVAD (HeartWare International, Inc, Framingham, MA) was implanted for recurrent heart failure. Excised apical CorMatrix samples showed cardiac tissue remodeling with viable cardiomyoblasts similar to native myocardium. Excised CorMatrix from the aorta showed organization of collagen and elastin similar to native aortic tissue.

Metabolic Impact of Rapamycin (Sirolimus) and B-Estradiol Using Mouse Embryonic Fibroblasts as a Model for Lymphangioleiomyomatosis

IntroductionLymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease that predominantly affects women of childbearing age. Exogenous rapamycin (sirolimus) has been shown to improve clinical outcomes and was recently approved to treat LAM, whereas estrogen (E2) is implicated in disease progression. No consistent metabolic model currently exists for LAM, therefore wild-type mouse embryonic fibroblasts (MEF +/+) and TSC2 knockout cells (MEF −/−) were used in this study as a model for LAM.MethodsOxygen consumption rates (OCR) and redox potential were measured to determine metabolic state across control cells, MEF +/+ and −/− cells treated with rapamycin (Rapa), and MEF +/+ and −/− cells treated with E2. An XF96 extracellular flux analyzer from Seahorse Bioscience® was used to measure OCR, and a RedoxSYS™ ORP was used to measure redox potential.ResultsOCR of MEF −/− cells treated with rapamycin (MEF −/− Rapa) versus MEF −/− control were significantly lower across all conditions. The static oxidation reduction potential of the MEF −/− Rapa group was also lower, approaching significance. The coupling efficiency and ratio of ATP-linked respiration to maximum respiration were statistically lower in MEF −/− Rapa compared to MEF +/+ Rapa. There were no significant metabolic findings across any of the MEF cells treated with E2. MEF −/− control cells versus MEF +/+ control cells were not found to significantly differ.ConclusionMEF cells are thought to be a feasible metabolic model for LAM, which has implications for future pharmacologic and biologic testing.

First North American 50 cc Total Artificial Heart Experience: Conversion from a 70 cc Total Artificial Heart.

The 70 cc total artificial heart (TAH) has been utilized as bridge to transplant (BTT) for biventricular failure. However, the utilization of 70 cc TAH has been limited to large patients for the low output from the pulmonary as well as systemic vein compression after chest closure. Therefore, the 50 cc TAH was developed by SynCardia (Tucson, AZ) to accommodate smaller chest cavity. We report the first TAH exchange from a 70 to 50 cc due to a fit difficulty. The patient failed to be closed with a 70 cc TAH, although the patient met the conventional 70 cc TAH fit criteria. We successfully closed the chest with a 50 cc TAH.

The Role of MHealth and Wearables for Anticipation in Medicine

As the market for health-tracking wearable devices continues to expand, there is an emerging niche for healthcare applications, and data acquisition and usage. Within this area exists a wealth of clinically relevant data already collected from wearers, including physiological and lifestyle data. This information allows us to not only optimize current medical treatments and health planning, but also to expand preventive medicine by applying anticipation to medicine. We propose that much of the data collected through these wearable devices can be used to inform both patient and clinician of long-term physiological trends, and to anticipate potential onset of illnesses with a view to stemming their progression, or even mitigating their occurrence altogether. This paper highlights important issues within the health-wearable paradigm and presents upcoming applications of wearable technologies in medicine.

Anti-inflammatory properties of amniotic membrane patch following pericardiectomy for constrictive pericarditis

BackgroundSince constrictive pericarditis is most often idiopathic and the pathophysiology remains largely unknown, both the diagnosis and the treatment can be challenging. However, by definition, inflammatory processes are central to this disease process. Amniotic membrane patches have been shown to possess anti-inflammatory properties and are believed to be immune privileged. Due to these properties, amniotic membrane patches were applied intraoperatively in a complicated patient presenting with constrictive pericarditis.Case presentationA patient with a history of multiple cardiac surgeries presented with marked fatigue, worsening dyspnea and sinus tachycardia. He was found to have constrictive physiology during cardiac catheterization, with cardiac MRI demonstrating hepatic vein dilatation, atrial enlargement and ventricular narrowing. After amniotic membrane patch treatment and pericardiectomy, post-operative cardiac MRI failed to demonstrate any appreciable pericardial effusion or inflammation, with no increased T2 signal that would suggest edema.ConclusionsGiven the positive results seen in this complex patient, we suggest continued research into the beneficial properties of amniotic membrane patches in cardiac surgery.