Publications by authors named "Anthony Pham"

43 Publications

Bench valvular surgery in donor's hearts before transplantation: Choice versus necessity.

J Card Surg 2022 Apr 19. Epub 2022 Apr 19.

Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, Florida, USA.

The severe shortage of donor's hearts has increased the mortality of patients on the transplant waiting list. However, donor hearts with valvular dysfunction are rarely used. Utilizing donor hearts with valvular lesions that can be repaired or replaced at the time of transplant will decrease waitlist mortality and offer many patients a second chance in life.
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http://dx.doi.org/10.1111/jocs.16533DOI Listing
April 2022

Effects of Adipose-Derived Biogenic Nanoparticle-Associated microRNA-451a on Toll-like Receptor 4-Induced Cytokines.

Pharmaceutics 2021 Dec 22;14(1). Epub 2021 Dec 22.

Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, FL 32224, USA.

Extracellular vesicles (EVs) are cell-released nanoparticles that transfer biomolecular content between cells. Among EV-associated biomolecules, microRNAs (miRNAs/miRs) represent one of the most important modulators of signaling pathways in recipient cells. Previous studies have shown that EVs from adipose-derived mesenchymal stromal cells (MSCs) and adipose tissue modulate inflammatory pathways in macrophages. In this study, the effects of miRNAs that are abundant in adipose tissue EVs and other biogenic nanoparticles (BiNPs) were assessed in terms of altering Toll-like receptor 4 (TLR4)-induced cytokines. TLR-4 signaling in macrophages is often triggered by pathogen or damage-induced inflammation and is associated with several diseases. This study demonstrates that miR-451a, which is abundant in adipose tissue BiNPs, suppresses pro-inflammatory cytokines and increases anti-inflammatory cytokines associated with the TLR4 pathway. Therefore, miR-451a may be partially responsible for immunomodulatory effects of adipose tissue-derived BiNPs.
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http://dx.doi.org/10.3390/pharmaceutics14010016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780819PMC
December 2021

Development of Nursing Workflows and Device Requirement Principles with the Implementation of an Electronic Medical Record System.

Stud Health Technol Inform 2021 Dec;284:113-117

Monash Health, Melbourne, Victoria, Australia.

The past decade has seen the implementation of electronic medical record (EMR) systems being implemented across large-scale healthcare organisations throughout Australia. A first-time implementation of an organisational-wide EMR system required a multi-modal approach to the development of new nursing workflows and appropriate selection of hardware devices to ensure acceptance and adoption of the EMR. The aim of this work was to develop new nursing workflows and associated device requirement principles to allow for continuation of safe, high quality nursing care with an EMR implementation. The incorporation of multi-disciplinary consultations, an audit, observational study and clinical and governance stakeholder engagement was used to develop device requirement principles. This ensured development of standardised nursing workflows were successfully adopted throughout the organisation with the EMR implementation.
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http://dx.doi.org/10.3233/SHTI210681DOI Listing
December 2021

Adjuvant hysterectomy following primary chemoradiation for stage IB2 and IIA2 cervical cancer: a retrospective comparison of complications for open versus minimally invasive surgery.

Radiat Oncol 2021 Jun 29;16(1):123. Epub 2021 Jun 29.

Division of Gynecologic Oncology, University of Southern California, 2020 Zonal Ave, IRD 526, Los Angeles, CA, 90033, USA.

Background: Adjuvant hysterectomy following chemoradiation for bulky, early stage cervical cancer has been shown to decrease local relapse rate. The objective of this study is to compare complications and recurrences between minimally invasive and open adjuvant hysterectomy for early stage cervical cancer.

Methods: Patients were identified who had undergone adjuvant hysterectomy following chemoradiation for 2009 FIGO stage IB2 and IIA2 cervical cancer from August 2006 to June 2018. Demographic information, treatment course, complications, recurrence data were retrospectively extracted from the medical record. Frequency of complications was compared with Fisher exact test or chi-square test as appropriate and inverse probability of treatment propensity score weighting was used to calculate the disease-free survival.

Results: Fifty-four patients met inclusion criteria with a median follow up time of 60.4 months (interquartile range 28.0-98.1 months). There were 24 (44%) open versus 30 (56%) minimally invasive hysterectomies performed. The overall grade 2 or worse complication rate was 43%. There were 8 (27%) patients with complications in the minimally invasive group compared to 4 (17%) in the open group (OR 1.82 (95% CI 0.5-7.0)). There were 9 vaginal cuff defects, dehiscences and/or fistulas in the minimally invasive group compared to 3 in the open group (OR 3.0 (95% CI 0.8-11.2)). There was no statistically significant difference between disease free survival and overall survival among the two groups, however there was a trend towards decreased disease-free survival in the minimally invasive group.

Conclusions: Among women undergoing adjuvant hysterectomy following chemoradiation for bulky, early stage cervical cancer, there was no difference in complication rates between an open or minimally invasive surgical approach. However, the overall complication rate was high, including a high rate of vaginal cuff defect, dehiscence and/or fistulas. Our findings suggest that an adjuvant hysterectomy should be reserved for patients in which chemoradiation is not anticipated to successfully treat the primary tumor and, if performed, an open approach should be considered.
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http://dx.doi.org/10.1186/s13014-021-01843-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244186PMC
June 2021

Bilateral lung transplantation for pulmonary artery aneurysm with severe pulmonary hypertension: An evolution or a revolution?

J Card Surg 2021 Aug 16;36(8):3000-3002. Epub 2021 May 16.

Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, Florida, USA.

The surgical treatment of pulmonary hypertension (PH), with or without pulmonary artery aneurysm, has evolved during the last 40 years from heart-lung transplants to bilateral lung transplants as the treatment of choice for PH patients with preserved right and left ventricular function and without complex cardiac abnomalies.
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http://dx.doi.org/10.1111/jocs.15654DOI Listing
August 2021

Quantitative Characterization of Tumor Proximity to Stem Cell Niches: Implications on Recurrence and Survival in GBM Patients.

Int J Radiat Oncol Biol Phys 2021 07 16;110(4):1180-1188. Epub 2021 Feb 16.

Department of Radiation Oncology, University of California - Los Angeles, California. Electronic address:

Purpose: Emerging evidence has linked glioblastoma multiforme (GBM) recurrence and survival to stem cell niches (SCNs). However, the traditional tumor-ventricle distance is insufficiently powered for an accurate prediction. We aimed to use a novel inverse distance map for improved prediction.

Methods And Materials: Two T1-magnetic resonance imaging data sets were included for a total of 237 preoperative scans for prognostic stratification and 55 follow-up scans for recurrent pattern identification. SCN, including the subventricular zone (SVZ) and subgranular zone (SGZ), were manually defined on a standard template. A proximity map was generated using the summed inverse distances to all SCN voxels. The mean and maximum proximity scores (PS and PS) were calculated for each primary/recurrent tumor, deformably transformed into the template. The prognostic capacity of proximity score (PS)-derived metrics was assessed using Cox regression and log-rank tests. To evaluate the impact of SCNs on recurrence patterns, we performed group comparisons of PS-derived metrics between the primary and recurrent tumors. For comparison, the same analyses were conducted on PS derived from SVZ alone and traditional edge/center-to-ventricle metrics.

Results: Among all SCN-derived features, PS was the strongest survival predictor (P < .0001). PS was the best in risk stratification, using either evenly sorted (P = .0001) or k-means clustering methods (P = .0045). PS metrics based on SVZ only also correlated with overall survival and risk stratification, but to a lesser degree of significance. In contrast, edge/center-to-ventricle metrics showed weak to no prediction capacities in either task. Moreover, PS,PS, and center-to-ventricle metrics revealed a significantly closer SCN distribution of recurrence than primary tumors.

Conclusions: We introduced a novel inverse distance-based metric to comprehensively capture the anatomic relationship between GBM tumors and SCN zones. The derived metrics outperformed traditional edge or center distance-based measurements in overall survival prediction, risk stratification, and recurrent pattern differentiation. Our results reveal the potential role of SGZ in recurrence aside from SVZ.
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http://dx.doi.org/10.1016/j.ijrobp.2021.02.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238898PMC
July 2021

Education and Outreach in Physical Sciences in Oncology.

Trends Cancer 2021 01 7;7(1):3-9. Epub 2020 Nov 7.

Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, FL, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Jacksonville, FL, USA; Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA; Center for Immunotherapeutic Transport Oncophysics, Houston Methodist Research Institute, Houston, TX, USA. Electronic address:

Physical sciences are often overlooked in the field of cancer research. The Physical Sciences in Oncology Initiative was launched to integrate physics, mathematics, chemistry, and engineering with cancer research and clinical oncology through education, outreach, and collaboration. Here, we provide a framework for education and outreach in emerging transdisciplinary fields.
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http://dx.doi.org/10.1016/j.trecan.2020.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895467PMC
January 2021

Harvesting left internal thoracic artery via clamshell incision for coronary bypass and lung transplant.

J Surg Case Rep 2020 Oct 27;2020(10):rjaa363. Epub 2020 Oct 27.

Department of Cardiothoracic Surgery, Mayo Clinic Florida, Jacksonville, FL, USA.

Concomitant lung transplantation and coronary artery bypass grafting operation became more prevalent over the last decade due to the advanced age of recipients. Median sternotomy approach is traditionally used when internal thoracic artery is utilized. Here we report a technique of harvesting the left internal thoracic artery via a clamshell incision for a combined coronary artery bypass and bilateral lung transplant operation in a 71-year-old male with terminal respiratory failure and coronary artery disease.
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http://dx.doi.org/10.1093/jscr/rjaa363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588304PMC
October 2020

Lipoprotein-based drug delivery.

Adv Drug Deliv Rev 2020 11;159:377-390. Epub 2020 Aug 11.

Department of Biochemistry and Molecular Biology, Department of Physiology and Biomedical Engineering, Department of Transplantation, Mayo Clinic, Jacksonville, FL 32224, USA; Department of Biology, University of North Florida, Jacksonville, FL 32224, USA; Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA. Electronic address:

Lipoproteins (LPs) are circulating heterogeneous nanoparticles produced by the liver and intestines. LPs play a major role in the transport of dietary and endogenous lipids to target cells through cell membrane receptors or cell surface-bound lipoprotein lipase. The stability, biocompatibility, and selective transport of LPs make them promising delivery vehicles for various therapeutic and imaging agents. This review discusses isolation, manufacturing, and drug loading techniques used for LP-based drug delivery, as well as recent applications for diagnosis and treatment of cancer, atherosclerosis, and other life-threatening diseases.
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http://dx.doi.org/10.1016/j.addr.2020.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747060PMC
August 2021

Three-dimensional printing facilitates surgical planning for resection of an atypical cardiac myxoma.

J Card Surg 2020 Oct 27;35(10):2863-2865. Epub 2020 Jul 27.

Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, Florida.

Background: Cardiac myxomas are common and account for 50% of primary intracardiac tumors. Atypical locations of cardiac myxoma increase the risk of intraoperative iatrogenic injuries. Herein, we report a case of using three-dimensional printing (3D) to facilitate the removal of an atypical cardiac myxoma in a 63-year-old woman.

Methods And Results: Mass in the high posterior atrial septum was confirmed through imaging. Due to the potential involvement of the mass to surrounding vital structures, 3D printing of the cardiac mass was performed. The tumor was completely resected via median sternotomy and the resulting defect was repaired with the bovine pericardium. The patient had an uncomplicated postoperative course except for the development of sick sinus syndrome. One-year follow-up showed no tumor recurrent.

Conclusion: 3D printing technology in patients with atypical cardiac tumors enhances our understanding of the extent of the tumor invasion and facilitates planning the operation to avoid intraoperative complications.
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http://dx.doi.org/10.1111/jocs.14896DOI Listing
October 2020

Absorbable antibiotic beads as an adjuvant therapy in treating ventricular assist devices driveline infection: A case report.

J Card Surg 2020 Aug 11;35(8):2073-2076. Epub 2020 Jul 11.

Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, Florida.

Background: Ventricular assist devices driveline infections are common, recalcitrant, and carry high morbidity and mortality. Herein, we reported a patient with driveline infection that was successfully treated with a combination of systemic antibiotics, surgical debridement, and instillation of absorbable antibiotic beads to the wound bed.

Methods And Results: A 39-year-old man with nonischemic cardiomyopathy underwent insertion of a continuous flow left ventricular assist device. Four years postoperatively, the patient presented with clinical, laboratory, and radiologic signs of driveline tract infection. He underwent extensive surgical debridement, installation of absorbable antibiotic beads that consisted of calcium sulfate, vancomycin, and tobramycin, into the wound bed, and systemic antibiotics. The patient was free of infection 9 month postoperatively.

Conclusion: Absorbable calcium sulfate antibiotic beads may serve as a beneficial adjunct to surgical debridement and systemic antibiotics for the treatment of ventricular assist device driveline infection, and merit further investigation.
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http://dx.doi.org/10.1111/jocs.14778DOI Listing
August 2020

Extracellular vesicles for treatment of solid organ ischemia-reperfusion injury.

Am J Transplant 2020 12 28;20(12):3294-3307. Epub 2020 Jul 28.

Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, Florida, USA.

As the incidence of ischemia-reperfusion (I-R) injury has substantially increased, there is a pressing need to develop effective strategies to treat this global health issue. I-R injury can affect all organs and is associated with high morbidity and mortality rates. Pathological settings such as myocardial infarction, stroke, hemorrhagic shock, and solid organ transplant are particularly prone to cause I-R injury. Ischemia (hypoxia) and/or reperfusion (reoxygenation) induces various forms of cellular and structural damage. A major cause of damage is local inflammatory responses, which may spread to produce more advanced systemic inflammation. Management of I-R injury relies primarily on supportive measures, as specific treatment strategies are lacking. Extracellular vesicles (EVs) are cell-secreted nano-scale structures containing various biomolecules involved in cell communication and multiple physiological processes. EVs derived from certain cell types have been shown to exhibit anti-inflammatory, antioxidant, and angiogenic properties. This review provides an overview of EV-based therapeutics for I-R injury in kidneys, liver, heart, lungs, and brain. Additionally, the mechanisms by which EVs protect against I-R injury are discussed. Promising preclinical findings highlight the potential clinical use of EVs for I-R injury.
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http://dx.doi.org/10.1111/ajt.16164DOI Listing
December 2020

Impact of pharmacist-managed immune checkpoint inhibitor toxicities.

J Oncol Pharm Pract 2021 Apr 6;27(3):596-600. Epub 2020 Jun 6.

Oncology Clinical Pharmacy Services, Kaiser Permanente, San Diego, CA, USA.

Background: Immune checkpoint inhibitors are associated with unique autoimmune side effects that differ from traditional cytotoxic chemotherapy. Pharmacists may play an important role in providing key supportive care measures necessary to aid patients and oncologists through immune-related adverse events (irAEs). This study aims to evaluate the impact of a pharmacist-managed irAE protocol in an oncology clinic.

Methods: This study is a retrospective chart review of the implementation of a pilot irAE pharmacy protocol. Patients treated with an immune checkpoint inhibitor and subsequently identified to have dermatologic, gastrointestinal, hepatic, or thyroid toxicities and managed under the pilot irAE pharmacy protocol from 1 October 2018 to 28 February 2019 were enrolled. Study endpoints included number of pharmacist interventions and physician satisfaction. Additional endpoints included pharmacotherapy initiated, dose adjustments, and patient follow-ups.

Results: From 1 October 2018, to 28 February 2019, 17 patients were referred and approved by their primary oncologists for pharmacy management under the pilot irAE protocol. During the pilot period, pharmacists initiated 21 new medications for the treatment of irAEs, including thyroid hormone replacement in 7 patients (41%) and oral corticosteroids in 6 patients (35%) with a total of 28 dose adjustments. In addition, the pilot protocol included an assessment of physician satisfaction, which showed a reduced number of physician hours per month managing irAEs, increased physician confidence in irAE management, and a desire for continued pharmacist-management of irAEs.

Conclusions: Oncology pharmacists had an impact on management of toxicities in our oncology clinic as indicated by the pharmacist interventions and physician satisfaction.
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http://dx.doi.org/10.1177/1078155220928407DOI Listing
April 2021

Adipose-Derived Biogenic Nanoparticles for Suppression of Inflammation.

Small 2020 03 18;16(10):e1904064. Epub 2020 Feb 18.

Department of Biochemistry and Molecular Biology, Department of Physiology and Biomedical Engineering, Mayo Clinic, Jacksonville, FL, 32224, USA.

Extracellular vesicles secreted from adipose-derived mesenchymal stem cells (ADSCs) have therapeutic effects in inflammatory diseases. However, production of extracellular vesicles (EVs) from ADSCs is costly, inefficient, and time consuming. The anti-inflammatory properties of adipose tissue-derived EVs and other biogenic nanoparticles have not been explored. In this study, biogenic nanoparticles are obtained directly from lipoaspirate, an easily accessible and abundant source of biological material. Compared to ADSC-EVs, lipoaspirate nanoparticles (Lipo-NPs) take less time to process (hours compared to months) and cost less to produce (clinical-grade cell culture facilities are not required). The physicochemical characteristics and anti-inflammatory properties of Lipo-NPs are evaluated and compared to those of patient-matched ADSC-EVs. Moreover, guanabenz loading in Lipo-NPs is evaluated for enhanced anti-inflammatory effects. Apolipoprotein E and glycerolipids are enriched in Lipo-NPs compared to ADSC-EVs. Additionally, the uptake of Lipo-NPs in hepatocytes and macrophages is higher. Lipo-NPs and ADSC-EVs have comparable protective and anti-inflammatory effects. Specifically, Lipo-NPs reduce toll-like receptor 4-induced secretion of inflammatory cytokines in macrophages. Guanabenz-loaded Lipo-NPs further suppress inflammatory pathways, suggesting that this combination therapy can have promising applications for inflammatory diseases.
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http://dx.doi.org/10.1002/smll.201904064DOI Listing
March 2020

Kidney transplantation on extracorporeal life support for primary cardiac allograft dysfunction.

J Card Surg 2020 Mar 4;35(3):725-728. Epub 2020 Feb 4.

Department of Cardiothoracic Surgery, Mayo Clinic, Jacksonville, Florida.

Patients undergoing heart-kidney transplants who have primary graft dysfunction (PGD) of the heart are at risk of losing both organs, which may cause reluctance on the part of the transplant team to proceed with transplanting the kidney while the transplanted heart is being supported by mechanical device. We describe a case series in which 2 patients received kidney transplants while on veno-arterial ECMO support for PGD after heart transplant. Both patients are alive more than 1 year following transplant, with good cardiac and renal function and no signs of cardiac rejection. Kidney transplant surgery is safe for patients on veno-arterial ECMO support for cardiac PGD. It allows the heart recipient to receive a kidney from the same donor with both immunologic and survival advantages.
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http://dx.doi.org/10.1111/jocs.14451DOI Listing
March 2020

Identifying Disparities in Care in Treating Glioblastoma: A Retrospective Cohort Study of Patients Treated at a Safety-net Versus Private Hospital Setting.

World Neurosurg 2020 05 27;137:e213-e220. Epub 2020 Jan 27.

Department of Neurosurgery, University of Southern California Keck School of Medicine, Los Angeles, California, USA.

Background: Patients of lower socioeconomic status (SES) may experience barriers to their oncologic care, but current data conflict over whether SES affects the prognosis of patients with glioblastoma (GB).

Objective: We sought to determine whether SES disparities impaired delivery of neuro-oncologic care and affected the prognosis of GB patients.

Methods: The records of GB patients treated from 2010 to 2014 at a safety-net hospital (SNH) or private hospital (PH), both served by 1 academic medical institution, were retrospectively reviewed and compared. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method.

Results: A total of 55 SNH and 39 PH GB patients were analyzed with median 11-month follow-up. SNH patients were predominantly Hispanic, low income, enrolled in Medicaid, were less likely to receive radiation (89% vs. 100%), took longer to start radiation (41 vs. 29 days), and were less likely to complete radiation treatment (80% vs. 95%). Concurrent and adjuvant temozolomide use were also lower (85% vs. 94% and 60% vs. 71%, respectively). OS and PFS were not significantly different (15 vs. 16 months and 8 vs. 11 months, respectively). On multivariate analysis, adjuvant chemotherapy and RT completion predicted for better OS, whereas hospital type, income, and insurance did not.

Conclusion: Although GB patients at our SNH received less adjuvant treatment compared with PH, outcomes were similar. Access to multidisciplinary care staffed by academic physicians may play an important role in overcoming socioeconomic barriers to treatment availability and quality at SNHs.
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http://dx.doi.org/10.1016/j.wneu.2020.01.133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8908807PMC
May 2020

Use of Omental Flap for Treating Cardiocutaneous Fistula After Ventricular Aneurysm Repair.

Ann Thorac Surg 2020 08 24;110(2):e127-e128. Epub 2020 Jan 24.

Department of Cardiothoracic Surgery, Mayo Clinic Florida, Jacksonville, Florida. Electronic address:

Infection of an endoventricular patch used for left ventricular aneurysm repair with formation of cardiocutaneous fistula is a rare but potentially serious complication. We report an adult patient who developed a cardiocutaneous fistula 1 year after repair of a third left ventricular aneurysm. The patient was successfully treated with a redo operation using a bovine pericardial patch with omental flap coverage. He is alive and well 10 years later.
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http://dx.doi.org/10.1016/j.athoracsur.2019.11.061DOI Listing
August 2020

Extracellular vesicle-based drug delivery systems for cancer treatment.

Theranostics 2019 17;9(26):8001-8017. Epub 2019 Oct 17.

Department of Transplantation/Department of Physiology and Biomedical Engineering, Mayo Clinic, Jacksonville, FL, 32224, USA.

Extracellular vesicles (EVs) are naturally occurring cell-secreted nanoparticles that play important roles in many physiological and pathological processes. EVs enable intercellular communication by serving as delivery vehicles for a wide range of endogenous cargo molecules, such as RNAs, proteins, carbohydrates, and lipids. EVs have also been found to display tissue tropism mediated by surface molecules, such as integrins and glycans, making them promising for drug delivery applications. Various methods can be used to load therapeutic agents into EVs, and additional modification strategies have been employed to prolong circulation and improve targeting. This review gives an overview of EV-based drug delivery strategies in cancer therapy.
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http://dx.doi.org/10.7150/thno.37097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857056PMC
September 2020

Adipose-derived cellular and cell-derived regenerative therapies in dermatology and aesthetic rejuvenation.

Ageing Res Rev 2019 09 24;54:100933. Epub 2019 Jun 24.

Center for Regenerative Medicine, Mayo Clinic, Jacksonville, FL, 32224, United States; Department of Orthopedic Surgery, Mayo Clinic, Jacksonville, FL, 32224, United States. Electronic address:

Cellular and cell-derived components of adipose-derived tissue for the purposes of dermatologic and aesthetic rejuvenation applications have become increasingly studied and integrated into clinical practice. These components include micro-fragmented fat (nanofat), the stromal vascular fraction (SVF), adipose-derived mesenchymal stem cells (ASC), and extracellular vesicles (EVs), which have all shown capability to repair, regenerate, and rejuvenate surrounding tissue. Various aesthetic applications including hair growth, scar reduction, skin ischemia-reperfusion recovery, and facial rejuvenation are reviewed. In particular, results from preclinical and clinical studies are discussed, with a focus on clarification of nomenclature.
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http://dx.doi.org/10.1016/j.arr.2019.100933DOI Listing
September 2019

Organotropic drug delivery: Synthetic nanoparticles and extracellular vesicles.

Biomed Microdevices 2019 04 15;21(2):46. Epub 2019 Apr 15.

Department of Transplantation Medicine, Mayo Clinic, Jacksonville, Florida, 32224, USA.

Most clinically approved drugs (primarily small molecules or antibodies) are rapidly cleared from circulation and distribute throughout the body. As a consequence, only a small portion of the dose accumulates at the target site, leading to low efficacy and adverse side effects. Therefore, new delivery strategies are necessary to increase organ and tissue-specific delivery of therapeutic agents. Nanoparticles provide a promising approach for prolonging the circulation time and improving the biodistribution of drugs. However, nanoparticles display several limitations, such as clearance by the immune systems and impaired diffusion in the tissue microenvironment. To overcome common nanoparticle limitations various functionalization and targeting strategies have been proposed. This review will discuss synthetic nanoparticle and extracellular vesicle delivery strategies that exploit organ-specific features to enhance drug accumulation at the target site.
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http://dx.doi.org/10.1007/s10544-019-0396-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686136PMC
April 2019

Trimodality therapy for bladder cancer: modern management and future directions.

Curr Opin Urol 2019 05;29(3):210-215

Department of Radiation Oncology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Purpose Of Review: This review examines both trimodality therapy (TMT) in the definitive management of bladder cancer as well as the use of adjuvant radiotherapy for bladder cancer with a specific focus on publications from the last 2 years.

Recent Findings: TMT is an effective management strategy for muscle invasive bladder cancer with outcomes similar to radical cystectomy. Effectiveness of this strategy exists in variant histologies and can be personalized with use of biomarkers. There is a role for adjuvant radiotherapy in locally advanced bladder cancer, especially in the age of improved imaging and modern radiotherapy techniques.

Summary: This review should provide the reader data necessary to support use of TMT and adjuvant radiation therapy in their clinic.
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http://dx.doi.org/10.1097/MOU.0000000000000601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440298PMC
May 2019

Temporal Changes in Esophageal Cancer Mortality by Geographic Region: A Population-based Analysis.

Cureus 2018 Nov 15;10(11):e3596. Epub 2018 Nov 15.

Radiation Medicine, Zucker School of Medicine at Hofstra / Northwell, New York, USA.

Purpose To analyze differences in esophageal cancer survival by geographic region of the U.S. from the 1970s to the 2000s, and attribute the causes of these discrepancies. Methods Raw data were obtained from the Surveillance Epidemiology and End Results (SEER) program of the National Cancer Institute. Patients were stratified by decade of diagnosis and by geographic region (East, Hawaii/Alaska, Midwest, Southwest, and West), containing SEER registries. The Kaplan-Meier method with the log-rank test was used to compare the overall survival (OS) among these geographic groups. A multivariate Cox Proportional Hazard analysis was conducted to evaluate the impact of the following factors on differences in survival: patient age, gender, race, tumor stage, site, histology, treatment method, and metropolitan size. Results A total of 87,834 patients were identified. OS has increased significantly since 1973, with five-year OS improving from 4.9% (the 1970s) to 15.3% (2000s) (<0.001). Residence in the East was prognostic for higher OS compared to all the other regions, with a median OS of six months in the 1970s and 12 months in the 2000s (<0.001). The multivariate analysis revealed increased age, African American race, distant disease, non-distal tumor location, squamous cell histology, and no radiation therapy were associated with worse OS. The West and East had the highest amount of cancer centers (12 and seven, respectively). And the East had the highest number of cancer centers per person (5.7E-07) while the South had the lowest (1.6E-07). Conclusions There are disparities in esophageal cancer survival and quality of care through different geographic regions of the U.S., which may be attributed to a combination of the unbalanced distribution of medical resources, the regional differences in cancer biology, and other lifestyle and socioeconomic factors. More research should be conducted to further characterize regional differences and guide the implementation of improvements in survival.
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http://dx.doi.org/10.7759/cureus.3596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338397PMC
November 2018

Acute toxicity of craniospinal irradiation with volumetric-modulated arc therapy in children with solid tumors.

Pediatr Blood Cancer 2018 07 6;65(7):e27050. Epub 2018 Apr 6.

Department of Radiation Oncology, Keck School of Medicine of the University of Southern California, Los Angeles, California.

Background: Craniospinal irradiation (CSI) is an important part of curative radiation therapy (RT) for many types of pediatric brain or solid tumors. After conventional CSI, long term survivors may experience sequelae due to unintended dose to normal tissue. Volumetric modulated arc therapy (VMAT) CSI reduces off-target doses at the cost of greater complexity and error risk, and we describe our initial experience in a group of pediatric patients with solid tumors presenting with disseminated or recurrent disease.

Procedure: Pediatric patients with brain tumors were identified at Children's Hospital Los Angeles from 2013 to 2015. Clinical characteristics, acute toxicity, and radiotherapy data were abstracted from their medical records. We identified 19 patients who received VMAT CSI. Quality assurance was performed with a cylindrical detector array and ion chamber measurements at the arc junctions.

Results: Patients had medulloblastoma or supratentorial primitive neuro-ectodermal tumor (n = 14, 11 high risk), germ cell tumors (two), relapsed neuroblastoma (two), and atypical teratoid/rhabdoid tumor (one). The most common acute toxicity was hematologic, including leukopenia (11% grade [Gr] 2, 26% Gr 3, and 63% Gr 4), anemia (89% Gr 2), and thrombocytopenia (16% Gr 1-2, 26% Gr 3, and 37% Gr 4). Despite leukopenia, we encountered only two Gr 3 infections (urinary tract and lung). The majority required blood products (89% red blood cells and 68% platelets). Weight loss was also common (47% Gr 1 and 26% Gr 2).

Conclusions: VMAT CSI, along with chemotherapy and anesthesia, is feasible with supportive care. Daily image-guided RT improves accuracy and reduces the risk of spinal cord overdose without increasing treatment time. Further research is needed to determine whether reducing doses to organs, such as thyroid, heart, or hippocampus, offsets the risk of increased volume of low-dose irradiation.
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http://dx.doi.org/10.1002/pbc.27050DOI Listing
July 2018

Toxic metals in ayurvedic preparations from a public health lead poisoning cluster investigation.

Int J Occup Environ Health 2017 07 12;23(3):187-192. Epub 2018 Mar 12.

a Department of Occupational and Environmental Health , College of Public Health, The University of Iowa , Iowa City , IA , USA.

Background Herbal formulations, traditional medicine, and complementary and alternative medicine are used by the majority of the world's population. Toxicity associated with use of Ayurvedic products due to metal content is an increasingly recognized potential public health problem. Objectives Report on toxic metals content of Ayurvedic products obtained during an investigation of lead poisoning among users of Ayurvedic medicine. Methods Samples of Ayurvedic formulations were analyzed for metals and metalloids following established US. Environmental Protection Agency methods. Results Lead was found in 65% of 252 Ayurvedic medicine samples with mercury and arsenic found in 38 and 32% of samples, respectively. Almost half of samples containing mercury, 36% of samples containing lead and 39% of samples containing arsenic had concentrations of those metals per pill that exceeded, up to several thousand times, the recommended daily intake values for pharmaceutical impurities. Conclusions Lack of regulations regarding manufacturing and content or purity of Ayurvedic and other herbal formulations poses a significant global public health problem.
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http://dx.doi.org/10.1080/10773525.2018.1447880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060866PMC
July 2017

Stereotactic Radiosurgery for Multiple Brain Metastases: Two Cases of Preserved Quality of Life.

Cureus 2017 Dec 28;9(12):e1995. Epub 2017 Dec 28.

Department of Radiation Oncology, Keck School of Medicine of the University of Southern California, Los Angeles, CA.

Brain metastases are the most common intracranial tumors in the adult population and have been historically treated with whole brain radiation therapy (WBRT). However, as medical advances improve life expectancy, stereotactic radiosurgery (SRS) has replaced WBRT as the standard of care for limited (one to three) brain metastases due to the relative sparing of neurocognitive function (NCF) and therefore quality of life (QoL). The use of SRS has been less documented in the case of multiple (four or more) brain metastases, with literature limited to non-randomized studies showing comparable survival and local control. In this series, we detail the case of two individuals who received SRS at our institution for multiple brain metastases and demonstrated remarkable response. The first patient is a 78-year-old woman who received Gamma Knife (GK) treatment to 17 lesions at our institution. This patient responded very well to treatment and maintains an excellent quality of life, with no deficits on serial neurological examination as she continues to travel and drive for ridesharing businesses. The second patient is an active 44-year-old woman who received SRS to 24 lesions at our institution. The patient has now been free of intracranial failures for two years and continues fulfilling her love for travel and long-distance biking. SRS is emerging as an acceptable alternative to WBRT in treating multiple brain metastases due to its preservation of NCF. Because omission of WBRT may lead to increased probability of distant brain metastasis failure, it is critical to follow these patients closely with frequent neuroimaging. In the event of a failure, it is also possible to use SRS salvage therapy with good response. Some patients who receive SRS alone demonstrate exceptional outcomes with excellent QoL, and it is possible that certain prognostication factors such as performance status, tumor histology, and tumor volume may play a role in identifying these patients. The decision to treat a patient with SRS alone for multiple brain metastases should be made carefully with consideration of systemic therapeutic options, overall prognosis, and the patient's goals of care, with adherence to a careful follow-up plan by the physician and patient.
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http://dx.doi.org/10.7759/cureus.1995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832392PMC
December 2017

Development of a Radiation Oncology Resident Continuity Clinic to Improve Clinical Competency and Patient Compliance.

Int J Radiat Oncol Biol Phys 2018 03 27;100(3):551-555. Epub 2017 Nov 27.

Department of Radiation Oncology, University of Southern California, Keck School of Medicine, Los Angeles, California.

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http://dx.doi.org/10.1016/j.ijrobp.2017.11.034DOI Listing
March 2018

Potential for Interfraction Motion to Increase Esophageal Toxicity in Lung SBRT.

Technol Cancer Res Treat 2017 Dec 2;16(6):935-943. Epub 2017 Jun 2.

Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Purpose: To characterize the effect of the relative motion of esophagus and tumor on radiation doses to the esophagus in patients treated with stereotactic body radiation therapy for central lung tumors.

Methods And Materials: Fifty fractions of stereotactic body radiation therapy in 10 patients with lung tumors within 2.5 cm of the esophagus were reviewed. The esophagus was delineated on each treatment's cone-beam computed tomography scan and compared to its position on the planning scan. Dose-volume histograms were calculated using the original treatment beams to determine the actual dose delivered to the esophagus for each fraction of stereotactic body radiation therapy.

Results: Median interfraction right-left shift of the esophagus was 0.9 mm (range, -5.4 to 3.3 mm) toward the left. Median interfraction anteroposterior shift was 0.7 mm (range, -3.7 to 11.5 mm) posteriorly. The median percentage increase in dose to 1 cm3, dose to 3.5 cm3, and dose to 5 cm was 1.7%, 5.6%, and 6.6%, respectively. Two cases of significant late esophageal toxicity were observed, with change in esophageal position relative to the planning target volume resulting in significantly higher D values than anticipated.

Conclusion: Interfraction shifts between the internal target volume and esophagus can lead to unanticipated increases in the volume of esophagus receiving high doses when treating central lung tumors with stereotactic body radiation therapy. Certain practical steps, such as considering deep breath hold for internal target volume reduction, using a planning risk volume for esophagus, and carefully visualizing and considering esophageal position at the time of stereotactic body radiation therapy, can be taken to minimize unanticipated dose increases that could cause unexpected esophageal toxicity.
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http://dx.doi.org/10.1177/1533034617711353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640496PMC
December 2017

Risk of histological transformation and therapy-related myelodysplasia/acute myeloid leukaemia in patients receiving radioimmunotherapy for follicular lymphoma.

Br J Haematol 2017 08 3;178(3):427-433. Epub 2017 May 3.

Department of Hematology, Mayo Clinic, Rochester, MN, USA.

Histological transformation (HT) of follicular lymphoma (FL) to an aggressive lymphoma after chemotherapy remains a key issue. The incidence of HT after radioimmunotherapy (RIT) is unknown. This single institution study analysed the risk of HT in FL after treatment with yttrium-90 ibritumomab tiuxetan in 115 consecutive patients treated during 1987-2012. RIT was administered for progressive FL in 111 (97%) patients and as first-line therapy in the remaining 4. 28% (n = 32) had HT, occurring at a median of 60 months from diagnosis and 20 months after RIT. 48% (12/25) of patients who received fludarabine developed HT. The estimated 10-year risk of HT in the fludarabine and non-fludarabine groups was 67% and 26% respectively (P = 0·015). Only prior fludarabine was significantly associated with predicting the risk of HT after RIT. 8% (9/115) of patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (tMDS/AML) at a median of 41·4 months (range, 5-89). The estimated 10-year risk of tMDS/AML in non-fludarabine treated patients (n = 90) versus fludarabine treated (n = 25) was 13% and 29%, respectively. The estimated overall risk of FL undergoing HT at 10 years without fludarabine exposure appears similar to patients reported in the literature that have not received RIT. Patients with prior purine-analogue therapy are at significantly higher risk of HT.
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http://dx.doi.org/10.1111/bjh.14688DOI Listing
August 2017

Accuracy of 18-F FDG PET/CT to detect bone marrow clearance in patients with peripheral T-cell lymphoma - tissue remains the issue.

Leuk Lymphoma 2017 Oct 14;58(10):2342-2348. Epub 2017 Mar 14.

a Division of Hematology , Mayo Clinic , Rochester , MN , USA.

Staging of peripheral T-cell non-Hodgkin lymphoma (PTCL) is determined by 18-F FDG PET scan and bone marrow biopsy. This study addressed the accuracy of PET at detecting bone marrow (BM) involvement at restaging in patients with known involvement pretreatment. We identified patients with biopsy proven BM PTCL at diagnosis and concomitant BM and PET at the end of therapy. Pre-treatment PET demonstrated 50% (8/16) had a false-negative PET scan of the BM. After induction, repeat biopsy revealed 62.5% (10/16) with BM involvement. Of these 10, two had a positive PET; eight were false negative by PET. Of the six patients with a negative posttherapy BM biopsy, four were PET negative and two false positive. The sensitivity of PET at end of treatment was 20% (2/10) with a specificity of 66.7% (4/6). PET/CT is not an accurate predictor of BM involvement in patients with known PTCL in the marrow.
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http://dx.doi.org/10.1080/10428194.2017.1300891DOI Listing
October 2017
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