Chirag Patel, MD, PhD

All Publications

• Tumor treating fields (TTFields) impairs aberrant glycolysis in glioblastoma as evaluated by [18F]DASA-23, a non-invasive probe of pyruvate kinase M2 (PKM2) expression Neoplasia Patel, C. B., Beinat, C., Xie, Y., Chang, E., Gambhir, S. S. 2021; 23 (1): 58-67

  View details for DOI 10.1016/j.neo.2020.11.003

• High levels of ubidecarenone (oxidized CoQ10) delivered using a drug-lipid conjugate nanodispersion (BPM31510) differentially affect redox status and growth in malignant glioma versus non-tumor cells. Scientific reports Sun, J., Patel, C. B., Jang, T., Merchant, M., Chen, C., Kazerounian, S., Diers, A. R., Kiebish, M. A., Vishnudas, V. K., Gesta, S., Sarangarajan, R., Narain, N. R., Nagpal, S., Recht, L. 2020; 10 (1): 13899

  Abstract

  Metabolic reprogramming in cancer cells, vs. non-cancer cells, elevates levels of reactive oxygen species (ROS) leading to higher oxidative stress. The elevated ROS levels suggest a vulnerability to excess prooxidant loads leading to selective cell death, a therapeutically exploitable difference. Co-enzyme Q10 (CoQ10) an endogenous mitochondrial resident molecule, plays an important role in mitochondrial redox homeostasis, membrane integrity, and energy production. BPM31510 is a lipid-drug conjugate nanodispersion specifically formulated for delivery of supraphysiological concentrations of ubidecarenone (oxidized CoQ10) to the cell and mitochondria, in both in vitro and in vivo model systems. In this study, we sought to investigate the therapeutic potential of ubidecarenone in the highly treatment-refractory glioblastoma. Rodent (C6) and human (U251) glioma cell lines, and non-tumor human astrocytes (HA) and rodent NIH3T3 fibroblast cell lines were utilized for experiments. Tumor cell lines exhibited a marked increase in sensitivity to ubidecarenone vs. non-tumor cell lines. Further, elevated mitochondrial superoxide production was noted in tumor cells vs. non-tumor cells hours before any changes in proliferation or the cell cycle could be detected. In vitro co-culture experiments show ubidecarenone differentially affecting tumor cells vs. non-tumor cells, resulting in an equilibrated culture. In vivo activity in a highly aggressive orthotopic C6 glioma model demonstrated a greater than 25% long-term survival rate. Based on these findings we conclude that high levels of ubidecarenone delivered using BPM31510 provide an effective therapeutic modality targeting cancer-specific modulation of redox mechanisms for anti-cancer effects.

  View details for DOI 10.1038/s41598-020-70969-0

  View details for PubMedID 32807842

• Intravital imaging reveals synergistic effect of CAR T-cells and radiation therapy in a preclinical immunocompetent glioblastoma model Oncoimmunology Murty, S., Haile, S. T., Beinat, C., Aalipour, A., Alam, I. S., Murty, T., Shaffer, T. M., Patel, C. B., Graves, E. E., Mackall, C. L., Gambhir, S. S. 2020; 9 (1)

  View details for DOI 10.1080/2162402X.2020.1757360

• Human biodistribution and radiation dosimetry of [18F]DASA-23, a PET probe targeting pyruvate kinase M2. European journal of nuclear medicine and molecular imaging Beinat, C., Patel, C. B., Haywood, T., Shen, B., Naya, L., Gandhi, H., Holley, D., Khalighi, M., Iagaru, A., Davidzon, G., Gambhir, S. S. 2020

  Abstract

  To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[18F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in healthy volunteers.We recruited 5 healthy volunteers who provided a written informed consent. Volunteers were injected with 295.0 ± 8.2 MBq of [18F]DASA-23 intravenously. Immediately following injection, a dynamic scan of the brain was acquired for 15 min. This was followed by serial whole-body PET/MRI scans acquired up to 3 h post-injection. Blood samples were collected at regular intervals, and vital signs monitored pre- and post-radiotracer administration. Regions of interest were drawn around multiple organs, time-activity curves were calculated, and organ uptake and dosimetry were estimated with OLINDA/EXM (version 1.1) software.All subjects tolerated the PET/MRI examination, without adverse reactions to [18F]DASA-23. [18F]DASA-23 passively crossed the blood-brain barrier, followed by rapid clearance from the brain. High accumulation of [18F]DASA-23 was noted in organs such as the gallbladder, liver, small intestine, and urinary bladder, suggesting hepatobiliary and urinary clearance. The effective dose of [18F]DASA-23 was 23.5 ± 5.8 μSv/MBq.We successfully completed a pilot first-in-human study of [18F]DASA-23. Our results indicate that [18F]DASA-23 can be used safely in humans to evaluate pyruvate kinase M2 levels. Ongoing studies are evaluating the ability of [18F]DASA-23 to visualize intracranial malignancies, NCT03539731.ClinicalTrials.gov, NCT03539731 (registered 28 May 2018).

  View details for DOI 10.1007/s00259-020-04687-0

  View details for PubMedID 31938892

• Visualization of diagnostic and therapeutic targets in glioma with molecular imaging Frontiers in Immunology Li, D., Patel, C. B., Xu, G., Iagaru, A., Zhu, Z., Zhang, L., Cheng, Z. 2020

  View details for DOI 10.3389/fimmu.2020.592389

• Evaluation of Glycolytic Response to Multiple Classes of Anti-glioblastoma Drugs by Noninvasive Measurement of Pyruvate Kinase M2 Using [18F]DASA-23. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Beinat, C., Patel, C. B., Xie, Y., Gambhir, S. S. 2019

  Abstract

  PURPOSE: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, the key process of tumor metabolism. PKM2 is found in high levels in glioblastoma (GBM) cells with marginal expression within healthy brain tissue, rendering it a key biomarker of GBM metabolic re-programming. Our group has reported the development of a novel radiotracer, 1-((2-fluoro- 6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA- 23), to non-invasively detect PKM2 levels with positron emission tomography (PET).PROCEDURE: U87 human GBM cells were treated with the IC50 concentration of various agents used in the treatment of GBM, including alkylating agents (temozolomide, carmustine, lomustine, procarbazine), inhibitor of topoisomerase I (irinotecan), vascular endothelial and epidermal growth factor receptor inhibitors (cediranib and erlotinib, respectively) anti-metabolite (5-fluorouracil), microtubule inhibitor (vincristine), and metabolic agents (dichloroacetate and IDH1 inhibitor ivosidenib). Following drug exposure for three or 6days (n=6 replicates per condition), the radiotracer uptake of [18F]DASA-23 and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) was assessed. Changes in PKM2 protein levels were determined via Western blot and correlated to radiotracer uptake.RESULTS: Significant interactions were found between the treatment agent (n=12 conditions total comprised 11 drugs and vehicle) and the duration of treatment (3- or 6-day exposure to each drug) on the cellular uptake of [18F]DASA-23 (p=0.0001). The greatest change in the cellular uptake of [18F]DASA-23 was found after exposure to alkylating agents (p<0. 0001) followed by irinotecan (p=0. 0012), erlotinib (p=0. 02), and 5-fluorouracil (p=0. 005). Correlation of PKM2 protein levels and [18F]DASA-23 cellular uptake revealed a moderate correlation (r=0.44, p=0.15).CONCLUSIONS: These proof of principle studies emphasize the superiority of [18F]DASA-23 to [18F]FDG in detecting the glycolytic response of GBM to multiple classes of anti-neoplastic drugs in cell culture. A clinical trial evaluating the diagnostic utility of [18F]DASA-23 PET in GBM patients (NCT03539731) is ongoing.

  View details for PubMedID 30989436

• Nanomedicine for Spontaneous Brain Tumors: A Companion Clinical Trial. ACS nano Arami, H., Patel, C. B., Madsen, S. J., Dickinson, P. J., Davis, R. M., Zeng, Y., Sturges, B. K., Woolard, K. D., Habte, F. G., Akin, D., Sinclair, R., Gambhir, S. S. 2019

  Abstract

  Nanoparticles' enhanced permeation and retention (EPR) variations due to tumor heterogeneity in naturally occurring brain tumors are commonly neglected in preclinical nanomedicine studies. Recent pathological studies have shown striking similarities between brain tumors in humans and dogs, indicating that canine brain tumors may be a valuable model to evaluate nanoparticles' EPR in this context. We recruited canine clinical cases with spontaneous brain tumors to investigate nanoparticles' EPR in different brain tumor pathologies using surface-enhanced Raman spectroscopy (SERS). We used gold nanoparticles due to their surface plasmon effect that enables their sensitive and microscopic resolution detection using the SERS technique. Raman microscopy of the resected tumors showed heterogeneous EPR of nanoparticles into oligodendrogliomas and meningiomas of different grades, without any detectable traces in necrotic parts of the tumors or normal brain. Raman observations were confirmed by scanning electron microscopy (SEM) and X-ray elemental analyses, which enabled localization of individual nanoparticles embedded in tumor tissues. Our results demonstrate nanoparticles' EPR and its variations in clinically relevant, spontaneous brain tumors. Such heterogeneities should be considered alongside routine preoperative imaging and histopathological analyses in order to accelerate clinical management of brain tumors using nanomedicine approaches.

  View details for PubMedID 30714717

• Positron emission tomography reporter gene strategy for use in the central nervous system PNAS Haywood, T., Beinat, C., Gowrishankar, G., Patel, C. B., Alam, I. S., Murty, S., Gambhir, S. S. 2019

  View details for DOI 10.1073/pnas.1901645116

• The characterization of 18F-hGTS13 for molecular imaging of xC- transporter activity with positron emission tomography. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Beinat, C., Gowrishankar, G., Shen, B., Alam, I. S., Robinson, E., Haywood, T., Patel, C. B., Azevedo, E. C., Castillo, J., Ilovich, O., Koglin, N., Schmitt-Willich, H., Berndt, M., Mueller, A., Zerna, M., Srinivasan, A., Gambhir, S. S. 2019

  Abstract

  Purpose: The aim of this study was development of an improved positron emission tomography (PET) radiotracer for measuring xC- activity with increased tumor uptake and reduced uptake in inflammatory cells compared to (S)-4-(3-18F-Fluoropropyl)-L-glutamic acid (18F-FSPG). Experimental design: A racemic glutamate derivative, 18F-hGTS13 was evaluated in cell culture and animal tumor models. 18F-hGTS13 was separated into C5-epimers and the corresponding 18F-hGTS13-isomer1 and 18F-hGTS13-isomer2 evaluated in H460 tumor bearing rats. Preliminary studies investigate the cellular uptake of 18F-hGTS13-isomer2 in multiple immune cell populations and states. Results:18F-hGTS13 demonstrated excellent H460 tumor visualization with high tumor-to-background ratios, confirmed by ex vivo biodistribution studies. Tumor associated radioactivity of 18F-hGTS13 (7.5±0.9%ID/g, n = 3) was significantly higher than with 18F-FSPG (4.6±0.7%ID/g, n = 3, P = 0.01). 18F-hGTS13-isomer2 exhibited excellent H460 tumor visualization (6.3±1.1%ID/g, n-3), and significantly reduced uptake in multiple immune cell populations relative to 18F-FSPG. 18F-hGTS13-isomer2 exhibited increased liver uptake relative to 18F-FSPG (4.6±0.8%ID/g vs. 0.7±0.01%ID/g) limiting its application in hepatocellular carcinoma. Conclusion:18F-hGTS13-isomer2 is a new PET radiotracer for molecular imaging of xC- activity which may provide information regarding tumor oxidation states. 18F-hGTS13-isomer2 has potential for clinical translation for imaging cancers of the thorax due to the low background signal in healthy tissue.

  View details for DOI 10.2967/jnumed.119.225870

  View details for PubMedID 31171595

• Engineered immune cells as highly sensitive cancer diagnostics. Nature biotechnology Aalipour, A., Chuang, H. Y., Murty, S., D'Souza, A. L., Park, S. M., Gulati, G. S., Patel, C. B., Beinat, C., Simonetta, F., Martinić, I., Gowrishankar, G., Robinson, E. R., Aalipour, E., Zhian, Z., Gambhir, S. S. 2019

  Abstract

  Endogenous biomarkers remain at the forefront of early disease detection efforts, but many lack the sensitivities and specificities necessary to influence disease management. Here, we describe a cell-based in vivo sensor for highly sensitive early cancer detection. We engineer macrophages to produce a synthetic reporter on adopting an M2 tumor-associated metabolic profile by coupling luciferase expression to activation of the arginase-1 promoter. After adoptive transfer in colorectal and breast mouse tumor models, the engineered macrophages migrated to the tumors and activated arginase-1 so that they could be detected by bioluminescence imaging and luciferase measured in the blood. The macrophage sensor detected tumors as small as 25-50 mm3 by blood luciferase measurements, even in the presence of concomitant inflammation, and was more sensitive than clinically used protein and nucleic acid cancer biomarkers. Macrophage sensors also effectively tracked the immunological response in muscle and lung models of inflammation, suggesting the potential utility of this approach in disease states other than cancer.

  View details for PubMedID 30886438

• Dosimetry Prediction for Clinical Translation of 64Cu-Pembrolizumab ImmunoPET Targeting Human PD-1 Expression. Scientific reports Natarajan, A., Patel, C. B., Habte, F., Gambhir, S. S. 2018; 8 (1): 633

  Abstract

  The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor-infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively quantifying the presence of PD-1 expression in the tumor microenvironment prior to initiation of immune checkpoint blockade may identify the patients likely to respond to therapy. We have developed a 64Cu-pembrolizumab radiotracer and evaluated human dosimetry. The tracer was utilized to image hPD-1 levels in two subcutaneous mouse models: (a) 293 T/hPD-1 cells xenografted into NOD-scid IL-2Rγnull mice (NSG/293 T/hPD-1) and (b) human peripheral blood mononuclear cells engrafted into NSG bearing A375 human melanoma tumors (hNSG/A375). In each mouse model two cohorts were evaluated (hPD-1 blockade with pembrolizumab [blk] and non-blocked [nblk]), for a total of four groups (n = 3-5/group). The xenograft-to-muscle ratio in the NSG/293 T/hPD-1 model at 24 h was significantly increased in the nblk group (7.0 ± 0.5) compared to the blk group (3.4 ± 0.9), p = 0.01. The radiotracer dosimetry evaluation (PET/CT ROI-based and ex vivo) in the hNSG/A375 model revealed the highest radiation burden to the liver. In summary, we validated the 64Cu-pembrolizumab tracer's specific hPD-1 receptor targeting and predicted human dosimetry.

  View details for PubMedID 29330552

• A Novel Engineered Small Protein for Positron Emission Tomography Imaging of Human Programmed Death Ligand-1 : Validation in Mouse Models and Human Cancer Tissues Clinical Cancer Res Natarajan, A., Patel, C. B., Ramakrishnan, S., Panesar, P. S., Long, S. R., Gambhir, S. S. 2018

  View details for DOI 10.1158/1078-0432.CCR-18-1871

• Tumor Treating Fields Increases Membrane Permeability in Glioblastoma Cells Cell Death Discovery Chang, E., Patel, C. B., Pohling, C., Young, C., Song, J., Flores, T., Zeng, Y., Joubert, L. M., Arami, H., Natarajan, A., Sinclair, R., Gambhir, S. S. 2018; 4

  View details for DOI 10.1038/s41420-018-0130-x

• The Utility of [18F]DASA-23 for Molecular Imaging of Prostate Cancer with Positron Emission Tomography. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Beinat, C., Haywood, T., Chen, Y. S., Patel, C. B., Alam, I. S., Murty, S., Gambhir, S. S. 2018

  Abstract

  There is a strong, unmet need for superior positron emission tomography (PET) imaging agents that are able to measure biochemical processes specific to prostate cancer. Pyruvate kinase M2 (PKM2) catalyzes the concluding step in glycolysis and is a key regulator of tumor growth and metabolism. Elevation of PKM2 expression was detected in Gleason 8-10 tumors compared to Gleason 6-7 carcinomas, indicating that PKM2 may potentially be a marker of aggressive prostate cancer. We have recently reported the development of a PKM2-specific radiopharmaceutical [18F]DASA-23 and herein describe its evaluation in cell culture and preclinical models of prostate cancer.The cellular uptake of [18F]DASA-23 was evaluated in a panel of prostate cancer cell lines and compared to that of [18F]FDG. The specificity of [18F]DASA-23 to measure PKM2 levels in cell culture was additionally confirmed through the use of PKM2-specific siRNA. PET imaging studies were then completed utilizing subcutaneous prostate cancer xenografts using either PC3 or DU145 cells in mice.[18F]DASA-23 uptake values over 60-min incubation period in PC3, LnCAP, and DU145 respectively were 23.4 ± 4.5, 18.0 ± 2.1, and 53.1 ± 4.6 % tracer/mg protein. Transient reduction in PKM2 protein expression with siRNA resulted in a 50.1 % reduction in radiotracer uptake in DU145 cells. Small animal PET imaging revealed 0.86 ± 0.13 and 1.6 ± 0.2 % ID/g at 30 min post injection of radioactivity in DU145 and PC3 subcutaneous tumor bearing mice respectively.Herein, we evaluated a F-18-labeled PKM2-specific radiotracer, [18F]DASA-23, for the molecular imaging of prostate cancer with PET. [18F]DASA-23 revealed rapid and extensive uptake levels in cellular uptake studies of prostate cancer cells; however, there was only modest tumor uptake when evaluated in mouse subcutaneous tumor models.

  View details for PubMedID 29736561

• 18F-FDOPA PET and MRI characteristics correlate with degree of malignancy and predict survival in treatment-naïve gliomas: a cross-sectional study. Journal of neuro-oncology Patel, C. B., Fazzari, E., Chakhoyan, A., Yao, J., Raymond, C., Nguyen, H., Manoukian, J., Nguyen, N., Pope, W., Cloughesy, T. F., Nghiemphu, P. L., Czernin, J., Lai, A., Ellingson, B. M. 2018

  Abstract

  To report the potential value of pre-operative 18F-FDOPA PET and anatomic MRI in diagnosis and prognosis of glioma patients.Forty-five patients with a pathological diagnosis of glioma with pre-operative 18F-FDOPA PET and anatomic MRI were retrospectively examined. The volume of contrast enhancement and T2 hyperintensity on MRI images along with the ratio of maximum 18F-FDOPA SUV in tumor to normal tissue (T/N SUVmax) were measured and used to predict tumor grade, molecular status, and overall survival (OS).A significant correlation was observed between WHO grade and: the volume of contrast enhancement (r = 0.67), volume of T2 hyperintensity (r = 0.42), and 18F-FDOPA uptake (r = 0.60) (P < 0.01 for each correlation). The volume of contrast enhancement and 18F-FDOPA T/N SUVmax were significantly higher in glioblastoma (WHO IV) compared with lower grade gliomas (WHO I-III), as well as for high-grade gliomas (WHO III-IV) compared with low-grade gliomas (WHO I-II). Receiver-operator characteristic (ROC) analyses confirmed the volume of contrast enhancement and 18F-FDOPA T/N SUVmax could each differentiate patient groups. No significant differences in 18F-FDOPA uptake were observed by IDH or MGMT status. Multivariable Cox regression suggested age (HR 1.16, P = 0.0001) and continuous measures of 18F-FDOPA PET T/N SUVmax (HR 4.43, P = 0.016) were significant prognostic factors for OS in WHO I-IV gliomas.Current findings suggest a potential role for the use of pre-operative 18F-FDOPA PET in suspected glioma. Increased 18F-FDOPA uptake may not only predict higher glioma grade, but also worse OS.

  View details for DOI 10.1007/s11060-018-2877-6

  View details for PubMedID 29679199

• From Subsistence to Sustenance in Physician-Scientist Training. Academic medicine : journal of the Association of American Medical Colleges Patel, C. B. 2018

  View details for DOI 10.1097/ACM.0000000000002139

  View details for PubMedID 29342000

• A single demyelinating attack is enough to limit brain growth in children. Neurology Hacohen, Y., Patel, C. B., Hintzen, R. 2017

  View details for DOI 10.1212/WNL.0000000000003894

  View details for PubMedID 28381511

• Southern California neuroinvasive West Nile virus case series. Neurological Sciences Patel, C. B., Trikamji, B. V., Mathisen, G. E., Mishra, S. K. 2017

  View details for DOI 10.1007/s10072-017-3164-6

• Movements Here Today, Gone Tomorrow: Images in Clinical Neurology Case of Hyperglycemic Hemichorea. The Neurohospitalist Chang, T. S., Patel, C. B., Keener, A. M., Keselman, I., Jamal, N. I. 2017; 7 (3): 150

  View details for DOI 10.1177/1941874416671648

  View details for PubMedID 28634509

  View details for PubMedCentralID PMC5467814

• Synergistic inhibition of glioma cell proliferation by Withaferin A and tumor treating fields. Journal of neuro-oncology Chang, E., Pohling, C., Beygui, N., Patel, C. B., Rosenberg, J., Ha, D. H., Gambhir, S. S. 2017

  Abstract

  Glioblastoma (GBM) is the most aggressive and lethal form of brain cancer. Standard therapies are non-specific and often of limited effectiveness; thus, efforts are underway to uncover novel, unorthodox therapies against GBM. In previous studies, we investigated Withaferin A, a steroidal lactone from Ayurvedic medicine that inhibits proliferation in cancers including GBM. Another novel approach, tumor treating fields (TTFields), is thought to disrupt mitotic spindle formation and stymie proliferation of actively dividing cells. We hypothesized that combining TTFields with Withaferin A would synergistically inhibit proliferation in glioblastoma. Human glioblastoma cells (GBM2, GBM39, U87-MG) and human breast adenocarcinoma cells (MDA-MB-231) were isolated from primary tumors. The glioma cell lines were genetically engineered to express firefly luciferase. Proliferative potential was assessed either by bioluminescence imaging or cell counting via hemocytometer. TTFields (4 V/cm) significantly inhibited growth of the four cancer cell lines tested (n = 3 experiments per time point, four measurements per sample, p < 0.02 at least; 2-way ANOVA, control vs. treatment). The combination of Withaferin A (10-100 nM) with TTFields significantly inhibited the growth of the glioma cells to a degree beyond that of Withaferin A or TTFields alone. The interaction of the Withaferin A and TTFields on glioma cells was found to be synergistic in nature (p < 0.01, n = 3 experiments). These findings were validated by both bioluminescence and hemocytometric measurements. The combination of Withaferin A with TTFields represents a novel approach to treat GBM in a manner that is likely better than either treatment alone and that is synergistic.

  View details for PubMedID 28681243

• Natural Language Processing-Enabled and Conventional Data Capture Methods for Input to Electronic Health Records: A Comparative Usability Study. JMIR medical informatics Kaufman, D. R., Sheehan, B., Stetson, P., Bhatt, A. R., Field, A. I., Patel, C., Maisel, J. M. 2016; 4 (4)

  Abstract

  The process of documentation in electronic health records (EHRs) is known to be time consuming, inefficient, and cumbersome. The use of dictation coupled with manual transcription has become an increasingly common practice. In recent years, natural language processing (NLP)-enabled data capture has become a viable alternative for data entry. It enables the clinician to maintain control of the process and potentially reduce the documentation burden. The question remains how this NLP-enabled workflow will impact EHR usability and whether it can meet the structured data and other EHR requirements while enhancing the user's experience.The objective of this study is evaluate the comparative effectiveness of an NLP-enabled data capture method using dictation and data extraction from transcribed documents (NLP Entry) in terms of documentation time, documentation quality, and usability versus standard EHR keyboard-and-mouse data entry.This formative study investigated the results of using 4 combinations of NLP Entry and Standard Entry methods ("protocols") of EHR data capture. We compared a novel dictation-based protocol using MediSapien NLP (NLP-NLP) for structured data capture against a standard structured data capture protocol (Standard-Standard) as well as 2 novel hybrid protocols (NLP-Standard and Standard-NLP). The 31 participants included neurologists, cardiologists, and nephrologists. Participants generated 4 consultation or admission notes using 4 documentation protocols. We recorded the time on task, documentation quality (using the Physician Documentation Quality Instrument, PDQI-9), and usability of the documentation processes.A total of 118 notes were documented across the 3 subject areas. The NLP-NLP protocol required a median of 5.2 minutes per cardiology note, 7.3 minutes per nephrology note, and 8.5 minutes per neurology note compared with 16.9, 20.7, and 21.2 minutes, respectively, using the Standard-Standard protocol and 13.8, 21.3, and 18.7 minutes using the Standard-NLP protocol (1 of 2 hybrid methods). Using 8 out of 9 characteristics measured by the PDQI-9 instrument, the NLP-NLP protocol received a median quality score sum of 24.5; the Standard-Standard protocol received a median sum of 29; and the Standard-NLP protocol received a median sum of 29.5. The mean total score of the usability measure was 36.7 when the participants used the NLP-NLP protocol compared with 30.3 when they used the Standard-Standard protocol.In this study, the feasibility of an approach to EHR data capture involving the application of NLP to transcribed dictation was demonstrated. This novel dictation-based approach has the potential to reduce the time required for documentation and improve usability while maintaining documentation quality. Future research will evaluate the NLP-based EHR data capture approach in a clinical setting. It is reasonable to assert that EHRs will increasingly use NLP-enabled data entry tools such as MediSapien NLP because they hold promise for enhancing the documentation process and end-user experience.

  View details for PubMedID 27793791

• MRI Ventral Nerve Root Enhancement in Five Patients Presenting With Extremity Weakness Secondary to Neuroinvasive West Nile Virus. Journal of clinical neuromuscular disease Patel, C. B., Trikamji, B., Mathisen, G., Yim, C., Zipser, B., Mishra, S. 2016; 18 (1): 41-43

  View details for DOI 10.1097/01.cnd.0000496973.95654.fd

  View details for PubMedID 27552389

• Multiple calcifying pseudoneoplasms of the neuraxis (MCAPNON): Distinct entity, CAPNON variant, or old neurocysticercosis? Neuropathology : official journal of the Japanese Society of Neuropathology Abdaljaleel, M., Mazumder, R., Patel, C. B., Im, K., Pope, W., Liau, L. M., Vinters, H. V., Yong, W. H. 2016

  Abstract

  We report a case of multiple calcifying pseudoneoplasms of the neuraxis (MCAPNON) with associated multifocal perivascular microcalcifications and vascular calcinosis. Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a very rare condition that may arise in extra-axial and occasionally, in intra-axial locations. Moreover, it is nearly always a solitary mass with only one case with two lesions reported. While the etiology and pathogenesis of CAPNON remains unclear, the histopathology findings of this entity have been well described. We report a case of a 62-year-old woman with 18 calcifying radiologic lesions involving bilateral cerebral hemispheres. Histologically, these lesions have features similar to that reported for CAPNON, including nodular calcification with fibro-osseous components and peripheral histiocytic reaction. The patient had a poorly documented diagnosis of neurocyticercosis 32 years prior, although without tissue confirmation. The lack of detectable cysticercus serum antibody titers, and absence of residual larval or cyst wall tissue render multifocal calcific involution of that parasite unprovable although still plausible. We also raise the possibility of a blood-brain barrier derangement and/or a metabolic disorder as an alternative etiology. Whether this case of MCAPNON shares the same pathogenesis as the usual solitary CAPNON is unclear.

  View details for DOI 10.1111/neup.12349

  View details for PubMedID 27862397

• The effects of anesthesia on the morphoproteomic expression of head and neck squamous cell carcinoma: a pilot study TRANSLATIONAL RESEARCH Ferrell, J. K., Cattano, D., Brown, R. E., Patel, C. B., Karni, R. J. 2015; 166 (6): 674-682

  View details for DOI 10.1016/j.trsl.2015.09.001

  View details for Web of Science ID 000366444400013

  View details for PubMedID 26423449

• Challenges and opportunities for reinvigorating the physician-scientist pipeline JOURNAL OF CLINICAL INVESTIGATION Daye, D., Patel, C. B., Ahn, J., Nguyen, F. T. 2015; 125 (3): 883-887

  Abstract

  Physician-scientists, with in-depth training in both medicine and research, are uniquely poised to address pressing challenges at the forefront of biomedicine. In recent years, a number of organizations have outlined obstacles to maintaining the pipeline of physician-scientists, classifying them as an endangered species. As in-training and early-career physician-scientists across the spectrum of the pipeline, we share here our perspective on the current challenges and available opportunities that might aid our generation in becoming independent physician-scientists. These challenges revolve around the difficulties in recruitment and retention of trainees, the length of training and lack of support at key training transition points, and the rapidly and independently changing worlds of medical and scientific training. In an era of health care reform and an environment of increasingly sparse NIH funding, these challenges are likely to become more pronounced and complex. As stakeholders, we need to coalesce behind core strategic points and regularly assess the impact and progress of our efforts with appropriate metrics. Here, we expand on the challenges that we foresee and offer potential opportunities to ensure a more sustainable physician-scientist workforce.

  View details for DOI 10.1172/JCI80933

  View details for Web of Science ID 000350616500001

  View details for PubMedID 25689260

  View details for PubMedCentralID PMC4362227

• Predictive Analytics: The Fifth Clinical Element SOUTHERN MEDICAL JOURNAL Peiris, A. N., Patel, C. B. 2013; 106 (4): 290-291

  View details for DOI 10.1097/SMJ.0b013e31828d95f5

  View details for Web of Science ID 000317104700010

  View details for PubMedID 23558420

• Diffuse large B-cell lymphoma: A metabolic disorder? The American journal of case reports Tanios, G., Aranguren, I. M., Goldstein, J. S., Patel, C. B. 2013; 14: 518-525

  Abstract

  Patient Male, 81 FINAL DIAGNOSIS: Non-Hodgkin lymphoma Symptoms: General weakness • hypoglycemia • metabolic acidosis- Clinical Procedure: - Specialty: Hematology.Challenging differential diagnosis.B cell lymphoma constitutes 80-85% of cases of Non Hodgkin's lymphoma in the Untied States. Metabolic complications may arise from the disease itself or through its end organ involvement.We describe a case of a diffuse large B cell lymphoma diagnosed by abdominal computed tomography after it initially presented as hypoglycemia not correctable by dextrose infusion that instead resulted in increased anion gap metabolic acidosis with elevated lactate levels.The case illustrates how lymphomas can present unusually with hypoglycemia and lactic acidosis, the latter being an ominous sign that can occur without liver involvement. In this regard, the case demonstrates the metabolic sequelae of lymphoma that should raise suspicion for an underlying process. This has implications for diagnosis, treatment, and patient survival. Attention should be paid especially in the primary care setting in order to minimize delays in diagnosis.

  View details for PubMedID 24349605

  View details for PubMedCentralID PMC3859735

• Efficacy of 3% saline vs. conivaptan in achieving hyponatremia treatment goals. Methodist DeBakey cardiovascular journal Dominguez, M., Perez, J. A., Patel, C. B. 2013; 9 (1): 49-53

  Abstract

  Hyponatremia is the most common electrolyte abnormality encountered in clinical practice, but its optimal management is still evolving. While guidelines for infusion rates of hypertonic saline (HS) have been introduced, there is a risk of underestimating the response in serum sodium concentration after therapy. Guidelines also have evaluated the use of vasopressin receptor antagonists as alternatives or supplements to standard therapies. This single-center retrospective study from The Methodist Hospital (TMH) compared the effect of HS and conivaptan intervention in the management of 49 patients with hyponatremia from January 2009 through November 2010. Demographics, volume status, medical history, medication data, and serum sodium concentration correction over 48 hours were analyzed. No significant difference was noted with regard to age, ethnicity, gender, volume status, use of medications known to cause hyponatremia, or comorbidities. Baseline serum sodium concentration was not significantly different between HS (120.5 ± 3.8 mEq/L) and conivaptan (118.3 ± 6.7 mEq/L) groups. Regardless of whether the patient was euvolemic or hypervolemic, no significant difference was noted in serum sodium concentration at 4, 12, 24, or 48 hours after initiation of treatment or in frequency of over-correction between groups. This study compares the effect of HS to conivaptan intervention in the management of hyponatremia. No significant differences were identified in adherence to treatment guidelines. Further, based on this small retrospective study, neither agent poses a significant risk of over-correction at 4, 24, or 48 hours of therapy.

  View details for PubMedID 23519387

  View details for PubMedCentralID PMC3600885

• Toward a Better Understanding of the Retention of Physician-Scientists in the Career Pipeline ACADEMIC MEDICINE Patel, C. B., Schauberger, E. M., Nguyen, F. T. 2012; 87 (4): 390-391

  View details for DOI 10.1097/ACM.0b013e318248c0ad

  View details for Web of Science ID 000302143200006

  View details for PubMedID 22452911

• Xenon exposure in the neonatal rat brain: effects on genes that regulate apoptosis MINERVA ANESTESIOLOGICA Cattano, D., Valleggi, S., Cavazzana, A. O., Patel, C. B., Ma, D., Maze, M., Giunta, F. 2011; 77 (6): 571-578

  Abstract

  In the developing rodent brain, exposure to volatile anesthetics causes widespread neuronal apoptosis in several regions of the brain. Increasing evidence points to a possible neuroprotective role for the anesthetic gas xenon, following neuronal injury. To address this gap in understanding, we explored the transcriptional consequences of xenon in the brains of postnatal day 7 (P7) rats exposed to xenon compared to those of air-breathing animals, with particular emphasis on the mRNA transcript levels of Akt and c-Jun N-terminal kinase kinase 1 (JNKK1), which are important for cell survival and the activation of extrinsic neuroapoptotic pathways, respectively.P7 Sprague/Dawley rats were exposed to air (75% nitrogen, 25% oxygen) or xenon (75% xenon, 25% oxygen) for 120 min (N=6/group). Forebrains were harvested for reverse transcription polymerase chain reaction, which enabled quantification of Akt and JNKK1 mRNA transcripts. Suppression subtractive hybridization was used to explore the "genetic signature" of xenon exposure.Compared to control air-breathing animals, xenon-breathing rats exhibited a 0.7-fold decrease in Akt mRNA expression (P<0.01) and a 1.6-fold increase in JNKK1 mRNA levels (P<0.05).The concomitant decrease in the Akt mRNA expression level and increase in the JNKK1 mRNA transcript level provide evidence that xenon has a neuroapoptotic effect in the developing rodent forebrain. Given these results, further study into the paradoxical neuroprotective and neuroapoptotic effects of xenon is warranted.

  View details for Web of Science ID 000292058300004

  View details for PubMedID 21617619

• Diagnostic nuclear medicine in the ED AMERICAN JOURNAL OF EMERGENCY MEDICINE Amini, B., Patel, C. B., Lewin, M. R., Kim, T., Fisher, R. E. 2011; 29 (1): 91-101

  Abstract

  Although the decision to use nuclear medicine (NM) modalities in the acute care setting is limited by several factors, there are instances in which the use of NM techniques can provide elegant and efficient solutions to otherwise expensive and resource consuming situations. Herein, we describe the indications and NM techniques used for the evaluation of low-risk patients with chest pain, suspected pulmonary embolus, acute cholecystitis, gastrointestinal bleeding, acute scrotum, and the radiographically occult fracture.

  View details for DOI 10.1016/j.ajem.2009.03.008

  View details for Web of Science ID 000285400500016

  View details for PubMedID 20825918

• Management of extensive squamous cell carcinoma on the site of radiation-induced dermatitis with severe fibrosis: a case report J Radiother Pract Patel, C. B., Rashid, R. M., Nguyen, T. H. 2010; 9 (2): 125-8

  View details for DOI 10.1017/S1460396909990318

• Consider using diffusion tensor imaging in Geron phase I trial. AJNR. American journal of neuroradiology Patel, C. B. 2009; 30 (7): E97-?

  View details for DOI 10.3174/ajnr.A1632

  View details for PubMedID 19386734

• Letter by Patel Regarding Article, "A Primer in Longitudinal Data Analysis" CIRCULATION Patel, C. B. 2009; 120 (4): E25-E25

  View details for DOI 10.1161/CIRCULATIONAHA.108.836767

  View details for Web of Science ID 000268377500015

  View details for PubMedID 19635976

• Effect of VEGF Treatment on the Blood-Spinal Cord Barrier Permeability in Experimental Spinal Cord Injury: Dynamic Contrast-Enhanced Magnetic Resonance Imaging JOURNAL OF NEUROTRAUMA Patel, C. B., Cohen, D. M., Ahobila-Vajjula, P., Sundberg, L. M., Chacko, T., Narayana, P. A. 2009; 26 (7): 1005-1016

  Abstract

  Compromised blood-spinal cord barrier (BSCB) is a factor in the outcome following traumatic spinal cord injury (SCI). Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis and vascular permeability. The role of VEGF in SCI is controversial. Relatively little is known about the spatial and temporal changes in the BSCB permeability following administration of VEGF in experimental SCI. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies were performed to noninvasively follow spatial and temporal changes in the BSCB permeability following acute administration of VEGF in experimental SCI over a post-injury period of 56 days. The DCE-MRI data was analyzed using a two-compartment pharmacokinetic model. Animals were assessed for open field locomotion using the Basso-Beattie-Bresnahan score. These studies demonstrate that the BSCB permeability was greater at all time points in the VEGF-treated animals compared to saline controls, most significantly in the epicenter region of injury. Although a significant temporal reduction in the BSCB permeability was observed in the VEGF-treated animals, BSCB permeability remained elevated even during the chronic phase. VEGF treatment resulted in earlier improvement in locomotor ability during the chronic phase of SCI. This study suggests a beneficial role of acutely administered VEGF in hastening neurobehavioral recovery after SCI.

  View details for DOI 10.1089/neu.2008.0860

  View details for Web of Science ID 000267965500006

  View details for PubMedID 19226205

• Blood-spinal cord barrier permeability in experimental spinal cord injury: dynamic contrast-enhanced MRI NMR IN BIOMEDICINE Cohen, D. M., Patel, C. B., Ahobila-Vajjula, P., Sundberg, L. M., Chacko, T., Liu, S., Narayana, P. A. 2009; 22 (3): 332-341

  Abstract

  After a primary traumatic injury, spinal cord tissue undergoes a series of pathobiological changes, including compromised blood-spinal cord barrier (BSCB) integrity. These vascular changes occur over both time and space. In an experimental model of spinal cord injury (SCI), longitudinal dynamic contrast-enhanced MRI (DCE-MRI) studies were performed up to 56 days after SCI to quantify spatial and temporal changes in the BSCB permeability in tissue that did not show any visible enhancement on the post-contrast MRI (non-enhancing tissue). DCE-MRI data were analyzed using a two-compartment pharmacokinetic model. These studies demonstrate gradual restoration of BSCB with post-SCI time. However, on the basis of DCE-MRI, and confirmed by immunohistochemistry, the BSCB remained compromised even at 56 days after SCI. In addition, open-field locomotion was evaluated using the 21-point Basso-Beattie-Bresnahan scale. A significant correlation between decreased BSCB permeability and improved locomotor recovery was observed.

  View details for DOI 10.1002/nbm.1343

  View details for Web of Science ID 000264578200012

  View details for PubMedID 19023867

• The effect of dental artifacts, contrast media, and experience on interobserver contouring variations in head and neck anatomy Am J Clin Oncol O'Daniel, J. C., Rosenthal, D. I., Garden, A. S., Barker, J. L., Ahamad, A. A., Ang, K. K., Asper, J. A., Blanco, A. I., de Crevoisier, R., Holsinger, F. C., Patel, C. B., Schwartz, D. L., Wang, H., Dong, L. 2007; 30 (2): 191-8

  View details for DOI 10.1097/01.coc.0000256704.58956.45

• Cultural humility in medicine: beyond the K-20 pipeline. Texas medicine Patel, C. B. 2006; 102 (4): 7-?

  View details for PubMedID 17128753

• Sinusoidal modeling of ictal activity along a thalamus-to-cortex seizure pathway I: New coherence approaches ANNALS OF BIOMEDICAL ENGINEERING Sherman, D. L., Patel, C. B., Zhang, N., Rossell, L. A., Tsai, Y. C., Thakor, N. V., Mirski, M. A. 2004; 32 (9): 1252-1264

  Abstract

  Understanding associations in neuronal circuitry is critical for tracing epilepsy pathways. Two new methods of measuring coherence between field potentials and EEG channels are proposed for modeling the level of linear association between channels during epileptic seizures. These methods rely upon modeling the repetitive clonic seizure activity as a sum of sinusoids with varying degrees of phase locking. Estimating the amplitude of sinusoids from correlation and cross-correlation time domain data, we can find the coherences from a ratio of these amplitudes. One method utilizes amplitude finding from the multiple signal classification (MUSIC) technique. The other method uses alterations in amplitude of individual sinusoids and their ratios in a matrix pencil equation formed from cross- and auto-correlation matrices. The corresponding generalized eigenvalues of these equations form the coherence ratios. This utilizes the estimation of signal parameters using rotational invariance techniques (ESPRIT) algorithm to arrive at coherence amplitude ratios. Simulations illustrate that the MUSIC method provides better noise immunity as it out-performs the conventional Fourier transform-based method for coherence estimation. Both coherence estimators reflect presence of sinusoidal components that are propagated or not propagated along a particular transmission pathway. We illustrate the value of both methods by examining the strength of correlation between seizure EEG from specific thalamic nuclei and cortex in a rodent model of generalized epilepsy. The pentylenetetrazol (PTZ) chemoconvulsant model in rats reflects selective activation of the anterior thalamic nucleus. Using both methods, this neuronal element has much larger coherence with cortex than another thalamic region, the posterior thalamus (p < 0.05). These methods isolate the unique contribution of anterior thalamus in the formation of an ictal network and corroborate earlier conventional or periodogram techniques.

  View details for Web of Science ID 000223549700008

  View details for PubMedID 15493512

• Prediction of PTZ-induced seizures using wavelet-based residual entropy of cortical and subcortical field potentials IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Paul, J. S., Patel, C. B., Al-Nashash, H., Zhang, N., Ziai, W. C., Mirski, M. A., Sherman, D. L. 2003; 50 (5): 640-648

  Abstract

  Our proposed algorithm for seizure prediction is based on the principle that seizure build-up is always preceded by constantly changing bursting levels. We use a novel measure of residual subband wavelet entropy (RSWE) to directly estimate the entropy of bursts, which is otherwise obscured by the ongoing background activity. Our results are obtained using a slow infusion anesthetized pentylenetetrazol (PTZ) rat model in which we record field potentials (FPs) from frontal cortex and two thalamic areas (anterior and posterior nuclei). In each frequency band, except for the theta-delta frequency bands, we observed a significant build-up of RSWE from the preictal period to the first ictal event (p < or = 0.05) in cortex. Significant differences were observed between cortical and thalamic RSWE (p < or = 0.05) subsequent to seizure development. A key observation is the twofold increase in mean cortical RSWE from the preictal to interictal period. Exploiting this increase, we develop a slope change detector to discern early acceleration of entropy and predict the approaching seizure. We use multiple observations through sequential detection of slope changes to enhance the sensitivity of our prediction. Using the proposed method applied to a cohort of four rats subjected to PTZ infusion, we were able to predict the first seizure episode 28 min prior to its occurrence.

  View details for DOI 10.1109/TBME.2003.810683

  View details for Web of Science ID 000182870900012

  View details for PubMedID 12769440

• Residual entropy reveals effects of deep brain stimulation on neural activity in PTZ-induced epilepsy Patel, C. B., Sherman, D. L., Paul, J. S., Zhang, N., Mirski, M. A. 2003: 2281–84

  View details for DOI 10.1109/IEMBS.2003.1280370

• Wilms' tumor suppressor gene (WT1) is expressed in primary breast tumors despite tumor-specific promoter methylation CANCER RESEARCH Loeb, D. M., Evron, E., Patel, C. B., Sharma, P. M., Niranjan, B., Buluwela, L., Weitzman, S. A., Korz, D., Sukumar, S. 2001; 61 (3): 921-925

  Abstract

  We analyzed Wilms' tumor suppressor 1 (WT1) expression and its regulation by promoter methylation in a panel of normal breast epithelial samples and primary carcinomas. Contrary to previous reports, WT1 protein was strongly expressed in primary carcinomas (27 of 31 tumors) but not in normal breast epithelium (1 of 20 samples). Additionally, the WT1 promoter was methylated in 6 of 19 (32%) primary tumors, which nevertheless expressed WT1. The promoter is not methylated in normal epithelium. Thus, although tumor-specific methylation of WT1 is established in primary breast cancer at a low frequency, other transcriptional regulatory mechanisms appear to supercede its effects in these tumors. Our results demonstrate expression of WT1 in mammary neoplasia, and that WT1 may not have a tumor suppressor role in breast cancer.

  View details for Web of Science ID 000167020100027

  View details for PubMedID 11221883