68 results on '"Carmen Tong"'
Search Results
2. 446 Immunopeptidome changes mediated by a novel ERAP1 inhibitor leads to tumor growth inhibition
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Fergus Poynton, Lesley Young, Peter Joyce, Martin Quibell, Jason Shiers, Carmen Tong, Kristopher Clark, Edd James, Emma Reeves, Alihussein Remtulla, Henry Leonard, Camila de Almeida, Elisa Lori, Nicola Ternette, and Andrew Leishman
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2020
- Full Text
- View/download PDF
3. Gaussia Luciferase as a Reporter for Quorum Sensing in Staphylococcus aureus
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Isobel Blower, Carmen Tong, Xiaohui Sun, Ewan Murray, Jeni Luckett, Weng Chan, Paul Williams, and Philip Hill
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Gaussia luciferase ,quorum sensing ,Staphylococcus aureus ,agr ,Chemical technology ,TP1-1185 - Abstract
Gaussia luciferase (GLuc) is a secreted protein with significant potential for use as a reporter of gene expression in bacterial pathogenicity studies. To date there are relatively few examples of its use in bacteriology. In this study we show that GLuc can be functionally expressed in the human pathogen Staphylococcus aureus and furthermore show that it can be used as a biosensor for the agr quorum sensing (QS) system which employs autoinducing peptides to control virulence. GLuc was linked to the P3 promoter of the S. aureusagr operon. Biosensor strains were validated by evaluation of chemical agent-mediated activation and inhibition of agr. Use of GLuc enabled quantitative assessment of agr activity. This demonstrates the utility of Gaussia luciferase for in vitro monitoring of agr activation and inhibition.
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- 2020
- Full Text
- View/download PDF
4. Pediatric Stone Disease: Current Trends and Future Directions
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Carmen Tong, Ching Man, Ellison, Jonathan S., and Tasian, Gregory E.
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- 2023
- Full Text
- View/download PDF
5. PD55-02 INFLUENCE OF A NATIONAL PEDIATRIC KIDNEY STONE NETWORK ON ADHERENCE TO POSTOPERATIVE IMAGING ACQUISITION: A BI-INSTITUTIONAL EXPERIENCE
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Carmen Tong, Ching Man, primary, Bicknell, Brenton T., additional, Garner, Melissa, additional, Flanery, Alicia, additional, Tasian, Gregory, additional, and Ching, Christina, additional
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- 2024
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6. Pediatric Stone Disease
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Carmen Tong, Ching Man, primary, Ellison, Jonathan S., additional, and Tasian, Gregory E., additional
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- 2023
- Full Text
- View/download PDF
7. A Blunt Scrotal Trauma With More Than Meets the Eye
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Jennifer Rosen, Camila Munoz, and Carmen Tong
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Urology - Published
- 2023
8. Pediatric Stone Disease
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Ching Man Carmen Tong, Jonathan S. Ellison, and Gregory E. Tasian
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Urology - Published
- 2023
9. Inhibition of hypoxia-inducible factor-prolyl hydroxylation protects from cyclophosphamide-induced bladder injury and urinary dysfunction
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Douglass B. Clayton, Ching Man Carmen Tong, Belinda Li, Abby S. Taylor, Shuvro De, Matthew D. Mason, Anne G. Dudley, Olena Davidoff, Hanako Kobayashi, and Volker H. Haase
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Inflammation ,Physiology ,Urinary Bladder ,Procollagen-Proline Dioxygenase ,Hydroxylation ,Hypoxia-Inducible Factor 1, alpha Subunit ,Prolyl Hydroxylases ,Hypoxia-Inducible Factor-Proline Dioxygenases ,Disease Models, Animal ,Mice ,Animals ,Hypoxia ,Cyclophosphamide ,Research Article - Abstract
Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Activation of the oxygen-regulated hypoxia-inducible factor (HIF) pathway has been shown to protect mucosal membranes by increasing the expression of cytoprotective genes and by suppressing inflammation. The activity of HIF is controlled by prolyl hydroxylase domain (PHD) dioxygenases, which have been exploited as therapeutic targets for the treatment of anemia of chronic kidney disease. Here, we established a mouse model of acute cyclophosphamide (CYP)-induced blood-urine barrier disruption associated with inflammation and severe urinary dysfunction to investigate the HIF-PHD axis in inflammatory bladder injury. We found that systemic administration of dimethyloxalylglycine or molidustat, two small-molecule inhibitors of HIF-prolyl hydroxylases, profoundly mitigated CYP-induced bladder injury and inflammation as assessed by morphological analysis of transmural edema and urothelial integrity and by measuring tissue cytokine expression. Void spot analysis to examine bladder function quantitatively demonstrated that HIF-prolyl hydroxylase inhibitor administration normalized micturition patterns and protected against CYP-induced alteration of urinary frequency and micturition patterns. Our study highlights the therapeutic potential of HIF-activating small-molecule compounds for the prevention or therapy of bladder injury and urinary dysfunction due to blood-urine barrier disruption. NEW & NOTEWORTHY Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Here, we demonstrate that pharmacological inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylation prevented bladder injury and protected from urinary dysfunction in a mouse model of cyclophosphamide-induced disruption of the blood-urine barrier. Our study highlights a potential role for HIF-activating small-molecule compounds in the prevention or therapy of bladder injury and urinary dysfunction and provides a rationale for future clinical studies.
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- 2022
10. Lower Urinary Tract Reconstruction
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Heather J. Rankin, David B. Joseph, and Ching Man Carmen Tong
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- 2022
11. MP17-14 IS EXCRETORY PHASE COMPUTERIZED TOMOGRAPHY IMPORTANT FOR EVALUATION OF HIGH GRADE RENAL TRAUMA?: RESULTS FROM THE TRAUMATIC RENAL INJURY COLLABORATION FOR KIDS (TRICK)
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Ching Man Carmen Tong, Jacob Lucas, Albert Lee, Vinaya Bhatia, Benjamin Abelson, Christopher Long, Dana Weiss, Christina Ho, Jeffrey Ellis, Harold Lovvorn, Teressa Duong, Jonathan Gerber, Gabriella Crane, Xiaoyi Zhuo, Robert Russell, Soo Kim, Ming-Hsien Wang, Douglass Clayton, and David Kitchens
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Urology - Published
- 2022
12. MP17-15 PEDIATRIC INGUINAL HERNIA MANAGEMENT BETWEEN PEDIATRIC SURGEONS AND PEDIATRIC UROLOGISTS
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Teressa Duong, Vincent Mortellaro, David Kitchens, David Joseph, and Ching Man Carmen Tong
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Urology - Published
- 2022
13. A Review of Literature on Long-Term Outcomes of Proximal Hypospadias — Urinary, Sexual, and Psychosocial
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Pankaj P. Dangle, Amanda Hua Fang, Sheila Mallenahalli, and Ching Man Carmen Tong
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Surgical repair ,Pediatrics ,medicine.medical_specialty ,030219 obstetrics & reproductive medicine ,business.industry ,Urology ,Urinary system ,030232 urology & nephrology ,Obstetrics and Gynecology ,Surgical correction ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Hypospadias ,Long term outcomes ,medicine ,In patient ,business ,Psychosocial ,Urinary flow - Abstract
Proximal hypospadias management involves complex surgical interventions that can lead to the need for long-term specialized care. This review aims to explore the urinary, sexual, and psychosocial outcomes in patients with proximal hypospadias. Patients undergoing surgical correction of proximal hypospadias have generally acceptable urinary flow rates but can still suffer from increased rates of urinary tract infections, voiding difficulties, and leakage as compared to controls. Sexual outcomes of surgical repair closely mimic those of controls. However, a significant proportion of patients report dissatisfaction with their penile appearance after cosmetic surgery. While patients may report hesitancy in approaching sexual or emotional relationships, overall psychosocial outcomes were close to those reports in controls. While still generally very successful, proximal hypospadias surgery has been shown to have more complications in these areas than other milder forms of hypospadias and thus care must be taken to ensure patients are being treated with a holistic mindset throughout their journey.
- Published
- 2021
14. Kidney epithelial targeted mitochondrial transcription factor A deficiency results in progressive mitochondrial depletion associated with severe cystic disease
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Meghan E. Kapp, Andraia Li, Navdeep S. Chandel, Ken Ishii, Carmen Tong, Nan Guan, Volker H. Haase, Craig R. Brooks, Olena Davidoff, Pamela V. Tran, Hanako Kobayashi, Kensei Taguchi, Madhulika Sharma, and Agnes B. Fogo
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0301 basic medicine ,Mitochondrial DNA ,030232 urology & nephrology ,Kidney development ,Biology ,Mitochondrion ,Kidney ,Mitochondrial depletion ,Article ,Mitochondrial Proteins ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Polycystic kidney disease ,medicine ,Animals ,Humans ,High Mobility Group Proteins ,TFAM ,medicine.disease ,Cell biology ,DNA-Binding Proteins ,030104 developmental biology ,Nephrology ,Transcription Factors ,Mitochondrial DNA replication ,Abnormal mitochondrial morphology - Abstract
Abnormal mitochondrial function is a well-recognized feature of acute and chronic kidney diseases. To gain insight into the role of mitochondria in kidney homeostasis and pathogenesis, we targeted mitochondrial transcription factor A (TFAM), a protein required for mitochondrial DNA replication and transcription that plays a critical part in the maintenance of mitochondrial mass and function. To examine the consequences of disrupted mitochondrial function in kidney epithelial cells, we inactivated TFAM in sine oculis-related homeobox 2-expressing kidney progenitor cells. TFAM deficiency resulted in significantly decreased mitochondrial gene expression, mitochondrial depletion, inhibition of nephron maturation and the development of severe postnatal cystic disease, which resulted in premature death. This was associated with abnormal mitochondrial morphology, a reduction in oxygen consumption and increased glycolytic flux. Furthermore, we found that TFAM expression was reduced in murine and human polycystic kidneys, which was accompanied by mitochondrial depletion. Thus, our data suggest that dysregulation of TFAM expression and mitochondrial depletion are molecular features of kidney cystic disease that may contribute to its pathogenesis.
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- 2021
15. MP17-14 IS EXCRETORY PHASE COMPUTERIZED TOMOGRAPHY IMPORTANT FOR EVALUATION OF HIGH GRADE RENAL TRAUMA?: RESULTS FROM THE TRAUMATIC RENAL INJURY COLLABORATION FOR KIDS (TRICK)
- Author
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Carmen Tong, Ching Man, primary, Lucas, Jacob, additional, Lee, Albert, additional, Bhatia, Vinaya, additional, Abelson, Benjamin, additional, Long, Christopher, additional, Weiss, Dana, additional, Ho, Christina, additional, Ellis, Jeffrey, additional, Lovvorn, Harold, additional, Duong, Teressa, additional, Gerber, Jonathan, additional, Crane, Gabriella, additional, Zhuo, Xiaoyi, additional, Russell, Robert, additional, Kim, Soo, additional, Wang, Ming-Hsien, additional, Clayton, Douglass, additional, and Kitchens, David, additional
- Published
- 2022
- Full Text
- View/download PDF
16. Defining a Molecular Signature for Uropathogenic versus Urocolonizing Escherichia coli: The Status of the Field and New Clinical Opportunities
- Author
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Maria Hadjifrangiskou, John A. McLean, Charles W. Stratton, Gerald T. Van Horn, Emily K. Apple, Alexandra C. Schrimpe-Rutledge, Jonathan E. Schmitz, Simona G. Codreanu, Stacy D. Sherrod, Madison J. Fitzgerald, Douglass B. Clayton, Ching Man Carmen Tong, Allison R. Eberly, Hamilton D. Green, Connor J. Beebout, and Shuvro De
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Adult ,Male ,Adolescent ,Population ,Acute infection ,Biology ,medicine.disease_cause ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Structural Biology ,Cystitis ,medicine ,Humans ,Metabolomics ,Uropathogenic Escherichia coli ,education ,Molecular Biology ,Escherichia coli ,Asymptomatic bacteriuria ,Escherichia coli Infections ,Aged ,030304 developmental biology ,Aged, 80 and over ,Genetics ,0303 health sciences ,education.field_of_study ,Microbial pathogenesis ,Genetic heterogeneity ,Biofilm ,Middle Aged ,Phenotype ,Biofilms ,Urinary Tract Infections ,Female ,030217 neurology & neurosurgery - Abstract
Urinary tract infections (UTIs) represent a major burden across the population, although key facets of their pathophysiology and host interaction remain unclear. Escherichia coli epitomizes these obstacles: this gram-negative bacterial species is the most prevalent agent of UTIs worldwide and can also colonize the urogenital tract in a phenomenon known as asymptomatic bacteriuria (ASB). Unfortunately, at the level of the individual E. coli strains, the relationship between UTI and ASB is poorly defined, confounding our understanding of microbial pathogenesis and strategies for clinical management. Unlike diarrheagenic pathotypes of E. coli, the definition of uropathogenic E. coli (UPEC) remains phenomenologic, without conserved phenotypes and known genetic determinants that rigorously distinguish UTI- and ASB-associated strains. This article provides a cross-disciplinary review of the current issues from interrelated mechanistic and diagnostic perspectives and describes new opportunities by which clinical resources can be leveraged to overcome molecular challenges. Specifically, we present our work harnessing a large collection of patient-derived isolates to identify features that do (and do not) distinguish UTI- from ASB-associated E. coli strains. Analyses of biofilm formation, previously reported to be higher in ASB strains, revealed extensive phenotypic heterogeneity that did not correlate with symptomatology. However, metabolomic experiments revealed distinct signatures between ASB and cystitis isolates, including in the purine pathway (previously shown to be critical for intracellular survival during acute infection). Together, these studies demonstrate how large-scale, wild-type approaches can help dissect the physiology of colonization versus infection, suggesting that the molecular definition of UPEC may rest at the level of global bacterial metabolism.
- Published
- 2020
17. Urine leaks in children sustaining blunt renal trauma
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Muhammad Owais Abdul Ghani, Elizabeth Snyder, Mark C. Xu, Katlyn G. McKay, Jarrett Foster, Carmen Tong, Douglas B. Clayton, Amber Greeno, Bassil Azam, Shilin Zhao, Marta Hernanz-Schulman, and Harold N. Lovvorn
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Urinary Incontinence ,Trauma Centers ,Humans ,Surgery ,Ureter ,Critical Care and Intensive Care Medicine ,Child ,Kidney ,Wounds, Nonpenetrating ,Nephrectomy ,Retrospective Studies - Abstract
Few consensus statements exist to guide the timely diagnosis and management of urine leaks in children sustaining blunt renal trauma (BRT). The aims of this study were to characterize kidney injuries among children who sustain BRT, evaluate risk factors for urine leaks, and describe the negative impact of urinoma on patient outcomes and resource consumption.A retrospective review was performed of 347 patients, younger than 19 years, who presented with BRT to a single American College of Surgeons-verified Level I Pediatric Trauma Center between 2005 and 2020. Frequency of and risk factors for urine leak after BRT were evaluated, and impact on patient outcomes and resource utilization were analyzed.In total, 44 (12.7%) patients developed urine leaks, which exclusively presented among injury Grade 3 (n = 5; 11.4%), Grade 4 (n = 27; 61.4%), and Grade 5 (n = 12; 27.3%). A minority of urine leaks (n = 20; 45.5%) were discovered on presenting CT scan but all within 3 days. Kidney-specific operative procedures (nephrectomy, cystoscopy with J/ureteral stent, percutaneous nephrostomy) were more common among urine leak patients (n = 17; 38.6%) compared with patients without urine leaks (n = 3; 1.0%; p = 0.001). Patients with urine leak had more frequent febrile episodes during hospital stay (n = 24; 54.5%; p = 0.001) and showed increased overall 90-day readmission rates (n = 14; 33.3%; p0.001). Independent risk factors that associated with urine leak were higher grade (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.6-24.3; p0.001), upper-lateral quadrant injuries (OR, 2.9; 95% CI, 1.2-7.1; p = 0.02), and isolated BRT (OR, 2.6; 95% CI, 1.0-6.5; p = 0.04).In a large cohort of children sustaining BRT, urine leaks result in considerable morbidity, including more febrile episodes, greater 90-day readmission rates, and increased operative or image-guided procedures. This study is the first to examine the relationship between kidney quadrant injury and urine leaks. Higher grade (Grade 4-5) injury, upper lateral quadrant location, and isolated BRT were independently predictive of urine leaks.Therapeutic/Care Management; Level III.
- Published
- 2022
18. 553 First-in-class inhibitors of ERAP1 alter the immunopeptidome of cancer, driving a differentiated T cell response leading to tumor growth inhibition
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Jason Shiers, Kate Anderton, Kristopher Clark, Nicola Ternette, Martin Quibell, Peter Joyce, Carmen Tong, Jessica Sette, Wayne Paes, and Andrew Leishman
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Pharmacology ,Cancer Research ,Class (set theory) ,Immunology ,Cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Biology ,T cell response ,medicine.disease ,Oncology ,Cancer research ,medicine ,Molecular Medicine ,Immunology and Allergy ,Tumor growth inhibition ,RC254-282 - Abstract
BackgroundClinical data demonstrates increased antigen presentation diversity is an important factor in determining response rates to checkpoint inhibitors.1 In addition to tumor mutational burden, increased HLA heterozygosity and HLA evolutionary diversity are non-overlapping factors which further diversify the immunopeptidome and improve clinical response to checkpoint therapies.2 3 Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an enzyme that trims peptides loaded into classical and nonclassical MHC Class I molecules.4 5 Ablation of mouse ERAAP modifies the immunopeptidome, resulting in improved immunogenicity, generation of CD8+ T cell responses and tumor growth inhibition.6 7 We report the characterisation of ERAP1 inhibitors in syngeneic tumor models and development of biomarkers to enable translation of this mechanism into the clinic.MethodsHuman and mouse cancer cell lines treated with ERAP1 inhibitors were assessed by immunopeptidomics8 to profile peptide repertoire changes. ERAP1 inhibitor with and without checkpoint inhibition were used to treat syngeneic mouse tumor models, followed by analysing effects on the T cell receptor (TCR) repertoire, RNA sequencing profile, immune cell infiltration and tumor growth inhibition.ResultsExtensive analysis of the immunopeptidomes of diverse cancer cell lines robustly show that ERAP1 inhibition modulates the cancer-related antigen repertoire across diverse ERAP1 and HLA genotypes and cancer-type backgrounds. ERAP1 inhibition drives changes in T cell activation and response, leading to increased T cell infiltration into CT26 syngeneic tumors and alteration of the TCR repertoire at early and late timepoints in tumor growth. Consistent peptide length changes in the immunopeptidome, caused by ERAP1 inhibition, is a proof of mechanism biomarker, whilst tumor immunohistochemisty, TCR repertoire analysis and RNA sequencing are potential proof of principle biomarkers that can all be translated into the clinic. Importantly, the antigen and T cell changes we see following ERAP1 inhibition lead to robust tumor growth inhibition in different syngeneic mouse models when combined with anti-PD-1. We are also exploring the potential of ERAP1 inhibitors to enhance tumour immune responses in combination with additional therapies (e.g. chemotherapy and radiotherapy), across different tumor microenvironments.ConclusionsGrey Wolf Therapeutics ERAP1 inhibitors significantly modify the immunopeptidome and combination with anti PD-1 leads to significant TCR repertoire change, T cell infiltration and tumor growth inhibition in syngeneic mouse tumor models. These data provide the foundation from which we will explore the potential of our first-in-class ERAP1 inhibitor development candidate in the clinic, as well as identifying useful biomarkers to demonstrate desired biological activity.ReferencesRizvi N, Hellmann MD, Snyder A, et al. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science 2015;348(6230):124–128.Chowell D, uc G T Morris LGT,2 3, Grigg CM, et al Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy. Science 2018;359 (6375):582–587.Chowell D, Chirag Krishna, Federica Pierini, et al Evolutionary divergence of HLA class I genotype impacts efficacy of cancer immunotherapy. Nature Medicine 2019;25(11):1715–1720.Shastri N, Nagarajan N, Lind KC, et al. Monitoring peptide processing for MHC class I molecules in the endoplasmic reticulum. Curr Opin Immunol 2014;26:123–127.Mpakali A, Maben Z, Stern LJ, et al. Molecular pathways for antigenic peptide generation by ER aminopeptidase 1. Mol Immunol 2018;13:50–57.James E, Bailey I, Sugiyarto G, et al. Induction of protective antitumor immunity through attenuation of ERAAP function. J Immunol 2013;190(11):5839–5846.Manguso RT, Pope, HW, MD Zimmer, et al In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature 2017;547(7664):413–418.Purcell AW, Ramarathinam SH, Ternette N. Mass spectrometry–based identification of MHC-bound peptides for immunopeptidomics. Nat Protoc 2019;14(6):1687–1707.
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- 2021
19. MP47-07 FOLLOW-UP PATTERNS AND POST-INJURY PHYSICAL ACTIVITY RECOMMENDATIONS IN PEDIATRIC HIGH-GRADE RENAL TRAUMA: A MULTI-CENTER, RETROSPECTIVE ANALYSIS FROM THE TRAUMATIC RENAL INJURY COLLABORATIVE IN KIDS (TRICK) CONSORTIUM
- Author
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Sumit Singh, Albert S. Lee, Ching Man Carmen Tong, Christina Ho, Douglass B. Clayton, Pankaj P. Dangle, Kirstin Simmons, Xiaoyi Zhuo, Gabriella L. Crane, Jacob Lucas, Ming Wang, Benjamin Abelson, Vinaya Bhatia, Robert T. Russell, Daniel Mecca, Jonathan Gerber, Dana A. Weiss, Harold N. Lovvorn, Madhushree Zope, Jeffrey L. Ellis, and Christopher J. Long
- Subjects
medicine.medical_specialty ,Renal injury ,business.industry ,Urology ,Emergency medicine ,Physical activity ,Retrospective analysis ,Medicine ,Center (algebra and category theory) ,business ,Post injury - Published
- 2021
20. MP44-01 CLINICAL CHARACTERISTICS AND VARIABLE MANAGEMENT OF PATIENTS WITH MICROPENIS, A SINGLE CENTER EXPERIENCE
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Carmen Tong, Pankaj P. Dangle, Bhuvana Sunil, Thomas Kozar, and Sol Moon
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Variable (computer science) ,Pediatrics ,medicine.medical_specialty ,business.industry ,Urology ,medicine ,Micropenis ,Single Center ,medicine.disease ,business - Published
- 2021
21. MP47-07 FOLLOW-UP PATTERNS AND POST-INJURY PHYSICAL ACTIVITY RECOMMENDATIONS IN PEDIATRIC HIGH-GRADE RENAL TRAUMA: A MULTI-CENTER, RETROSPECTIVE ANALYSIS FROM THE TRAUMATIC RENAL INJURY COLLABORATIVE IN KIDS (TRICK) CONSORTIUM
- Author
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Lucas, Jacob W., primary, Carmen Tong, Ching Man, additional, Bhatia, Vinaya, additional, Ellis, Jeffrey L., additional, Abelson, Benjamin, additional, Lee, Albert S., additional, Clayton, Douglass B., additional, Simmons, Kirstin, additional, Crane, Gabriella, additional, Lovvorn, Harold N., additional, Gerber, Jonathan, additional, Wang, Ming, additional, Zhuo, Xiaoyi, additional, Zope, Madhushree, additional, Dangle, Pankaj P., additional, Russell, Robert T., additional, Singh, Sumit, additional, Mecca, Daniel, additional, Ho, Christina, additional, Long, Christopher J., additional, and Weiss, Dana A., additional
- Published
- 2021
- Full Text
- View/download PDF
22. Use of Google Trends to Track Online Behavior and Interest in Kidney Stone Surgery
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Paulette Cutruzzula Dreher, Justin I. Friedlander, Eric Ghiraldi, and Carmen Tong
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medicine.medical_specialty ,Urology ,medicine.medical_treatment ,Information Seeking Behavior ,030232 urology & nephrology ,MEDLINE ,Information Storage and Retrieval ,Nephrolithotomy, Percutaneous ,Lithotripsy ,Kidney Calculi ,03 medical and health sciences ,0302 clinical medicine ,Information seeking behavior ,Prevalence ,Ureteroscopy ,medicine ,Humans ,Percutaneous nephrolithotomy ,Internet ,Modalities ,medicine.diagnostic_test ,business.industry ,Laser lithotripsy ,United States ,Surgery ,Index (publishing) ,Data Interpretation, Statistical ,030220 oncology & carcinogenesis ,business - Abstract
Objective To explore internet search trends data as a unique resource for monitoring online health information-seeking behavior. We utilized Google trends to sample population interest and search inquiries into surgical treatment options of kidney stones, and we examined the relative frequency of searches across the United States. Methods Google trends was queried via the Google Insights for Search ( http://google.com/trends ) using terms related to kidney stone surgeries from 2011 to 2017. "Kidney stone surgery" was identified to be the most common term. The search volume index graph for the U.S. was recorded as well as regional distribution and related queries. For specific surgical treatment modalities, the following medical terminology was used: percutaneous nephrolithotomy, extracorporeal shockwave lithotripsy, ureteroscopy, and laser lithotripsy. Each query was then compared and analyzed to assess changes in the interest in these search terms over time. Results The research trends for the search "kidney stone surgery" as well as specific surgical modalities remained constant over time. extracorporeal shockwave lithotripsy had the highest search volume index and laser lithotripsy had the lowest. The top 5 US states with greatest search volume was Tennessee, Indiana, Ohio, Michigan, and North Carolina, whereas the top 5 metropolitan regions were Atlanta, Tampa, Detroit, Philadelphia, and Boston. Conclusion Google trends data is a useful tool to analyze online health information-seeking behavior. Despite an increase in stone prevalence over the past decade, search rates have remained relatively constant. High relative search volume was seen from states within and outside the traditional stone belt, suggesting a possible changing trend.
- Published
- 2018
23. A Rare, Unusual Presentation of Newberyite Urolithiasis in Adolescent Female -A Case Report and Review of Literature
- Author
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Ching Man Carmen Tong, Pankaj P. Dangle, and Sydney Weir
- Subjects
Past medical history ,medicine.medical_specialty ,Stone formation ,Adolescent ,business.industry ,Genitourinary system ,Urology ,Urinary system ,030232 urology & nephrology ,Magnesium Compounds ,Autoimmune hepatitis ,medicine.disease ,Dermatology ,Phosphates ,03 medical and health sciences ,Kidney Calculi ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Medicine ,Humans ,Female ,Ammonium Acid Urate ,Presentation (obstetrics) ,business ,Young female - Abstract
We report a rare case of newberyite (magnesium monohydrate phosphate trihydrate) urolithiasis in a young female with a past medical history significant for longstanding autoimmune hepatitis. She presented to the emergency department with newly diagnosed nephrolithiasis. Over the next 2 years, she had recurrent renal calculi and 3 urologic procedures. Notably, she did not have any history of urinary tract infections or genitourinary abnormalities. Her last stone analysis revealed the unusual combination of newberyite and ammonium acid urate. The pathophysiology of ammonium acid urate and newberyite stone formation as well as risk factors of development are discussed in this report.
- Published
- 2021
24. 446 Immunopeptidome changes mediated by a novel ERAP1 inhibitor leads to tumor growth inhibition
- Author
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Elisa Lori, Camila de Almeida, Carmen Tong, Alihussein Remtulla, Jason Shiers, Fergus Poynton, Henry Leonard, Edd James, Emma Reeves, Martin Quibell, Andrew Leishman, Nicola Ternette, Kristopher Clark, Lesley Young, and Peter Joyce
- Subjects
medicine.medical_treatment ,T cell ,Antigen presentation ,Biology ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Major histocompatibility complex ,lcsh:RC254-282 ,medicine.anatomical_structure ,Cancer immunotherapy ,Antigen ,MHC class I ,Cancer research ,medicine ,biology.protein ,Cytotoxic T cell ,Checkpoint Blockade Immunotherapy - Abstract
Background Clinical data demonstrates increased antigen presentation diversity is a key factor in determining response rates to checkpoint inhibitors.1 In addition to tumour mutational burden/microsatellite instability, increased HLA heterozygosity and HLA evolutionary diversity are non-overlapping factors recently identified to further diversify the immunopeptidome and improve clinical response to checkpoint therapies.2 3 Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an enzyme that trims peptides loaded into classical and nonclassical class I MHC molecules.4 5 Ablation of mouse ERAAP modifies the immunopeptidome, resulting in improved immunogenicity, generation of CD8 T cell responses and tumor growth inhibition.6 7 Recently identified selective small molecules potently inhibit ERAP1 across key species and haplotypes.8 We report the further profiling of lead candidate ERAP1 inhibitors in human primary T cell in vitro assays and in vivo tumor models in mice. Methods Human cancer cell lines treated with ERAP1 inhibitors in vitro or in vivo in xenograft mouse models were assessed by immunopeptidomics9 to profile peptide repertoire changes. Novel or upregulated peptides were also tested in human immunogenicity assays. FACS analysis of T cells stimulated with Tyrosinase mRNA transfected human dendritic cells ± ERAP1 inhibition was to assess T cell repertoire changes. ERAP1 inhibitor and anti PD-1 mAb combination was assessed in syngeneic mouse tumor models to investigate tumour growth inhibition and PD end-points (e.g. IHC). Results Analysis of human cervical, lung, colorectal and melanoma cell lines carrying distinct HLA haplotypes demonstrates a consistent and profound effect of ERAP1 inhibition on the immunopeptidome. Novel and upregulated cancer associated antigens identified in association with multiple different HLA-A and B alleles stimulate IFNγ production in primary naive human T cell immunogenicity assays. The impact of ERAP1 inhibition on the T cell repertoire to the melanoma antigen tyrosinase is ongoing. The combination of ERAP1 inhibitor and anti PD-1 mAb led to significant tumor growth inhibition in the CT26 syngeneic mouse tumor model that correlated with increased infiltration of T cells to the tumor. Further PD end-points to be analysed include immune gene array and TCR Vbeta repertoire. Conclusions Grey Wolf ERAP1 inhibitors significantly modify the immunopeptidome both in vitro and in vivo across a broad range of HLA and tumor types. Combination of these inhibitors with anti PD-1 leads to significant T cell infiltration and tumor growth inhibition. Thus, ERAP1 mediated modulation of the immunopeptidome has the potential to drive anti tumor T cell responses and be a transformative immunotherapy. References Rizvi N, Hellmann MD, Snyder A, et al. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science. 2015;348(6230):124–128. Chowell D, Morris LGT, Grigg CM, et al. Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy. Science 2018;359 (6375):582–587. Chowell D, Krishna C, Pierini F, et al. Evolutionary divergence of HLA class I genotype impacts efficacy of cancer immunotherapy. Nature Medicine 2019;25(11):1715–1720. Shastri N, Nagarajan N, Lind KC, et al. Monitoring peptide processing for MHC class I molecules in the endoplasmic reticulum. Curr Opin Immunol 2014; 26:123–127. Mpakali A, Maben Z, Stern LJ, et al. Molecular pathways for antigenic peptide generation by ER aminopeptidase 1. Mol Immunol 2018; 13:50–57. James E, Bailey I, Sugiyarto G, et al. Induction of protective antitumor immunity through attenuation of ERAAP function. J Immunol 2013;190(11):5839–5846. Manguso RT, Pope HW, Zimmer MD, et al. In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature 2017;547(7664):413–418. Leonard, H Remtulla A, Poynton F, et al. AACR Annual Meeting 2020. Purcell AW, Ramarathinam SH, Ternette N. Mass spectrometry–based identification of MHC-bound peptides for immunopeptidomics. Nat Protoc 2019;14(6):1687–1707.
- Published
- 2020
25. Inhibition of hypoxia-inducible factor-prolyl hydroxylation protects from cyclophosphamide-induced bladder injury and urinary dysfunction.
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Clayton, Douglass B., Ching Man Carmen Tong, Li, Belinda, Taylor, Abby S., Shuvro De, Mason, Matthew D., Dudley, Anne G., Davidoff, Olena, Hanako Kobayashi, and Haase, Volker H.
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CYCLOPHOSPHAMIDE , *BLADDER , *CYSTITIS , *HYPOXIA-inducible factors , *CHRONIC kidney failure , *HYDROXYLATION - Abstract
Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Activation of the oxygen-regulated hypoxia-inducible factor (HIF) pathway has been shown to protect mucosal membranes by increasing the expression of cytoprotective genes and by suppressing inflammation. The activity of HIF is controlled by prolyl hydroxylase domain (PHD) dioxygenases, which have been exploited as therapeutic targets for the treatment of anemia of chronic kidney disease. Here, we established a mouse model of acute cyclophosphamide (CYP)-induced blood-urine barrier disruption associated with inflammation and severe urinary dysfunction to investigate the HIF-PHD axis in inflammatory bladder injury. We found that systemic administration of dimethyloxalylglycine or molidustat, two small-molecule inhibitors of HIF-prolyl hydroxylases, profoundly mitigated CYP-induced bladder injury and inflammation as assessed by morphological analysis of transmural edema and urothelial integrity and by measuring tissue cytokine expression. Void spot analysis to examine bladder function quantitatively demonstrated that HIF-prolyl hydroxylase inhibitor administration normalized micturition patterns and protected against CYP-induced alteration of urinary frequency and micturition patterns. Our study highlights the therapeutic potential of HIF-activating small-molecule compounds for the prevention or therapy of bladder injury and urinary dysfunction due to blood-urine barrier disruption. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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26. Gaussia Luciferase as a Reporter for Quorum Sensing in Staphylococcus aureus
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Ewan Murray, Isobel Blower, Paul Williams, Carmen Tong, Philip J. Hill, Jeni Luckett, Weng Chan, and Xiaohui Sun
- Subjects
Staphylococcus aureus ,agr ,Operon ,Gaussia luciferase ,Virulence ,Human pathogen ,Biology ,lcsh:Chemical technology ,medicine.disease_cause ,Biochemistry ,Article ,Analytical Chemistry ,Microbiology ,03 medical and health sciences ,Gaussia ,Bacterial Proteins ,medicine ,Bacteriology ,Humans ,lcsh:TP1-1185 ,Luciferase ,Electrical and Electronic Engineering ,Luciferases ,Instrumentation ,030304 developmental biology ,0303 health sciences ,030306 microbiology ,quorum sensing ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,biology.organism_classification ,Atomic and Molecular Physics, and Optics ,Quorum sensing ,Trans-Activators ,bacteria - Abstract
Gaussia luciferase (GLuc) is a secreted protein with significant potential for use as a reporter of gene expression in bacterial pathogenicity studies. To date there are relatively few examples of its use in bacteriology. In this study we show that GLuc can be functionally expressed in the human pathogen Staphylococcus aureus and furthermore show that it can be used as a biosensor for the agr quorum sensing (QS) system which employs autoinducing peptides to control virulence. GLuc was linked to the P3 promoter of the S. aureusagr operon. Biosensor strains were validated by evaluation of chemical agent-mediated activation and inhibition of agr. Use of GLuc enabled quantitative assessment of agr activity. This demonstrates the utility of Gaussia luciferase for in vitro monitoring of agr activation and inhibition.
- Published
- 2020
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27. Data highlighting phenotypic diversity of urine-associated Escherichia coli isolates
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Simona G. Codreanu, Emily K. Apple, Maria Hadjifrangiskou, Gerald T. Van Horn, Charles W. Stratton, Connor J. Beebout, Douglass B. Clayton, Shuvro De, John A. McLean, Madison J. Fitzgerald, Stacy D. Sherrod, Ching Man Carmen Tong, Allison R. Eberly, Jonathan E. Schmitz, Hamilton D. Green, and Alexandra C. Schrimpe-Rutledge
- Subjects
Urine ,Biology ,medicine.disease_cause ,lcsh:Computer applications to medicine. Medical informatics ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Metabolomics ,Cystitis ,medicine ,Uropathogenic Escherichia coli ,University medical ,Colonization ,lcsh:Science (General) ,Escherichia coli ,030304 developmental biology ,0303 health sciences ,Urinary tract infection ,Multidisciplinary ,Biofilm ,Phenotype ,Metabolomics data ,lcsh:R858-859.7 ,Asymptomatic bacteriuria ,030217 neurology & neurosurgery ,lcsh:Q1-390 - Abstract
This article provides a reusable dataset describing detailed phenotypic and associated clinical parameters in n=303 clinical isolates of urinary Escherichia coli collected at Vanderbilt University Medical Center. De-identified clinical data collected with each isolate are detailed here and correlated to biofilm abundance and metabolomics data. Biofilm-abundance data were collected for each isolate under different in vitro conditions along with datasets quantifying biofilm abundance of each isolate under different conditions. Metabolomics data were collected from a subset of bacterial strains isolated from uncomplicated cases of cystitis or cases with no apparent symptoms accompanying colonization. For more insight, please see “Defining a Molecular Signature for Uropathogenic versus Urocolonizing Escherichia coli: The Status of the Field and New Clinical Opportunities” [1] .
- Published
- 2020
28. Data highlighting phenotypic diversity of urine-associated
- Author
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Allison R, Eberly, Connor J, Beebout, Ching Man Carmen, Tong, Gerald T, Van Horn, Hamilton D, Green, Madison J, Fitzgerald, Shuvro, De, Emily K, Apple, Alexandra C, Schrimpe-Rutledge, Simona G, Codreanu, Stacy D, Sherrod, John A, McLean, Douglass B, Clayton, Charles W, Stratton, Jonathan E, Schmitz, and Maria, Hadjifrangiskou
- Subjects
Urinary tract infection ,Biochemistry, Genetics and Molecular Biology ,Biofilm ,Cystitis ,Metabolomics ,Uropathogenic Escherichia coli ,Asymptomatic bacteriuria - Abstract
This article provides a reusable dataset describing detailed phenotypic and associated clinical parameters in n=303 clinical isolates of urinary Escherichia coli collected at Vanderbilt University Medical Center. De-identified clinical data collected with each isolate are detailed here and correlated to biofilm abundance and metabolomics data. Biofilm-abundance data were collected for each isolate under different in vitro conditions along with datasets quantifying biofilm abundance of each isolate under different conditions. Metabolomics data were collected from a subset of bacterial strains isolated from uncomplicated cases of cystitis or cases with no apparent symptoms accompanying colonization. For more insight, please see “Defining a Molecular Signature for Uropathogenic versus Urocolonizing Escherichia coli: The Status of the Field and New Clinical Opportunities” [1].
- Published
- 2020
29. Let's Talk About Sex: Special Considerations in Reproductive Care and Sexual Education in Young Women With Spina Bifida
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Ching Man Carmen Tong and Stacy T. Tanaka
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Gerontology ,congenital, hereditary, and neonatal diseases and abnormalities ,Adolescent ,Reproductive care ,Urology ,Urologists ,030232 urology & nephrology ,MEDLINE ,Human sexuality ,Genetic Counseling ,Sex Education ,Pelvic Floor Disorders ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,medicine ,Vulnerable population ,Humans ,Urinary Bladder, Neurogenic ,Child ,Physician's Role ,Contraception Behavior ,Spinal Dysraphism ,Spina bifida ,business.industry ,medicine.disease ,nervous system diseases ,Sexual Dysfunction, Physiological ,030220 oncology & carcinogenesis ,Urologic Surgical Procedures ,Female ,Sexual Health ,Sexual function ,business - Abstract
Medical advances in the last several decades have allowed an increasing number of children with spina bifida to reach adolescence and adulthood. As they reach puberty, girls with spina bifida face unique social and health challenges to their sexuality, such as orthopedic restrictions, continence, and pelvic floor disorders. Recent research efforts have focused on better understanding female sexual desires, dysfunctions, and activity and the role of the physician in educating this vulnerable population. This article aims to summarize current literature on sexual function, knowledge gaps, and the importance of tailored sexual education from providers in women with spina bifida.
- Published
- 2020
30. Defining a Molecular Signature for Uropathogenic versus Urocolonizing Escherichia coli: The Status of the Field and New Clinical Opportunities
- Author
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Eberly, Allison R., primary, Beebout, Connor J., additional, Carmen Tong, Ching Man, additional, Van Horn, Gerald T., additional, Green, Hamilton D., additional, Fitzgerald, Madison J., additional, De, Shuvro, additional, Apple, Emily K., additional, Schrimpe-Rutledge, Alexandra C., additional, Codreanu, Simona G., additional, Sherrod, Stacy D., additional, McLean, John A., additional, Clayton, Douglass B., additional, Stratton, Charles W., additional, Schmitz, Jonathan E., additional, and Hadjifrangiskou, Maria, additional
- Published
- 2020
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31. Abstract 1715: First in class inhibitors of ERAP1 have the potential to be a transformative immunotherapy in oncology
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Kristopher Clark, Jason Shiers, Fergus Poynton, Andrew Leishman, Camila de Almeida, Emma Reeves, Peter Joyce, Henry Leonard, Nicola Ternette, Carmen Tong, Edd James, Martin Quibell, and Elisa Lori
- Subjects
Cancer Research ,Class (computer programming) ,Psychotherapist ,Transformative learning ,Oncology ,medicine.medical_treatment ,medicine ,Immunotherapy ,Psychology - Abstract
Clinical data demonstrates increased antigen presentation diversity is an important factor in determining response rates to checkpoint inhibitors. In addition to tumor mutational burden, increased HLA heterozygosity and HLA evolutionary diversity are non-overlapping factors which further diversify the immunopeptidome and improve clinical response to checkpoint therapies. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an enzyme that trims peptides loaded into classical and nonclassical MHC Class I molecules. Human genome-wide association studies have identified single nucleotide polymorphisms within ERAP1 that are associated with immune-related diseases, such as ankylosing spondylitis, providing human genetic validation for ERAP1's role in human disease and antigen presentation. Further, ablation of mouse ERAAP modifies the immunopeptidome, resulting in improved immunogenicity, generation of CD8+ T cell responses and tumor growth inhibition. Grey Wolf Therapeutics have developed highly potent and selective ERAP1 inhibitors. These inhibitors demonstrate significant modulation of the cancer-related antigen repertoire across diverse ERAP1 and HLA genotypes and cancer-type backgrounds, both in vitro and in vivo. These changes in the antigen repertoire drive changes in T cell activation and response, leading to increased T cell infiltration into CT26 syngeneic tumors and T cell receptor (TCR) diversification when combined with anti-PD-1. We have identified immune related markers that are modulated following ERAP1 inhibition in syngeneic tumor models which have the potential to be used as biomarkers. Importantly, ERAP1 inhibitor induced immunopeptidome and T cell changes lead to significant tumor growth inhibition in syngeneic mouse models when combined with anti-PD-1. In parallel, we have demonstrated the ability of ERAP1 inhibitor induced novel cancer associated antigens to stimulate human CD8+ T cell responses. Extensive assessment of the potential of ERAP1 inhibitors to enhance tumor immune responses in combination with additional therapies (e.g. chemotherapy and radiotherapy), across different tumor microenvironments, is ongoing. These data provide the foundation from which we plan to explore the potential of our first-in-class ERAP1 inhibitor development candidate in the clinic. Citation Format: Andrew Leishman, Fergus Poynton, Nicola Ternette, Elisa Lori, Camila de Almeida, Henry Leonard, Emma Reeves, Edd James, Kristopher Clark, Carmen Tong, Jason Shiers, Martin Quibell, Peter Ian Joyce. First in class inhibitors of ERAP1 have the potential to be a transformative immunotherapy in oncology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1715.
- Published
- 2021
32. A chronology of Hong Kong’s umbrella movement: January 2013–December 2014
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Carmen Tong
- Subjects
Electoral reform ,Movement (music) ,05 social sciences ,050109 social psychology ,050105 experimental psychology ,Education ,film.subject ,Universal suffrage ,Umbrella Movement ,Politics ,History and Philosophy of Science ,film ,Civil disobedience ,Political science ,Political economy ,0501 psychology and cognitive sciences ,Student Protest ,Chronology - Abstract
The Umbrella Movement in Hong Kong is a 79 days political protest and occupy campaigns in major areas in the city. This chronology lists the key events prior to and during the movement.
- Published
- 2017
33. Urological Findings in Beckwith-Wiedemann Syndrome With Chromosomal Duplications of 11p15.5: Evaluation and Management
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Jennifer M. Kalish, Douglas A. Canning, Arun K. Srinivasan, Carmen Tong, Kelly A. Duffy, Dana A. Weiss, and David I. Chu
- Subjects
Male ,0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Pathology ,Beckwith-Wiedemann Syndrome ,Urology ,Beckwith–Wiedemann syndrome ,030105 genetics & heredity ,Article ,03 medical and health sciences ,Chromosome Duplication ,Gene duplication ,Macroglossia ,Humans ,Medicine ,Genetic testing ,Omphalocele ,medicine.diagnostic_test ,business.industry ,Chromosomes, Human, Pair 11 ,Infant ,Chromosome ,medicine.disease ,030104 developmental biology ,Child, Preschool ,DNA methylation ,medicine.symptom ,Presentation (obstetrics) ,business - Abstract
Beckwith-Wiedemann Syndrome (BWS) is an overgrowth disorder with various congenital anomalies. Although the most classic constellation includes macrosomia, macroglossia, and omphalocele, nephrourological findings are commonly associated with BWS. Clinical presentation is highly variable because of its complex molecular heterogeneity, which involves changes in DNA methylation and disruption of growth regulatory genes. We report 3 pediatric patients, ages 13 months to 3 years old, who presented with clinical features consistent with BWS. A variety of nephrourological abnormalities were also noted, including posterior urethral valves, hydroureteronephrosis, and undescended testes. Genetic testing for all 3 patients revealed duplication of the region chromosome 11p15.5.
- Published
- 2017
34. Leptospirosis in Pregnancy: A Rare Condition Mimicking HELLP Syndrome
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Carmen Tong and Manisha Mathur
- Published
- 2018
35. Abstract 5551: Potent oral ERAP1 inhibitors modify the immunopeptidome in vivo and are novel immunotherapy agents
- Author
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Carmen Tong, Lesley Young, Henry Leonard, Camila de Almeida, Peter Joyce, Michael J. Ford, Kristopher Clark, Jason Shiers, Martin Quibell, Jamie Ware, Nicola Ternette, Fergus Poynton, Edd James, Emma Reeves, Elisa Lori, Alihussein Remtulla, and Patrick McIntyre
- Subjects
Cancer Research ,biology ,medicine.medical_treatment ,T cell ,Antigen presentation ,Immunotherapy ,Major histocompatibility complex ,Immune checkpoint ,Immune system ,medicine.anatomical_structure ,Oncology ,Antigen ,Cancer research ,medicine ,biology.protein ,Cytotoxic T cell - Abstract
Immune checkpoint therapy has changed the cancer treatment paradigm, however the majority of patients respond poorly to T cell checkpoint blockade alone. Emerging evidence suggests factors that increase the diversity of the immunopeptidome such as high tumor mutation burden and HLA-I evolutionary divergence (HED), improve clinical response to checkpoint blockade providing an impetus to develop strategies that increase the presentation of cancer associated antigens to the immune system. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an aminopeptidase that trims peptides loaded into classical and nonclassical MHC molecules. Human genome-wide association studies have identified single nucleotide polymorphisms within ERAP1 that are associated with immune-related diseases, such as ankylosing spondylitis, providing human genetic validation for ERAP1's role in human disease and antigen presentation. Furthermore, in mice, genetic ablation, reduction or pharmacological inhibition of ERAP1 changes the immune repertoire, creating novel antigens with improved immunogenicity that lead to the generation of productive CD8 T cell responses and tumor growth inhibition in various syngeneic models. We have generated and profiled highly potent, species cross reactive and selective ERAP1 inhibitors through a suite of in vitro and in vivo assays to develop these as novel immunotherapy agents. In vitro CETSA measurements show potent cellular target engagement that correlates with in vitro SPR and enzyme potency. Using the model antigen SIINFEKL and Class I MHC expression as key pharmacodynamic measurements, we demonstrate Class I modulation in vitro and in vivo in line with published data from ERAP1 knockout mice. These assays are being used to elucidate the kinetics and temporal dynamics of the antigen change to optimise dosing schedules for in vivo studies. Implementation of our immunopeptidomics pipeline has demonstrated treatment with ERAP1 inhibitors both generate novel antigens in vitro and in vivo and lead to profound and consistent increased overall immunopeptidome length in mouse and human cells. To establish the functional consequence of these changes, we developed a human primary T cell immunogenicity platform. The immunogenic potential of these novel cancer associated antigens has been confirmed by the ability to stimulate IFNγ production in naïve T cells and suggests responses to these antigens could reinvigorate anti-tumor responses. Extensive assessment of mouse and human CD8 T cells responses is ongoing, in order to characterise and select Grey Wolf Therapeutics' first lead ERAP1 inhibitor for use as monotherapy or in combination with other immunotherapies such as checkpoint blockade. Citation Format: Jamie Ware, Patrick McIntyre, Kristopher Clark, Carmen Tong, Jason Shiers, Elisa Lori, Camila de Almeida, Emma Reeves, Henry Leonard, Alihussein Remtulla, Michael Ford, Nicola Ternette, Fergus Poynton, Edd James, Lesley Young, Martin Quibell, Peter I. Joyce. Potent oral ERAP1 inhibitors modify the immunopeptidome in vivo and are novel immunotherapy agents [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5551.
- Published
- 2020
36. MP32-13 NOVEL MULTIMODAL ANALGESIA (MMA) PROTOCOL SIGNIFICANTLY DECREASES POSTOPERATIVE OPIOID REQUIREMENTS IN INFLATABLE PENILE PROSTHESIS (IPP) PATIENTS
- Author
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Jacob Lucas, Carmen Tong, Matthew S. Brennan, Jay Simhan, Ankur Shah, and Christopher Foote
- Subjects
Inflatable penile prosthesis ,Opioid ,business.industry ,Urology ,Anesthesia ,Medicine ,business ,medicine.drug - Published
- 2018
37. MP31-09 A PREDICTIVE MODEL TO HELP IDENTIFY FACTORS ASSOCIATED WITH SUBMITTING 24-HOUR URINE COLLECTIONS
- Author
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Carmen Tong, Eric Ghiraldi, Justin Friedlander, Leonard E. Braitman, and Ryan Griggs
- Subjects
medicine.medical_specialty ,business.industry ,Urology ,Emergency medicine ,Medicine ,business ,24 h urine - Published
- 2018
38. Novel Multi-Modal Analgesia Protocol Significantly Decreases Opioid Requirements in Inflatable Penile Prosthesis Patients
- Author
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Jay Simhan, Jacob Lucas, Ankur Shah, Ching Man Carmen Tong, and Christopher Foote
- Subjects
Male ,medicine.drug_class ,Visual analogue scale ,Narcotic ,Urology ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Analgesic ,030232 urology & nephrology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Medicine ,Humans ,Pain Management ,Postoperative Period ,Anesthetics, Local ,Penile pain ,Aged ,Pain Measurement ,Retrospective Studies ,Analgesics ,Pain, Postoperative ,030219 obstetrics & reproductive medicine ,business.industry ,Local anesthetic ,Perioperative ,Middle Aged ,Analgesics, Opioid ,Psychiatry and Mental health ,Regimen ,Reproductive Medicine ,Opioid ,Anesthesia ,Female ,Penile Prosthesis ,business ,medicine.drug - Abstract
Background Inflatable penile prosthesis (IPP) surgery is associated with significant perioperative pain that may reduce patient satisfaction. Though various pain management strategies have been proposed, most implanters manage postoperative patients with only prescription opioids. No protocol to date has been implemented and reported for pain management in IPP patients throughout the entire recovery process following surgery. Aim Develop a multimodal analgesic (MMA) regimen consisting of perioperative administration of acetaminophen, meloxicam, and gabapentin with intraoperative local anesthetic injections, and compare post-operative pain control to a matched cohort of patients managed with an opioid-based (OB) regimen. Methods We retrospectively analyzed our prospectively maintained IPP database from November 2015–January 2018. The MMA protocol was instituted for all patients beginning June 2017, and these patients were matched in a 1:2 ratio to a cohort of eligible IPP patients managed through an OB protocol. Only patients receiving a 3-piece IPP were included; those with a history of narcotic dependence, neuropathy, or chronic non-steroidal anti-inflammatory drug use were excluded. Postoperative pain scores (visual analog scale) and opioid usage (total morphine equivalents [TME] in milligrams) were compared temporally in the post-anesthesia care unit, postoperative day (POD) 0, POD 1, and following discharge. Outcomes The primary outcomes of the study are postoperative pain scores and narcotic usage. Results 57 patients were eligible for analysis: 19 (33%) and 38 (66%) in the MMA and OB groups, respectively. Groups were similar in demographics. MMA patients had significantly lower visual analog scale scores in post-anesthesia care unit, POD 0, or POD 1 (mean 0.84 vs 2.97, P = .01; 2.62 vs 4.73, P = .003; and 2.26 vs 4.0, P = .01, respectively) and used fewer narcotics on POD 0 (mean 4.08 vs 13.8 mg TME, P < .001) and POD 1 (mean 5.05 vs 25.1 mg TME, P < .001). MMA patients were discharged home with fewer narcotics (mean 12.7 vs 51.3 tabs, P < .001), and despite this, the MMA group needed less narcotic medication refills (11% vs 49%, P = .007). Neither group experienced a medication-related postoperative adverse event. Clinical Implications Multimodal pain management allows for effective pain control with minimal side effects, enhancing recovery. Strengths & Limitations This is the first report to assess use of a multi-modal pain regimen on IPP recipients with demonstration of tangible benefit throughout the recovery process. Limitations include a single-surgeon and retrospective study design. Conclusion In our rigorous assessment of IPP patients, implementation of a novel MMA protocol achieved equivalent and effective pain control, while resulting in substantially fewer narcotics throughout the entire post-operative period following IPP implantation.
- Published
- 2018
39. Laparoscopic inguinal hernia repair by modified peritoneal leaflet closure: description and initial results in children
- Author
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Trudy Kawal, Carmen Tong, David I. Chu, Jason P. Van Batavia, and Arun K. Srinivasan
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Intraoperative Complication ,Adolescent ,Urology ,medicine.medical_treatment ,Operative Time ,Hernia, Inguinal ,Article ,03 medical and health sciences ,0302 clinical medicine ,Hydrocele ,medicine ,Humans ,Hernia ,Laparoscopy ,Child ,Herniorrhaphy ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Infant ,Hernia repair ,medicine.disease ,Surgery ,Inguinal hernia ,Dissection ,Treatment Outcome ,Barbed suture ,Child, Preschool ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Female ,030211 gastroenterology & hepatology ,Peritoneum ,business ,Follow-Up Studies - Abstract
Summary Introduction Inguinal hernias are common in infants and children. While the gold standard for hernia repair in the pediatric period has been via an open inguinal incision with dissection and high ligation of the hernia sac, over the past two decades laparoscopic herniorrhaphy has increased in popularity. The advantages of laparoscopy include decreased post-operative pain, improved cosmetic results, ability to easily assess the contralateral side for an open internal inguinal ring, and decreased risk of metachronous hernias. Herein, we describe a modified laparoscopic herniorrhaphy using a peritoneal leaflet closure and report our operative experience with intermediate-term results. Methods We retrospectively reviewed our IRB-approved registry for all children who underwent initial laparoscopic herniorrhaphy at our tertiary care center over a 2.5-year period. All surgeries were performed by a single surgeon using a technique we have termed the peritoneal leaflet closure. This technique involves incising the peritoneum circumferentially around the open internal ring and developing peritoneal leaflets which are then closed together over the ring with a running non-absorbable barbed stitch ( Figure ). Intraoperative findings and complications, operative times, and post-operative complications were reviewed for all children. Results A total of 50 initial laparoscopic hernia repairs (4 bilateral, 42 unilateral) were performed in 46 children (43 boys, 3 girls) at a median age of 5.9 years (range 0.5–16.7). Median operative time was 73 min (range 48–138) for unilateral and 106 min (range 104–135) for bilateral herniorrhaphy. No patient had an intraoperative complication. Two children (4%) had contralateral open rings discovered at time of surgery and underwent unplanned bilateral laparoscopic hernia repair. All patients went home on the same day as the procedure and three children (6%) had minor post-operative complaints (umbilical bulge, thigh pain, and urine holding) that all self-resolved. Thirty-nine children had follow-up data available. Intermediate-term complications occurred in two children (5%): one boy developed a contralateral hydrocele (despite a closed ring at surgery) and one boy had a hernia recurrence that required open repair. Overall, operative success with the modified peritoneal leaflet closure technique was therefore 97% (38 of 39 children with follow-up). All 37 boys who followed up had bilateral descended testes of normal size and consistency. Conclusions Laparoscopic herniorrhaphy using a peritoneal leaflet closure technique is safe and effective when used in infants and children to close an indirect hernia (i.e. patent processus vaginalis). No intraoperative complications occurred in this cohort and success rate was 97%. Download : Download high-res image (316KB) Download : Download full-size image Figure . Intraoperative images of modified peritoneal leaflet closure technique in a right-sided inguinal hernia. (A) An incision is made circumferentially in the peri-orificial peritoneum just proximal to the internal inguinal ring (dashed white line). Care must be taken to identify and preserve the vas deferens (yellow arrow) and testicular vessels (red arrow) during this step. (B) Image immediately after dissection and development of the peritoneal leaflets. (C) The peritoneal leaflets are then closed together over the internal inguinal ring with a running, non-absorbable barbed suture.
- Published
- 2018
40. Miliary Tuberculosis Presenting as Pyrexia of Unknown Origin in Pregnancy
- Author
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Carmen, Tong, primary, Bte Zailan, Liyana, additional, Singh, Ravinder, additional, and Wright, Ann, additional
- Published
- 2019
- Full Text
- View/download PDF
41. Editorial Comment
- Author
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Carmen Tong and Jay Simhan
- Subjects
Urethral Stricture ,Wound Healing ,Urology ,Humans ,Constriction, Pathologic - Published
- 2017
42. Sarcomatoid Squamous Cell Carcinoma of the Renal Pelvis Masquerading as Emphysematous Pyelonephritis with Staghorn Calculus
- Author
-
Justin Friedlander, Dana Kivlin, Patricia Perosio, Jay Simhan, and Carmen Tong
- Subjects
medicine.medical_specialty ,business.industry ,Urology ,Urinary system ,medicine.medical_treatment ,030232 urology & nephrology ,Case Report ,medicine.disease ,Malignancy ,urologic and male genital diseases ,Nephrectomy ,Malignant transformation ,03 medical and health sciences ,stomatognathic diseases ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,medicine ,Urothelium ,Presentation (obstetrics) ,business ,Renal pelvis ,Calculus (medicine) - Abstract
Background: Staghorn calculi are well-established risk factors for recurrent urinary tract infections (UTIs) and subsequent renal deterioration. Less commonly, long-term urothelial irritation from a calculus may also pose a risk of malignant transformation. Case Presentation: A 77-year-old male with multiple medical comorbidities presented with a chronic right renal pelvic staghorn calculus and findings concerning for emphysematous pyelonephritis. He was subsequently taken to the operating room for a planned laparoscopic right nephrectomy. Final pathology analysis revealed sarcomatoid squamous cell carcinoma (SCC) of the renal pelvis with superimposed pyelonephritis and renal abscesses. Preoperative imaging was not suggestive of malignancy. Conclusion: Although SCC of the urothelium can be caused by chronic irritation, its presentation is usually isolated to the lower urinary tract and is rarely encountered in the renal pelvis. Our patient's presentation with sarcomatoid SCC is an even rarer entity. Chronic staghorn calculi must be considered as a potential risk factor for the development of both UTI and malignant urothelial transformation.
- Published
- 2016
43. Extracorporeal Shock Wave Therapy: Current Perspectives and Future Directions
- Author
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Carmen Tong, Eric Ghiraldi, Justin I. Friedlander, and Andrew C. Lawler
- Subjects
medicine.medical_specialty ,Extracorporeal shock wave therapy ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,03 medical and health sciences ,Kidney Calculi ,0302 clinical medicine ,Urolithiasis ,Lithotripsy ,medicine ,Humans ,Percutaneous nephrolithotomy ,Intensive care medicine ,Stone disease ,business.industry ,Patient Selection ,Urinary tract stones ,General Medicine ,Extracorporeal shock wave lithotripsy ,Surgery ,Treatment Outcome ,Treatment modality ,030220 oncology & carcinogenesis ,Urinary Calculi ,business - Abstract
Since its introduction, extracorporeal shock wave lithotripsy (ESWL) has undergone a variety of changes; however, it remains one of the most utilized treatment modalities for urolithiasis. The goal of this review is to provide the practicing urologist an update on contemporary trends, new technologies, and related controversies in utilizing ESWL for stone treatment. ESWL use has come under scrutiny with a shift in focus to cost-effectiveness and healthcare outcomes. Fortunately, advances in lithotripter technology have spawned several generations of devices that strive to improve stone-free rates and decrease complications. Most of all, a focus on patient selection criteria has helped improve procedural success. Years of experience utilizing ESWL for stone treatment have helped urologists better optimize its use and minimize complications. Improvements in technique along with more stringent patient and stone selection have helped ESWL remain a mainstay in the treatment of stone disease.
- Published
- 2017
44. Reconstructive Management Options of Delayed Complications Following Bladder Outlet Surgery
- Author
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Nora Baker, Jay Simhan, and Carmen Tong
- Subjects
Male ,medicine.medical_specialty ,Urinary Fistula ,Urology ,Fistula ,medicine.medical_treatment ,030232 urology & nephrology ,Urinary incontinence ,Pelvic Floor Muscle ,03 medical and health sciences ,0302 clinical medicine ,Erectile Dysfunction ,medicine ,Humans ,Ejaculation ,Transurethral resection of the prostate ,medicine.diagnostic_test ,business.industry ,Urinary diversion ,Urinary Bladder Diseases ,General Medicine ,Plastic Surgery Procedures ,medicine.disease ,Endoscopy ,Surgery ,Neck of urinary bladder ,Erectile dysfunction ,030220 oncology & carcinogenesis ,medicine.symptom ,business - Abstract
Technological advancements in urologic endoscopy within the last decades have improved outcomes following bladder outlet reduction surgery while minimizing risks of short- and intermediate-term complications. This review aims to examine late complications of endoscopic reduction of the prostate and the various treatment options available. Urinary incontinence, ejaculatory dysfunction, urethral strictures, bladder neck contractures, and fistula formations are the most common delayed complications following bladder outlet reduction surgery. Evaluation of these complications typically involves a combination of endoscopic examination, urodynamic findings, pelvic imaging, and review of pre-existing symptoms. Treatment options range from conservative measures such as pelvic floor muscle therapy to complex reconstructive procedures including anti-incontinence surgery, urethral reconstruction, and permanent urinary diversion. Although rare, late complications of bladder outlet reduction surgery are important to recognize in order to manage appropriately. Careful evaluation involving multiple diagnostic modalities with consideration for referral to a dedicated reconstructive urologist may be warranted in complex cases.
- Published
- 2017
45. Malignant Infiltration of the Penis From Urothelial Carcinoma of the Bladder
- Author
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David Cahn, Nikolas Daskalakis, Carmen Tong, Daniel M. Geynisman, Daniel C. Edwards, and Laurence Belkoff
- Subjects
Male ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Nephrectomy ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Carcinoma ,Humans ,Neoplasm Invasiveness ,Penile Neoplasms ,Urothelial carcinoma ,Carcinoma, Transitional Cell ,business.industry ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,business ,Infiltration (medical) ,Penis - Published
- 2017
46. Author Reply to Editorial Comment on 'Novel Multimodal Analgesia Protocol Significantly Decreases Opioid Requirements in Inflatable Penile Prosthesis Patients'
- Author
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Jay Simhan, Ankur Shah, Ching Man Carmen Tong, Jacob Lucas, and Christopher Foote
- Subjects
Protocol (science) ,medicine.medical_specialty ,business.industry ,Urology ,Endocrinology, Diabetes and Metabolism ,Surgery ,Psychiatry and Mental health ,Endocrinology ,Reproductive Medicine ,Inflatable penile prosthesis ,Opioid ,medicine ,Medical science ,business ,medicine.drug - Published
- 2018
47. Author Reply to Editorial Comment on “Novel Multimodal Analgesia Protocol Significantly Decreases Opioid Requirements in Inflatable Penile Prosthesis Patients”
- Author
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Carmen Tong, Ching Man, primary, Lucas, Jacob, additional, Shah, Ankur, additional, Foote, Christopher, additional, and Simhan, Jay, additional
- Published
- 2018
- Full Text
- View/download PDF
48. Metastatic Prostate Cancer Presenting as Lower Extremity Soft Tissue Mass: A Rare Case Presentation
- Author
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Laurence Belkoff, Daniel C. Edwards, David J Cahn, Dana Kivlin, Carmen Tong, and Paulette Cutruzzula
- Subjects
Oncology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Urology ,030232 urology & nephrology ,Disease ,medicine.disease ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,medicine.anatomical_structure ,Antigen ,Prostate ,030220 oncology & carcinogenesis ,Internal medicine ,Biopsy ,medicine ,Lymph ,Presentation (obstetrics) ,business ,Right Thigh - Abstract
A 69-year-old homeless African American male with prostate cancer diagnosed 2 years prior presents a large mass in the right thigh. An evaluation of the patient revealed a prostate-specific antigen of 9362 ng/mL. Biopsy of the leg mass was performed and final pathology indicated metastatic adenocarcinoma of the prostate. Although metastatic prostate cancer presents most commonly in bone, lymph nodes, lungs, and liver, metastatic disease presenting as a soft tissue mass is extremely rare (Bubendorf et al, 2000; Molenaar et al, 1996; Ward and Bourken, 1984). The advent of screening with prostate-specific antigen has led to earlier diagnosis of lower-grade disease, yet underserved populations continue to present with aggressive and morbid disease (Winer et al, 2014).
- Published
- 2016
49. MP55-13 ROBOTIC ASSISTED LAPAROSCOPIC IPSILATERAL URETEROURETEROSTOMY: A REPORT OF EFFICACY AND COMPARISON TO OPEN SURGERY
- Author
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Aseem R. Shukla, Dhirendra K Shrivastava, Carmen Tong, and Arun Srinivasan
- Subjects
medicine.medical_specialty ,Robotic assisted ,Urinary retention ,business.industry ,Urology ,Open surgery ,Clinical success ,Surgery ,Ureteroureterostomy ,Cohort ,medicine ,Complication rate ,medicine.symptom ,business ,Ureteral reimplantation - Abstract
(2.6%) of transient urinary retention requiring short-term catheterization. CONCLUSIONS: In this large, multi-institutional cohort that includes complex clinical situations, we determined that RALUR-EV is a safe procedure with a low complication rate consistent with published series of open ureteral reimplantation. While clinical success rate is on par with open series, radiographic success is slightly lower. These findings necessitate critical thinking on potential technique improvements and further prospective, collaborative investigation into the efficacy of this procedure.
- Published
- 2016
50. Acute Rectovesicoprostatic Fistula Formation after Intensity-Modulated Radiation Therapy for Localized High Risk Prostate Cancer: A Case Report
- Author
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Francis J Schanne, Juan Lucas Poggio David B Cahn, Shaun Hager, Carmen Tong, Daniel C. Edwards, and James Latronica
- Subjects
medicine.medical_specialty ,Prostate cancer ,business.industry ,Fistula ,medicine ,Radiology ,Intensity-modulated radiation therapy ,medicine.disease ,business - Published
- 2017
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