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  1. Article ; Online: The CXCR3alt-CXCL11 axis in bladder cancer: potential for prediction of neoadjuvant chemotherapy response.

    Chenard, Stephen / Robert Siemens, D / Koti, Madhuri

    Cellular & molecular immunology

    2021  Volume 18, Issue 7, Page(s) 1631–1633

    MeSH term(s) Chemokine CXCL11 ; Humans ; Neoadjuvant Therapy ; Urinary Bladder Neoplasms/drug therapy
    Chemical Substances CXCL11 protein, human ; Chemokine CXCL11
    Language English
    Publishing date 2021-05-14
    Publishing country China
    Document type Journal Article ; Comment
    ZDB-ID 2435097-7
    ISSN 2042-0226 ; 1672-7681
    ISSN (online) 2042-0226
    ISSN 1672-7681
    DOI 10.1038/s41423-021-00692-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6681: Show issues Location:
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  2. Article ; Online: Operating room efficiency of orthopedic surgery during the COVID-19 era.

    Koester, Stefan W / Chenard, Stephen / Ani, Chinonso / Moo Young, Justin P / Liles, D Campbell / Dambrino, Robert / Tiwari, Vikram / Stephens, Byron F

    The American journal of managed care

    2023  Volume 29, Issue 11, Page(s) e348–e352

    Abstract: Objective: The COVID-19 pandemic forced operating rooms (ORs) to adopt new safety protocols. Although these measures protected the health of patients and providers, their impact on OR efficiency remains unclear. Our objective was to further elucidate ... ...

    Abstract Objective: The COVID-19 pandemic forced operating rooms (ORs) to adopt new safety protocols. Although these measures protected the health of patients and providers, their impact on OR efficiency remains unclear. Our objective was to further elucidate the effects of COVID-19 on orthopedic surgery OR efficiency.
    Study design: This was a retrospective study of 14,856 orthopedic surgeries performed between December 1, 2019, and October 31, 2021.
    Methods: Institutional perioperative databases were used to identify relevant orthopedic surgeries. The onset of the COVID-19 period was set as March 12, 2020, when a state of emergency was declared in Tennessee. Both 90-day periods before and after this date were used for comparative analysis of the pre-COVID-19, peak-restrictions, and post-peak-restrictions time periods. Delay of first case start time and turnover time between cases were used as primary measures of efficiency.
    Results: There were 1853 pre-COVID-19 cases, 1299 peak-restrictions cases, and 11,704 post-peak-restrictions cases analyzed. Delay of first case start time was found to be significantly different among the time periods (mean [SD] minutes, 7 [14] vs 8 [18] vs 7 [17], respectively; P < .001). Turnover time between cases was also significantly different among the time periods (62 [49] vs 66 [51] vs 64 [51]; P = .002).
    Conclusions: Although significant, there was minimal absolute change in orthopedic OR efficiency during the onset of the pandemic. These results suggest that the protocols enacted at our institution appropriately maintained orthopedic OR efficiency, even in the context of the rapidly increasing COVID-19 burden.
    MeSH term(s) Humans ; COVID-19/epidemiology ; Operating Rooms ; Retrospective Studies ; Pandemics ; Orthopedic Procedures
    Language English
    Publishing date 2023-11-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2035781-3
    ISSN 1936-2692 ; 1088-0224 ; 1096-1860
    ISSN (online) 1936-2692
    ISSN 1088-0224 ; 1096-1860
    DOI 10.37765/ajmc.2023.89460
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    Jg. 1995 - 2021: Lesesall (2.OG)
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    Zs.MG 86: Show issues

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  3. Article ; Online: Cancer cell genotype associated tumor immune microenvironment exhibits differential response to therapeutic STING pathway activation in high-grade serous ovarian cancer.

    Shakfa, Noor / Li, Deyang / Conseil, Gwenaelle / Lightbody, Elizabeth D / Wilson-Sanchez, Juliette / Hamade, Ali / Chenard, Stephen / Jawa, Natasha A / Laight, Brian J / Afriyie-Asante, Afrakoma / Tyryshkin, Kathrin / Koebel, Martin / Koti, Madhuri

    Journal for immunotherapy of cancer

    2023  Volume 11, Issue 4

    Abstract: Background: High-grade serous ovarian carcinoma (HGSC) is the most lethal gynecologic malignancy characterized by resistance to chemotherapy and high rates of recurrence. HGSC tumors display a high prevalence of tumor suppressor gene loss. Given the ... ...

    Abstract Background: High-grade serous ovarian carcinoma (HGSC) is the most lethal gynecologic malignancy characterized by resistance to chemotherapy and high rates of recurrence. HGSC tumors display a high prevalence of tumor suppressor gene loss. Given the type 1 interferon regulatory function of
    Methods: Expression of PTEN protein was evaluated in tissue microarrays generated using pretreatment tumors collected from a cohort of 110 patients with HGSC. Multiplex immunofluorescence staining was performed to determine spatial profiles and density of selected lymphoid and myeloid cells. In vivo studies using the syngeneic murine HGSC cell lines, ID8-
    Results: Patient tumors with absence of PTEN protein exhibited a significantly decreased disease specific survival and intraepithelial CD68+ macrophage infiltration as compared with intact PTEN expression. In vivo studies demonstrated that
    Conclusions: This study reveals the importance of considering the influence of cancer cell intrinsic genetic alterations on the TIME for therapeutic selection. We establish the rationale for the optimal incorporation of interferon activating therapies as a novel combination strategy in PTEN-deficient HGSC.
    MeSH term(s) Humans ; Mice ; Female ; Animals ; PTEN Phosphohydrolase/genetics ; Ascites/genetics ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Antineoplastic Agents/therapeutic use ; Genotype ; Interferons ; Tumor Microenvironment/genetics
    Chemical Substances PTEN Phosphohydrolase (EC 3.1.3.67) ; Antineoplastic Agents ; Interferons (9008-11-1)
    Language English
    Publishing date 2023-04-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2022-006170
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  4. Article ; Online: Sexual Dimorphism in Outcomes of Non-muscle-invasive Bladder Cancer: A Role of CD163+ Macrophages, B cells, and PD-L1 Immune Checkpoint.

    Chenard, Stephen / Jackson, Chelsea / Vidotto, Thiago / Chen, Lina / Hardy, Céline / Jamaspishvilli, Tamara / Berman, David / Siemens, D Robert / Koti, Madhuri

    European urology open science

    2021  Volume 29, Page(s) 50–58

    Abstract: Background: Non-muscle-invasive bladder cancer (NMIBC) is over three times as common in men as it is in women; however, female patients do not respond as well to immunotherapeutic treatments and experience worse clinical outcomes than their male ... ...

    Abstract Background: Non-muscle-invasive bladder cancer (NMIBC) is over three times as common in men as it is in women; however, female patients do not respond as well to immunotherapeutic treatments and experience worse clinical outcomes than their male counterparts. Based on the established sexual dimorphism in mucosal immune responses, we hypothesized that the tumor immune microenvironment of bladder cancer differs between the sexes, and this may contribute to discrepancies in clinical outcomes.
    Objective: To determine biological sex-associated differences in the expression of immune regulatory genes and spatial organization of immune cells in tumors from NMIBC patients.
    Design setting and participants: Immune regulatory gene expression levels in tumors from male (
    Outcome measurements and statistical analysis: Transcriptome sequencing data were analyzed using DESeq2 in R v4.0.1, followed by application of the Kruskal-Wallis test to determine gene expression differences between tumors from males and females. Immunofluorescence data analyses were conducted using R version 3.5.3. Survival analysis was performed using survminer packages.
    Results and limitations: High-grade tumors from female patients exhibited significantly increased expression of B-cell recruitment (
    Conclusions: These novel findings highlight the necessity of considering sexual dimorphism in the design of future immunotherapy trials in NMIBC.
    Patient summary: In this study, we measured the abundance of various immune cell types between tumors from male and female patients with non-muscle-invasive bladder cancer. We demonstrate that tumors from female patients have a significantly higher abundance of immunosuppressive macrophages that express CD163. Higher abundance of tumor-associated CD163-expressing macrophages and B cells is associated with shorter recurrence-free survival in both male and female patients.
    Language English
    Publishing date 2021-06-03
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 3040546-4
    ISSN 2666-1683 ; 2058-4881
    ISSN (online) 2666-1683
    ISSN 2058-4881
    DOI 10.1016/j.euros.2021.05.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Sex differences in the aging murine urinary bladder and influence on the tumor immune microenvironment of a carcinogen-induced model of bladder cancer.

    Hamade, Ali / Li, Deyang / Tyryshkin, Kathrin / Xu, Minqi / Conseil, Gwenaelle / Yolmo, Priyanka / Hamilton, Jake / Chenard, Stephen / Robert Siemens, D / Koti, Madhuri

    Biology of sex differences

    2022  Volume 13, Issue 1, Page(s) 19

    Abstract: Sex and age associated differences in the tumor immune microenvironment of non-muscle invasive bladder (NMIBC) cancer and associated clinical outcomes are emerging indicators of treatment outcomes. The incidence of urothelial carcinoma of the bladder is ... ...

    Abstract Sex and age associated differences in the tumor immune microenvironment of non-muscle invasive bladder (NMIBC) cancer and associated clinical outcomes are emerging indicators of treatment outcomes. The incidence of urothelial carcinoma of the bladder is four times higher in males than females; however, females tend to present with a more aggressive disease, a poorer response to immunotherapy and suffer worse clinical outcomes. Recent findings have demonstrated sex differences in the tumor immune microenvironment of non-muscle invasive and muscle invasive bladder cancer and associated clinical outcomes. However, a significant gap in knowledge remains with respect to the current pre-clinical modeling approaches to more precisely recapitulate these differences towards improved therapeutic design. Given the similarities in mucosal immune physiology between humans and mice, we evaluated the sex and age-related immune alterations in healthy murine bladders. Bulk-RNA sequencing and multiplex immunofluorescence-based spatial immune profiling of healthy murine bladders from male and female mice of age groups spanning young to old showed a highly altered immune landscape that exhibited sex and age associated differences, particularly in the context of B cell mediated responses. Spatial profiling of healthy bladders, using markers specific to macrophages, T cells, B cells, activated dendritic cells, high endothelial venules, myeloid cells and the PD-L1 immune checkpoint showed sex and age associated differences. Bladders from healthy older female mice also showed a higher presence of tertiary lymphoid structures (TLSs) compared to both young female and male equivalents. Spatial immune profiling of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen exposed male and female bladders from young and old mice revealed a similar frequency of TLS formation, sex differences in the bladder immune microenvironment and, age associated differences in latency of tumor induction. These findings support the incorporation of sex and age as factors in pre-clinical modeling of bladder cancer and will potentially advance the field of immunotherapeutic drug development to improve clinical outcomes.
    MeSH term(s) Aging ; Animals ; Butylhydroxybutylnitrosamine/adverse effects ; Carcinogens ; Carcinoma, Transitional Cell ; Female ; Humans ; Male ; Mice ; Sex Characteristics ; Tumor Microenvironment ; Urinary Bladder/pathology ; Urinary Bladder Neoplasms/chemically induced ; Urinary Bladder Neoplasms/pathology
    Chemical Substances Carcinogens ; Butylhydroxybutylnitrosamine (3817-11-6)
    Language English
    Publishing date 2022-05-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2587352-0
    ISSN 2042-6410 ; 2042-6410
    ISSN (online) 2042-6410
    ISSN 2042-6410
    DOI 10.1186/s13293-022-00428-0
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  6. Article: Innate immune memory is associated with increased disease-free survival in bladder cancer patients treated with bacillus Calmette-Guérin.

    Graham, Charles H / Paré, Jean-François / Cotechini, Tiziana / Hopman, Wilma / Hindmarch, Charles C T / Ghaffari, Abdi / Marginean, Diana / Chenard, Stephen / Koti, Madhuri / Siemens, D Robert

    Canadian Urological Association journal = Journal de l'Association des urologues du Canada

    2021  Volume 15, Issue 8, Page(s) E412–E417

    Abstract: Introduction: While studies suggest that innate immune memory acquired by circulating monocytes may mediate the benefit of bacillus Calmette-Guérin (BCG) in the treatment of patients with high-risk non-muscle-invasive bladder cancer (NMIBC), prospective ...

    Abstract Introduction: While studies suggest that innate immune memory acquired by circulating monocytes may mediate the benefit of bacillus Calmette-Guérin (BCG) in the treatment of patients with high-risk non-muscle-invasive bladder cancer (NMIBC), prospective studies are lacking. Innate immune memory is defined by enhanced release of pro-inflammatory cytokines by innate immune cells following a secondary challenge with pattern recognition receptor (PRR) ligands.
    Methods: Peripheral blood monocytes isolated from 33 patients with intermediate- or high-risk NMIBC before and after two or five induction BCG instillations were stimulated with the PRR ligand lipopolysaccharide (LPS). Inflammatory cytokine levels in the culture medium were measured. Extent of innate immune memory acquisition was determined by dividing the levels of cytokines released after BCG instillation by the levels released prior to BCG therapy.
    Results: Monocytes secreted variable levels of TNFα, IL-1β, IL-6, IFNγ, IL-12, and IL-10. Compared with patients with recurrences, the post-BCG:pre-BCG ratio of IL-12 in monocyte cultures from patients without recurrences after five BCG instillations was significantly increased. Patients with no innate immune memory (based on IL-12 ratios) had significantly shorter time to recurrence than patients with innate immune memory (p<0.001). Eighty-four percent (16/19) of patients with innate immune memory vs. only 22% (2/9) of patients without memory had disease-free survival of over 500 days.
    Conclusions: Results demonstrate a potential link between BCG-induced innate immune memory peripherally and local anti-tumor responses. Further validation will increase our understanding of the mode of action of BCG and, therefore, will be used to enhance its effectiveness.
    Language English
    Publishing date 2021-01-06
    Publishing country Canada
    Document type Journal Article
    ZDB-ID 2431403-1
    ISSN 1911-6470
    ISSN 1911-6470
    DOI 10.5489/cuaj.7066
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  7. Article ; Online: Anesthetic technique and oncological outcomes in urology: A clinical practice review.

    Lusty, Avril J / Hosier, Gregory W / Koti, Madhuri / Chenard, Stephen / Mizubuti, Glenio B / Jaeger, Melanie / Siemens, D Robert

    Urologic oncology

    2019  Volume 37, Issue 12, Page(s) 845–852

    Abstract: Introduction: There is increasing awareness that different anesthetic and analgesic techniques may impact outcomes after oncological surgery, generally through modifying effects on the immune system but potentially via other mechanisms including ... ...

    Abstract Introduction: There is increasing awareness that different anesthetic and analgesic techniques may impact outcomes after oncological surgery, generally through modifying effects on the immune system but potentially via other mechanisms including mitigating the surgical stress response. This narrative review aims to summarize the mechanisms underlying the effect of perioperative factors on oncological outcomes, with an emphasis on the available urologic literature.
    Methods: Literature on anesthetic technique (i.e., general vs. regional) and oncological outcomes were reviewed with a particular focus on urological studies.
    Results: In prostate cancer surgery, the risk of mortality has been reported to be reduced with the use of regional (i.e., neuraxial) anesthesia, but there was no association between anesthetic technique and progression-free or biochemical recurrence-free survival. In nonmuscle invasive bladder cancer, regional anesthesia has been associated with lower recurrence rates and longer time to recurrence following transurethral resection of bladder tumor.
    Conclusions: This review highlights the role of regional anesthesia to improve oncoimmunological responses after surgery, potentially through decreased use of volatile anesthetics and opioids, decreased activation of the surgical stress response, and a direct local anesthetic-mediated anti-inflammatory effect. Available urological literature suggests an association of anesthetic type and outcomes for nonmuscle invasive bladder cancer and prostate cancer surgeries but the evidence is limited. Prospective studies are needed to further investigate the relationship between anesthetic technique and urologic oncological outcomes.
    MeSH term(s) Anesthesia/adverse effects ; Anesthesia/methods ; Anesthetics/administration & dosage ; Anesthetics/adverse effects ; Disease Progression ; Humans ; Immune Tolerance/drug effects ; Male ; Pain, Postoperative/etiology ; Pain, Postoperative/prevention & control ; Perioperative Care/adverse effects ; Perioperative Care/methods ; Prostatic Neoplasms/immunology ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms/surgery ; Randomized Controlled Trials as Topic ; Stress, Psychological/etiology ; Stress, Psychological/immunology ; Treatment Outcome ; Urinary Bladder Neoplasms/immunology ; Urinary Bladder Neoplasms/pathology ; Urinary Bladder Neoplasms/surgery ; Urologic Surgical Procedures/adverse effects ; Urologic Surgical Procedures/psychology
    Chemical Substances Anesthetics
    Language English
    Publishing date 2019-09-13
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1336505-8
    ISSN 1873-2496 ; 1078-1439
    ISSN (online) 1873-2496
    ISSN 1078-1439
    DOI 10.1016/j.urolonc.2019.08.004
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    Zs.A 4817: Show issues Location:
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