作者: Joosten, Leo A B ; Zuiverloon, Tahlita C M ; Aben, Katja K H ; Witjes, J Alfred ; Novakovic, Boris ; Kiemeney, Lambertus A L M ; Vermeulen, Sita H ; Galesloot, Tessel E ; van Puffelen, Jelmer H ; van Emst, Liesbeth ; Oosterwijk, Egbert ; Oldenhof, Ursula T H ; Boormans, Joost L ; Netea, Mihai G ; Vrieling, Alina ; Kooper, Denise ; van der Heijden, Antoine G

BackgroundBCG is recommended as intravesical immunotherapy to reduce the risk of tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). Currently, it is unknown whether intravesical BCG application induces trained immunity.MethodsThe aim of this research was to determine whether BCG immunotherapy induces trained immunity in NMIBC patients. We conducted a prospective observational cohort study in 17 NMIBC patients scheduled for BCG therapy and measured trained immunity parameters at 9 time points before and during a 1-year BCG maintenance regimen. Ex vivo cytokine production by peripheral blood mononuclear cells, epigenetic modifications, and changes in the monocyte transcriptome were measured. The frequency of respiratory infections was investigated in two larger cohorts of BCG-treated and non-BCG treated NMIBC patients as a surrogate measurement of trained immunity. Gene-based association analysis of genetic variants in candidate trained immunity genes and their association with recurrence-free survival and progression-free survival after BCG therapy was performed to investigate the hypothesized link between trained immunity and clinical response.ResultsWe found that intravesical BCG does induce trained immunity based on an increased production of TNF and IL-1β after heterologous ex vivo stimulation of circulating monocytes 6–12 weeks after intravesical BCG treatment; and a 37% decreased risk (OR 0.63 (95% CI 0.40 to 1.01)) for respiratory infections in BCG-treated versus non-BCG-treated NMIBC patients. An epigenomics approach combining chromatin immuno precipitation-sequencing and RNA-sequencing with in vitro trained immunity experiments identified enhanced inflammasome activity in BCG-treated individuals. Finally, germline variation in genes that affect trained immunity was associated with recurrence and progression after BCG therapy in NMIBC.ConclusionWe conclude that BCG immunotherapy induces trained immunity in NMIBC patients and this may account for the protective effects against respiratory infections. The data of our gene-based association analysis suggest that a link between trained immunity and oncological outcome may exist. Future studies should further investigate how trained immunity affects the antitumor immune responses in BCG-treated NMIBC patients

2022-10-01·Alzheimer Disease & Associated Disorders

Results From an Administrative Dataset

Article

作者: Gore, John L. ; Holt, Sarah K. ; Makrakis, Dimitrios ; Grivas, Petros ; Wright, Jonathan L. ; Bernick, Charles

Introduction:Alzheimer disease (AD) is a common neurodegenerative disease, and immunomodulation offers treatment opportunities. Preclinical data suggest that intravesical Bacillus Calmette-Guerin (BCG) treatment could delay AD development. We investigated this relationship in a population-based cancer database.Sample and Methods:We queried the Surveillance, Epidemiology, and End Results-Medicare database for patients with high-risk nonmuscle-invasive bladder cancer (hrNMIBC). BCG dosage and subsequent Alzheimer diagnosis were collected through ICD-9/10 codes. Multivariable Cox regression was performed to assess the association between BCG therapy and subsequent Alzheimer diagnosis.Results:We identified 26,584 hrNMIBC patients; 51% received BCG and 8.3% were diagnosed with Alzheimer. BCG exposure was significantly associated with lower Alzheimer occurrence (hazard ratio: 0.73, P<0.05), which was dose-dependent. Increasing age, female sex, Black race, and increasing comorbidity index were significantly associated with a greater risk of subsequent Alzheimer diagnosis.Discussion:Treatment with intravesical BCG among patients with hrNMIBC was associated with a significantly lower risk for subsequent Alzheimer diagnosis, which seemed dose-dependent.

2021-03-01·Urology3区 · 医学

Side Effects of Intravesical BCG and Chemotherapy for Bladder Cancer: What They Are and How to Manage Them

3区 · 医学

Review

作者: Smelser, Woodson W ; Koch, George E ; Chang, Sam S

Intravesical therapy for nonmuscle invasive bladder cancer decreases recurrence and progression but carries a high risk of side effects, which limit patient adherence. Appropriate management of the toxicities from intravesical therapy requires consideration of the agent used, the side effects experienced, and the timing of those side effects. Management strategies for intravesical toxicities ideally improve patient tolerance without sacrificing oncologic outcomes. This review aims to provide a comprehensive overview of the available evidence regarding the side effects of intravesical therapies for nonmuscle invasive bladder cancer and to propose practical strategies for toxicity management.

100 项与膀胱灌注用卡介苗(China Medical System Holdings) 相关的药物交易

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适应症	国家/地区	公司	日期
膀胱尿路上皮癌	德国	medac Gesellschaft für klinische Spezialpräparate mbH	2001-10-02
膀胱癌	欧洲	深圳市康哲药业有限公司	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


AACR2023	N/A	非肌层浸润性膀胱肿瘤	40	intravesical Bacillus Calmette-Guérin instillation (TERT C228T mutation)	(鏇觸鹹衊網獵築窪壓選) = 構構繭醖顧網襯艱窪壓鏇糧餘衊獵選製蓋範憲 (顧衊艱鏇築鹹選窪齋糧 )	-	2023-04-04
				intravesical Bacillus Calmette-Guérin instillation (KDM6A alteration)	(鏇觸鹹衊網獵築窪壓選) = 鑰鑰艱繭築襯築繭淵憲鏇糧餘衊獵選製蓋範憲 (顧衊艱鏇築鹹選窪齋糧 )
ESMO_ASIA2022	N/A	非肌层浸润性膀胱肿瘤	140	Intravesical Chemohyperthermia with Mitomycin C	(廠襯積範齋範簾範範襯) = 衊遞鹽築夢衊餘簾築鹽壓積簾夢窪糧鑰齋選簾 (憲衊鹹願製觸鬱繭鏇衊 )	积极	2022-12-02
				Intravesical BCG Immunotherapy	(廠襯積範齋範簾範範襯) = 淵簾夢淵餘繭選壓廠膚壓積簾夢窪糧鑰齋選簾 (憲衊鹹願製觸鬱繭鏇衊 ) 更多
MP82-18 (AUA2020)	N/A	非肌层浸润性膀胱肿瘤	1,128	INTRAVESICAL BCG INSTILLATION (BCG instillation)	蓋淵範顧鬱膚糧觸選膚(網餘網構淵選觸觸廠積) = 窪鹹鑰鹹鬱醖鏇鏇築鹹膚觸膚糧廠網構製夢淵 (蓋製願壓觸蓋憲製鏇構 ) 更多	-	2020-04-01
AUA2016	N/A	非肌层浸润性膀胱肿瘤辅助	96	Intravesical instillation of BCG plus 2 gm of tranexamic acid	(艱窪廠蓋淵淵蓋膚築壓) = 齋範築鬱築衊選膚築繭鹹艱膚鏇範構鹹壓蓋鑰 (範繭鏇網廠網憲願廠顧 ) 更多	积极	2016-04-01
				Intravesical instillation of BCG alone	(艱窪廠蓋淵淵蓋膚築壓) = 窪窪鬱觸齋觸餘鬱積範鹹艱膚鏇範構鹹壓蓋鑰 (範繭鏇網廠網憲願廠顧 ) 更多
PD10-09 (AUA2015)	N/A	神经性膀胱功能障碍	50	Gentamicin intravesical instillations	醖繭膚糧選襯選蓋願鑰(憲衊鬱構醖衊獵齋醖鏇) = 糧憲製製襯憲鑰顧顧範遞廠壓鏇範選蓋鹹鑰築 (繭齋獵壓築獵網觸鹹壓 )	-	2015-04-01
536 (AUA2012)	临床2期	肾盂和输尿管尿路上皮癌	72	Intravesical instillation of pyrarubicin (THP)	餘選蓋鬱遞構鑰糧醖蓋(淵壓遞淵鏇獵繭簾鹹鹹) = 齋襯襯憲鬱蓋觸觸鏇廠構鹽顧壓夢醖獵淵鑰齋 (鏇鹹艱膚廠構構淵簾築 )	-	2012-04-01
				PIRARUBICIN (No instillation)	餘選蓋鬱遞構鑰糧醖蓋(淵壓遞淵鏇獵繭簾鹹鹹) = 淵衊壓窪壓鑰膚積襯憲構鹽顧壓夢醖獵淵鑰齋 (鏇鹹艱膚廠構構淵簾築 )