Treatment failure after intravesical instillation of Bacillus Calmette-Guerin immunotherapy (BCG) for non-muscle-invasive bladder cancer (BCa) occurs frequently. The exact effects of BCG on cellular redox status and gene expression remain unclear. We assessed oxidative stress biomarkers and changes in miR-155-5p expression in response to BCG. Twenty-seven patients with BCa were recruited for measuring tissue and serum malondialdehyde (MDA) and total antioxidant capacity (TAC) levels, and tissue expression of miR-155-5p at two-time points: pre and 6 weeks post BCG. Recurrence of BCa was observed after 20 months. R statistical software was used for paired comparisons of biomarkers, as well as the correlation between variables. Significant increases in TAC were observed after BCG (P= <0.001). Tissue MDA levels were significantly reduced (P= 0.003). miR-155-5p was slightly overexpressed after BCG (median fold change=1.3, P=0.25). At the 20-month follow-up, it was observed that improved MDA and TAC changes were significant only in patients without recurrence of BCa. In patients with recurrence, the pre-treatment expression ratio of miR-155-p5 was positively correlated with TAC (R=0.63, P= 0.032) and negatively correlated with MDA (R=-0.72, P=0.037). In patients with recurrence of BCa pre-treatment miR-155-5p showed negative correlation with its expression changes after BCG (R=-0.78, P=0.004). Conclusions: Treatment with BCG has some beneficial effects on the oxidative stress status, which is probably modulated by miR-155-5p. A well-controlled oxidative balance may enhance overall survival of BCa. Considering its high recurrence rate, our pilot experiment can open a window toward better management of patients with BCa.

Tuberculosis (TB) has been and still is a global emergency for centuries. Prevention of disease through vaccination would have a major impact on disease prevalence, but the only available current vaccine, BCG, has insufficient impact. In this article, a novel subunit vaccine against TB was developed, using the Ag85B-ESAT6-Rv2034 fusion antigen, two adjuvants - CpG and MPLA, and a cationic pH-sensitive liposome as a delivery system, representing a new TB vaccine delivery strategy not previously reported for TB. In vitro in human dendritic cells (DCs), the adjuvanted formulation induced a significant increase in the production of (innate) cytokines and chemokines compared to the liposome without additional adjuvants. In vivo, the new vaccine administrated subcutaneously significantly reduced Mycobacterium tuberculosis (Mtb) bacterial load in the lungs and spleens of mice, significantly outperforming results from mice vaccinated with the antigen mixed with adjuvants without liposomes. In-depth analysis underpinned the vaccine\'s effectiveness in terms of its capacity to induce polyfunctional CD4+ and CD8+ T-cell responses, both considered essential for controlling Mtb infection. Also noteworthy was the differential abundance of various CD69+ B-cell subpopulations, which included IL17-A-producing B cells. The vaccine stimulated robust antigen-specific antibody titers, further extending its potential as a novel protective agent against TB.

BACKGROUND: Adjuvant bacillus Calmette-Guérin (BCG) is recommended for high-risk (HR) non-muscle invasive bladder cancer (NMIBC), but BCG shortages have led to exploration of reduced-dose regimens and shortened maintenance durations out of necessity, with limited data on treatment efficacy in Latin America.
OBJECTIVE: Oncological outcomes of HR-NMIBC patients treated with reduced (RD,1/4th dose) vs full dose (FD) BCG instillations of Danish Strain 1331 BCG.
METHODS: We performed a retrospective study of HR-NMIBC patients treated with BCG between 2003 and 2022 at our center in Santiago Chile. We stratified patients according to either RD (1/4th dose) or FD BCG. Univariate and multivariable Cox regression models were used to predict recurrence. Kaplan-Meier method was used to calculate survival estimates.
RESULTS: Of a total of 200 patients, 116 (58%) had RD and 84 (42%) FD BCG. Median follow-up was 57 months (IQR: 29-100). Patients who received FD BCG had a lower risk of recurrence (HR: 0.41, 95% CI 0.22-0.74) and high-grade (HG)-recurrence (HR: 0.30, 95% CI 0.15-0.61; p = 0.001). More patients in the RD vs FD group progressed to MIBC (10/84 vs 2/116; p = 0.18). Additionally, patients were less likely to stop BCG treatment in the RD group compared to the FD group due to toxicity (5% vs 11%, p = 0.14).
CONCLUSIONS: A 1/4th dose of Danish Strain 1331 BCG treatment was associated with worse recurrence free rate and HG-recurrence rate in our cohort. Patients with RD had lower discontinuation treatment rates due to a reduced toxicity profile. These findings would suggest that RD BCG would compromise oncological outcomes in HR-NMIBC patients.

When it comes to the treatment of patients with non-muscle-invasive bladder cancer (NMIBC) with intravesical bacillus Calmette-Guérin (BCG), two questions must be considered: 1) what dose to give, and 2) for how long? The issue of optimal dose and duration has been the subject of several randomized trials and is especially pertinent in the context of a global BCG shortage. Despite this, there appears to be uncertainty as to whether BCG dose or duration may be compromised in the event of shortage. As such, we wish to summarize the available evidence as an aid to the practicing urologist.

BACKGROUND: Devices that increase the penetrance of intravesical chemotherapeutics are emerging as alternatives to classical Bacillus Calmette Guérin (BCG) treatment.
OBJECTIVE: To compare the efficacy of mitomycin C applied with the electromotive drug delivery device (MMC-EMDA) versus BCG in patients with intermediate and high-risk non-muscle-invasive bladder cancer (NMIBC) without carcinoma in situ (CIS).
METHODS: Prospective non-randomized study in which 47 patients received MMC-EMDA (40 mg of MMC diluted in 50 mg of distilled water at 20 mA for 30 min. Regimen of 6 weekly and then 6 monthly instillations) and 48 patients received BCG (50 mg of OncoCITE® diluted in 50 ml of normal saline for 60 min. Regimen of 6 weekly instillations and then 3 weekly instillations at months 3, 6 and 12). The primary endpoint was the recurrence-free rate (RFR) at 24 months. Secondary endpoints were time to recurrence and progression-free rate (PFR) at 24 months follow-up.
RESULTS: Baseline patient assessment and mean follow-up time were similar in both groups (MMC-EMDA group: 26.4 months; BCG group: 28.4 months (p = 0.44)). The RFR at 24 months was 80.9% for the MMC-EMDA group and 77.1% for the BCG group (p = 0.969). The mean time to recurrence was 12.5 months in the MMC-EMDA group and 14 months in the BCG group (p = 0.681). At 24 months, PFR was 97.9% in the MMC-EMDA group and 93.8% in the BCG group (p = 0.419).
CONCLUSIONS: No differences were found between MMC-EMDA and BCG treatments in patients with high-risk and intermediate-risk NMIBC without CIS.

UNASSIGNED: This is a summary of two studies that looked at the safety and effectiveness of a potential new treatment, N-803 (Anktiva), in combination with a standard treatment bacillus Calmette-Guerin (BCG) for people with non-muscle invasive bladder cancer (NMIBC).One study was a Phase 1b study that tested increasing doses of N-803 in combination with the same dose of BCG in people with NMIBC who had never received BCG previously (BCG-naive). The other study is a Phase 2/3 study of N-803 and BCG in people with NMIBC whose cancer wasn\'t eliminated by BCG alone (BCGunresponsive).
UNASSIGNED: In the Phase 1b study, the nine participants were split into three groups of 3 participants who received a dose of 100, 200, or 400 μg N-803 along with a standard 50 mg dose of BCG. In the Phase 2/3 study, one group (cohort A) of participants with carcinoma in situ (CIS) disease and another group (cohort B) with papillary disease were treated with 400 μg N-803 plus 50 mg BCG. There was also a cohort C that received only 400 μg N-803. Treatments were delivered directly into the bladder once a week for 6 weeks in a row.
UNASSIGNED: N-803 plus BCG eliminated NMIBC in all nine BCG-naive participants and the effects were long-lasting, with participants remaining NMIBC-free for a range of 8.3 to 9.2 years.As reported in 2022, cancer was eliminated in 58 of 82 (71%) participants with BCG-unresponsive CIS disease and the effect was also long-lasting. Importantly, approximately 90% of the successfully treated participants avoided surgical removal of the bladder. In cohort B participants with papillary disease, 40 of 72 (55.4%) were cancer-free 12 months after treatment. N-803 used alone was only effective in 2 of 10 participants. In both studies, the combination of N-803 and BCG was found to be associated with very few adverse events.Based on results from the Phase 2/3 study, the U.S. Food and Drug Association (FDA) approved the use of N-803 plus BCG for the treatment of BCG-unresponsive bladder CIS with or without Ta/T1 papillary disease.Clinical Trial Registration: NCT02138734 (Phase 1b study), NCT03022825 (Phase 2/3 study).
Addition of the IL-15 superagonist N-803 to BCG therapy produces a high rate of success in eliminating non-muscle invasive bladder cancer in both BCG-naive and BCG-unresponsive patients, with long-lasting effects that allow patients to avoid surgical removal of the bladder.

UNASSIGNED: BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) represent a significant therapeutic challenge in the treatment of bladder cancer. Nadofaragene firadenovec, represents a breakthrough in this area, offering a novel approach for the treatment of BCG-unresponsive NMIBC.
UNASSIGNED: This overview explores the historical development of nadofaragene firadenovec, assessing its efficacy and safety, and discusses future NMIBC therapy directions.
UNASSIGNED: Patients with high grade NMIBC who are BCG unresponsive will have a growing number of treatment alternatives to bladder removal. Nadofaragene firadenovec offers good short-term efficacy but lacks significant durability for most patients. Its strengths include ease of administration and low risk of adverse events. This will need to balance with risk of progression and cost. Furthermore, the likely approval of other agents will require consideration of which therapy to use and for which patient. The need for biomarkers to tailor treatment choices to individual patient needs is becoming more critical. The treatment field is rapidly advancing, with several Phase 3 single-arm trials underway, indicating a potential broader range of treatment options for NMIBC. Further research will be necessary to determine the optimal choice for patients.

BACKGROUND: The introduction of a national evaluation of newborn screening for Severe Combined Immunodeficiency (SCID) in England triggered a change to the selective Bacillus Calmette-Guerin (BCG) vaccination programme delivery pathway, as this live attenuated vaccine is contraindicated in infants with SCID. The neonatal BCG vaccination programme is a targeted programme for infants at increased risk of tuberculosis and used to be offered shortly after birth. Since September 2021 the BCG vaccine is given to eligible infants within 28 days of birth, when the SCID screening outcome is available. We explore the experiences of those implementing the new pathway, and how they made sense of, engaged with, and appraised the change.
METHODS: A mixed-methods evaluation was conducted between October 2022 and February 2023. This involved national online surveys with BCG commissioners and providers and qualitative semi-structured interviews with commissioners, providers, and Child Health Information System stakeholders in two urban areas. Survey data was analysed using descriptive statistics and interview data was analysed thematically. The data was triangulated using Normalization Process Theory as a guiding framework.
RESULTS: Survey respondents (n = 65) and qualitative interviewees (n = 16) revealed that making sense of the new pathway was an iterative process. Some expressed a desire for more direction on how to implement the new pathway. The perceived value of the change varied from positive, ambivalent, to concerned. Some felt well-prepared and that improvements to data capture, eligibility screening, and accountably brought by the change were valuable. Others were concerned about the feasibility of the 28-day target, reductions in vaccination coverage, increased resource burden, and the outcome of the SCID evaluation. New collaborations and communities of practice were required to facilitate the change. Three main challenges in implementing the pathway and meeting the 28-day vaccination target were identified: appointment non-attendance; appointment and data systems; and staffing and resourcing. Feedback mechanisms were informal and took place in tandem with implementation.
CONCLUSIONS: The new NHS neonatal BCG service specification has created an effective structure for monitoring and managing the BCG vaccination programme, but further work is required to support delivery of the 28-day vaccination target and improve uptake rates.

OBJECTIVE: Aimed to investigate the role of multiparametric magnetic resonance imaging (mp-MRI) in the diagnosis of granulomatous prostatitis caused by intravesical Bacillus Calmette-Guérin (BCG).
METHODS: In this prospective, single-center study, 10 male patients who were given intravesical BCG due to intermediate- and high-risk bladder cancer were included. Before transurethral resection of bladder tumors (TURB), all patients were evaluated by mp-MRI, serum prostate-specific antigen (PSA), and digital rectal examination (DRE). Serum PSA levels and DRE findings were evaluated before and after intravesical BCG treatment. Prostate mp-MRI was performed for patients with elevated levels of serum PSA and/or with abnormal DRE findings. Then, MRI fusion + systematic prostate biopsy was performed. Demographic data of the patients before and after intravesical BCG were compared.
RESULTS: The average age of the patients was 66.9 years (55-87 years). While PSA was 1.7 ng/ml before intravesical BCG treatment, it was 4.3 ng/ml after intravesical BCG treatment (p = 0.005). PSA density (PSAD) was 0.04 and 0.10 before and after the treatment, respectively (p = 0.012). DRE findings of all patients were normal before the treatment. However, abnormal findings were detected in 80% of them after the treatment (p = 0.008). PI-RADS ≥ 3 lesions were found to be significantly higher in all patients after intravesical BCG (p = 0.004).
CONCLUSIONS: Granulomatous prostatitis is a rare complication of intravesical BCG. High PSA, abnormal DRE, and PI-RADS ≥ 3 lesions detected after intravesical BCG should suggest granulomatous prostatitis and unnecessary biopsies may be avoided.

BACKGROUND: The aim of the study was to examine whether disinfection of bacillus Calmette-Guerin-containing urine with etaprocohol® (ethanol 76.9-81.4 vol % and isopropanol as an additive) is safer than disinfection with sodium hypochlorite.
METHODS: In prospective research, safety and efficacy was analyzed in 5 patients in the etaprocohol® disinfection group and 5 patients in the sodium hypochlorite disinfection group. The primary endpoint was the temperature change after disinfection and the secondary endpoint was the unpleasantness of the odor caused by disinfection. Additionally, concentration of gas produced was also examined. Sensory tests were taken from staff who performed urine disinfection and the odor generated by disinfection was evaluated. As a safety protocol, post-BCG-treated urine is cultured to verify the negativity for mycobacteria.
RESULTS: Mycobacteria were disinfected in all cases. The temperature rise following disinfection was significantly higher in the sodium hypochlorite group. The sensory test outcomes were significantly worse in the group disinfected with sodium hypochlorite. The concentration of gas generated immediately after disinfection in both groups reached the maximum value and declined quickly.
CONCLUSIONS: Disinfection of bacillus Calmette-Guerin-containing urine with etaprocohol® was safer than disinfection with sodium hypochlorite, and an equivalent disinfection effect was achieved.