Bacillus Calmette Research Articles

Long-Term Outcomes of Intravesical Mitomycin C Administered via Electromotive Drug Administration or Conductive Chemo-Hyperthermia in Non-Muscle-Invasive Bladder Cancer

Background/Objectives: Non-muscle-invasive bladder cancer (NMIBC) is a common form of bladder cancer with a significant risk of recurrence and progression, especially in intermediate- and high-risk patients. Bacillus Calmette–Guérin (BCG) therapy has been the gold standard, but its limitations have prompted the exploration of alternative therapies. This study aims to compare the long-term effectiveness of two such alternatives—hyperthermia-induced potentiation of mitomycin C (HIVEC) and electromotive drug administration (EMDA)—in preventing recurrence and progression in NMIBC patients. Methods: A prospective observational study was conducted at a Spanish center, including patients with intermediate- and high-risk NMIBC who were treated between August 2018 and December 2024. Participants were allocated to receive either HIVEC or EMDA based on their preferences. Both treatments followed a similar protocol, with an initial induction phase and maintenance sessions. Patient follow-up included regular cystoscopy, cytology, and imaging. Results: At 36 months, the disease-free survival rate was 62.4% for the HIVEC group and 67% for the EMDA group. Statistical analysis showed no significant difference between the two groups in terms of long-term efficacy. The adjusted hazard ratio for the treatment effect was 0.95, indicating comparable outcomes. Conclusions: Both HIVEC and EMDA demonstrate similar long-term efficacy in preventing recurrence and progression in intermediate- and high-risk NMIBC. These findings suggest that both treatments show promise as potential future options for managing NMIBC, providing clinicians with additional considerations based on patient characteristics and preferences. Further studies, particularly randomized controlled trials, are needed to confirm these results and optimize treatment protocols.

Immunogenicity and protective efficacy of a multi-antigenic adenovirus-based vaccine candidate against Mycobacterium tuberculosis

IntroductionThe inadequate efficacy of the Bacillus Calmette–Guérin (BCG) vaccine against adult pulmonary tuberculosis (TB) necessitates the development of new and effective vaccines. Human adenovirus serotype 5 (Ad5), which induces T-cell response, is a widely used viral vector. In this study, we aimed to evaluate the efficacy of a multi-antigenic recombinant Ad5 vectored vaccine and determine the optimal immunization route for enhanced immune response against Mycobacterium tuberculosis.MethodsWe constructed a multi-antigenic recombinant Ad5 vectored vaccine expressing four antigens (Ag85B-ESAT6-MPT64-Rv2660c) of M. tuberculosis (rAd-TB4), immunized with rAd-TB4 (5 × 107 infectious virus units/mouse) twice at an interval of 4 weeks starting at 10 weeks after BCG priming, and evaluated its boosting efficacy in a BCG-primed mouse model, and determined the optimal immunization route.ResultsCompared with the BCG-only (2 × 105 colony forming units/mouse), subcutaneous injection of rAd-TB4 (1 × 107 infectious virus units/mL; two doses) elicited a T-cell response and cytokine production in lung lymphocytes and splenocytes. rAd-TB4 immunization significantly reduced bacterial loads and inflamed lung areas compared to BCG immunization (p < 0.01) and protected against the H37Rv challenge performed at 17 weeks of BCG priming. RNA sequencing of the whole blood of rAd-TB4-vaccinated mice collected pre- and, 1 and 4 weeks post-infection, identified differentially expressed genes associated with immune and inflammatory responses, especially those in the Wnt signaling pathway.ConclusionOur results indicate that rAd-TB4 immunization enhances the immune response to the vaccine boosting antigens in BCG-primed mice, making it a potential adult pulmonary TB vaccine candidate.

Insights into newborn health; Integrating anthropometric measurements and immunization status at community health center deliveries in rural India: An observational study

Abstract Introduction: Newborn health is crucial for long-term well-being and development, especially in rural India, where healthcare access is limited. This study integrates anthropometric measurements and immunization status during community health center delivery. Integrating these metrics is essential as it helps identify early growth issues and ensures timely vaccinations, which are vital for preventing malnutrition and vaccine-preventable diseases in a setting where healthcare resources are scarce, and follow-up care is often challenging. Materials and Methods: The present study is based on baseline data of a larger prospective follow-up study conducted from November 2022 to February 2024 in rural areas of North India, including newborns delivered through cesarean section or vaginal delivery. Data were collected using a semi-structured questionnaire including weight, height, head circumference, chest circumference, and mid-arm circumference of the newborns. Results: The study included 150 newborns, with the mean age of mothers and fathers being 25.27 ± 2.81 years and 29.01 ± 3.76 years, respectively. Immunization coverage was high for hepatitis B (Hep-B) (99.3%) and oral polio vaccine (OPV) (99.3%) but lower for Bacillus Calmette–Guérin (BCG) (74.7%). Strong correlations were found among the five anthropometric measurements, indicating consistent growth patterns. Conclusions: The study highlights the demographic characteristics and immunization coverage among newborns in rural India. Despite high coverage for Hep-B and OPV, the lower uptake of the BCG vaccine indicates gaps in immunization outreach. The strong correlations among anthropometric measurements suggest consistent growth patterns, reinforcing the need for integrating such assessments into routine care to monitor and support healthy development.

Coley’s Toxin to First Approved Therapeutic Vaccine—A Brief Historical Account in the Progression of Immunobiology-Based Cancer Treatment

Cancer immunobiology is one of the hot topics of discussion amongst researchers today, and immunotherapeutic modalities are among the selected few emerging approaches to cancer treatment that have exhibited a promising outlook. However, immunotherapy is not a new kid on the block; it has been around for centuries. The origin of cancer immunotherapy in modern medicine can be traced back to the initial reports of spontaneous regression of malignant tumors in some patients following an acute febrile infection, at the turn of the twentieth century. This review briefly revisits the historical accounts of immunotherapy, highlighting some of the significant developments in the field of cancer immunobiology, that have been instrumental in bringing back the immunotherapeutic approaches to the forefront of cancer research. Some of the topics covered are: Coley’s toxin—the first immunotherapeutic; the genesis of the theory of immune surveillance; the discovery of T lymphocytes and dendritic cells and their roles; the role of tumor antigens; relevance of tumor microenvironment; the anti-tumor (therapeutic) ability of Bacillus Calmette– Guérin; Melacine—the first therapeutic vaccine engineered; theories of immunoediting and immunophenotyping of cancer; and Provenge—the first FDA-approved therapeutic vaccine. In this review, head and neck cancer has been taken as the reference tumor for narrating the progression of cancer immunobiology, particularly for highlighting the advent of immunotherapeutic agents.

Leveraging computer-aided design and artificial intelligence to develop a next-generation multi-epitope tuberculosis vaccine candidate

BackgroundTuberculosis (TB) remains a global public health challenge. The existing Bacillus Calmette–Guérin vaccine has limited efficacy in preventing adult pulmonary TB, necessitating the development of new vaccines with improved protective effects. MethodsComputer-aided design and artificial intelligence technologies, combined with bioinformatics and immunoinformatics approaches, were used to design a multi-epitope vaccine (MEV) against TB. Comprehensive bioinformatics analyses were conducted to evaluate the physicochemical properties, spatial structure, immunogenicity, molecular dynamics (MD), and immunological characteristics of the MEV. ResultsWe constructed a MEV, designated ZL12138L, containing 13 helper T lymphocyte epitopes, 12 cytotoxic T lymphocyte epitopes, 8 B-cell epitopes, as well as Toll-like receptor (TLR) agonists and helper peptides. Bioinformatics analyses revealed that ZL12138L should exhibit excellent immunogenicity and antigenicity, with no toxicity or allergenicity, and had potential to induce robust immune responses and high solubility, the immunogenicity score was 4.14449, the antigenicity score was 0.8843, and the immunological score was 0.470. Moreover, ZL12138L showed high population coverage for human leukocyte antigen class I and II alleles, reaching 92.41% and 90.17%, respectively, globally. Molecular docking analysis indicated favorable binding affinity of ZL12138L with TLR-2 and TLR-4, with binding energies of −1173.4 and −1360.5 kcal/mol, respectively. Normal mode analysis and MD simulations indicated the stability and dynamic properties of the vaccine construct. Immune simulation predictions suggested that ZL12138L could effectively activate innate and adaptive immune cells, inducing high levels of Type 1 T helper cell cytokines. ConclusionsThis study provides compelling evidence for ZL12138L as a promising TB vaccine candidate. Future research will focus on experimental validation and further optimization of the vaccine design.

Repeat TURBT in large volume high-grade non-invasive bladder cancer

Background The American Urological Association (AUA)/Society of Urology Oncology (SUO) guidelines recommend a repeat transurethral resection of bladder tumor (TURBT) for high-risk, non-invasive (HR Ta) nonmuscle invasive bladder cancer (NMIBC) patients. The evidence base for this recommendation is weak (grade C) and fraught with methodological shortcomings, such as the lack of adjuvant intravesical Bacillus Calmette Guerin (BCG) and single-center study designs. Objective We sought to evaluate the effect of repeat TURBT on recurrence-free survival at a population level in HR Ta NMIBC patients who completed BCG induction therapy. Methods High-grade Ta NMIBC patients who underwent TURBT for a ≥5 cm tumor were identified within the SEER-Medicare database. All patients completed induction BCG and were stratified into two groups: repeat TURBT within eight weeks of initial TURBT and a group without repeat TURBT (control group). The primary endpoint was the 3-year high-risk recurrence rate. Results A cohort of 604 patients was identified, with 93 (15.4%) undergoing a repeat TURBT within eight weeks of initial TURBT and 511 (84.6%) without a repeat TURBT. Patient demographic and clinical characteristics were similar overall. No significant difference in the 3-year recurrence rate was noted (repeat TURBT: 20.4% vs. control group: 15.7%, p = 0.25). After adjusting for demographic and clinical characteristics, no association between repeat TURBT and 3-year high-risk recurrence was observed (HR (95% CI): 1.27 (0.76, 2.11); p = 0.36). Conclusion Although our study contains several major limitations, our results suggest that repeat TURBT in large volume HG Ta NMIBC treated with induction BCG therapy was not associated with improved high-risk recurrence-free survival.

Regulation of Bacillus Calmette-Guérin-induced macrophage autophagy and apoptosis by the AMPK–mTOR–ULK1 pathway

Tuberculosis (TB) is a chronic wasting infectious disease caused by Mycobacterium tuberculosis (MTB) or Mycobacterium bovis that can be transmitted among people and domestic animals. During the development of TB, macrophages of the innate immune system can act against MTB via autophagy and apoptosis to prevent the spread of the disease. Among the many autophagy regulatory pathways, the adenosine monophosphate (AMP)–activated protein kinase (AMPK)–mammalian rapamycin target protein (mTOR)–Unc-51-like kinase 1 (ULK1) pathway has received considerable attention. This study investigates the regulatory role of the AMPK–mTOR–ULK1 pathway in attenuating M. bovis Bacillus Calmette–Guérin (BCG)-induced autophagy and apoptosis in murine monocyte macrophages (RAW264.7). Changes in macrophage autophagy and apoptosis were analyzed using the AMPK activator AICAR and inhibitor Compound C to interfere with the AMPK–mTOR–ULK1 pathway and siRNA to silence the pathway. Consequently, BCG stimulation of macrophages significantly activated the AMPK–mTOR–ULK1 pathway while BCG-induced macrophage AMPK activation promoted macrophage autophagy and apoptosis. Activation of the AMPK–mTOR–ULK1 pathway by AICAR significantly improved autophagy occurrence in BCG-induced macrophages and increased apoptosis while Compound C with siRNA produced opposing effects by attenuating autophagy and apoptosis in BCG-induced macrophages. Thus, the AMPK–mTOR–ULK1 pathway has a dual regulatory role in BCG-induced macrophage autophagy and apoptosis and may have synergistic effects. This study analyzes the mechanism of resistance of host cells to MTB and provides a theoretical basis for new therapeutic strategies and related drug development.

Reliability of mpMRI in diagnosing cancer prostate following intravesical BCG for bladder cancer.

Detecting carcinoma prostate (CaP) after intravesical Bacillus Calmette Guerin (BCG) immunotherapy for non-muscle invasive bladder cancer (NMIBC) poses diagnostic challenges. Granulomatous prostatitis (GP) has an incidence of 0.8%-3.3% in post-intravesical BCG patients and 6% incidence in a PIRADS 5 lesion on multiparametric MRI (mpMRI). Patients with GP after intravesical BCG may have clinical, biochemical, and radiological features similar to CaP. In our study, we evaluate the reliability of mpMRI in diagnosing CaP after intravesical BCG therapy. We reviewed the NMIBC patients treated with intravesical BCG therapy between 2017 and 2023 and investigated those who underwent mpMRI and MR fusion biopsy in suspicion of CaP. A total of 120 patients had intravesical BCG immunotherapy, and 10 patients met our selection criteria. We performed a descriptive analysis of these patients and assessed the sensitivity and specificity of mpMRI in diagnosing CaP. The sensitivity of mpMRI in detecting CaP was 100%, and the specificity was 28.6%. Similarly, the negative predictive value for detecting CaP was 100%, and the positive predictive value was 37.5%. Among patients evaluated with mpMRI, a PIRADS 4 or 5 lesion was seen in 8 (80%) patients, and there was no lesion in 2 (20%) patients. The mpMRI detected 1 lesion in 6 patients (60%) and 2 (20%) in 2 patients. The lesions had a PIRADS score of 4 and 5 in 6 (60%) and 2 (20%) patients, respectively. Among these lesions, 8 (80%) were in the peripheral zone and 2 (20%) in the transition zone. In the MR fusion biopsy of these 10 patients, 7 (70%) had granulomatous prostatitis, and 3 (30%) had CaP. In our study on evaluating the reliability of mpMRI in diagnosing CaP among post-intravesical BCG patients, we noted that although PIRADS in mpMRI had high sensitivity in identifying prostate lesions, its specificity for detecting CaP is limited.

Intra-arterial chemotherapy combined with BCG immunotherapy is more effective than intra-arterial chemotherapy plus intravesical chemotherapy or standard BCG immunotherapy in preventing the recurrence and progression of high-risk non–muscle-invasive bladder cancer

BackgroundUp to 45% of patients with high-risk non–muscle-invasive bladder cancer (NMIBC) will not benefit from adjuvant intravesical instillation. We aimed to introduce intra-arterial chemotherapy (IAC) to existing intravesical treatment and evaluate its feasibility and safety. Materials and methodsWe collected data from 170 patients who had been diagnosed with high-risk NMIBC and underwent transurethral resection of bladder tumor (TURBT) over the last 5 years. Twenty-seven patients were excluded according to specific exclusion criteria. The remaining 143 patients were divided into 3 groups according to their treatment: intravesical instillation of Bacillus Calmette – Guerin (BCG), BCG+ intra-arterial chemotherapy (IAC), and intravesical chemotherapy (IVC)+IAC groups. All groups received standard intravesical instillation of BCG or chemotherapeutic agents. In contrast, both the BCG+IAC and IVC+IAC groups received four courses of IAC (injection of cisplatin [60 mg/m2] and epirubicin [50 mg/m2] in the internal iliac arteries via Seldinger's percutaneous technique). ResultsThe median follow-up time was 47 months, ranging from 20 to 60 months. The restricted mean survival time (RMST), which represents the recurrence and progression rate of the BCG+IAC group, differed significantly when compared with the BCG group (P = 0.029 and 0.004, respectively) and the IVC+IAC group (P = 0.004 and 0.006, respectively). Kaplan-Meier plots revealed that the recurrence and progression-free survival of the BCG+IAC group were significantly higher than the BCG and IVC+IAC groups (P = 0.033 and 0.028, respectively). In contrast, the BCG and IVC+IAC groups showed similar RMST (P = 0.156 and 0.935, respectively), recurrence (P = 0.627), and progression-free (P = 0.931) survival. A small proportion of patients (20%) suffered from the adverse effects of IAC while 65% suffered from adverse reactions to intravesical instillation. Most adverse effects were ranked as grade I or II according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. ConclusionAnalysis showed that tumor recurrence and progression rate in the BCG+IAC group was lower than the BCG and IVC+IAC groups while patients in the IVC+IAC group suffered from milder adverse effects in cystitis and flu-like symptoms. Our findings may provide a new perspective for urologists when treating patients with high-risk NMIBC.

262 - Intravesical administration of combined hyaluronic acid and chondroitin sulfate as add- on therapy for chemical cystitis induced by Bacillus Calmette- Guérin immunotherapy

262 - Intravesical administration of combined hyaluronic acid and chondroitin sulfate as add- on therapy for chemical cystitis induced by Bacillus Calmette- Guérin immunotherapy

The role of TERT C228T and KDM6A alterations and TME in NMIBC treated with BCG

We aimed to investigate the genomic and tumor microenvironmental (TME) profiles in non-muscle invasive bladder cancer (NMIBC) and explore potential predictive markers for Bacillus Calmette–Guérin (BCG) treatment response in high-risk NMIBC patients (according to European Association of Urology (EAU) risk stratification). 40 patients with high-risk NMIBC (cTis-T1N0M0) who underwent en bloc resection followed by BCG instillation were retrospectively enrolled. Surgical samples were subjected to Next Generation Sequencing (NGS) and multiplex immunofluorescence (mIF) assay. Genomic profiling revealed high prevalences of alterations in TERT (55%), KDM6A (32.5%), FGFR3(30%), PIK3CA (30%), TP53(27.5%) and ARID1A (20%). TME analysis showed different proportions of macrophages, NK cells, T cells subsets in tumoral and stromal compartment. Multivariate analysis identified TERT C228T and alteration in KDM6A as two independent factors associated with inferior RFS. The study comprehensively depicted the genomic and TME profiles in NMIBC and identified potential predictive biomarkers for BCG treatment.

Young age and adequate BCG are key factors for optimal BCG treatment efficacy in non-muscle-invasive bladder cancer

ObjectiveTo investigate the impact of ageing on survival outcomes in Bacillus Calmette–Guérin (BCG) treated non-muscle invasive bladder cancer (NMIBC) patients and its synergy with adequate BCG treatment.MethodPatients with NMIBC who received BCG treatment from 2001 to 2020 were divided into group 1 (< = 70 years) and group 2 (> 70 years). Overall Survival (OS), Cancer-Specific Survival (CSS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS) were analyzed using the Kaplan–Meier method. Multivariable Cox regression analysis was used to adjust potential confounding factors and to estimate Hazard Ratio (HR) and 95% Confidence Interval (CI). Subgroup analysis was performed according to adequate versus inadequate BCG treatment.ResultsOverall, 2602 NMIBC patients were included: 1051 (40.4%) and 1551 (59.6%) in groups 1 and 2, respectively. At median follow-up of 11.0 years, group 1 (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS as compared to group 2 (> 70 years). At subgroup analysis, patients in group 1 treated with adequate BCG showed better OS, CSS, RFS, and PFS as compared with inadequate BCG treatment in group 2, while patients in group 2 receiving adequate BCG treatment had 41% less progression than those treated with inadequate BCG from the same group.ConclusionsBeing younger (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS. Older patients (> 70 years) who received adequate BCG treatment had similar PFS as those younger with adequate BCG treatment.

Consensus document on the implications of standardization of BCG supply in the management of patients with non-muscle-invasive bladder cancer

Patients with non-muscle-invasive bladder cancer (NMIBC) in the intermediate and high-risk groups must receive adjuvant treatment with intravesical Bacillus Calmette–Guérin (BCG) following transurethral resection (TUR), as it reduces the risk of recurrence and presumably the risk of progression as well. Optimization of BCG efficacy is achieved by administering maintenance therapy. However, since many immunological aspects of the mechanism of action of BCG in the bladder remain unknown, the implementation of the optimal dose, number of instillations, strains and adequate maintenance regimen over the last decades has been heterogeneous. Additionally, this has hindered the interpretation of efficacy in terms of oncologic outcomes. This, together with the shortages of BCG in recent years, have forced scientific societies to adapt their clinical practice guidelines and modify their protocols of adjuvant treatment with BCG. This includes changes to strains, doses, and maintenance during this period of time. This consensus document evaluates the current status of adjuvant BCG treatment and the implications of BCG supply availability in the treatment of patients with NMIBC. It also addresses the implementation of novel therapies that will improve cancer prognosis and the quality of life of patients with NMIBC in the future.

Tuberculosis in otherwise healthy adults with inherited TNF deficiency

Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette–Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses. Their leukocytes, including monocytes and monocyte-derived macrophages (MDMs) do not produce TNF, even after stimulation with IFNγ. Blood leukocyte subset development is normal in these patients. However, an impairment in the respiratory burst was observed in granulocyte–macrophage colony-stimulating factor (GM-CSF)-matured MDMs and alveolar macrophage-like (AML) cells2 from both patients with TNF deficiency, TNF- or TNFR1-deficient induced pluripotent stem (iPS)-cell-derived GM-CSF-matured macrophages, and healthy control MDMs and AML cells differentiated with TNF blockers in vitro, and in lung macrophages treated with TNF blockers ex vivo. The stimulation of TNF-deficient iPS-cell-derived macrophages with TNF rescued the respiratory burst. These findings contrast with those for patients with inherited complete deficiency of the respiratory burst across all phagocytes, who are prone to multiple infections, including both Bacillus Calmette–Guérin disease and tuberculosis3. Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but is surprisingly redundant otherwise, including for inflammation and immunity to weakly virulent mycobacteria and many other infectious agents.

New therapeutic approaches for non-muscle invasive bladder cancer-is organ preservation also possible after BCG (Bacillus Calmette Guérin)?

Bacillus Calmette-Guérin (BCG) therapy is the standard of care in the treatment of high-risk non-muscle invasive bladder cancer (NMIBC). In the absence of aresponse to BCG and persistent high-grade disease, cystectomy is recommended depending on the clinical risk. Avariety of targeted therapy approaches, which aim at immune- and gene-based molecular targets, such as PD-(L)1 and FGFR, are currently being investigated in randomized studies for BCG-unresponsive NMIBC. Furthermore, novel forms of application for instillation therapy, such as the TAR device, in combination with gemcitabine or erdafitinib are being investigated in clinical trials in order to extend the duration of action of the active substance on the urothelium. Thus, there are now many developments that could make bladder-preserving therapy with comparable survival data possible as an alternative to BCG or in the event of BCG failure. In the future, it will be necessary to clarify how BCG response can be predicted by using molecular markers and how to define risk groups that should primarily be given an alternative therapy to BCG.

RORα negatively regulates BCG-induced trained immunity

Trained immunity is a long-lasting change in the responsiveness of innate immune cells, leading to a stronger response upon an unrelated secondary challenge. Epigenetic, transcriptional, and metabolic reprogramming contribute to the development of trained immunity. By investigating the impact of gene variants on trained immunity responses after Bacillus Calmette–Guérin (BCG) vaccination, we identified a strong association between polymorphisms in the RORA gene and BCG-induced trained immunity in PBMCs isolated from healthy human donors. RORα, encoded by the RORA gene in humans, is a nuclear receptor and a transcription factor, regulating genes involved in circadian rhythm, inflammation, cholesterol, and lipid metabolism. We found that natural RORα agonists in the circulation negatively correlate with the strength of trained immunity responses after BCG vaccination. Moreover, pharmacological inhibition of RORα in human PBMCs led to higher cytokine production capacity and boosted trained immunity induction by BCG. Blocking RORα activity also resulted in morphological changes and increased ROS and lactate production of BCG-trained cells. Blocking lactate dehydrogenase A (LDHA) and glycolysis with sodium oxamate reduced the cytokine production capacity of cells trained with a combination of BCG and the RORα agonist. In conclusion, this study highlights the potential role of RORα in trained immunity, and its impact on human vaccination and diseases should be further investigated.

Storable Polydopamine Nanoparticles Combined with Bacillus Calmette‐Guérin for Photothermal‐Immunotherapy of Colorectal Cancer

AbstractPhotothermal immunotherapy emerges as a promising strategy for treating tumors. However, the majority of current photothermal immunotherapy approaches do not yet show significant potential for clinical translation. In this study, lyophilized polydopamine (PDA) nanoparticles combined with Bacillus Calmette–Guérin (BCG) are investigated for photothermal immunotherapy against colorectal cancer. By simply mixing with two lyophilized powders, PDA nanoparticles can covalently bond onto BCG to form BCG@PDA. This combination demonstrates a potent photothermal cytotoxic effect on tumor cells by utilizing PDA nanoparticles. In addition, a heightened immune response triggered by the BCG vaccine, as evidenced by the secretion of important pro‐inflammatory cytokines and the activation of antigen‐presenting cells, is observed. In vivo testing on a murine colon cancer model demonstrates that the combined treatment significantly inhibits tumor growth. Further, the lyophilized PDA nanoparticles can be stored at −20 °C for up to 1 year with stable photothermal properties. Therefore, this study not only presents a reliable method for storing the therapeutic PDA nanoparticles but also demonstrates the potential application of BCG@PDA in photothermal immunotherapy for colorectal cancer.

Mitomycin C vs. Bacillus Calmette–Guerin for treatment of intermediate-risk nonmuscle invasive bladder cancer patients—A comparative analysis from a single center

BackgroundInduction followed by 1 year maintenance instillation of intravesical Bacillus Calmette–Guerin (BCG) is the standard treatment for intermediate-risk (IR) nonmuscle invasive bladder cancer (NMIBC) patients. Few data exist on the efficacy of Mitomycin C (MMC) instillation in this setting. MethodsWe retrospectively analyzed 226 IR-NMIBC patients classified by the International Bladder Cancer Group (IBCG) and 250 IR-NMIBC intravescical treatment-naïve patients classified by the European Association of Urology (EAU). All patients received either a full induction course of BCG or 40 mg/40 ml MMC from 2012 to 2022. Optimal treatment was defined as 1-year maintenance for BCG and 11 monthly maintenance instillations for MMC. Kaplan–Meier analysis estimated recurrence-free survival (RFS) before and after inverse probability of treatment-weighting (IPTW) and progression-free survival (PFS). Multivariable Cox regression was used to evaluate difference in recurrence after adjustment for clinically relevant variables before and after IPTW. ResultsOptimal BCG and MMC courses were administered to 21% of IR-IBCG and 23% of IR-EAU patients. At 4-years, patients treated with optimal MMC and BCG treatment had similar RFS and PFS in both EAU and IBCG groups. Patients receiving nonoptimal BCG compared to optimal MMC exhibited lower 4-year RFS after IPTW (82% vs. 68% in EAU and 82% vs. 65% in IBCG). At 4-year optimal MMC had greater PFS non optimal BCG. Optimal MMC treatment predicted recurrence in EAU (adjusted and weighted HR 0.33, 95% CI, 0.11-0.98) and IBCG (adjusted and weighted HR 0.29, 95% CI, 0.08-0.97) groups compared to nonoptimal BCG. ConclusionsOptimal 40 mg/40 ml MMC treatment was as effective as optimal BCG in IR-IBCG and IR-EAU NMIBC patients, reducing both recurrence and progression compared to nonoptimal BCG. MMC could be a valid first line alternative to BCG for both IR-EAU and IR-IBCG intravescical treatment-naïve patients, during BCG shortages.

Comparing efficacy and safety of in-house gemcitabine to mitomycin for bladder instillation in intermediate-risk NMIBC

IntroductionIntermediate-risk (IR) Non-Muscle Invasive Bladder Cancer (NMIBC) is associated with a high rate of tumor recurrence. To improve patient outcomes, it is recommended to use adjuvant intravesical therapy, by mitomycin C (MMC) or Bacillus Calmette Guerin (BCG). Gemcitabine (GMC) is a known molecule used in urothelial cancer. We aimed to study the efficacy and safety profile of a gemcitabine solution, compared to mitomycin C, in the treatment of IR NMIBC. MaterialIn this retrospective study, patients with IR NMIBC treated between 2016 and 2020 were selected from two participating centers using either gemcitabine (center A) as the intravesical chemotherapy regimen or mitomycin C (center B). The primary endpoint was recurrence rate and secondary end points were treatment interruption and its causes. ResultsIn our cohort of 102 IR NMIBC patients, 49 patients received GMC and 53 MMC with a median follow-up of 30 months. Overall recurrence rate was 42.1% with 22.4% in the GMC group and 60.3% in the MMC group (P<0.01). This difference was also found in the multifactorial analysis. Course interruption was observed in 14.7% of all patients, primarily attributed to adverse events (46.6%), without difference between groups. ConclusionAdjuvant intravesical gemcitabine in patients with IR NMIBC seems to be an interesting option associated with a lower tumor recurrence rate and a favorable tolerance profile when compared to MMC. Larger scale prospective randomized trials are needed to validate our findings. Level of evidenceIII.

Vaccination in children living with HIV – review of Polish recommendations

Vaccines are an extremely effective primary prevention tool recommended for routine use in children worldwide. Vaccination is crucial for patients with underlying diseases, including children living with HIV, because of their increased risk of morbidity and mortality from various vaccine-preventable diseases. Complex care for patients living with HIV includes antiretroviral therapy (which has dramatically improved survival), prophylaxis and treatment of common infections, prophylaxis and treatment of opportunistic infections, and vaccination. Immunisation is generally safe and beneficial for children living with HIV, although HIV-induced immune suppression reduces the benefits. All inactivated vaccines, whether killed whole organism or subunit, recombinant, toxoid, polysaccharide or conjugate (which includes diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b, hepatitis B, hepatitis A, Streptococcus pneumoniae vaccines, Neisseria meningitidis, influenza, HPV), can be administered safely. Live attenuated measles–mumps–rubella and varicella vaccines are indicated in children without severe immunodeficiency. The Bacillus Calmette–Guérin vaccine is contraindicated due to the risk of disseminated BCG infection. Although a live attenuated influenza vaccine is available, it is contraindicated for people living with HIV because of the paucity of safety data and the availability of alternative vaccines. The study reviews the current paediatric immunisation recommendations in HIV infection in Poland. Additionally, we focus on vaccine effectiveness, especially HBV protection based on anti-Hbs antibodies.