Bacillus Calmette-Guérin Research Articles

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.

New horizon of the combined BCG vaccine with probiotic and liraglutide in augmenting beta cell survival via suppression of TXNIP/NLRP3 pyroptosis signaling in Streptozocin–Induced diabetes mellitestype-1 in rats

BackgroundAn ideal anti-diabetic type-1 pharmacotherapy should combine abrogation of beta cell pyroptosis with enhancement of beta cell mass. ObjectivesThe study investigated the potential synergism from combining the Bacillus Calmette-Guerin (BCG) vaccine with liraglutide (LIR) and probiotics in mitigating Streptozocin (STZ)-induced Type1diabetes mellitus in albino rats via suppression of TXNIP/NLRP3 signaling. Methods: Induction of diabetes was performed by two I.V. injections of 50 mg/kg of STZ in male Wistar rats. Forty-eight rats were randomly allocated into six groups: Normal control group; STZ -diabetic group; BCG group; BCG + LIR group; BCG + probiotic group; BCG + LIR + probiotic group. The rats were sacrificed after 8 weeks of treatment. ResultsThe STZ-diabetic group exhibited significant elevation of fasting blood sugar and HbA1c with remarkably decreased serum insulin along with a considerable increase in pancreatic proinflammatory cytokines (TNF-α, NLRP3, IL-1β, and NFκB) and apoptotic markers (ASK-1, IAPP, TXNIP, and Caspase-3) with prominently compromised oxidative scavenging capacity in addition to structural alteration in the pancreatic histoarchitecture with decreased insulin immunostaining. Conversely, diabetic-treated groups, especially the BCG + LIR + probiotic group, were superior in amelioration of STZ-induced pyroptosis of pancreatic islets evidenced by a significant decline in inflammatory cytokines and apoptotic markers with a remarkable upgrade in redox balance, Furthermore, the mitigation in the altered histopathological picture of the pancreas with enhanced insulin immunostaining has been was mirrored on the significant improvement of glucose homeostasis parameters. ConclusionsNoteworthy, BCG combination with liraglutide and probiotic might be a promising repurposed therapeutic modality in the management of type-1 diabetes mellites via targeting pancreatic TXNIP/NLRP3 signaling pathway.

Mtb-Specific HLA-E-Restricted T Cells Are Induced during Mtb Infection but Not after BCG Administration in Non-Human Primates and Humans.

Background: Novel vaccines targeting the world's deadliest pathogen Mycobacterium tuberculosis (Mtb) are urgently needed as the efficacy of the Bacillus Calmette-Guérin (BCG) vaccine in its current use is limited. HLA-E is a virtually monomorphic unconventional antigen presentation molecule, and HLA-E-restricted Mtb-specific CD8+ T cells can control intracellular Mtb growth, making HLA-E a promising vaccine target for Mtb. Methods: In this study, we evaluated the frequency and phenotype of HLA-E-restricted Mtb-specific CD4+/CD8+ T cells in the circulation and bronchoalveolar lavage fluid of two independent non-human primate (NHP) studies and from humans receiving BCG either intradermally or mucosally. Results: BCG vaccination followed by Mtb challenge in NHPs did not affect the frequency of circulating and local HLA-E-Mtb CD4+ and CD8+ T cells, and we saw the same in humans receiving BCG. HLA-E-Mtb T cell frequencies were significantly increased after Mtb challenge in unvaccinated NHPs, which was correlated with higher TB pathology. Conclusions: Together, HLA-E-Mtb-restricted T cells are minimally induced by BCG in humans and rhesus macaques (RMs) but can be elicited after Mtb infection in unvaccinated RMs. These results give new insights into targeting HLA-E as a potential immune mechanism against TB.

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.

Rationale of restaging transurethral resection of bladder tumor in patients with nonmuscle invasive bladder cancer in the current era

Background: We present retrospective data of patients with nonmuscle invasive bladder cancer (NMIBC) who underwent restaging transurethral resection of bladder tumor (Re-TURBT) at a tertiary care center. Materials and Methods: Records of all NMIBC patients undergoing Re-TURBT between March 2021 and September 2023 were retrospectively analyzed. Patients were risk stratified based on TURBT pathology. Re-TURBT was performed between 4 and 6 weeks. Adverse features such as number, size, and appearance were noted. Patients with persistent disease at Re-TURBT were counseled for early cystectomy with urinary diversion or intravesical Bacillus Calmette–Guerin (BCG). In case of disease upstaging, patients were counseled for radical cystectomy. Results: Thirty-eight NMIBC patients (30 males and 8 females) underwent Re-TURBT. Six patients had residual/persistent disease at 6 weeks, all high risk and high grade (HG, P value not significant, P = 0.31). There was no association with number and appearance of tumors with residual/persistence at 6 weeks. The mean lesion size on imaging in cases with and without residual disease was 3.32 ± 0.86 versus 3.39 ± 0.92 cm, respectively, P value not significant (0.868). There was no residual disease in the low-grade (LG) pT1 group, but HG pTa and pT1 (n = 3) had residual disease. Four HG pT1 patients opted for early cystectomy. Two patients each had pT0 and two pT2. At 3 months of follow-up, urethral strictures were seen both in high risk and intermediate risk. Among four patients who had stricture, meatal stenosis was common (50%, n = 2). Two patients had long-segment stricture requiring perineal urethrostomy with stage I Johannsen repair. All HG pT1 lesion patients eventually underwent cystectomy (3 were under staged and two treated completely with TURBT, one with TURBT + BCG and one patient progressed to metastasis). Conclusion: Re-TURBT is essential for the management of HG pTa and HG pT1 lesions for accurate staging and treatment of residual disease. However, LG pT1 patients can safely be excluded from Re-TURBT.

Multilevel Proteomics Reveals Epigenetic Signatures in BCG-Mediated Macrophage Activation

The bacillus Calmette-Guérin BCG vaccine (Mycobacterium bovis) is primarily used to prevent tuberculosis (TB) infections but has wide-ranging immunogenic effects. One of its most notable properties is its ability to induce trained immunity, a memory-like response in innate immune cells such as macrophages. Through targeted analyses of well-established histone marks, prior research has shown that these changes are generated through epigenetic modification. Mass spectrometry-based proteomic approaches provide a way to globally profile various aspects of the proteome, providing data to further identify unexplored mechanisms of BCG-mediated immunomodulation. Here we use multi-level proteomics (total, histone, and phospho to identify networks and potential mechanisms that mediate BCG induced immunomodulation in macrophages. Histone-focused proteomics and total proteomics were performed at the University of Cape Town (data available via ProteomeXchange with identifier PXD051187), while phosphoproteomics data was retrieved from the ProteomeXchange Repository (identifier PXD013171). We identify several epigenetic mechanisms that may drive BCG-induced training phenotypes. Evidence across the proteomics and histone-focused proteomics data sets pair 6 epigenetic effectors (NuA4, NuRD, NSL, Sin3A, SIRT2, SIRT6) and their substrates.

Does increased CCL2-mediated immune cell recruitment during mucosal BCG vaccination provide superior protection against TB?

Does increased CCL2-mediated immune cell recruitment during mucosal BCG vaccination provide superior protection against TB?

Correlation Of BCG Vaccination And COVID-19 Disease Through Measurement Of Immunological Markers IFN-Γ And Anti-BCG Igg In Different Age Groups Running Title: Correlation Between BCG Vaccination And COVID-19 Disease

Introduction Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China in December 2019 and then became a pandemic. BCG vaccination has conferred non-specific (targeted-off) protective effects against unrelated pathogens including respiratory viral infections that have been hypothesized to it could reduce the severity of COVID-19 disease. Objective: Assess whether BCG vaccination has a role in the prevention of COVID-19. Methods: A cross-sectional study including 111 healthy people was carried out from October 2021 to December 2022. Specific anti-BGC-IgG and IFN-γ levels were estimated in blood samples after stimulation with BCG vaccine for 2 days. All participants were examined for BCG scar status and COVID-19 confirmation. Results: There was no significant difference in anti-BCG IgG levels or IFN-γ levels (p>0.05) in relation to COVID-19 infection. There was no statistically significant association between BCG scar diameter and COVID-19 infection (p>0.05). Furthermore, there was no statistically significant association between the BCG scar diameter and COVID-19 severity (p>0.05). There was no significant difference in anti-BCG IgG levels (p>0.05) in relation to COVID-19 severity. Likewise, there was no significant difference in between IFN γ levels and COVID-19 severity (p>0.05). Conclusion: There was no correlation between BCG vaccination and infection or severity of COVID-19.

Incorporating Microbial Stimuli for Osteogenesis in a Rabbit Posterolateral Spinal Fusion Model.

Autologous bone grafts are commonly used to repair defects in skeletal tissue, however, due to their limited supply there is a clinical need for alternatives. Synthetic ceramics present a promising option but currently lack biological activity to stimulate bone regeneration. One potential approach to address this limitation is the incorporation of immunomodulatory agents. In this study, we investigate the application of microbial stimuli to stimulate bone formation. Three different microbial stimuli were incorporated in a biphasic calcium phosphate (BCP) ceramic: Bacille Calmette-Guérin (BCG), gamma-irradiated Staphylococcus aureus (γi-S. aureus), or Candida albicans (γi-C. Albicans). The constructs were then implanted in both a rabbit posterolateral spinal fusion (PLF) and an intramuscular implant model for 10 weeks and compared to a non-stimulated control construct. For the PLF model, the formation of a bony bridge was evaluated by manual palpation, micro-CT, and histology. While complete fusion was not observed, the BCG condition was most promising with higher manual stiffness and almost twice as much bone volume in the central fusion mass compared to the control (9±4.4% bone area vs 4.6±2.3%, respectively). Conversely, the γi-S. aureus or γi-C. albicans appeared to inhibit bone formation (1.4±1.4% and 1.2±0.6% bone area). Bone induction was not observed in any of the intramuscular implants. This study indicates that incorporating immunomodulatory agents in ceramic bone substitutes can affect bone formation, which can be positive when selected carefully. The readily available and clinically approved BCG showed promising results, which warrants further research for clinical translation.

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.

Real-word outcomes for high-risk non-muscle-invasive bladder cancer: screened patients for the BRAVO trial.

To report real-world outcomes for high-risk non-muscle-invasive bladder cancer (HRNMIBC), including bacillus Calmette-Guérin (BCG) and radical cystectomy (RC), as randomised comparisons of these have not been possible. We detail consecutive participants screened for the BRAVO randomised controlled trial comparing RC with BCG (International Standard Randomised Controlled Trial Number [ISRCTN]12509361). Patients were prospectively registered and case-note review used for outcomes. The primary outcome was overall survival. Secondary outcomes included recurrence, progression, metastasis, and bladder cancer-specific survival. A total of 193 patients were screened, including 106 (54.9%) who received BCG, 43 (22.3%) primary RC, 37 (19.2%) 'other' treatment and seven (3.6%) hyperthermic intravesical mitomycin C. All-cause death occurred in 55 (28.5%) patients at median (interquartile range [IQR]) of 29.0 (19.5-42.0) months. In multivariable analysis, overall mortality was more common in older patients (hazard ratio [HR] 2.63, 95% confidence interval [CI] 1.35-5.13; Cox P = 0.004 for age >70 years), those recruited from district hospitals (HR 0.53, 95% CI 0.3-0.95; P = 0.032) and those who did not undergo RC as their first treatment (HR 2.16, 95% CI 1.17-3.99; P = 0.014). In all, 17 (8.8%) patients died from bladder cancer (BC) at median (IQR) of 22.5 (19-36.25) months. In multivariable analysis, BC-specific mortality was more common in older patients (HR 4.87, 95% CI 1.1-21.6; P = 0.037) and those with Tis/T1 disease (HR 2.26, 95% CI 1.23-4.16; P = 0.008) but did not vary with initial treatment. Patients with HRNMIBC are at high-risk of mortality. Those choosing RC as their initial treatment have lower risks of mortality than others, although this may reflect fitness and selection.

The Impact of Vaccination Programs on the Prevention of Infectious Disease Tuberculosis: A Case Study with Gasabo District in Rwanda

Introduction Tuberculosis (TB) remained a significant public health challenge globally, including in Gasabo District, Rwanda. Vaccination programs, particularly Bacille Calmette-Guérin (BCG) vaccination, played a crucial role in TB prevention. This study aimed to assess the impact of vaccination programs on TB prevention in Gasabo District, Rwanda, by analyzing vaccination coverage, TB incidence rates, demographic characteristics, and healthcare system factors.  Methods A retrospective cohort study design was employed, utilizing secondary data sources from healthcare facilities in Gasabo District. Data on vaccination coverage, TB incidence rates, demographic characteristics, and healthcare system factors were collected and analyzed. Statistical methods, including regression analysis and descriptive statistics, were used to assess the association between vaccination programs and TB prevention outcomes.  Findings The study found a significant association between BCG vaccination coverage and lower TB incidence rates in Gasabo District. Higher vaccination coverage was associated with reduced TB incidence rates, particularly among children. However, challenges such as incomplete vaccination data, potential confounding factors, and socio-economic disparities were identified. Despite these challenges, vaccination programs were found to be effective in reducing TB transmission and protecting vulnerable populations from TB infection.  Conclusion The findings highlighted the importance of vaccination programs in TB prevention efforts in Gasabo District, Rwanda. Strengthening vaccination coverage, enhancing healthcare system capacity, addressing socio-economic determinants, fostering collaborations, promoting research and innovation, and strengthening surveillance and monitoring systems are essential for optimizing TB prevention efforts. By implementing these recommendations, we can accelerate progress towards ending the TB epidemic and improving public health outcomes in Gasabo District and beyond.

Intravenous Bacillus Calmette-Guérin (BCG) Induces a More Potent Airway and Lung Immune Response than Intradermal BCG in Simian Immunodeficiency Virus-infected Macaques.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the leading causes of death due to an infectious agent. Coinfection with HIV exacerbates M. tuberculosis infection outcomes in people living with HIV. Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, is effective in infants, but its efficacy in adolescents and adults is limited. In this study, we investigated the immune responses elicited by BCG administered via i.v. or intradermal (i.d.) routes in SIV-infected Mauritian cynomolgus macaques (MCM) without the confounding effects of M. tuberculosis challenge. We assessed the impact of vaccination on T cell responses in the airway, blood, and tissues (lung, thoracic lymph nodes, and spleen), as well as the expression of cytokines, cytotoxic effectors, and key transcription factors. Our results showed that i.v. BCG induces a robust and sustained immune response, including tissue-resident memory T cells in lungs, polyfunctional CD4+ and CD8αβ+ T cells expressing multiple cytokines, and CD8αβ+ T cells and NK cells expressing cytotoxic effectors in airways. We also detected higher levels of mycobacteria-specific IgG and IgM in the airways of i.v. BCG-vaccinated MCM. Although i.v. BCG vaccination resulted in an influx of tissue-resident memory T cells in lungs of MCM with controlled SIV replication, MCM with high plasma SIV RNA (>105 copies/ml) typically displayed reduced T cell responses, suggesting that uncontrolled SIV or HIV replication would have a detrimental effect on i.v. BCG-induced protection against M. tuberculosis.

Bacillus Calmette-Guérin Instillations May Mimic Prostate Cancer on Multiparametric Magnetic Resonance Imaging.

Granulomatous prostatitis (GP) is a rare and benign inflammatory condition of the prostate, often mimicking prostate cancer (PCa) in clinical and radiological evaluations. This study examines the characteristics and diagnostic challenges of GP in a cohort of 12 patients who received Bacillus Calmette-Guérin (BCG) therapy following treatment for non-muscle-invasive bladder urothelial carcinoma. In this case series, we analyze their clinical presentations, MRI findings, and histopathological results. Patients presented with elevated PSA levels and firm or nodular prostates on digital rectal examination, complicating the differentiation from PCa. Multiparametric MRI showed lesions with hypointensity on T2-weighted images, hypersignal on diffusion-weighted imaging and hyposignal on the apparent diffusion coefficient map, further mimicking malignancy. Histopathological examination remains the gold standard for diagnosing GP, distinguishing it from PCa through the identification of granulomas and associated inflammatory cells. This study underscores the importance of awareness and accurate diagnosis of GP to avoid unnecessary biopsies and treatments, highlighting the need for a multidisciplinary approach combining clinical, imaging, and pathological data.

Age and gender in drug resistance tuberculosis: A cross-sectional case study at a national tuberculosis reference hospital in Nigeria

ObjectivesDrug resistance in tuberculosis (TB) is a very important public health threat that should not be ignored. Understanding the gender, age, and characteristics of individuals affected by TB (without HIV, diabetes, or hepatitis B complications), particularly in terms of drug resistance or susceptibility, is crucial for effective prevention and management strategies, as most studies focus on TB/HIV co-infection. MethodsA cross-sectional case study of age and gender was carried out in 140 individuals grouped into drug-resistant tuberculosis (DR-TB), drug-susceptible tuberculosis (DS-TB), and apparently healthy controls (AHCs). Data collection was through medical records and a structured questionnaire. Statistical analyses compared age, gender, and selected risk factors across the groups. ResultsThe mean age of the DR-TB group was 32 years (SD ≈ 2). A total of 80.0% were ≤40 years of age and four times more likely to have DR-TB; 55% were male, with 1.22 times more likelihood of DR-TB in males. The mean age of the DS-TB group was 34 years (SD ≈ 12); 66.7% were ≤40 years old. The odds ratio of DS-TB in males was 2.16. Only 10% of DR-TB enrolees had BCG scars compared with 65% AHCs. A high percentage of the DR-TB group reported handling raw meat (75%) and drinking unpasteurised milk (70%) compared with the DS-TB group. ConclusionsThe observed gender disparities and age-related factors, particularly among the DR-TB group, highlight the importance of considering age and gender factors in DR-TB prevention, diagnosis, and treatment. Our findings also highlight the need to bridge gaps in awareness as well as for the prevention of zoonotic TB and issues around effective BCG vaccination and coverage.

Enhanced Antimicrobial Peptide Response Following Bacillus Calmette-Guerin Vaccination in Elderly Individuals.

Antimicrobial peptides are an important component of host defense against Mycobacterium tuberculosis. However, the ability of BCG to induce AMPs as part of its mechanism of action has not been investigated in detail. We investigated the impact of Bacillus Calmette-Guerin (BCG) vaccination on circulating plasma levels and TB-antigen stimulated plasma levels of AMPs in a healthy elderly population. We assessed the association of AMPs, including Human Beta Defensin 2 (HBD-2), Human Neutrophil Peptide 1-3 (HNP1-3), Granulysin, and Cathelicidin (LL37), in circulating plasma and TB-antigen stimulated plasma (using IGRA supernatants) at baseline (pre-vaccination) and at Month 1 and Month 6 post vaccination. Post BCG vaccination, both circulating plasma levels and TB-antigen stimulated plasma levels of AMPs significantly increased at Month 1 and Month 6 compared to pre-vaccination levels in the elderly population. However, the association of AMP levels with latent TB (LTB) status did not exhibit statistical significance. Our findings indicate that BCG vaccination is linked to heightened circulating levels of AMPs in the elderly population, which are also TB-antigen-specific. This suggests a potential mechanism underlying the immune effects of BCG in enhancing host defense against TB.

Impact of Bacille Calmette-Guérin vaccination on the therapeutic schedule of infantile epileptic spasms syndrome: A 25-year Japanese single-center survey

Adrenocorticotropic hormone (ACTH) therapy is effective for infantile epileptic spasms syndrome (IESS) but can induce immunosuppression. In Japan, Bacille Calmette-Guérin (BCG) vaccination, modified in 2013 to reduce osteitis/osteomyelitis risk, coincides with the peak onset age of IESS. This raises concerns about infection risks when administering ACTH therapy post-vaccination. To evaluate the impact of BCG vaccination timing on treatment decisions, we retrospectively reviewed the medical records of 86 IESS patients at our hospital (1996–2020). Infants who received ACTH therapy within eight weeks of BCG vaccination experienced no serious adverse events. Four patients deferred or opted out of ACTH therapy, with seizure remission taking 2–15 weeks. The overlap between IESS onset and BCG vaccination period presents clinical challenges in determining the appropriate timing for ACTH therapy. Further epidemiological and immunological research is needed to clarify the relationship between ACTH therapy and BCG-associated adverse events and to optimize treatment strategies and vaccination schedules.

Nutraceuticals and pharmacological to balance the transitional microbiome to extend immunity during COVID-19 and other viral infections

Abstract Scope The underlying medical conditions and gut dysbiosis is known to influence COVID-19 severity in high-risk patients. The current review proposed the optimal usage of nutraceuticals &amp; pharmacological interventions can help regulate the protective immune response and balance the regulatory functionality of gut microbiota. Summary Many studies have revealed that the probiotic interventions viz., Lactobacillus rhamnosus, L. plantarum &amp; other bacterial spp. reduce IFNγ &amp; TNF-α and increase IL-4 &amp; IL-10 secretions to control the immunostimulatory effects in upper respiratory tract infection. Dietary fibres utilized by beneficial microbiota and microbial metabolites can control the NF-kB regulation. Vitamin C halts the propagation of pathogens and vitamin D and A modulate the GM. Selenium and Flavonoids also control the redox regulations. Interferon therapy can antagonize the viral replications, while corticosteroids may reduce the death rates. BCG vaccine reprograms the monocytes to build trained immunity. Bifidobacterium and related microbes were found to increase the vaccine efficacy. Vaccines against COVID-19 and season flu also boost the immunity profile for robust protection. Over all, the collective effects of these therapeutics could help increase the opportunities for faster recovery from infectious diseases. Conclusion The nutraceutical supplements and pharmacological medicines mediate the modulatory functionalities among beneficial microbes of gut, which in turn eliminate pathogens, harmonize the activity of immune cells to secrete essential regulatory molecular receptors and adaptor proteins establishing the homeostasis in the body organs through essential microbiome. Therefore, the implementation of this methodology could control the severity events during clinical sickness and reduce the mortalities.

Organ-preserving treatment for urothelial carcinoma of the upper urinary tract

Urothelial carcinoma of the upper urinary tract is rare but the incidence is currently increasing in western countries. Radical nephroureterectomy has long been the standard treatment; however, it can lead to chronic kidney failure and also the necessity for dialysis. Therefore, organ-preserving treatment is now recommended for selected patients with low-risk tumors. The choice of treatment depends on the tumor characteristics, comorbidities and individual risk factors. Surgical options for organ preservation include ureterorenoscopy (URS), percutaneous treatment and partial ureteral resection. The URS is the most frequently used method for organ preservation. Photodynamic diagnostics (PDD) and narrow band imaging (NBI) can potentially also be used for tumor detection in the upper urinary tract. Conservative options such as topical treatment with mitomycinC or Bacillus Calmette-Guérin (BCG) and systemic treatment options are also possible.

Study on Trend of Immunization Coverage in Mutum Biyu Ward "B" From 2016-2019 in Gassol Local Government Area, Taraba State, Nigeria

This study examines the trend of immunisation coverage for Bacille Calmette-Guerin (BCG), Oral Polio Vaccine (OPV), Measles, and Yellow Fever in Mutum Biyu Ward 'B' of Gassol local Government Area, Taraba State, Nigeria, from 2016 to 2019. The DHIS2 Nigeria platform was used to gather secondary data using a quantitative, cross-sectional approach. In order to analyse the completion and non-completion rates of Routine Immunisation (RI) schedules, vaccination cards and carer recollection were the main sources of immunisation histories. One-way ANOVA testing and descriptive statistics were used in the data analysis. The study's findings showed that vaccination coverage varied over time. The BCG coverage saw notable fluctuations, peaking in the years 2017 and 2019. In 2018, OPV coverage rose on average but somewhat decreased. Measles vaccination rates were steady at first, then they fell in 20l8 and then sharply recovered in 2019. The vaccination rate for yellow fever was low in 20l6, improved slightly in 2017, declined sharply in 2018, and then reached its peak in 2019. The study recommended localized use of geo-mapping to identify and map communities with low immunisation coverage in Mutum Biyu Ward "B" of Gassol LGA, Taraba State.