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1.
Korean J Radiol ; 23(1): 60-67, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34983094

RESUMO

OBJECTIVE: To categorize multiparametric MRI features of Bacillus Calmette-Guérin (BCG)-related granulomatous prostatitis (GP) and discover potential manifestations for its differential diagnosis from prostate cancer. MATERIALS AND METHODS: The cases of BCG-related GP in 24 male (mean age ± standard deviation, 66.0 ± 9.4 years; range, 50-88 years) pathologically confirmed between January 2011 and April 2019 were retrospectively reviewed. All patients underwent intravesical BCG therapy followed by a MRI scan. Additional follow-up MRI scans, including diffusion-weighted imaging (DWI), were performed in 19 patients. The BCG-related GP cases were categorized into three: A, B, or C. The lesions with diffusion restriction and homogeneous enhancement were classified as type A. The lesions with diffusion restriction and a poorly enhancing component were classified as type B. A low signal intensity on high b-value DWI (b = 1000 s/mm²) was considered characteristic of type C. Two radiologists independently interpreted the MRI scans before making a consensus about the types. RESULTS: The median lesion size was 22 mm with the interquartile range (IQR) of 18-26 mm as measured using the initial MRI scans. The lesion types were A, B, and C in 7, 15, and 2 patients, respectively. Cohen's kappa value for the inter-reader agreement for the interpretation of the lesion types was 0.837. On the last follow-up MRI scans of 19 patients, the size decreased (median, 5.8 mm; IQR, 3.4-8.5 mm), and the type changed from A or B to C in 11 patients. The lesions resolved in four patients. In five patients who underwent prostatectomy, caseous necrosis on histopathology matched with the non-enhancing components of type B lesions and the entire type C lesions. CONCLUSION: BCG-related GP demonstrated three imaging patterns on multiparametric MRI. Contrast-enhanced T1-weighted imaging and DWI may play a role in its differential diagnosis from prostate cancer.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Prostatite , Neoplasias da Bexiga Urinária , Idoso , Idoso de 80 Anos ou mais , Vacina BCG/efeitos adversos , Imagem de Difusão por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico por imagem , Prostatite/induzido quimicamente , Prostatite/diagnóstico por imagem , Estudos Retrospectivos
2.
Support Care Cancer ; 30(1): 887-895, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34398288

RESUMO

PURPOSE: We investigated sleep parameters and patient-reported outcomes before, during, and after induction Bacillus Calmette-Guerin therapy using questionnaires and actigraphy in patients with non-muscle invasive bladder cancer. METHODS: We investigated 10 patients who received Bacillus Calmette-Guerin therapy once weekly for 8 weeks. The International Prostate Symptom Score, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, Functional Assessment of Cancer Therapy-Bladder, and multi-item Short Form-8 tools were used to assess patient-reported outcomes. Participants completed all questionnaires before (baseline), at the 4th and 8th doses, and 1 month after the last Bacillus Calmette-Guerin dose. The MotionWatch8 was fastened to patients' waist throughout the study. Composite sleep quality was determined based on sleep duration, efficiency, and fragmentation. RESULTS: We observed a transient increase in frequency/nocturia subscores and the insomnia subscore. The number of patients with poor sleep quality increased from 0 (0%) at baseline to 7 (70%) at the 4th dose and to 6 (60%) patients at the 8th dose. Among 10 patients, 6 (60%) were assigned to the sleep deterioration group and 4 (40%) to the non-deterioration group. Sleep quality was restored to baseline levels in 5 of 6 patients (83%) within 1 month after the last dose in the sleep deterioration group, and the nocturia subscore of the International Prostate Symptom Score was significantly increased only in this group (P=0.03). CONCLUSIONS: This is the first study that confirms intravesical Bacillus Calmette-Guerin-induced sleep quality deterioration based on a questionnaire survey and actigraphy.


Assuntos
Vacina BCG , Neoplasias da Bexiga Urinária , Actigrafia , Vacina BCG/efeitos adversos , Humanos , Masculino , Invasividade Neoplásica , Avaliação de Resultados em Cuidados de Saúde , Qualidade de Vida , Inquéritos e Questionários , Neoplasias da Bexiga Urinária/tratamento farmacológico
3.
BMC Infect Dis ; 21(1): 1264, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930152

RESUMO

BACKGROUND: From May 2020 to January 2021, we enrolled 1233 health care workers (HCW) from Danish Hospitals in a randomized trial evaluating whether Bacille Calmette-Guérin (BCG) provides protection against COVID-19. Participants were randomized 1:1 to BCG vs saline and followed for 6 months. From December 2020, Covid-19 vaccines were offered to the HCW. In most cases, BCG vaccination results in a characteristic scar. Reactivation of the BCG scar has been described in children during viral infections and following influenza vaccination, but is mostly associated to Kawasaki's disease, a disease entity with pathogenesis likely similar to the child Covid-19 complication MIS-C: Multi-System Inflammatory Syndrome. Reactivation of scars after neonatal BCG vaccination has recently been described in four women after Covid-19 mRNA vaccination. Two of our trial participants experienced reactivation of their novel BCG scars after receiving mRNA Covid-19 vaccination 6 to 8 months post-BCG. CASE PRESENTATIONS: Two female HCW participants that had been randomly allocated to BCG in the BCG-DENMARK-COVID trial, spontaneously reported itching and secretion at the BCG scar site after having received mRNA Covid-19 vaccination (Moderna and Pfizer-BioNTech) 6 to 8 months following inclusion and BCG vaccination. One participant, who had a larger BCG skin reaction, noticed re-appearing symptoms after both the first and the second COVID-vaccine dose, while the other participant only noted symptoms after the second dose. Both had been BCG vaccinated during childhood, and no reactivation was noted in the older scars. No treatment was needed or provided. CONCLUSIONS: The reactivation of the BCG scar after receiving mRNA vaccine might have been caused by cross-reactivity between BCG and SARS-CoV-2. In both cases, the symptoms were bothersome, but self-limiting and left no sequelae. The risk of reactivation at the scar site is thus not a reason to avoid vaccination with either vaccine.


Assuntos
Vacina BCG , COVID-19 , Vacina BCG/efeitos adversos , COVID-19/complicações , Vacinas contra COVID-19 , Criança , Cicatriz , Feminino , Humanos , Recém-Nascido , RNA Mensageiro/genética , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica , Vacinação , Vacinas Sintéticas
4.
J Investig Med High Impact Case Rep ; 9: 23247096211066287, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34937411

RESUMO

Mycobacterium tuberculosis complex (MTBC) false-positive cultures are commonly attributed to laboratory cross-contamination, but cross-contamination in the operating room (OR) is seldom reported. We report an investigation of cross-contamination in the OR for our case patient, who underwent surgical intervention for a chronic, left-sided breast lesion. Although the case patient had never received Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine or chemotherapy, a subsequent surgical sample culture was identified as MTBC by high-performance liquid chromatography and M. bovis BCG-type by genotyping. A collaborative false-positive investigation was initiated, and we discovered a cross-contamination event in the OR from a source case who received BCG intravesical instillation. Clinicians, public health, and infection control staff should be aware that MTBC cross-contamination in the OR is rare, but possible, and should recognize the importance of conducting thorough false-positive investigations.


Assuntos
Vacina BCG , Reações Falso-Positivas , Salas Cirúrgicas , Administração Intravesical , Vacina BCG/efeitos adversos , Contaminação de Equipamentos , Humanos , Mycobacterium bovis
5.
BMJ Case Rep ; 14(11)2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34815228

RESUMO

Mycotic aneurysms are rare and if left untreated, can have devastating outcomes. In this case, a 72-year-old man presented to hospital with fevers, night sweats and abdominal pain. A CT scan revealed the development an infrarenal pseudoaneurysm over the course of 8 weeks, increasing from 2.8 cm to a 3.1 cm. The aneurysm was not present on a CT scan performed 6 months earlier. The patient underwent an emergency endovascular repair of the aortic aneurysm (EVAR) and was placed on broad-spectrum antibiotics. Intra-aortic blood cultures aspirated adjacent to the aneurysm and tissue biopsy confirmed tuberculosis bovis as the cause of the mycotic aneurysm. The patient had been treated with intravesical BCG for transitional cell carcinoma of the bladder several months prior. The patient was treated with an extended course of antituberculosis medication. He recovered well and was back to his baseline function within weeks.


Assuntos
Aneurisma Infectado , Aneurisma da Aorta Abdominal , Aneurisma Aórtico , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Administração Intravesical , Idoso , Aneurisma Infectado/diagnóstico por imagem , Aneurisma Infectado/tratamento farmacológico , Aneurisma Infectado/etiologia , Antituberculosos/uso terapêutico , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/tratamento farmacológico , Aneurisma da Aorta Abdominal/cirurgia , Vacina BCG/efeitos adversos , Carcinoma de Células de Transição/tratamento farmacológico , Humanos , Masculino , Neoplasias da Bexiga Urinária/tratamento farmacológico
6.
Scand J Immunol ; 94(4): e13084, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34780073

RESUMO

BCG infections occur more frequently in patients with underlying primary immunodeficiency disease (PIDD). In this study, we aimed to evaluate the ratio of PIDD in the patients with BCG infections. Patients with BCG infections were analyzed in a tertiary referral centre in the 2015-2020 period. Forty-seven patients with BCGitis/BCGosis were evaluated; thirty-four (72.3%) had BCGitis, and 13 (27.7%) had BCGosis. Common tissue and organs affected are lymph nodes (57.4%), skin and subcutaneous tissue (48.9%), lungs (23.4%) and liver (17%). PIDD was shown in 26 patients (55.3%), including 92.3% of patients with BCGosis and 41.2% of patients with BCGitis. Ten patients had Mendelian susceptibility to Mycobacterial disease (MSMD) (21.2%), six had predominantly antibody deficiency (PAD) (12.7%), five had severe combined immunodeficiency (SCID) (10.6%), three had CGD (6.3%), and two had CID (4.2%). Mortality was reported in two patients (4.2%) with CID (ZAP70 deficiency (n = 1) and PIK3R1 deficiency (n = 1)). Parental consanguinity (84%), axillary lymphadenopathy (65%), mycobacterial lung disease (42%), hepatomegaly (30%) and growth retardation (19%) were significantly high in patients with PIDD diagnosis. Isolated vaccination site infection was also recorded in patients with PIDD (CID (n = 1), SCID (n = 1), PAD (n = 5)). BCG vaccination should be planned with caution for the cases with suspected PIDD. This study indicates that almost all patients (92.3%) with BCGosis and one in every two patients (41.2%) with BCGitis have an underlying PIDD. Parental consanguinity, axillary lymphadenopathy, mycobacterial lung disease, hepatomegaly and growth retardation (19%) are important clinical features in the differential diagnosis of PIDD.


Assuntos
Mycobacterium bovis , Doenças da Imunodeficiência Primária/complicações , Doenças da Imunodeficiência Primária/diagnóstico , Tuberculose/complicações , Vacina BCG/administração & dosagem , Vacina BCG/efeitos adversos , Pré-Escolar , Estudos de Coortes , Diagnóstico Diferencial , Suscetibilidade a Doenças , Feminino , Humanos , Lactente , Masculino , Especificidade de Órgãos , Doenças da Imunodeficiência Primária/imunologia , Estudos Retrospectivos , Tuberculose/etiologia , Tuberculose/imunologia
7.
Arch Esp Urol ; 74(9): 875-882, 2021 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34726624

RESUMO

OBJECTIVES: To evaluate the oncological results of hyperthermic Mitomycin C (MMC) in adjuvant treatment of high-risk non-muscle invasive bladder cancer and to assess its side-effect profile. METHODS: Patients who were followed up in two reference university hospitals due to high-risk non-muscle invasive bladder tumors were included in the study. High-risk patients according to the EAU non-muscle invasive bladder cancer guideline, patients who were rejected early cystectomy, patients who could not be treated with BCG due to a shortage, and patients for whom the cystectomy would be too risky due to their comorbidities were included in the study. All patients were followed up forat least 24 months with physical examination, cystoscopy, and urine cytology at 3-month intervals. Transurethral tumor resection was performed in all patients and a non-muscle invasive urothelial carcinoma was diagnosed pathologically. Hyperthermic MMC was administered with Synergo system SB-TS 101. Records were kept prospectively and evaluated retrospectively. RESULTS: Fifty-eight high-risk group patients 18 (31%) of whom were at pTa stage and 40 (69%) at pT1 stage were included in the study. During a mean follow-up of 42 months, 34 (58%) patients had recurrence, while 5 (8%) patients progressed to muscle-invasive disease. Eleven (19%) of the patients under went radical cystectomy. The mean time to relapse was 10 months (3-34 months), and the mean time to progression was 41 months (6-87 months). Five-year overall survival, cancer-specific survival, progression-free survival, and relapse-free survival of the patients were 76%, 88%, 90% and 38%, respectively. Multifocality alone was found to be an independent risk factor (HR: 0.26; 95% Cl: 0.08-0.78; p=0.016) affecting recurrence. The observed side effects included tachycardia, cystitis, dysuria, macrohematuria, procedure-related pain, and allergic skin reactions. Treatment had to be discontinued in one patient due to a diffuse skin reaction. CONCLUSIONS: Thermal intravesical MMC therapyis a safe treatment and it could be effective treatment option in preventing disease progression in patients with high risk and non-muscle invasive bladder cancer with unsuccessful Bacillus Calmette-Guérin (BCG) or who could not be treated with BCG for other reasons.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Vacina BCG/efeitos adversos , Carcinoma de Células de Transição/tratamento farmacológico , Quimioterapia Adjuvante , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico
8.
BMJ Case Rep ; 14(11)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753717

RESUMO

Immunotherapy with BCG is an effective and widely used treatment for non-muscle-invasive bladder cancer. BCG sepsis is a rare but life-threatening and frequently not a straightforward complication of this treatment; in cases with a high index of suspicion, anti-bacillary treatment should not wait for laboratory confirmation and be instituted immediately. We report a severe case of BCG sepsis, in which timely diagnosis and initiation of antituberculosis agents enabled a full recovery.


Assuntos
Vacina BCG , Sepse , Neoplasias da Bexiga Urinária , Administração Intravesical , Vacina BCG/efeitos adversos , Humanos , Imunoterapia , Neoplasias da Bexiga Urinária/tratamento farmacológico
10.
Am J Case Rep ; 22: e933006, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34654796

RESUMO

BACKGROUND Bladder cancer (BC) is the second most common cancer involving the urinary system. In non-muscle-invading BC, transurethral resection of a bladder tumor followed by intravesical immunotherapy with Bacillus Calmette-Guerin (BCG) is the usual treatment. Disseminated (or systemic) BCG infection (BCGitis) represents the most severe adverse effect of intravesical BCG therapy, presenting with high-grade fever, with or without symptoms in the urinary tract, leading to severe sepsis and death if left untreated. The treatment of choice consists of isoniazid, rifampicin, and ethambutol (with or without corticosteroids) for 6 months, and the recovery rate is extremely high. Given the fact that these drugs are hepatotoxic, treating a patient with liver cirrhosis is challenging. CASE REPORT We present a patient with a medical history of BC treated with transurethral resection and intravesical BCG therapy, presenting with fever, transaminasemia, and generalized weakness. Liver and bone marrow biopsies revealed liver cirrhosis and granulomas in both organs. A diagnose of BCGitis was made and the patient was treated with isoniazid, rifampicin, and ethambutol; rifampicin was substituted with moxifloxacin after 1 month due to worsening of liver laboratory results, and moxifloxacin was substituted with levofloxacin later on due to tonic-clonic seizures. The patient was treated for 4 more months with levofloxacin and for 7 more months with isoniazid and ethambutol, with no other adverse effects, preserving liver function and achieving cure of BCGitis. CONCLUSIONS We present the case of a cirrhotic patient presenting with fever and deterioration of liver laboratory results, found to have BCGitis, and discuss possible difficulties in diagnosing and treating such patients.


Assuntos
Mycobacterium bovis , Tuberculose , Neoplasias da Bexiga Urinária , Administração Intravesical , Vacina BCG/efeitos adversos , Humanos , Cirrose Hepática , Neoplasias da Bexiga Urinária/tratamento farmacológico
13.
BMC Infect Dis ; 21(1): 801, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380453

RESUMO

BACKGROUND: The management strategy of Bacille Calmette-Guérin (BCG) vaccine-induced regional suppurative lymphadenitis in children is still controversial and more clinical studies are needed. We therefore present a surgical case series to explore the role of surgical management for this dilemma. METHODS: From January 2013 to June 2020, data from 65 patients diagnosed with BCG vaccine-induced regional suppurative lymphadenitis were retrospectively reviewed. Clinical characteristics, ultrasonographic findings, surgical procedures, perioperative management, and outcome were analyzed. The association between postoperative seroma and symptom duration, skin involvement, and postoperative hospital stay were compared using Yates's corrected Chi-square test and Student's t-test for statistical analysis. The follow-up period ranged from three to six months. RESULTS: Of the 65 cases, the median age at presentation was 3.4 months. All patients were full-term with normal range of birth weight and received a BCG vaccination in the first 24 h of life. All patients underwent surgical excision of the abscess with the involved lymph node(s). Postoperative seroma formation was found in 20 patients and fine needle aspiration was needed. There was no significant association between postoperative seroma formation with symptom duration, skin involvement, and postoperative hospital stay. No oral anti-tubercular agents were given postoperatively. The mean length of postoperative hospital stay was 6.02 ± 1.62 days. Sixty-four cases (98.46%) received only one procedure and recovered. One patient required a second procedure due to postoperative sinus. CONCLUSIONS: The present study showed that surgical excision of the abscess with involved lymph node(s) is one of the choices for BCG vaccine-induced suppurative lymphadenitis, but special attention should be paid to controlling the surgical indications. Intraoperative meticulous manipulation and postoperative care are crucial to achieve a good outcome.


Assuntos
Vacina BCG , Linfadenite , Vacina BCG/efeitos adversos , Criança , Humanos , Lactente , Linfonodos , Linfadenite/induzido quimicamente , Estudos Retrospectivos , Vacinação/efeitos adversos
15.
Urologe A ; 60(9): 1184-1187, 2021 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34100955

RESUMO

We present the case of a 57-year-old man who developed an intraperitoneal bladder fistula with BCG-induced (bacillus Calmette-Guérin) abdominal granulomatosis after transurethral resection of a papillary non-muscle invasive bladder cancer and subsequent BCG-instillation therapy. The bladder fistula was eliminated surgically. The detection of Mycobacterium tuberculosis in the operative sample drawings as well as the histological detection of BCG-granuloma led to specific treatment and a report to the responsible health department.


Assuntos
Doenças da Bexiga Urinária , Neoplasias da Bexiga Urinária , Administração Intravesical , Vacina BCG/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Bexiga Urinária/induzido quimicamente , Doenças da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia
16.
J Cancer Res Ther ; 17(2): 609-612, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34121722

RESUMO

Intravesical instillation of Bacillus Calmette-Guérin (BCG) immunotherapy remains the most effective adjuvant treatment for noninvasive bladder cancer. Systemic BCG-related complications are rare and usually related to infective agent or an immune-mediated reaction. We discussed a case with perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) vasculitis, developing after instillation of BCG for non-invasive bladder cancer. A 68-year-old man presented with nephritic syndrome a few months after BCG instillations which was performed for his non-muscle-invasive bladder cancer adjuvant therapy. The renal function had declined slowly after the first instillation and urinary sediment reveals the new onset of nephritic proteinuria and hematuria. High titer of p-ANCA was present. His renal biopsy was consistent with acute renal vasculitis. The patient's creatinine level regressed with immunosuppressive therapy and he was clinically followed up without hemodialysis. Here, we presented a patient that diagnosed as p-ANCA related vasculitis occurred after BCG instillation.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vacina BCG/efeitos adversos , Carcinoma de Células de Transição/tratamento farmacológico , Síndrome Nefrótica/diagnóstico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/induzido quimicamente , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Vacina BCG/administração & dosagem , Carcinoma de Células de Transição/imunologia , Humanos , Masculino , Síndrome Nefrótica/sangue , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/imunologia , Neoplasias da Bexiga Urinária/imunologia
17.
Scand J Urol ; 55(4): 281-286, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34124993

RESUMO

INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) is one of the most frequent neoplasms in Denmark. Treatment of high-risk NMIBC usually consists of transurethral resection of bladder (TUR-B) followed by intravesical Bacillus Calmette-Guérin (BCG) instillations. Unfortunately, some patients are BCG-unresponsive and will relapse over time. Radical cystectomy is the recommended salvage treatment following BCG-failure or BCG-intolerance. However, not all patients are candidates for surgery and thus, in need of other treatment. This study investigates the adverse events of Hyperthermic Intravesical Chemotherapy (HIVEC) treatment. METHODS: Twenty-three high-risk NMIBC patients, who were BCG-unresponsive or had contraindications for BCG, received HIVEC with Mitomycin C. Prior to each instillation, patients were interviewed by a nurse, using a systematic questionnaire regarding the adverse events. Patients were followed with cytology and cystoscopy every fourth month. The primary outcome was adverse event related to the HIVEC treatment. RESULTS: In general, the adverse events were mild to moderate and often self-limiting. The most common adverse events were urinary frequency (23.6%), incontinence (19.4%) and urinary tract pain (12.2%). CONCLUSION: In the current study, we found that HIVEC was a well-tolerated treatment. HIVEC might be a feasible option for patients, who experienced BCG-failure or BCG-intolerance and could potentially postpone or avoid radical cystectomy.


Assuntos
Hipertermia Induzida , Neoplasias da Bexiga Urinária , Administração Intravesical , Vacina BCG/efeitos adversos , Humanos , Hipertermia Induzida/efeitos adversos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/tratamento farmacológico
18.
Sci Rep ; 11(1): 12417, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127755

RESUMO

A single intradermal vaccination with an antibiotic-less version of BCGΔBCG1419c given to guinea pigs conferred a significant improvement in outcome following a low dose aerosol exposure to M. tuberculosis compared to that provided by a single dose of BCG Pasteur. BCGΔBCG1419c was more attenuated than BCG in murine macrophages, athymic, BALB/c, and C57BL/6 mice. In guinea pigs, BCGΔBCG1419c was at least as attenuated as BCG and induced similar dermal reactivity to that of BCG. Vaccination of guinea pigs with BCGΔBCG1419c resulted in increased anti-PPD IgG compared with those receiving BCG. Guinea pigs vaccinated with BCGΔBCG1419c showed a significant reduction of M. tuberculosis replication in lungs and spleens compared with BCG, as well as a significant reduction of pulmonary and extrapulmonary tuberculosis (TB) pathology measured using pathology scores recorded at necropsy. Evaluation of cytokines produced in lungs of infected guinea pigs showed that BCGΔBCG1419c significantly reduced TNF-α and IL-17 compared with BCG-vaccinated animals, with no changes in IL-10. This work demonstrates a significantly improved protection against pulmonary and extrapulmonary TB provided by BCGΔBCG1419c in susceptible guinea pigs together with an increased safety compared with BCG in several models. These results support the continued development of BCGΔBCG1419c as an effective vaccine for TB.


Assuntos
Vacina BCG/administração & dosagem , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/prevenção & controle , Vacinação/métodos , Animais , Vacina BCG/efeitos adversos , Vacina BCG/imunologia , Modelos Animais de Doenças , Feminino , Cobaias , Humanos , Imunogenicidade da Vacina , Injeções Intradérmicas , Pulmão/imunologia , Pulmão/microbiologia , Camundongos , Mycobacterium tuberculosis/imunologia , Células RAW 264.7 , Tuberculose/diagnóstico , Tuberculose/imunologia , Tuberculose/microbiologia
20.
Oncoimmunology ; 10(1): 1912885, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33996264

RESUMO

Intravesical BCG is active against non-muscle invasive bladder cancer (NMIBC), but bladder cancer will recur and even progress in a significant number of patients. To improve the response rate, N-803, an IL-15 superagonist was administered in combination with BCG. To evaluate the safety and efficacy associated with the use of intravesical N-803 and BCG in patients with BCG-naïve NMIBC. This phase 1b clinical trial used a 3 + 3 dose-escalation design. Participants were enrolled from July 2014 and July 2015, with follow-up and analyses through January 15, 2021. Eligibility criteria included histologically confirmed non-muscle invasive urothelial carcinoma of intermediate or high risk who had not received prior treatment with intravesical BCG (ie, BCG-naïve). All 9 participants met the eligibility criteria, received treatment according to the protocol, and were included in all analyses. Treatment was done once weekly for 6 consecutive weeks with bladder infusion of the standard dose of BCG, 50 mg/instillation, in combination with increasing doses of N-803 (100, 200, or 400 µg N-803 per instillation). No DLTs were noted in any of the dose cohorts. All adverse events (AEs) were manageable and less than grade 3. During the 2-year follow-up, all 9 participants were disease free. Furthermore, 6 y after treatment, all 9 participants (100%) were disease free with no evidence of disease progression and an intact bladder. This phase 1b trial found the combination of intravesical N-803 and BCG to be associated with modest toxic effects, low immunogenicity, and substantial prolonged antitumoral activity; phase 2 trials are in progress.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Administração Intravesical , Vacina BCG/efeitos adversos , Carcinoma de Células de Transição/tratamento farmacológico , Humanos , Interleucina-15/uso terapêutico , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/tratamento farmacológico
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