European Organization for Research and Treatment of Cancer

BCG immunotherapy is the gold-standard treatment for non-muscle-invasive bladder cancer at high risk of recurrence or progression. Preclinical and clinical studies have revealed that a robust inflammatory response to BCG involves several steps: attachment of BCG; internalization of BCG into resident immune cells, normal cells, and tumour urothelial cells; BCG-mediated induction of innate immunity, which is orchestrated by a cellular and cytokine milieu; and BCG-mediated initiation of tumour-specific immunity. As an added layer of complexity, variation between clinical BCG strains might influence development of tumour immunity. However, more than 40 years after the first use of BCG for bladder cancer, many questions regarding its mechanism of action remain unanswered. Clearly, a better understanding of the mechanisms underlying BCG-mediated tumour immunity could lead to improved efficacy, increased tolerance of treatment, and identification of novel immune-based therapies. Indeed, enthusiasm for bladder cancer immunotherapy, and the possibility of combining BCG with other therapies, is increasing owing to the availability of targeted immunotherapies, including checkpoint inhibitors. Understanding of the mechanism of action of BCG immunotherapy has advanced greatly, but many questions remain, and further basic and clinical research efforts are needed to develop new treatment strategies for patients with bladder cancer.

Mechanisms of BCG immunotherapy and its outlook for bladder cancer.

In Deutschland ist seit 2015 ein deutlicher Anstieg der gemeldeten Tuberkulosefalle zu verzeichnen. Zuruckzufuhren ist dieser vor allem auf die aktuell vermehrte Migration. Durch die niedrige Inzidenz in den vorhergehenden Jahren konzentriert sich die Erfahrung im Umgang mit Tuberkulose immer mehr auf spezialisierte Zentren. Pneumologen wie auch andere Fachbereiche sind nun aber wieder haufiger an der Behandlung einer Tuberkulose beteiligt, sodass Fachwissen zur Standardtherapie wie auch zu selteneren Therapiesituationen benotigt wird. Die aktuelle Leitlinie zur Diagnostik und Therapie, einschlieslich Chemopravention und -prophylaxe im Erwachsenenalter fasst den derzeitigen Wissensstand zusammen und passt die Empfehlungen an die Situation in Deutschland an. Realisiert wurde die AWMF S2k-Leitlinie durch das Deutsche Zentralkomitee zur Bekampfung der Tuberkulose e. V. (DZK) im Auftrag der Deutschen Gesellschaft fur Pneumologie und Beatmungsmedizin e. V. (DGP). Zur Behandlung der Tuberkulose im padiatrischen Bereich wird in Kurze eine eigenstandige Leitlinie der entsprechenden Fachgesellschaften veroffentlicht. Im Vergleich zu den Empfehlungen von 2012 sind eigenstandige Kapitel zur Labordiagnostik und zum therapeutischen Medikamentenmanagement entstanden. Die Kapitel Mehrfachresistenzen gegen Medikamente der Standardtherapie, HIV-Koinfektion und die Ubersicht der Arzneimittel wurden erweitert. Die umfangreiche Uberarbeitung der Empfehlungen soll Arzten und auch anderen Beschaftigten im Gesundheitswesen helfen, den aktuellen Herausforderungen im Umgang mit dem selten gewordenen Tuberkuloseerreger zu begegnen.

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S2k-Leitlinie: Tuberkulose im Erwachsenenalter

Genitourinary Tuberculosis (GUTB) is the second most common extra-pulmonary manifestation of tuberculosis (Tb) and an isolated involvement of genital organs is reported in 5–30% of the cases. Genital involvement results from primary reactivation of latent bacilli either in the epididymis or the prostate or by secondary spread from the already infected urinary organs. The epididymis are the commonest involved organs affected primarily by a hematogenous mode of spread. Tb is characterized by extensive destruction and fibrosis, thus an early diagnosis may prevent function and organ loss. The gold standard for diagnosis is the isolation and culture of mycobacterium tuberculosis bacilli and in the cases of suspected GUTB, it is commonly looked for in the urinary samples. All body fluid specimens from possible sites of infection and aspirates from nodules must also be subjected to examination. Radiologic investigations including ultrasonography and contrast imaging may provide supportive evidence. Anti-tubercular chemotherapy is the first line of management for all forms of genital Tb and a 6 months course is the standard of care. Most patients with tubercular epididymo-orchitis respond to antitubercular therapy but may require open or percutaneous drainage. Infertility resulting from the tubercular affliction of the genitalia is multifactorial in origin and may persist even after successful chemotherapy. Multiple organ involvement with obstruction at several sites is characteristic and most of these cases are not amenable to surgical reconstruction. Thus, assisted reproduction is usually required. Post treatment, regular annual follow up is recommended even though, with the current multi drug therapy, the chances of relapse are low.

Genital tuberculosis: current status of diagnosis and management

https://www.research.unipd.it/bitstream/11577/3194216/3/accepted%20paper.pdf

A pH-sensitive stearoyl-PEG-poly(methacryloyl sulfadimethoxine)-decorated liposome system for protein delivery: An application for bladder cancer treatment.

Bacillus Calmette-Guérin (BCG) infection following intravesical BCG administration as adjunctive therapy for bladder cancer: incidence, risk factors, and outcome in a single-institution series and review of the literature.

Objectives. This study aimed to compare the characteristics of fully and partially vaccinated or unvaccinated coronavirus disease 2019 (COVID-19) patients who were hospitalised in a population of 220,000 habitants. Methods: Retrospective, observational, and population studies were conducted on patients who were hospitalised due to COVID-19 from March to October 2021. We assessed the impact of vaccination and other risk factors through Cox multivariate analysis. Results: A total of 500 patients were hospitalised, among whom 77 (15.4%) were fully vaccinated, 86 (17.2%) were partially vaccinated, and 337 (67.4%) were unvaccinated. Fully vaccinated (FV) patients were older and had a higher Charlson index than those of partially vaccinated and unvaccinated patients (NFV). Bilateral pneumonia was more frequent among NFV (259/376 (68.9%)) than among FV patients (32/75 (42.7%)). The former had more intensive care unit admissions (63/423) than the latter (4/77); OR: 2.80; CI (1.07–9.47). Increasing age HZ: 1.1 (1.06–1.14)) and haematological disease at admission HZ: 2.99 (1.26–7.11)) were independent risk factors for higher mortality during the first 30 days of hospitalisation. The probability of an earlier discharge in the subgroup of 440 patients who did not die during the first 30 days of hospitalisation was related to age (older to younger: HZ: 0.98 (0.97–0.99)) and vaccination status. Conclusions: Among the patients hospitalised because of COVID-19, complete vaccination was associated with less severe forms of COVID-19, with an earlier discharge date. Age and haematological disease were related to a higher mortality rate during the first 30 days of hospitalisation.

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Comparative Study of Vaccinated and Unvaccinated Hospitalised Patients: A Retrospective Population Study of 500 Hospitalised Patients with SARS-CoV-2 Infection in a Spanish Population of 220,000 Inhabitants

To study the serological response (SR) and tolerability of COVID-19 vaccine in patients with inflammatory bowel disease (IBD) and its relation with IBD treatment and type of vaccine. Observational, cross-sectional study in patients with IBD vaccinated against COVID-19 without known previous infection. SR was analyzed by the determination of IgG antibodies against the S1 subunit. Safety was studied using a questionnaire to identify adverse effects (AE). 280 patients with IBD were included. Type of vaccines: Comirnaty® 68.8%; Spikevax® 10.8%, Vaxzevria® 18.3%, Ad26.COV2-S® 2.2%. 51.3% had AE, being 100% mild. 65% developed IgG antibodies after vaccination. The SR was higher for vaccines with mRNA technology (100% Spikevax®, 68.5% Comirnaty®) compared to those based on adenovirus vector (38.0% Vaxzevria®, 33.3% Ad26.COV2-S®) (P < .001). In the multivariate analysis, SR was related to age (<60 years; OR: 3.8, 95% CI 1.9–7.0; P < .001). The SR in patients with aminosalicylates was 65.4%, 61.4% with immunosuppressants, 65.8% with anti-TNF, and 68.7% with non-anti-TNF biologicals (P = .9). One third of patients with IBD did not develop antibodies with the initial vaccination against SARS-CoV-2. The SR to vaccines based on mRNA technology was higher, and it was related to age (higher in younger patients). Immunosuppressants and biologicals did not decrease SR. More than half of the patients presented AD, being mild in all cases. Estudiar la respuesta serológica (RS) y tolerabilidad frente a la vacuna COVID-19 en pacientes con enfermedad inflamatoria intestinal (EII) y su relación con el tratamiento de la EII y tipo de vacuna. Estudio observacional, transversal en pacientes con EII vacunados contra COVID-19 sin infección previa conocida. La RS se analizó mediante la determinación de anticuerpos IgG frente a la subunidad S1. La seguridad se estudió mediante cuestionario para identificación de efectos adversos (EA). Se incluyeron 280 pacientes con EII. Tipo de vacunas: Comirnaty® 68,8%; Spikevax® 10,8%, Vaxzevria® 18,3%, Ad26.COV2-S® 2,2%. Un 51,3% tuvo EA, siendo el 100% leves. Un 65% desarrolló anticuerpos IgG tras la vacunación. La RS fue superior para vacunas con tecnología ARNm (100% Spikevax®, 68,5% Comirnaty®) frente a las basadas en vector con adenovirus (38,0% Vaxzevria®, 33,3% Ad26.COV2-S®) (P < ,001). En el análisis multivariante la RS se relacionó con la edad (<60 años; OR: 3,8, IC 95% 1,9–7,0; P < ,001). La RS en pacientes con aminosalicilatos fue del 65,4%, 61,4% con inmunosupresor, 65,8% con anti-TNF y 68,7% con biológicos no anti-TNF (P = ,9). Un tercio de pacientes con EII no desarrolló anticuerpos con la pauta vacunal inicial frente a SARS-CoV-2. La RS a las vacunas basadas en tecnología ARNm fue superior, y estuvo relacionada con la edad (mayor en pacientes más jóvenes). Los inmunosupresores y biológicos no disminuyeron la RS. Más de la mitad de los pacientes presentaron EA, leves en todos los casos. 

https://doi.org/10.1016/j.gastre.2022.05.001

Santiago Prieto

Papers

Bacillus Calmette-Guérin (BCG) infection following intravesical BCG administration as adjunctive therapy for bladder cancer: incidence, risk factors, and outcome in a single-institution series and review of the literature.

Comparative Study of Vaccinated and Unvaccinated Hospitalised Patients: A Retrospective Population Study of 500 Hospitalised Patients with SARS-CoV-2 Infection in a Spanish Population of 220,000 Inhabitants

Serological response to vaccines against SARS-CoV-2 in patients with inflammatory bowel disease