Journal of internal medicine
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The incidence of cutaneous melanoma and the mortality rate of advanced melanoma patients continue to rise globally. Despite the recent success of immunotherapy including ipilimumab and pembrolizumab checkpoint inhibitors, a large proportion of patients are refractory to such treatment modalities. The application of mycobacteria such as Bacillus Calmette-Guérin (BCG) in the treatment of various malignancies, including cutaneous melanoma, has been clearly demonstrated after almost a century of observations and experimentation. ⋯ In this review, we discuss the immunostimulatory potential of different BCG substrains and highlight clinical studies utilizing BCG immunotherapy for the treatment of cutaneous melanoma. Furthermore, the review focuses on the cellular and molecular mechanisms of the BCG-induced immune responses of both the innate and adaptive arms of the immune system. Furthermore, the review discussed the administration of BCG as a monotherapy or in combination with other immunotherapeutic or chemotherapeutic agents.
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The COVID-19 pandemic has affected most parts of the global society since its emergence, and the scientific community has been challenged with questions urgently demanding answers. One of the early hypotheses on COVID-19 outcome was that some protection could be offered by the tuberculosis vaccine (BCG), and several clinical studies were initiated along with the emergence of numerous observational studies on the relationship between BCG and COVID-19 severity. ⋯ Further analyses of age groups in two European countries with comparably few confounding factors and easily identifiable groups of BCG-vaccinated and non-vaccinated subgroups suggest a population-level effect of BCG on national outcomes of COVID-19. This phenomenon of 'heterologous herd immunity' deserves further investigation, both in epidemiological and experimental studies.
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Senolytics are a class of drugs that selectively clear senescent cells (SC). The first senolytic drugs Dasatinib, Quercetin, Fisetin and Navitoclax were discovered using a hypothesis-driven approach. SC accumulate with ageing and at causal sites of multiple chronic disorders, including diseases accounting for the bulk of morbidity, mortality and health expenditures. ⋯ Early pilot trials of senolytics suggest they decrease senescent cells, reduce inflammation and alleviate frailty in humans. Clinical trials for diabetes, idiopathic pulmonary fibrosis, Alzheimer's disease, COVID-19, osteoarthritis, osteoporosis, eye diseases and bone marrow transplant and childhood cancer survivors are underway or beginning. Until such studies are done, it is too early for senolytics to be used outside of clinical trials.
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The prognosis of patients with biliary atresia (BA) after Kasai portoenterostomy (KPE) varies, and precisely predicting the outcomes of KPE before surgery is still challenging. ⋯ The combined nomogram model based on 2D SWE values, age, GGT and APRI prior to KPE can effectively predict NLS in BA infants.