Nonlinear Analysis of the C-Peptide Variable Related to Type 1-Diabetes Mellitus

Type-1 diabetes mellitus is a chronic disease that is constantly monitored worldwide by researchers who are strongly determined to establish mathematical and experimental strategies that lead to a breakthrough toward an immunological treatment or a mathematical model that would update the UVA/Padova algorithm. In this work, we aim at a nonlinear mathematical analysis related to a fifth-order ordinary differential equations model that describes the asymmetric relation between C-peptides, pancreatic cells, and the immunological response. The latter is based on both the Localization of Compact Invariant Set (LCIS) appliance and Lyapunov’s stability theory to discuss the viability of implementing a possible treatment that stabilizes a specific set of cell populations. Our main result is to establish conditions for the existence of a localizing compact invariant domain that contains all the dynamics of diabetes mellitus. These conditions become essential for the localizing domain and stabilize the cell populations within desired levels, i.e., a state where a patient with diabetes could consider a healthy stage. Moreover, these domains demonstrate the cell populations’ asymmetric behavior since both the dynamics and the localizing domain of each cell population are defined into the positive orthant. Furthermore, closed-loop analysis is discussed by proposing two regulatory inputs opening the possibility of nonlinear control. Additionally, numerical simulations show that all trajectories converge inside the positive domain once given an initial condition. Finally, there is a discussion about the biological implications derived from the analytical results.

ABORDAGENS TERAPÊUTICAS IMUNOLÓGICAS NO MANEJO DA EPIDERMÓLISE BOLHOSA: UMA REVISÃO DE LITERATURA

Introdução: A epidermólise bolhosa (EB) é uma doença congênita, rara, autossômica dominante, autoimune da pele que pode ter acometimento multissistêmico e levar a malignidade. Ocorre devido a mutações nas proteínas de ancoragem entre a epiderme e a derme, e se caracteriza pela formação de vesículas ou bolhas principalmente em locais de maior atrito. Essa patologia é subdivida em quatro tipos de acordo com a sua proteína mutante: simples, juncional, distrófica e síndrome de Kindler. Além disso, a EB apresenta elevada morbimortalidade pois não há tratamento específico. Objetivos: Realizar um levantamento bibliográfico para descrever e comparar as principais atualizações terapêuticas de caráter imunológico que auxiliam no tratamento da epidermólise bolhosa a fim de conscientizar os profissionais da saúde acerca do tema. Material e métodos: Trata-se de um estudo de revisão de literatura de cunho descritivo e analítico. Foi realizada uma busca eletrônica nas bases de dados Pubmed, Biblioteca Virtual em Saúde, Schoolar Google e Scielo publicados entre 2013 e 2021. As palavras de busca foram: epidermólise bolhosa, tratamento imunológico, epidermolysis bullosa, immunological treatment. Foram selecionados 14 estudos contendo dados sobre atualizações em tratamentos imunológicos para EB. Resultados: Houve predomínio de 8 opções terapêuticas imunológicas: transplante de células tronco alogênicas, infusão de células tronco mesenquimais, transplante de medula óssea, tratamento subcutâneo com fator estimulador de colônia de granulócitos, rituximab, imunoglobulina intravenosa, apremilast e calcipotrol tópico. Desses, a maioria indicou evidências de melhora clínica na redução de 75% na formação de bolhas, remissão prolongada de bolhas e vesículas por mais de 12 meses e boa resposta ao tratamento, elevando assim a qualidade vida dos portadores de EB. No entanto, ainda não existem evidências de cura e apesar da terapêutica atual resultar em queda da mortalidade, essa ainda representa cerca de 15%. Conclusão: A epidermólise bolhosa apresenta baixa prevalência e tem ampla manifestação clínica. O tratamento ideal se relaciona diretamente com a sintomatologia do paciente, subtipo e extensão da patologia. Portanto, tornam-se necessárias abordagens individualizadas para que a terapêutica possa ser viável, eficaz e com reações adversas toleráveis a fim de melhorar a qualidade de vida dos portadores da doença.

Autoimplantation – An Immunological Treatment For Multiple Warts

Introduction. Warts are benign epithelial lesions that involve skin and mucosa. Successful management depends on the patient’s immunity, site and type of wart. In spite of huge therapeutic armory available, no treatment has been found to be effective so far. Objective. To evaluate the effectiveness of autoimplantation in the management of multiple warts. Material and Methods. This is a hospital based prospective study of forty patients with multiple warts. A prospective, hospital-based study included forty cases of multiple warts for autoimplantation. Resolution of warts within three months was taken as complete clearance; the follow up of any recurrence lasted six months. Results. The majority of patients were males (69.7%), belonging to 21–30 years age group (57.6%). Complete resolution was observed in 25 patients, partial response was achieved in 5 patients and there was no response in 3 patients. The majority of patients did not have any complication or recurrence Conclusion. Autoimplantation is a simple, daycare, effective procedure. It provides resistance by inducing cell mediated immunity and also prevents recurrence to a great extent.

Successful treatment of a critically ill patient with COVID-19 using tocilizumab and human umbilical cord mesenchymal stem cells: a case report

Background A worldwide outbreak of coronavirus disease 2019 (COVID-19) has drawn global attention. However, up to now, no standard and effective therapy are available. Case presentation A 62-year-old man with a history of hypertension and diabetes was diagnosed with COVID-19 pneumonia. He suffered from obvious shortness of breath and severe hyoxemia. Normal treatments like supportive therapy and antiviral drugs didn’t seem to improve his conditions. Then, he was given tocilizumab and human umbilical cord mesenchymal stem cells. After that, his respiratory symptoms and lung infectious lesions gradually subsided, and he was successfully discharged eventually. Conclusions For critically ill COVID-19 patients, immunological treatment like tocilizumab human umbilical cord mesenchymal stem cells should be considered.

SARS-CoV-2 Inflammatory Syndrome. Clinical Features and Rationale for Immunological Treatment

The current pandemic coronavirus, SARS-CoV-2, is a global health emergency because of its highly contagious nature, the great number of patients requiring intensive care therapy, and the high fatality rate. In the absence of specific antiviral drugs, passive prophylaxis, or a vaccine, the treatment aim in these patients is to prevent the potent virus-induced inflammatory stimuli from leading to the acute respiratory distress syndrome (ARDS), which has a severe prognosis. Here, the mechanism of action and the rationale for employing immunological strategies, which range from traditional chemically synthesized drugs, anti-cytokine antibodies, human immunoglobulin for intravenous use, to vaccines, are reviewed.

Management of hepatitis B in the era of checkpoint inhibition

Hepatitis B virus (HBV) is a major global health concern, affecting more than 350 million people worldwide. Its management in the setting of cancer treatment can be problematic, particularly with the use of immunological treatment modalities, but also with chemotherapy. Immunological perturbations by chemo or immunotherapy have the potential to permit viral hepatitis reactivation and acute hepatic failure. HBV management algorithms have evolved, based on host tumor factors, viral serological factors, and the specific antitumor agents planned. As new agents enter the antitumor armamentarium, their impact on HBV infection needs to be defined. Zhanget alprovide data on the utility of antiviral therapy in the management of HBV antigen positive patients receiving checkpoint inhibitors (CPIs) in preventing hepatitis reactivation, and offers guidance for such management in endemic areas, suggesting that prophylaxis is highly effective in preventing reactivation. This is pertinent to Western cancer therapy also, as a recent study has documented the silent existence of positive hepatitis antigenemia among newly diagnosed cancer patients. Whereas antigen and viral DNA screening is standard of care in Asia and Western Pacific oncology practice, evaluation for latent hepatitis may become a necessary part of management worldwide as CPIs continue to expand their role.

Updates and new perspectives in nonmelanoma skin cancer therapy: highlights from ‘Immunotherapy Bridge’

Over the last few years, extensive research has improved our understanding of tumor immunology and has enabled the development of novel treatments. The state of the art of immunotherapy in various types of malignancies was exhaustively discussed in the ‘Immunotherapy Bridge’ meeting, which was held in Naples on 4–5 December 2019. Highlights related to the immunological treatment of nonmelanoma skin cancer are the content of this article.