Rheumatoid arthritis and myasthenia gravis: a case-based review of the therapeutic options

Introduction Myasthenia gravis is an autoimmune disease affecting the neuromuscular junction, often associated with other autoimmune diseases, including rheumatoid arthritis. Patients with rheumatoid arthritis present an increased prevalence of myasthenia gravis compared to the general population. While these two diseases share some therapeutic options, such as glucocorticoids, methotrexate, and rituximab, there are no guidelines for treating concomitant disease. We aim to review the available evidence and to discuss the efficacy and safety of the therapeutic options in patients with rheumatoid arthritis associated with myasthenia gravis. Method We described three patients with rheumatoid arthritis associated with myasthenia gravis and we performed a systematic review of the associated literature. Results A 48-year-old man and two women (48 and 55 years old) with concomitant diagnoses of active rheumatoid arthritis and well-controlled myasthenia gravis are described. They were treated with methotrexate, leflunomide, upadacitinib, and adalimumab. None of them experienced changes in their myasthenic symptoms. We found 9 additional cases from our literature review. Methotrexate, rituximab, upadacitinib, diphenyl sulfone, auranofin, and loxoprofen sodium did not show an impact on the seven patients with previously well-controlled myasthenia. Glucocorticoids, methotrexate, and rituximab proved effective in active myasthenia gravis and arthritis. Conflicting data emerged for Tumor-necrosis factor inhibitors. Conclusions Although the available evidence remains scarce, we consider glucocorticoids, methotrexate, and rituximab as safe and effective options. The role of tumor-necrosis factor inhibitors remains uncertain. Eventually, Janus Kinase inhibitors are a novel interesting option for these patients. Key Points• To date, the only evidence on the treatment of patients with rheumatoid arthritis and concomitant myasthenia gravis derives from case reports.• Based on the review of the available case reports and on the cases we described, we consider glucocorticoids, methotrexate, and rituximab as safe and effective options, while the role of Tumor-necrosis factor inhibitors remains uncertain.• Based on the cases we described, Janus Kinase inhibitors are a novel interesting option for patients with concomitant rheumatoid arthritis and myasthenia gravis.

Immunotherapy for Biliary Tract Cancer in the Era of Precision Medicine: Current Knowledge and Future Perspectives

Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the complex molecular landscape of biology is rapidly changing the therapeutic armamentarium. However, while 40–50% of patients there are molecular drivers susceptible to target therapy, for the remaining population new therapeutic options represent an unsatisfied clinical need. The role of immunotherapy in the continuum of treatment of patients with BTC is still debated. Despite initial signs of antitumor-activity, single-agent immune checkpoint inhibitors (ICIs) demonstrated limited efficacy in an unselected population. Therefore, identifying the best partner to combine ICIs and predictive biomarkers represents a key challenge to optimize the efficacy of immunotherapy. This review provides a critical analysis of completed trials, with an eye on future perspectives and possible biomarkers of response.

Potential therapeutic options for COVID-19: an update on current evidence

SARS-CoV-2, a novel coronavirus, is the agent responsible for the COVID-19 pandemic and is a major public health concern nowadays. The rapid and global spread of this coronavirus leads to an increase in hospitalizations and thousands of deaths in many countries. To date, great efforts have been made worldwide for the efficient management of this crisis, but there is still no effective and specific treatment for COVID-19. The primary therapies to treat the disease are antivirals, anti-inflammatories and respiratory therapy. In addition, antibody therapies currently have been a many active and essential part of SARS-CoV-2 infection treatment. Ongoing trials are proposed different therapeutic options including various drugs, convalescent plasma therapy, monoclonal antibodies, immunoglobulin therapy, and cell therapy. The present study summarized current evidence of these therapeutic approaches to assess their efficacy and safety for COVID-19 treatment. We tried to provide comprehensive information about the available potential therapeutic approaches against COVID-19 to support researchers and physicians in any current and future progress in treating COVID-19 patients.

Recent Advances in Modeling Mitochondrial Cardiomyopathy Using Human Induced Pluripotent Stem Cells

Around one third of patients with mitochondrial disorders develop a kind of cardiomyopathy. In these cases, severity is quite variable ranging from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. ATP is primarily generated in the mitochondrial respiratory chain via oxidative phosphorylation by utilizing fatty acids and carbohydrates. Genes in both the nuclear and the mitochondrial DNA encode components of this metabolic route and, although mutations in these genes are extremely rare, the risk to develop cardiac symptoms is significantly higher in this patient cohort. Additionally, infants with cardiovascular compromise in mitochondrial deficiency display a worse late survival compared to patients without cardiac symptoms. At this point, the mechanisms behind cardiac disease progression related to mitochondrial gene mutations are poorly understood and current therapies are unable to substantially restore the cardiac performance and to reduce the disease burden. Therefore, new strategies are needed to uncover the pathophysiological mechanisms and to identify new therapeutic options for mitochondrial cardiomyopathies. Here, human induced pluripotent stem cell (iPSC) technology has emerged to provide a suitable patient-specific model system by recapitulating major characteristics of the disease in vitro, as well as to offer a powerful platform for pre-clinical drug development and for the testing of novel therapeutic options. In the present review, we summarize recent advances in iPSC-based disease modeling of mitochondrial cardiomyopathies and explore the patho-mechanistic insights as well as new therapeutic approaches that were uncovered with this experimental platform. Further, we discuss the challenges and limitations of this technology and provide an overview of the latest techniques to promote metabolic and functional maturation of iPSC-derived cardiomyocytes that might be necessary for modeling of mitochondrial disorders.

Sitafloxacin Expresses Potent Anti-Mycobacterium abscessus Activity

Therapeutic options for treating Mycobacterium abscessus infections are extremely limited; quinolones are important. The in vitro anti-M. abscessus activities of nine quinolones, emphasizing sitafloxacin, were investigated. Antimicrobial susceptibility testing was performed on 10 non-tuberculous mycobacterium reference strains and 194 clinical, M. abscessus isolates. The activity of sitafloxacin against intracellular M. abscessus residing within macrophages was also evaluated. A checkerboard assay was conducted to determine synergy between sitafloxacin and 10 clinically important antibiotics. Among the nine quinolones tested, sitafloxacin exhibited the greatest anti-M. abscessus activity with MIC50 and MIC90 of 1 and 2 mg/L, respectively. Sitafloxacin exerted a bacteriostatic effect on M. abscessus and inhibited the intracellular growth of M. abscessus at concentrations equivalent to clarithromycin. No antagonism between sitafloxacin and 10 clinically important anti-M. abscessus antibiotics was evident. In summary, sitafloxacin exhibited a significant advantage relative to other quinolones in inhibiting the growth of M. abscessus in vitro, suggesting the potential inclusion of sitafloxacin in new strategies to treat M. abscessus infections.

Healthy lifestyles and their beneficial effects on sexual function and dysfunction

Sexual dysfunction is a common malady. It causes immense emotional suffering and interferes with social wellbeing. Many physical and psychological ailments are frequently implicated in its development and progression. There are several therapeutic options available for its attenuation. However, more recently, the focus has shifted significantly to several lifestyle factors that can help in its prevention. A brief review of these influences exerted by the five major lifestyles, namely, smoking, obesity, exercise, alcohol intake, and diet is done in this manuscript.

Diabetic Mastopathy. Review of Diagnostic Methods and Therapeutic Options

Diabetic mastopathy is a rare breast condition that may occur in insulin-treated men and women of any age. The etiology is still unclear; however, the autoimmunological background of the disease is highly suspected. The changes in diabetic mastopathy may mimic breast cancer; therefore, its diagnostic process is demanding, and treatment options are not clear and limited. Lesions in DM are usually multiple; therefore, surgical removal is not fully effective. A well-done anamnesis with core-needle biopsy is essential and definitive in most cases. In this review, we summarize up-to-date knowledge of diagnostic methods and therapeutic options for diabetic mastopathy treatment and present three cases of diabetic mastopathy-type lesions in ultrasound and radiological examinations.