A review of the BCG vaccine and other approaches toward tuberculosis eradication.

Despite aggressive eradication efforts, Tuberculosis (TB) remains a global health burden, one that disproportionally affects poorer, less developed nations. The only vaccine approved for TB, the Bacillus of Calmette and Guérin (BCG) vaccine remains controversial because it's stated efficacy has been cited as anywhere from 0 to 80%. Nevertheless, there have been exciting discoveries about the mechanism of action of the BCG vaccine that suggests it has a role in immunization schedules today. We review recent data suggesting the vaccine imparts protection against both tuberculosis and non-tuberculosis pathogens via a newly discovered immune system called trained immunity. BCG's efficacy also appears to be tied to its affect on granulocytes at the epigenetic and hematopoietic stem cell levels, which we discuss in this article at length. We also write about how the different strains of the BCG vaccine elicit different immune responses, suggesting that certain BCG strains are more immunogenic than others. Finally, our review delves into how the current vaccine is being reformulated to be more efficacious, and track the development of the next generation vaccines against TB.

Potentials of Host-Directed Therapies in Tuberculosis Management.

Tuberculosis (TB) remains as a leading cause of mortality in developing countries, persisting as a major threat to the global public health. Current treatment involving a long antibiotic regimen brings concern to the topic of patient compliance, contributing to the emergence of drug resistant TB. The current review will provide an updated outlook on novel anti-TB therapies that can be given as adjunctive agents to current anti-TB treatments, with a particular focus on modulating the host immune response to effectively target all forms of TB. Additional potential therapeutic pathway targets, including lipid metabolism alteration and vascular endothelial growth factor (VEGF)-directed therapies, are discussed.

The Changing Landscape of Management of Metastatic Renal Cell Carcinoma: Current Treatment Options and Future Directions.

OPINION STATEMENT: For the practicing clinician, the dilemma becomes how most appropriate to sequence the aforementioned regimens. It is challenging to be dogmatic, as there are no comparative studies juxtaposing novel front-line options directly-all of the available studies utilize a comparator arm of sunitinib. With this in mind, the selection of front-line therapy with a patient with mRCC should involve a thorough discussion of both efficacy and safety of available options. The oncologist must also weigh their ability to manage complex immune-related adverse events that can emerge from checkpoint inhibitors, particularly with dual regimens such as nivolumab/ipilimumab. For the patient with good-risk disease, VEGF-directed therapies should remain a component of treatment. The data from CheckMate-214 does not support the use of nivolumab/ipilimumab in this setting, and in fact suggests superiority with the approach of VEGF-TKIs. Until regulatory decisions have been made around bevacizumab/atezolizumab and axitinib/avelumab, sunitinib and pazopanib remain options for patients with good-risk disease, although cabozantinib should be a consideration as well. Although the CABOSUN study did not include patients with good-risk disease, it is important to bear in mind that this was more of a pragmatic decision-inclusion of these patients in the original design could have potentially lengthened the extent of necessary follow-up. From a mechanistic standpoint, there is no reason to assume that cabozantinib would not also achieve superiority to sunitinib in patients with good-risk disease. For patients with intermediate- and poor-risk disease, cabozantinib and nivolumab/ipilimumab represent the only reasonable options thus far that have achieved regulatory approval. As previously noted, nivolumab/ipilimumab has proven benefit in this setting, but should be used only by the oncologist who has ready access to subspecialists who can aid in managing immune-related adverse events. Prompt recognition of colitis, hepatitis, and other sequelae from these therapies is critical, as these toxicities can be life-threatening. If such resources are not available, then cabozantinib should be considered. Cabozantinib should further be contemplated in the subset of patients with bony metastatic disease, where it appears to offer substantial control. Of course, it also represents an option for those individuals who have contraindications to immunotherapy, such as rheumatologic and autoimmune disorders.When combinations of VEGF-directed and immunotherapies are approved, the clinician will have an even more complicated dilemma. Regimens such as a bevacizumab/atezolizumab offer an exceptional safety profile, which may weigh heavily in frail patients who cannot tolerate the side effect profile associated with VEGF-TKIs.

Assessment of Treatment Patterns for Metastatic Renal Cell Carcinoma in Brazil.

BACKGROUND: Although multiple therapies have emerged for the treatment of metastatic renal cell carcinoma (mRCC), it is unclear whether application of these agents is consistent in developed and developing countries. We sought to determine patterns of care for mRCC in Brazil as a representative developing country. MATERIAL AND METHODS: A commercial database was used to acquire information pertaining to patients with mRCC receiving treatment at private or public hospitals in Brazil between March 2013 and October 2016. Basic clinical and demographic criteria were available, as well as information to ascertain the International Metastatic Renal Cell Carcinoma Database Consortium risk. Treatment-related data across multiple lines of therapy were collected. RESULTS: Of 4,379 patients assessed, 3,990 (91%) had metastatic disease, and 26%, 48%, and 26% of patients had good, intermediate, and poor International Metastatic Renal Cell Carcinoma Database Consortium risk disease, respectively. Although 3,149 patients (79%) received first-line therapy, only 641 (20%) and 152 (5%) received second- and third-line therapy, respectively. In the first-line setting, vascular endothelial growth factor-directed agents represented the most commonly used therapy, whereas in the second-line setting, vascular endothelial growth factor- and mammalian target of rapamycin-directed agents were used with similar frequency. Marked differences were seen in receipt of systemic therapy on the basis of treatment in private or public hospitals. CONCLUSION: Relative to developed countries, marked attrition is noted between each subsequent line of therapy in Brazil. Patterns of care also vary greatly in private and public settings, pointing to financial constraints as a potential cause for discordances in treatment.