Comparison of Parasitological,Serological, and Molecular Tests for Visceral Leishmaniasis in HIV-Infected Patients: A Cross-Sectional Delayed-Type Study

The aim of this study was to evaluate the accuracy of invasive and non-invasive tests for diagnosis of visceral leishmaniasis (VL) in a large series of human immunodeficiency virus (HIV)-infected patients. In this delayed-type cross-sectional study, 113 HIV-infected symptomatic patients were evaluated by an adjudication committee after clinical follow-up to establish the presence or absence of VL as the target condition (reference test). The index tests were recombinant K39 antigen-based immunochromatographic test (rK39), indirect fluorescent antibody test (IFAT), prototype kit of direct agglutination test (DAT-LPC), and real-time polymerase chain reaction (qPCR) in peripheral blood. Compared with parasitological test and adjudication committee diagnosis or latent class model analyses, IFAT and rk39 dipstick test presented the lowest sensitivity. DAT-LPC exhibited good overall performance, and there was no statistical difference between DAT-LPC and qPCR diagnosis accuracy. Real-time PCR emerges as a less invasive alternative to parasitological examination for confirmation of cases not identified by DAT.     

Mortality impact of thoracic aortic disease in S?o Paulo state from 1998 to 2007

Background

The epidemiological characteristics of thoracic aortic diseases (TAD) in the State of São Paulo and in Brazil, as well as their impact on the survival of these patients have yet to be analyzed.

Objectives

To evaluate the mortality impact of TAD and characterize it epidemiologically.

Methods

Retrospective analysis of data from the public health system for the TAD registry codes of hospitalizations, procedures and deaths, from the International Code of Diseases (ICD-10), registered at the Ministry of Health of São Paulo State from January 1998 to December 2007.

Results

They were 9.465 TAD deaths, 5.500 men (58.1%) and 3.965 women (41.9%); 6.721 dissections (71%) and 2.744. aneurysms. In 86.3% of cases the diagnosis was attained during autopsy. There were 6.109 hospitalizations, of which 67.9% were males; 21.2% of them died (69% men), with similar proportions of dissection and aneurysm between sexes, respectively 54% and 46%, but with different mortality. Men with TAD die more often than women (OR = 1.5). The age distribution for deaths and hospitalizations was similar with predominance in the 6^th decade. They were 3.572 surgeries (58% of hospitalizations) with 20.3% mortality (patients kept in clinical treatment showed 22.6% mortality; p = 0.047). The number of hospitalizations, surgeries, deaths of in-patients and general deaths by TAD were progressively greater than the increase in population over time.

Conclusions

Specific actions for the early identification of these patients, as well as the viability of their care should be implemented to reduce the apparent progressive mortality from TAD seen among our population.     

Angioplasty Guided by Intravascular Ultrasound: Meta-Analysis of Randomized Clinical Trials

Background

The impact of intravascular ultrasound (IVUS) use on stenting has shown inconclusive results.

Objective

Systematic review and meta-analysis of the impact of IVUS on stenting regarding the clinical and angiographic evolution.

Methods

A search was performed in Medline/Pubmed, CENTRAL, Embase, Lilacs, Scopus and Web of Science databases. It included randomized clinical trials (RCTs) that evaluated the implantation of stents guided by IVUS, compared with those using angiography alone (ANGIO). The minimum follow-up duration was six months and the following outcomes were assessed: thrombosis, mortality, myocardial infarction, percutaneous and surgical revascularization, major adverse cardiovascular events (MACE) and restenosis. The binary outcomes were presented considering the number of events in each group; the estimates were generated by a random effects model, considering Mantel-Haenszel statistics as weighting agent and magnitude of effect for the relative risk (RR) with its respective 95% confidence interval (95%CI). Higgins I² test was used to quantify the consistency between the results of each study.

Results

A total of 2,689 articles were evaluated, including 8 RCTs. There was a 27% reduction in angiographic restenosis (RR: 0.73, 95% CI: 0.54-0.97, I² = 51%) and statistically significant reduction in the rates of percutaneous revascularization and overall (RR: 0.88; 95% CI: 0.51 to 1.53, I² = 61%, RR: 0.73, 95% CI: 0.54 to 0.99, I² = 55%), with no statistical difference in surgical revascularization (RR: 0.95, 95% CI: 0.52-1.74, I² = 0%) in favor of IVUS vs. ANGIO. There were no differences regarding the other outcomes in the comparison between the two strategies.

Conclusion

Angioplasty with stenting guided by IVUS decreases the rates of restenosis and revascularization, with no impact on MACE, acute myocardial infarction, mortality or thrombosis outcomes.     

Next Wave of Targets in the Treatment of Advanced Renal Cell Carcinoma

While surgical resection has remained the mainstay of treatment in early-stage renal cell carcinoma (RCC), therapeutic options in the advanced setting have remarkably expanded over the last 20 years. Tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor (VEGF-TKIs) and anti-programmed cell death 1 (PD-1)/anti-programmed death-ligand 1 (PD-L1)-based immune checkpoint inhibitors (ICIs) have become globally accepted options in the upfront metastatic setting, with different ICI-based combination strategies improving overall survival compared to single-agent Sunitinib. Although some patients benefit from long-term responses, most eventually develop disease progression. Ongoing efforts to better understand the biology of RCC and the different mechanisms of acquired resistance have led to the identification of promising therapeutic targets. Belzutifan, a novel agent targeting the angiogenic pathway involving hypoxia-inducible factors (HIFs), has already been approved for the treatment of early-stage tumors associated with VHL disease and represents a very promising therapy in advanced RCC. Other putative targets include epigenetic regulation enzymes, as well as several metabolites such as adenosine, glutaminase and tryptophan, which are critical players in cancer cell metabolism and in the tumor microenvironment. Different methods of immune regulation are also being investigated, including CAR-T cell therapy and modulation of the gut microbiome, in addition to novel agents targeting the interleukin-2 (IL-2) pathway. This review aims to highlight the emergent novel therapies for RCC and their respective completed and ongoing clinical trials.