Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Current Treatment Options for HIV Elite Controllers: a Review

Opinion statementInitiating antiretroviral therapy (ART) in human immunodeficiency virus (HIV) elite controllers remains controversial, because current evidence does not definitively demonstrate that the benefits of ART outweigh risk in this patient population. However, it is the opinion of the authors that in developed countries, where first-line ART regimens have minimal toxicities, treatment of elite controllers should be strongly considered. Treatment of elite controllers has the potential to minimize the size of the HIV reservoir, which benefits elite controllers who choose to pursue future cure, dampen immune activation, diminish risk of transmission, and encourage linkage and engagement in care allowing HIV providers the opportunity to address HIV-associated non-AIDS conditions and other co-morbidities.Purpose of reviewThis review aims to summarize literature relevant to the management of elite controllers for clinicians caring for patients living with HIV. Key topics include timing of antiretroviral therapy (ART) and ART in the unique populations of elite controllers with concomitant cardiovascular disease and hepatitis C co-infection, and undergoing immunosuppressive therapy for other co-morbidities.Recent findingsThe persistent HIV reservoir in elite controllers has two main implications. First, increased immune activation appears to adversely impact clinical outcomes in elite controllers, but the role of ART in addressing this effect remains unclear. Second, elite control duration can be limited, but certain factors may help to predict disease progression with implications on timing of ART.SummaryInitiation of ART during elite control remains controversial, although there are multiple theoretical benefits. Elite controllers comprise a heterogeneous population of patients living with HIV, and optimal management involves weighing the risk and benefit of ART as well as monitoring of clinical consequences of increased immune activation

Skeletal muscle metastasis from the most common carcinomas orthopedic surgeons deal with. A systematic review of the literature

There is scarce information in the literature dealing with the clinical presentation, management and oncologic outcomes of skeletal muscle metastases (SMM). We sought to perform a systematic review of the literature to investigate: (1) tumor characteristics of SMM, (2) therapeutic approach, and (3) oncological outcomes. A systematic review of the literature was performed using PubMed and EMBASE search engines. A total of 3231 references were reviewed and 49 studies were included. Demographic data, presentation characteristics, and oncological outcomes were recorded. Statistical analysis was performed using SPSS 22.0 software (IBM; Armonk, New York) and Comprehensive Meta-Analysis software version 3 (Biostat, Inc.), with p < 0.05 as statistically significant. A total of 231 patients were included. These tumors presented more commonly on males 58.4% (135/231), with a mean age of 60.08 ± 10.6 years, and in the axial area 39.6% (88/222). The most common carcinoma type was lung 41.1% (95/231). Resection of a single metastases did not change survival significantly (p = 0.992). LRR was higher within the group of patients that underwent WLE compared with non-WLE [31.3% (23/74) vs. 8.7% (2/23), p ≤ 0.001]. Kaplan-Meier survival analysis for the entire cohort showed an estimate of 15.3 months [95% confidence interval (CI) 11.6-19; standard error (SE) 0.432], with lung carcinoma carrying the worst prognosis 6.7 months (95% CI 5.4-8.07; SE 0.68). Patients with a single SMM showed a worse estimate mean survival time compared to patients with multiple metastases limited to muscles [8.6 months (95% CI 4.7-12.5; SE 2.0) vs 25.4 months (95% CI 19.8-31.05; SE 2.8; p ≤ 0.001)]. Overall survival is poor and is driven mainly by the type of carcinoma. An Increased LRR might be present due to the systemic nature of the condition, and degree of control of the primary carcinoma

Crop pests and predators exhibit inconsistent responses to surrounding landscape composition.

The idea that noncrop habitat enhances pest control and represents a win-win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win-win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies

A global synthesis reveals biodiversity-mediated benefits for crop production.

Human land use threatens global biodiversity and compromises multiple ecosystem functions critical to food production. Whether crop yield-related ecosystem services can be maintained by a few dominant species or rely on high richness remains unclear. Using a global database from 89 studies (with 1475 locations), we partition the relative importance of species richness, abundance, and dominance for pollination; biological pest control; and final yields in the context of ongoing land-use change. Pollinator and enemy richness directly supported ecosystem services in addition to and independent of abundance and dominance. Up to 50% of the negative effects of landscape simplification on ecosystem services was due to richness losses of service-providing organisms, with negative consequences for crop yields. Maintaining the biodiversity of ecosystem service providers is therefore vital to sustain the flow of key agroecosystem benefits to society

Manipulation of Agricultural Habitats to Improve Conservation Biological Control in South America

International audienceStable and diversified agroecosystems provide farmers with important ecosystem services, which are unfortunately being lost at an alarming rate under the current conventional agriculture framework. Nevertheless, this concern can be tackled by using ecological intensification as an alternative strategy to recuperate ecosystem services (e.g., biological control of pests). To this end, the manipulation of agricultural habitats to enhance natural enemy conservation has been widely explored and reported in Western Europe and North America, whereas in other parts of the world, the investigation of such topic is lagging behind (e.g., South America). In this forum, we gathered published and unpublished information on the different ecological habitat management strategies that have been implemented in South America and their effects on pest control. Additionally, we identify the various challenges and analyze the outlook for the science of conservation biological control in South America. More specifically, we reviewed how different agricultural practices and habitat manipulation in South America have influenced pest management through natural enemy conservation. The main habitat manipulations reported include plant diversification (intercropping, insectary plants, agroforestry), conservation and management of non-crop vegetation, and application of artificial foods. Overall, we noticed that there is a significant discrepancy in the amount of research on conservation biological control among South American countries, and we found that, although intercropping, polycultures, and crop rotation have been reported in agroecosystems since pre-Inca times, more systematic studies are required to evaluate the true effects of habitat management to implement conservation biological control for pest control in South America