TD-1792 versus Vancomycin for Treatment of Complicated Skin and Skin Structure Infections

TD-1792 is a first-in-class glycopeptide-cephalosporin heterodimer that exhibits bactericidal activity against Gram-positive pathogens. We conducted a randomized, double-blind, active-control, phase II trial in patients with complicated skin and skin structure infections caused by suspected or confirmed Gram-positive organisms. Patients 18 to 65 years old were randomized to receive 7 to 14 days of either TD-1792 (2 mg/kg of body weight intravenously [i.v.] every 24 h [q24h]) or vancomycin (1 g i.v. q12h, with dosage regimens adjusted per site-specific procedures). A total of 197 patients were randomized and received at least one dose of study medication. Rates of clinical success at the test-of-cure evaluation were similar in all analysis populations. Among 170 clinically evaluable patients, cure rates were 91.7% and 90.7% in the TD-1792 and vancomycin groups, respectively (95% confidence interval [CI] of −7.9 to 9.7 for the difference). In microbiologically evaluable patients with methicillin-resistant Staphylococcus aureus at baseline (n = 75), cure rates were 94.7% in the TD-1792 group and 91.9% in the vancomycin group. Microbiological eradication of Gram-positive pathogens (n = 126) was achieved in 93.7% and 92.1% of patients in the TD-1792 and vancomycin groups, respectively. Seven patients were discontinued from study medication due to an adverse event (AE): 2 and 5 in the TD-1792 and vancomycin groups, respectively. AEs were of similar types and severities between the two groups, other than pruritus, which was more common in patients who received vancomycin. No patients in the TD-1792 group experienced a serious AE. This study supports further clinical development of TD-1792 in patients with Gram-positive infection.     

Platelet‐rich plasma enhances the integration of bioengineered cartilage with native tissue in an in vitro model

Current therapies for cartilage repair can be limited by an inability of the repair tissue to integrate with host tissue. Thus, there is interest in developing approaches to enhance integration. We have previously shown that platelet‐rich plasma (PRP) improves cartilage tissue formation. This raised the question as to whether PRP could promote cartilage integration . Chondrocytes were isolated from cartilage harvested from bovine joints, seeded on a porous bone substitute and grown in vitro to form an osteochondral‐like implant. After 7 days, the biphasic construct was soaked in PRP for 30 min before implantation into the core of a donut‐shaped biphasic explant of native cartilage and bone. Controls were not soaked in PRP. The implant–explant construct was cultured for 2–4 weeks. PRP‐soaked bioengineered implants integrated with host tissue in 73% of samples, whereas controls only integrated in 19% of samples. The integration strength, as determined by a push‐out test, was significantly increased in the PRP‐soaked implant group (219 ± 35.4 kPa) compared with controls (72.0 ± 28.5 kPa). This correlated with an increase in glycosaminoglycan and collagen accumulation in the region of integration in the PRP‐treated implant group, compared with untreated controls. Immunohistochemical studies revealed that the integration zone contained collagen type II and aggrecan. The cells at the zone of integration in the PRP‐soaked group had a 3.5‐fold increase in matrix metalloproteinase‐13 gene expression compared with controls. These results suggest that PRP‐soaked bioengineered cartilage implants may be a better approach for cartilage repair due to enhanced integration.     

An Analysis of Bronx-based Online Grocery Store Circulars for Nutritional Content of Food and Beverage Products

With the rising rates of diabetes and obesity in New York City’s poorest communities, efforts to assist low-income residents in spending money to promote nutritious food consumption have increased. The objective of this study was to assess the extent to which Bronx-based grocery stores offered nutritious foods on sale through their weekly circulars. Over a 2-month period, we analyzed 2,311 food and beverage products placed on the first page of online circulars for fifteen Bronx-based grocery stores. For each circular, we recorded the number of starchy and non-starchy fruits and vegetables; for each product, total fiber and carbohydrate content per serving (in grams), whether the product was processed, and sale price were recorded. Total sugar content (in grams) was recorded for all sugar-sweetened beverages. Over 84 % of the products were processed, and almost 40 % had at least one carbohydrate choice (15 g) per food serving. Only 16.5 % of the products were fresh fruits and green leafy vegetables, and 1.4 % had fiber content of 5 or more grams per serving. Requiring the purchase of multiples of unhealthy products to receive the sale price was also noted. Almost three-quarters of the sugar-sweetened beverages were advertised with promotional sales compared to over half of the fresh fruits and only one-third of fresh vegetables. We identified no other studies that address nutritional content of foods found in grocery store circulars. More research is necessary to determine if purchasing nutritious products at grocery stores in low-income neighborhoods is influenced by sale prices.     

Surveillance of iclaprim activity: In vitro susceptibility of gram-positive pathogens collected from 2012 to 2014 from the United States,Asia Pacific,Latin American and Europe

Iclaprim is a diaminopyrimidine, which inhibits bacterial dihydrofolate reductase, and it is highly active against Gram-positive pathogens including emerging drug-resistant pathogens. In vitro activity of iclaprim and comparators against 2814 Gram-positive clinical isolates from the United States, Asia Pacific, Latin American and Europe collected between 2012 and 2014 were tested. Susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Minimum inhibitory concentration (MIC) interpretations were based on CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. MIC₅₀/MIC₉₀ for all S. aureus, methicillin susceptible S. aureus, methicillin resistant S. aureus, beta-hemolytic streptococci, and Streptococcus pneumoniae were 0.06/0.12, 0.06/0.12, 0.06/0.5, 0.06/0.25, and 0.06/2 μg/mL, respectively. Iclaprim was 8 to 32-fold more potent than trimethoprim, the only FDA approved dihydrofolate reductase inhibitor, against all Gram-positive isolates including resistant phenotypes. The MIC₉₀ of iclaprim was also lower than most of the comparators including linezolid and vancomycin against Gram-positive pathogens. Iclaprim demonstrated potent activity against a contemporary collection (2012–2014) of Gram-positive clinical isolates from the United States, Asia Pacific, Latin America and Europe.     

Hot Off the Press: Peripheral Intravenous Cannula Insertion and Use in the Emergency Department

This is a prospective before–after study comparing peripheral intravenous cannulation (PIVC) placement and usage rates following a 10‐week‐long multimodal intervention provided to medical and nursing staff working in a tertiary emergency department (ED). The intervention focused on improving appropriate use of PIVCs in an emergency setting by emphasizing to clinicians that a PIVC should only be placed if it was believed there was more than an 80% chance that it would be used. Patients were eligible for the study if they presented to the ED and were >18 years of age. Patients were excluded from the study if they were triage category 1, already had a PIVC placed in an ambulance, or were transferred from another hospital. Among the 4,172 patients included in the analysis, there was a 9.8% reduction in the number of PIVCs inserted (95% confidence interval [CI] = 6.8–12.87) and a 12% increase in PIVC usage (95% CI = 8.7%–17.0%) in the postintervention cohort.     

Biology and targeting of the Jumonji-domain histone demethylase family in childhood neoplasia: a preclinical overview

Introduction: Epigenetic mechanisms of gene regulatory control play fundamental roles in developmental morphogenesis, and, as more recently appreciated, are heavily implicated in the onset and progression of neoplastic disease, including cancer. Many epigenetic mechanisms are therapeutically targetable, providing additional incentive for understanding of their contribution to cancer and other types of neoplasia.

Areas covered: The Jumonji-domain histone demethylase (JHDM) family exemplifies many of the above traits. This review summarizes the current state of knowledge of the functions and pharmacologic targeting of JHDMs in cancer and other neoplastic processes, with an emphasis on diseases affecting the pediatric population.

Expert opinion: To date, the JHDM family has largely been studied in the context of normal development and adult cancers. In contrast, comparatively few studies have addressed JHDM biology in cancer and other neoplastic diseases of childhood, especially solid (non-hematopoietic) neoplasms. Encouragingly, the few available examples support important roles for JHDMs in pediatric neoplasia, as well as potential roles for JHDM pharmacologic inhibition in disease management. Further investigations of JHDMs in cancer and other types of neoplasia of childhood can be expected to both enlighten disease biology and inform new approaches to improve disease outcomes.