Clinical response correlates with 4-week postinjection ustekinumab concentrations in patients with moderate-to-severe psoriasis

Background: Cost‐effective use of biologicals is important. As drug concentrations have been linked to clinical outcomes, monitoring drug concentrations is a valuable tool to guide clinical decision‐making. A concentration–response relationship for ustekinumab at trough is uncertain owing to the contradictory results reported. Objectives: To investigate the relationship between 4‐week postinjection ustekinumab concentrations and clinical response in patients with psoriasis. Methods: Forty‐nine patients with moderate‐to‐severe psoriasis treated with 45 mg or 90 mg ustekinumab every 12 weeks for ≥ 16 weeks were included. Ustekinumab serum concentrations and anti‐ustekinumab antibodies were measured at week 4 after injection and disease severity was assessed by Psoriasis Area and Severity Index (PASI). Results: At week 4 after injection, a significantly negative correlation was observed between ustekinumab concentrations and absolute PASI score up to 5·9 μg mL−1 (ρ = –0·357, P = 0·032). Ustekinumab concentrations were higher in optimal responders (PASI ≤ 2) than in suboptimal responders (PASI > 2) (4·0 vs 2·8 μg mL−1, P = 0·036). The ustekinumab concentration threshold associated with optimal response was determined to be 3·6 μg mL−1 (area under the curve 0·71, sensitivity 86%, specificity 63%). Only one patient (2%) had anti‐ustekinumab antibodies. Psoriatic arthritis was identified as an independent predictor of higher PASI scores and higher ustekinumab concentrations (P = 0·003 and P = 0·048, respectively). Conclusions: A concentration–response relationship at week 4 after injection was observed for patients with psoriasis treated with ustekinumab. Monitoring 4‐week postinjection ustekinumab concentrations could timely identify underexposed patients who might benefit from treatment optimization

Effect of ketogenic mediterranean diet with phytoextracts and low carbohydrates/high-protein meals on weight, cardiovascular risk factors, body composition and diet compliance in Italian council employees

<p>Abstract</p> <p>Background</p> <p>There has been increased interest in recent years in very low carbohydrate ketogenic diets (VLCKD) that, even though they are much discussed and often opposed, have undoubtedly been shown to be effective, at least in the short to medium term, as a tool to tackle obesity, hyperlipidemia and some cardiovascular risk factors. For this reason the ketogenic diet represents an interesting option but unfortunately suffers from a low compliance. The aim of this pilot study is to ascertain the safety and effects of a modified ketogenic diet that utilizes ingredients which are low in carbohydrates but are formulated to simulate its aspect and taste and also contain phytoextracts to add beneficial effects of important vegetable components.</p> <p>Methods</p> <p>The study group consisted of 106 Rome council employees with a body mass index of ≥ 25, age between 18 and 65 years (19 male and 87 female; mean age 48.49 ± 10.3). We investigated the effects of a modified ketogenic diet based on green vegetables, olive oil, fish and meat plus dishes composed of high quality protein and virtually zero carbohydrate but which mimic their taste, with the addition of some herbal extracts (KEMEPHY ketogenic Mediterranean with phytoextracts). Calories in the diet were unlimited. Measurements were taken before and after 6 weeks of diet.</p> <p>Results</p> <p>There were no significant changes in BUN, ALT, AST, GGT and blood creatinine. We detected a significant (p < 0.0001) reduction in BMI (31.45 Kg/m²to 29.01 Kg/m²), body weight (86.15 kg to 79.43 Kg), percentage of fat mass (41.24% to 34.99%), waist circumference (106.56 cm to 97.10 cm), total cholesterol (204 mg/dl to 181 mg/dl), LDLc (150 mg/dl to 136 mg/dl), triglycerides (119 mg/dl to 93 mg/dl) and blood glucose (96 mg/dl to 91 mg/dl). There was a significant (p < 0.0001) increase in HDLc (46 mg/dl to 52 mg/dl).</p> <p>Conclusions</p> <p>The KEMEPHY diet lead to weight reduction, improvements in cardiovascular risk markers, reduction in waist circumference and showed good compliance.</p

The prevention and reduction of weight loss in an acute tertiary care setting: Protocol for a pragmatic stepped wedge randomised cluster trial (the PRoWL Project)

Background: Malnutrition, with accompanying weight loss, is an unnecessary risk in hospitalised persons and often remains poorly recognised and managed. The study aims to evaluate a hospital-wide multifaceted intervention co-facilitated by clinical nurses and dietitians addressing the nutritional care of patients, particularly those at risk of malnutrition. Using the best available evidence on reducing and preventing unplanned weight loss, the intervention (introducing universal nutritional screening; the provision of oral nutritional supplements; and providing red trays and additional support for patients in need of feeding) will be introduced by local ward teams in a phased way in a large tertiary acute care hospital. Methods/Design: A pragmatic stepped wedge randomised cluster trial with repeated cross section design will be conducted. The unit of randomisation is the ward, with allocation by a random numbers table. Four groups of wards (n = 6 for three groups, n = 7 for one group) will be randomly allocated to each intervention time point over the trial. Two trained local facilitators (a nurse and dietitian for each group) will introduce the intervention. The primary outcome measure is change in patient’s body weight, secondary patient outcomes are: length of stay, all-cause mortality, discharge destinations, readmission rates and ED presentations. Patient outcomes will be measured on one ward per group, with 20 patients measured per ward per time period by an unblinded researcher. Including baseline, measurements will be conducted at five time periods. Staff perspectives on the context of care will be measured with the Alberta Context Tool. Discussion: Unplanned and unwanted weight loss in hospital is common. Despite the evidence and growing concern about hospital nutrition there are very few evaluations of system-wide nutritional implementation programs. This project will test the implementation of a nutritional intervention across one hospital system using a staged approach, which will allow sequential rolling out of facilitation and project support. This project is one of the first evidence implementation projects to use the stepped wedge design in acute care and we will therefore be testing the appropriateness of the stepped wedge design to evaluate such interventions.Alison L Kitson, Timothy J Schultz, Leslye Long, Alison Shanks, Rick Wiechula, Ian Chapman and Stijn Soene

Designed polyelectrolyte shell on magnetite nanocore for dilution-resistant biocompatible magnetic fluids.

Magnetite nanoparticles (MNPs) coated with poly(acrylic acid-co-maleic acid) polyelectrolyte (PAM) have been prepared with the aim of improving colloidal stability of core-shell nanoparticles for biomedical applications and enhancing the durability of the coating shells. FTIR-ATR measurements reveal two types of interaction of PAM with MNPs: hydrogen bonding and inner-sphere metal-carboxylate complex formation. The mechanism of the latter is ligand exchange between uncharged -OH groups of the surface and -COO(-) anionic moieties of the polyelectrolyte as revealed by adsorption and electrokinetic experiments. The aqueous dispersion of PAM@MNP particles (magnetic fluids - MFs) tolerates physiological salt concentration at composition corresponding to the plateau of the high-affinity adsorption isotherm. The plateau is reached at small amount of added PAM and at low concentration of nonadsorbed PAM, making PAM highly efficient for coating MNPs. The adsorbed PAM layer is not desorbed during dilution. The performance of the PAM shell is superior to that of poly(acrylic acid) (PAA), often used in biocompatible MFs. This is explained by the different adsorption mechanisms; metal-carboxylate cannot form in the case of PAA. Molecular-level understanding of the protective shell formation on MNPs presented here improves fundamentally the colloidal techniques used in core-shell nanoparticle production for nanotechnology applications

Neural Crest Cell Survival Is Dependent on Rho Kinase and Is Required for Development of the Mid Face in Mouse Embryos

Neural crest cells (NCC) give rise to much of the tissue that forms the vertebrate head and face, including cartilage and bone, cranial ganglia and teeth. In this study we show that conditional expression of a dominant-negative (DN) form of Rho kinase (Rock) in mouse NCC results in severe hypoplasia of the frontonasal processes and first pharyngeal arch, ultimately resulting in reduction of the maxilla and nasal bones and severe craniofacial clefting affecting the nose, palate and lip. These defects resemble frontonasal dysplasia in humans. Disruption of the actin cytoskeleton, which leads to abnormalities in cell-matrix attachment, is seen in the RockDN;Wnt1-cre mutant embryos. This leads to elevated cell death, resulting in NCC deficiency and hypoplastic NCC-derived craniofacial structures. Rock is thus essential for survival of NCC that form the craniofacial region. We propose that reduced NCC numbers in the frontonasal processes and first pharyngeal arch, resulting from exacerbated cell death, may be the common mechanism underlying frontonasal dysplasia

Antifungal activity of amphotericin B conjugated to nanosized magnetite in the treatment of paracoccidioidomycosis

This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications