KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース)

Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.

Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management

Side Effects of Immune Checkpoint Blockade The wide range of immune-related adverse effects associated with immune checkpoint blockade can complicate this effective therapy and limit its use in patients with cancer. This review surveys the adverse effects and their management.

https://www.nejm.org/doi/pdf/10.1056/NEJMra1703481

Immune-Related Adverse Events Associated with Immune Checkpoint Blockade

Nanoparticles (NPs) are increasingly used to target bacteria as an alternative to antibiotics. Nanotechnology may be particularly advantageous in treating bacterial infections. Examples include the utilization of NPs in antibacterial coatings for implantable devices and medicinal materials to prevent infection and promote wound healing, in antibiotic delivery systems to treat disease, in bacterial detection systems to generate microbial diagnostics, and in antibacterial vaccines to control bacterial infections. The antibacterial mechanisms of NPs are poorly understood, but the currently accepted mechanisms include oxidative stress induction, metal ion release, and non-oxidative mechanisms. The multiple simultaneous mechanisms of action against microbes would require multiple simultaneous gene mutations in the same bacterial cell for antibacterial resistance to develop; therefore, it is difficult for bacterial cells to become resistant to NPs. In this review, we discuss the antibacterial mechanisms of NPs against bacteria and the factors that are involved. The limitations of current research are also discussed.

/pdf/the-antimicrobial-activity-of-nanoparticles-present-455xafgyws.pdf

The antimicrobial activity of nanoparticles: present situation and prospects for the future

Natural products afford a window of opportunity to study important biology. If the natural product is used or abused by human beings, finding its biological target(s) is all the more significant. Hot pepper is eaten on a daily basis by an estimated one-quarter of the world’s population and

Vanilloid (Capsaicin) Receptors and Mechanisms

Objective:Multi-attribute decision-making (MADM) models evaluate competing solutions for complex problems to identify the closest fit to the ideal solution. MADM models may assist dermatologists when selecting between biologics for plaque psoriasis. Here, is described the development of a pilot model to identify the preferred biologic from the dermatologist's perspective.Research design and methods:A group of European dermatologists were surveyed to identify treatment attributes they consider when prescribing a biologic. The relative importance of each was determined by allocation of 100 importance points in the context of seven case vignettes, reflecting the breadth of disease encountered in dermatological practice. Biologic performance was rated anonymously on a scale of 1–10, scores entered into a MADM matrix, and TOPSIS (Technique for Ordered Preference by Similarity to the Ideal Solution) analysis applied to identify the biologic closest to the hypothetical ideal.Results:Long-term efficacy an...

Identifying the biologic closest to the ideal to treat chronic plaque psoriasis in different clinical scenarios: using a pilot multi-attribute decision model as a decision-support aid.

Several reports have been published on platelet hyperaggregation in psoriatic patients, which might be related to alterations in arachidonic acid (AA) metabolism by platelets. We have studied the AA metabolism pattern, total eicosanoid formation and biosynthesis rate in platelet from psoriatic patients and from normal subjects after incubation with exogenous AA. We have found no difference in the metabolic pattern of platelets. Total formation of 12-HETE was higher in the control group (p less than 0.01). The rate of synthesis of cyclooxygenase products was higher in the psoriatic group, but only that of thromboxane B2 was statistically significant (p less than 0.02). There was a close correlation between thromboxane B2 formation rate and the lag time of platelet aggregation in response to 1 mM AA (p less than 0.01). The percentage of aggregation of platelets from psoriatics was significantly higher than that from normal subjects (p less than 0.05) and the lag time was lower in psoriatic group, but the difference was not statistically significant.

Exogenous arachidonic acid metabolism in platelets from psoriatic patients.

Pulsed dye laser (PDL) has been used in adults to treat refractory cutaneous lupus erythematosus (CLE). We report the first case of CLE in a child successfully treated with PDL.

Pediatric cutaneous lupus erythematosus treated with pulsed dye laser.

Pigmented Paget's disease in a man previously treated with mammaplasty reduction for gynecomastia

Subcutaneous (SC) injection is a common route of drug administration; however, injection site pain (ISP) might create a negative patient experience. We evaluated ISP, bioequivalence, and overall safety of the citrate-free (CF) formulation of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A. Two phase 1, single-blind studies were conducted in healthy participants. The crossover study A (NCT03848403) evaluated pain intensity on injection as measured by visual analog scale of pain (VAS) scores. Subjects (N = 70) were randomized 1:1:1 at the beginning to three possible treatment sequences and received a 1 mL SC injection of the three formulations sequentially in the abdomen on days 1, 8, and 15, respectively. A mixed-effects repeated measures analysis model was used to analyze VAS score by time post-injection. Study B (NCT04259346) evaluated the bioequivalence of a single 80 mg dose of CF formulation compared to the original commercial formulation. Subjects (N = 245) were randomized 1:1 to either commercial or CF formulation and received a single SC injection into the abdomen, arm, or thigh. Primary endpoint was achieved in both studies. In study A, least-squares mean (LSM) difference of VAS scores immediately post injection between commercial (n = 61) and CF formulation (n = 63) was − 21.7 (p < 0.0001), indicating a lower degree of pain associated with CF formulation. In study B, bioequivalence of the CF formulation was established as 90% CIs for the ratio of geometric LSM AUC0–tlast, AUC0–∞, and Cmax between treatments were contained within the prespecified limits of 0.8 and 1.25. Except for less ISP in the CF formulation, overall safety profile was comparable. Ixekizumab CF formulation proved to be bioequivalent, was associated with less ISP, and had no other notable differences in the safety profile compared to the original commercial formulation. ClinicalTrials.gov identifier NCT03848403, NCT04259346. 

/pdf/ixekizumab-citrate-free-formulation-results-from-two-uovywet5.pdf

Lluís Puig

Papers

Identifying the biologic closest to the ideal to treat chronic plaque psoriasis in different clinical scenarios: using a pilot multi-attribute decision model as a decision-support aid.

Exogenous arachidonic acid metabolism in platelets from psoriatic patients.

Pediatric cutaneous lupus erythematosus treated with pulsed dye laser.

Pigmented Paget's disease in a man previously treated with mammaplasty reduction for gynecomastia

Ixekizumab Citrate-Free Formulation: Results from Two Clinical Trials