Tacrolimus overexposure in kidney transplant recipients during the first post‐operative week: caution is required in older patients

In liver transplantation, tacrolimus trough concentrations (Cmin) above 20 ng/mL during the first days led to worse outcome at 1 year but data in the kidney transplant (KT) era are scarce. The aim of this study was to evaluate the impact of tacrolimus overexposure during the first week post‐transplantation on the kidney function (KF) of KT recipients. In this retrospective study, 105 KT recipients were attributed to overexposure group (OG) or normal group according to their Cmin during the first week of treatment. KF was evaluated by comparing the rate of delayed graft function (DGF) and by collecting plasma creatinine from day 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 and at 1 year. Risk factors for developing DGF were also investigated using a multivariate model. DGF was more frequent in OG (43% of patients; P = 0.027) which has higher plasma creatinine on day 7, 14, and 21. OG patients were older with more extended criteria donor's grafts. In the multivariate analysis, only cold ischemia time (CIT) remained associated with DGF (OR = 1.003), while TAC overexposure did not reach significance (P = 0.06; OR = 3.9). In this study, we confirmed the predominant role of CIT as a risk factor for the onset of DGF in kidney transplantation. 43% of KT recipients were overexposed with more DGF, especially older patients.     

Risk of psychiatric disorders in rosacea: A nationwide,population‐based,cohort study in Taiwan

Rosacea has been reported to be associated with psychiatric disorders. Nevertheless, a nationwide study of the relationship between rosacea and comorbid psychiatric diseases in an Asian population has not been conducted. The aim of this study was to clarify the role of rosacea in the various psychiatric disorders by using a nationwide database in Taiwan. Data were obtained from the National Health Insurance Research Database of Taiwan from 2000 to 2013. In total, 7881 patients with rosacea and 31 524 age‐ and sex‐matched controls were enrolled. Patients with rosacea tended to have more coexisting psychiatric disorders. After adjusting for age, sex, comorbidity and residence/regions, the adjusted hazard ratio (HR) of psychiatric disorders for patients with rosacea was 2.761 (95% CI = 2.650–2.877, P < 0.001). Among them, the highest adjusted HR are phobic disorder and obsessive–compulsive disorder of 7.841 (95% CI = 7.526–8.170, P < 0.001) and 6.389 (95% CI = 6.132–6.657, P < 0.001), respectively. The National Health Insurance Research Database of Taiwan does not include the information about rosacea subtypes, severity and laboratory parameters. In conclusion, rosacea is related to various psychiatric disorders. In addition to anxiety and depression, patients are also at increased risk of phobic disorder and obsessive–compulsive disorder.     

Differential expression of inflammatory cytokines and chemokines in lipopolysaccharide‐stimulated melanocytes from lightly and darkly pigmented skin

Increasing evidence suggests that human epidermal melanocytes play an important role in the skin immune system; however, a role of their pigmentation in immune and inflammatory responses is poorly examined. In the study, the expression of Toll‐like receptor 4 (TLR4) and inflammatory cytokines and chemokines by cultured normal melanocytes derived from lightly and darkly pigmented skin was investigated after cell stimulation with lipopolysaccharide (LPS). The basal TLR4 mRNA level in heavily pigmented cells was higher as compared to their lightly pigmented counterparts. Melanocyte exposure to LPS upregulated the expression of TLR4 mRNA and enhanced the DNA‐binding activity of NF‐κB p50 and p65. We found substantial differences in the LPS‐stimulated expression of numerous genes encoding inflammatory cytokines and chemokines between the cells with various melanin contents. In lightly pigmented melanocytes, the most significantly upregulated genes were nicotinamide phosphoribosyltransferase (NAMPT/visfatin), the chemokines CCL2 and CCL20, and IL6, while the genes for CXCL12, IL‐16 and the chemokine receptor CCR4 were the most significantly upregulated in heavily pigmented cells. Moreover, the lightly pigmented melanocytes secreted much more NAMPT, CCL2 and IL‐6. The results of our study suggest modulatory effect of melanogenesis on the immune properties of normal epidermal melanocytes.     

Lichen planus: a comprehensive evidence‐based analysis of medical treatment

Lichen planus (LP) is a chronic‐relapsing inflammatory skin disease. Although many drugs have been used for the management of LP, some of them lack the backup by strong therapeutic evidence, while others are not suitable for some patients due to safety profile issues. The aim of this study was to review the recent status of available medical therapies for LP to help physicians make better decisions upon best medical practice while facing patients with this condition. A review of published articles on management of LP was conducted with the MEDLINE and PubMed databases. The quality of the evidence was graded as high, moderate, low or very low. A total of 1366 articles were retrieved, and 219 (16%) were included in the final analysis. Twenty‐one different treatment modalities were analysed. The quality of evidence was high for topical steroid and calcineurin inhibitor, while it was moderate for oral steroids. All the other modalities reached low or very low quality of evidence. Topical steroids and calcineurin inhibitors are the current first‐line therapies, while for other therapies the strength of recommendation is not so evident. Unfortunately, larger randomized, controlled trials to support the efficacy, safety and tolerability of other therapies in LP are lacking, and many of them are recommended based on studies with small sample sizes, lack of standardized outcome measures or lack of controlled duration or even in anecdotal evidence. Thus, large‐scale randomized clinical trials are still warranted to establish the exact benefits of other topical treatments, phototherapy, immunosuppressant and new immunomodulators for an optimized treatment of LP.