Toll-like receptor gene polymorphisms are associated with susceptibility to graves' ophthalmopathy in Taiwan males

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLRs) are a family of pattern-recognition receptors, which plays a role in eliciting innate/adaptive immune responses and developing chronic inflammation. The polymorphisms of TLRs have been associated with the risk of various autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis and rheumatorid arthritis. The aim of this study was to evaluate whether TLR genes could be used as genetic markers for the development of Graves' ophthalmopathy (GO).</p> <p>Methods</p> <p>6 TLR-4 and 2 TLR-9 gene polymorphisms in 471 GD patients (200 patients with GO and 271 patients without GO) from a Taiwan Chinese population were evaluated.</p> <p>Results</p> <p>No statistically significant difference was observed in the genotypic and allelic frequencies of TLR-4 and TLR-9 gene polymorphisms between the GD patients with and without GO. However, sex-stratified analyses showed that the association between TLR-9 gene polymorphism and GO phenotype was more pronounced in the male patients. The odds ratios (ORs) was 2.11 (95% confidence interval [CI] = 1.14-3.91) for rs187084 AàG polymorphism and 1.97 (95% CI = 1.07-3.62) for rs352140 AàG polymorphism among the male patients. Increasing one G allele of rs287084 and one A allele of rs352140 increased the risk of GO (<it>p </it>values for trend tests were 0.0195 and 0.0345, respectively). Further, in haplotype analyses, the male patients carrying the GA haplotype had a higher risk of GO (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.09-3.73) than those not carrying the GA haplotype.</p> <p>Conclusion</p> <p>The present data suggest that TLR-9 gene polymorphisms were significantly associated with increased susceptibility of ophthalmopathy in male GD patients.</p

Transition of adolescents with pediatric-onset hepatobiliary diseases: systematic review of literature

Objectives and Study: Long-term prognosis of adolescents with chronic paediatric-onset hepatobiliary diseases (POHD) has dramatically improved in recent decades. Since there is no accepted pathway of care for transition from paediatric (P) to adult (A) hepatologists, we aimed to provide a) a systematic review of literature, and b) an analysis of existing information derived from documents borrowed from other chronic diseases transition experiences. Method: Out of 657 screened studies published between 1980 and August 2017, identified on Pubmed and Google Scholar by means of keywords (“transition of care” or “health care” and “pediatrics” or “adolescence” or “young adults”), 87 were considered appropriate to be evaluated with the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). Evaluation of international corporate documents included American Academy of Paediatrics, Got transition, ON TRAC (Transitioning Responsibly to Adult Care), Good 2 Go, Stepping Up, National Institute for Health and Care Excellence guidelines. Results: Existing models of transition have rarely been assessed in randomized controlled trials (RCTs) with outcomes' measurements. Eighty-five per cent of the retrieved studies have a low level of evidence (C/D) according to GRADE system. Consistent with them, transition is generally defined as an active and evolving process that may benefit from a unified approach by P/A staff. Timing of transition should consider the young person's mental and physical development, the socio-economic family circumstances, and the availability of A physicians rather than chronological age only (usually 18 years). Although only 50% of the programs have performed a valid assessment of adolescents readiness for self-empowerment, it is accepted that early training predicts a successful transition. To implement an effective program, a well-coordinated multi-professional team and a integrated and multidisciplinary approach, is requested. Several barriers are reported to impede the transition process. The most relevant for patients/families are poor knowledge on health care system and rights to services, difficulties in identifying the appropriate A specialist, lack of knowledge of their own disease. Lack of a) time for the transition process, b) experienced adult-oriented centres, and c) financial reimbursement appear as critical aspects for P doctors. Adult's physicians consider as significant barriers the scarce training in paediatric diseases and poor communication with paediatricians. A few RCTs have recommended regular web-meetings and suitable technological connections to improve programs effectiveness. Conclusion: Our systematic review shows that 1. there is still no large unanimity on what constitutes a successful transition for adolescents with paediatric-onset diseases and even less for those with POHD; 2. an evidence-based implementation of an efficient transition policy is still limited by the relative lack of studies resulting in solid data. This preliminary analysis will be used in the making of a specific ESPGHAN/European Association for the Study of the Liver agreed document pointing to remove barriers, influence medical adherence, reduce the prevalence and severity of complications, and improve health-related quality of life for adolescent with POHD