Interactions between human microbiome,liver diseases,and immunosuppression after liver transplant

In liver transplant patients, solid tumors and post-transplant lymphoproliferative disorders have emerged as significant long-term mortality causes. In addition, it is assumed that de novo malignancy after liver transplantation (LT) is the second-leading cause of death after cardiovascular complications. Well-established risk factors for post-transplant lymphoproliferative disorders and solid tumors are calcineurin inhibitors, tacrolimus, and cyclosporine, the cornerstones of all immunosuppressive therapies used after LT. The loss of immunocompetence facilitated by the host immune system due to prolonged immunosuppressive therapy leads to cancer development, including LT patients. Furthermore, various mechanisms such as bacterial dysbiosis, activation through microbe-associated molecular patterns, leaky gut, and bacterial metabolites can drive cancer-promoting liver inflammation, fibrosis, and genotoxicity. Therefore, changes in human microbiota composition may contribute further to de novo carcinogenesis associated with the severe immunosuppression after LT.     

Envarsus,una novedad para los nefrólogos del trasplante: estudio observacional retrospectivo

The aim of this study was to evaluate the trough concentrations (Cp_trough) and the tacrolimus dosage regimen after the conversion of Prograf or Advagraf to Envarsus (new pharmaceutical form with MeltDose technology that improves the absorption of fat-soluble drugs) in patients with stable renal transplantation, and their renal function.We selected stable renal transplant patients who were converted to Envarsus. Two periods were defined: Baseline and Conversion (Envarsus) and they were stratified according to the pharmaceutical form used in the Baseline period. Sixty-one patients were included (24 with Advagraf and 37 with Prograf), with an average age of 52 years. The mean post-transplant time at the time of conversion to Envarsus was 76.3 months and the mean follow-up in the Baseline and Conversion period was 10.1 months and 11.6 months, respectively.In the Prograf and Envarsus group, the Cp_trough medians were 6.6 vs 6.4 ng/mL (P = .636), with a mean daily dose that decreased significantly from 3 mg to 2 mg (P < .001), respectively, maintaining the filtration rate.The median Cp_trough values in the Advagraf and Envarsus groups were 5.7 ng/mL and 6.3 ng/mL (P = .07), with a median daily dose of 7 mg and 4 mg (P < .001), respectively, and the same renal function.In stable renal transplant patients, the conversion from Advagraf to Envarsus has allowed the dose of tacrolimus to be reduced by 42.9% and, in the case of Prograf, by 33.3%, maintaining similar Cp_trough values, without renal function being altered.     

Therapeutic effects of topical 0.03% Tacrolimus ointment in children with refractory vernal keratoconjunctivitis in Middle East

ObjectiveThe purpose of this paper is to review the efficacy and safety profile in children treated with topical 0.03% Tacrolimus ointment for vernal keratoconjunctivitis in Middle East and to propose a treatment posology. According to recent studies, a complex non-IgE dependent mechanism plays a relevant role in the pathogenesis of vernal keratoconjunctivitis. Numerous cells and mediators have been found in the serum, conjunctiva and tears of patients with Vernal keratoconjunctivitis.DesignThis case series included 10 patients from a single centre, pediatric department of a tertiary hospital with active symptomatic vernal keratoconjunctivitis. All the patients had proliferative lesions and corneal involvement despite conventional medications, including topical steroids. All other medications, systemic and topical: steroids, antihistamines and cyclosporine, were unsuccessful. Patients were treated with topical 0.03% Tacrolimus ointment twice daily for 8 weeks and then once a day for the next two month followed by thrice a week for two months. The changes in symptoms and signs after treatment were evaluated, also the development of possible complications was assessed.ResultsThe results showed a significant reduction in signs and symptoms after 4 weeks of the treatment. Clinical resolution of giant papillae and corneal lesions were seen within eight weeks and no additional drug was required during that period, except tear substitutes. Treatment was continued for period of two months and then slowly reduced.ConclusionThe use of 0.03% Tacrolimus ointment is safe and effective in children refractory to conventional treatment of vernal keratoconjunctivitis even in high temperature climate as Middle East. Due to the effectiveness of the treatment, the dosage used may be proposed for conventional use.     

Influence of immunosuppressive drugs on the CD30 molecule in kidney transplanted patients

Background

Soluble CD30 (sCD30) is a suggested marker for kidney transplantation outcomes. We investigated whether sCD30 serum levels are influenced by immunosuppression and whether they correlate with findings in protocol biopsies and with CD30 gene expression in peripheral blood mononuclear cells (PBMC).

中西医结合治疗面部糖皮质激素依赖性皮炎疗效观察

目的:观察中西医结合治疗面部糖皮质激素依赖性皮炎的疗效。方法:98例患者,随机分成治疗组49例与对照组49例,治疗组口服百癣夏塔热片4片,3次/天,他克莫司软膏和湿润烧伤膏适量混匀,2次/天外搽患处;对照组仅给予他克莫司软膏外搽患处,2次/天。结果:两组痊愈率分别为68.89%,12.24%,有显著性差异;两组有效率分别为93.88%,40.81%,经比较有显著性差异。结论:中西医结合治疗面部糖皮质激素依赖性皮炎疗效显著。     

Significant reduction of Tacrolimus trough level after conversion from twice daily Prograf to once daily Advagraf in Chinese renal transplant recipients with or without concomitant diltiazem treatment

Abstract

A dose ratio of 1:1 was recommended for the conversion from Standard-release Tacrolimus (Prograf) to Prolonged-release Tacrolimus (Advagraf). We investigated the trough tacrolimus blood level in Chinese kidney transplant recipients after conversion, including subjects receiving concomitant treatment with diltiazem. Eighteen stable renal allograft recipients were followed prospectively for 12 weeks after conversion from Prograf to Advagraf at the same daily dose. Tacrolimus blood trough level decreased significantly within 8 weeks after conversion (p?<?0.01). Twelve patients required escalation of the Advagraf dose by 1.10?±?0.36?mg. For the whole group the daily tacrolimus dose was increased from 0.057?±?0.032?mg/kg to 0.068?±?0.033?mg/kg (p?<?0.0001). At week 12 the daily dose of Advagraf was 127?±?32% of the original daily dose of Prograf. In the subgroup of patients receiving diltiazem, their tacrolimus trough level decreased significantly after conversion (p?=?0.001), and the daily tacrolimus dose was increased from 0.060?±?0.036?mg/kg to 0.073?±?0.036?mg/kg (p?<?0.0001). At week 12, their daily dose of Advagraf was 131?±?34% of the original daily dose before conversion. To conclude, conversion from Prograf to Advagraf in renal allograft recipients with or without diltiazem co-treatment necessitated an increase in the daily dose by approximately 30% to maintain the target blood trough level unchanged.     

儿童肝移植术后罕见药物性肝损害1例报道并文献复习

目的探讨儿童肝移植术后药物性肝损害的诊疗经验。方法回顾性分析1例小儿肝移植术后药物性肝损害病例的临床资料并进行文献复习。结果患儿于肝移植术后1年4月余出现肝功能异常,其中血碱性磷酸酶(alkalinephos phatase,ALP)水平明显升高,经除外急性排斥反应、维生素D缺乏性佝偻病、胆汁淤积性疾病、病毒感染、骨代谢异常、甲状旁腺功能亢进症及血液系统疾患等原因后,考虑为他克莫司(FK506)不良反应所致肝损害,停用FK506,改为麦考酚吗乙酯(MMF)+环孢素(CsA)抗排斥治疗后,患儿肝功能逐渐好转。结论儿童患者的生理及药物代谢具有特殊性,小儿肝移植术后FK506所致药物性肝损害较为罕见,临床上应予以重视。