ABSTRACT
BACKGROUND: Graft rejection and chronic CNI toxicity remain obstacles to organ transplant success. Current formulations of tacrolimus, such as Prograf® and Advagraf™, exhibit limitations in terms of pharmacokinetics and tolerability, related in part to suboptimal bioavailability. As dosing non-compliance can result in graft rejection, the once daily formulation of tacrolimus, Advagraf™, was developed (vs 2x/day Prograf®). Benefits of Advagraf™ are counterbalanced by delayed achievement of therapeutic trough levels and need for up to 50% higher doses to maintain Prograf®-equivalent troughs. Envarsus® is also a prolonged-release once-daily tacrolimus formulation, developed using MeltDose™ drug-delivery technology to increase drug bioavailability; improved bioavailability results in low patient drug absorption variability and less pronounced peak-to-trough fluctuations. In phase III de novo kidney transplant studies, Envarsus® proved non-inferior to twice-daily tacrolimus; however, no phase IV studies show superiority of Envarsus® vs Advagraf™ in de novo liver transplant (LTx) recipients. METHODS: The EnGraft compares bioavailability and tests superiority of Envarsus® (test arm) versus Advagraf™ (comparator arm) in de novo LTx recipients. A total of 268 patients from 15 German transplant centres will be randomised 1:1 within 14 days post-LTx. The primary endpoint is dose-normalised trough level (C/D ratio) measured 12 weeks after randomisation. Secondary endpoints include the number of dose adjustments, time to reach first defined trough level and incidence of graft rejections. Additionally, clinical and laboratory parameters will be assessed over a 3-year period. DISCUSSION: C/D ratio is an estimate for tacrolimus bioavailability. Improving bioavailability and increasing C/D ratio using Envarsus could reduce renal dysfunction and other tacrolimus-related toxicities; previous trials have shown that a higher C/D ratio (i.e. slower tacrolimus metabolism) is not only associated with improved renal function but also linked to reduced neurotoxic side effects. A higher C/D ratio could improve clinical outcomes for LTx recipients; EnGraft has begun, with one third of patients recruited by January 2022. TRIAL REGISTRATION: This trial has been registered (4 May 2020) in the EU Clinical Trials Register, EudraCT-Nummer: 2020-000796-20. Additionally, this trial has been registered (22 January 2021) at ClinicalTrials.gov: NCT04720326. The trial received a favourable opinion from the concerned lead ethics committee at the University of Regensburg, under the reference 20-1842-112.
Subject(s)
Kidney Transplantation , Liver Transplantation , Humans , Biological Availability , Delayed-Action Preparations , Graft Rejection/prevention & control , Graft Rejection/drug therapy , Immunosuppressive Agents , Kidney Transplantation/adverse effects , Liver Transplantation/adverse effects , Multicenter Studies as Topic , Tacrolimus/adverse effects , Randomized Controlled Trials as TopicABSTRACT
INTRODUCTION: Rapid-onset of sensorineural hearing loss in a patient at risk of genital or oral exposure to treponema can be secondary to early neurosyphilis, for which delayed treatment may result in irreversible sequelae. SUMMARY OF THE CASE REPORT: A 40-year-old, HIV seropositive man with a CD4 lymphocyte count greater than 500/mm(3) presented with rapid-onset of bilateral sensorineural hearing loss over a period of one week. Otorhinolaryngological examination was normal. The audiogram showed bilateral hearing loss of 25 and 30 decibels, respectively. He subsequently developed loss of visual acuity, leading to the diagnosis of syphilitic meningitis affecting the optic and auditory nerves. DISCUSSION: In about one half of cases, neurosyphilis is an early manifestation of the disease occurring several weeks or months after contamination. Rapid- or even sudden-onset of hearing loss may be due to auditory neuritis. Clinical interview and syphilis serology in a patient at risk of exposure can allow rapid diagnosis and treatment, consisting of two weeks parenteral penicillin. Recovery of hearing loss is inconstant but can be complete.
Subject(s)
Hearing Loss, Bilateral/microbiology , Hearing Loss, Sudden/microbiology , Neurosyphilis/diagnosis , Adult , HIV Seropositivity , Humans , MaleABSTRACT
Paraduodenal hernia is a rare etiology of intestinal obstruction. Its preoperative diagnosis can only be made by a well-performed upper gastrointestinal series. We report a case of a 19 years old man with abdominal pains and recurrent Koenig's syndromes. The upper gastrointestinal series and CT scan showed a right paraduodenal hernia. we reviewed the anatomy. physiopathology, symptoms and radiographic criteria for the diagnosis of the paraduodenal hernia.
Subject(s)
Duodenal Diseases/pathology , Abdominal Pain/etiology , Adult , Duodenal Diseases/diagnosis , Hernia/diagnosis , Hernia/pathology , Humans , Male , Tomography, X-Ray ComputedABSTRACT
Emphysematous pyelonephritis is a rare and life-endangering suppurative infection characterized by the production of gas in the renal parenchyma and perirenal space. It affects mainly patients with diabetes mellitus. Authors report three cases of emphysematous pyelonephritis and insist on the role of radiological investigations in diagnosis. Through an exceptional case of emphysematous pyelonephritis revealed by hematemesis, they remind the progression route of infection from retroperitoneal to mediastinal space. Prognosis of emphysematous pyelonephritis depends on the patient's general health status and rapidity of diagnosis and treatment. Percutaneous drainage is an alternative to major surgery and is particularly indicated in cases of single kidney or in an inoperable patient.
