A multicentre, patient- and assessor-blinded, non-inferiority, randomised and controlled phase II trial to compare standard and torque teno virus-guided immunosuppression in kidney transplant recipients in the first year after transplantation: TTVguideIT.

BACKGROUND: Immunosuppression after kidney transplantation is mainly guided via plasma tacrolimus trough level, which cannot sufficiently predict allograft rejection and infection. The plasma load of the non-pathogenic and highly prevalent torque teno virus (TTV) is associated with the immunosuppression of its host. Non-interventional studies suggest the use of TTV load to predict allograft rejection and infection. The primary objective of the current trial is to demonstrate the safety, tolerability and preliminary efficacy of TTV-guided immunosuppression. METHODS: For this purpose, a randomised, controlled, interventional, two-arm, non-inferiority, patient- and assessor-blinded, investigator-driven phase II trial was designed. A total of 260 stable, low-immunological-risk adult recipients of a kidney graft with tacrolimus-based immunosuppression and TTV infection after month 3 post-transplantation will be recruited in 13 academic centres in six European countries. Subjects will be randomised in a 1:1 ratio (allocation concealment) to receive tacrolimus either guided by TTV load or according to the local centre standard for 9 months. The primary composite endpoint includes the occurrence of infections, biopsy-proven allograft rejection, graft loss, or death. The main secondary endpoints include estimated glomerular filtration rate, graft rejection detected by protocol biopsy at month 12 post-transplantation (including molecular microscopy), development of de novo donor-specific antibodies, health-related quality of life, and drug adherence. In parallel, a comprehensive biobank will be established including plasma, serum, urine and whole blood. The date of the first enrolment was August 2022 and the planned end is April 2025. DISCUSSION: The assessment of individual kidney transplant recipient immune function might enable clinicians to personalise immunosuppression, thereby reducing infection and rejection. Moreover, the trial might act as a proof of principle for TTV-guided immunosuppression and thus pave the way for broader clinical applications, including as guidance for immune modulators or disease-modifying agents. TRIAL REGISTRATION: EU CT-Number: 2022-500024-30-00.

Impact of COVID-19 pandemic on patients with intracranial aneurysm rupture.

BACKGROUND/OBJECTIVES: The present study aimed at evaluating the impact on the early outcome of patients with ruptured intracranial aneurysms. METHODS: Our study prospectively included 26 consecutive patients with ruptured intracranial aneurysm managed at our institution in context of COVID-19 pandemic between March 1st, 2020 and April, 26th, 2020 (2020 group). A group control included other 28 consecutive patients managed at the same institution for the same disease in 2019, during the same time frame (2019 group). On admission, poor neurological status was defined as WFNS score >3. Severe radiological status was defined by the presence of intracerebral hematoma, or/and acute hydrocephalus requiring further EVD or/and the presence of vasospasm on presentation. Statistical analysis was performed to compare the 2 distinct groups. RESULTS: Rates of poor neurological presentation and severe radiological presentation on hospital admission were higher in the 2020 group (p = 0.01 and p = 0.02, respectively). The delayed hospital admission was 2.7 days in 2020 group and 0.75 days in 2019 group (p = 0.005). Therefore, vasospasm's rate on presentation was also higher in the 2020 group (p = 0.04). CONCLUSION: To our knowledge, this is one of the first studies demonstrating influence of the COVID-19 pandemic on patients with urgent and severe intracranial aneurysmal disease. In case of recurrent COVID-19 pandemic, educating the population concerning specific symptoms such as sudden headache, neurological deficit or even sudden chest pain should be emphasized.