Transplantation最新文献

Background: Solid organ transplant recipients are at risk of severe coccidioidomycosis and are given prophylaxis to mitigate the risk. Patients with seropositive testing typically receive lifelong prophylaxis; currently, this prophylaxis strategy includes patients who are positive only for IgM by enzyme immunoassay (EIA-IgM-only), although this result may be falsely positive.

Methods: We conducted a retrospective study at a large-volume transplant center in an endemic coccidioidomycosis region to compare outcomes of non-lung transplant recipients who were seropositive for Coccidioides but discontinued prophylaxis (case patients) to outcomes of patients who continued prophylaxis (controls).

Results: No case or control patients developed active coccidioidomycosis during the follow-up period. Before transplant, 62 of 77 case patients (80.5%) had a single positive serologic test, of whom 27 of 62 were EIA-IgM-only positive (43.5%). In contrast, 57 of 77 controls (74.0%) had a single seropositive result (16/57 [28.1%] were EIA-IgM-only). The single EIA-IgM-only result was classified as falsely positive by infectious disease consultants in 20 of 43 patients (46.5%) compared with all other Coccidioides serologic results (13/111 [11.7%], P < 0.001). Lifetime antifungal prophylaxis was felt to be unnecessary for 28 of 43 patients (65.1%) who were EIA-IgM-only versus 31 of 111 patients (27.9%) with other serologic results (P < 0.001).

Conclusions: For patients repeatedly positive for EIA-IgM-only and no evidence of seroconversion, compatible clinical illness, or radiographic findings, discontinuing antifungal prophylaxis may be reasonable after the first posttransplant year.

Background: Recent studies suggest that approximately 10% of patients with chronic kidney disease (CKD) have disease-causing genetic variants, an observation relevant to evaluation of kidney transplant candidates.

Methods: We retrospectively investigated the diagnostic yield of genetic testing in kidney transplant candidates evaluated at our program (January 1, 2021-December 8, 2022). Inclusion criteria were as follows: first-degree relative(s) with CKD/end-stage kidney disease (ESKD), early-onset CKD, focal segmental glomerulosclerosis, cystic kidney disease, alternative complement pathway-associated diseases, or ESKD of unknown cause.

Results: One hundred eleven patients underwent genetic kidney disease testing. The most common indication for testing was early-onset CKD (34.2%), followed by a family history of CKD (23.4%), focal segmental glomerulosclerosis (18.0%), cystic kidney disease (9.0%), alternative complement pathway diseases (3.6%), and ESKD of unknown cause (11.7%). Overall diagnostic yield was 46.9% (52/111), and yield was highest among candidates with a family history of CKD (61.5%; 16/26). Among cases with positive testing, the most common diagnostic variant was APOL1, with 2 renal risk variants identified in 57.7% (30/52), while monogenic causes of CKD were identified in 42.3% (22/52). Genetic testing led to further evaluation or to a different diagnosis than the initial clinical diagnosis in 8.1% (9/111) of the cohort. For 24 transplant candidates, their identified diagnostic variants indicated the need for genetic testing of related living donor candidates; of these, 6 living donor candidates were evaluated and underwent testing, of whom donation was excluded in 1 candidate.

Conclusions: Pretransplant genetic testing increases understanding of CKD cause, and provides information for living donor evaluation and risk assessment of posttransplant disease recurrence.

Background: Hepatic ischemia/reperfusion (I/R) injury (HIRI) is an intrinsic phenomenon observed in the process of various liver surgeries. Unfortunately, there are currently few options available to prevent HIRI. Accordingly, we aim to explore the role and key downstream effects of B-cell lymphoma 6 (BCL6) in hepatic I/R (HIR).

Methods: BCL6 expression levels were measured in I/R liver tissue and primary hepatocytes stimulated by hypoxia/reoxygenation (H/R). Moreover, we ascertained the BCL6 effect on HIR in vivo using liver-specific BCL6 knockout mice and adenovirus-BCL6-infected mice. RNA-sequencing, luciferase, chromatin immunoprecipitation, and interactome analysis were combined to identify the direct target and corresponding molecular events contributing to BCL6 function. DNA pull-down was applied to identify upstream of BCL6 in the H/R challenge.

Results: HIR represses BCL6 expression in vivo and in vitro. Hepatic BCL6 overexpression attenuates inflammation and apoptosis after I/R injury, whereas BCL6 deficiency aggravates I/R-induced liver injury. RNA-sequencing showed that BCL6 modulated nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 inflammasome signaling in HIRI. Mechanistically, BCL6 deacetylated nuclear factor kappa-B p65 lysine 310 by recruiting sirtuin 1 (SIRT1), thereby inhibiting the nuclear factor kappa-B/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 pathway. Moreover, overexpression of SIRT1 blocked the detrimental effects of BCL6 depletion. Moreover, EX 527, a SIRT1 inhibitor, vanished protection from BCL6 overexpression. Furthermore, transcription factor 7 was found to mediate the transcription regulation of BCL6 on H/R challenge.

Conclusions: Our results provide the first evidence supporting BCL6 as an important protective agent of HIR. This suggests a potential therapeutic approach for HIR.