Cytomegalovirus Antiviral Resistance Among Kidney Transplant Recipients in a Phase 3 Trial of Letermovir vs Valganciclovir Prophylaxis.

Background: In a phase 3 trial, letermovir was noninferior to valganciclovir for cytomegalovirus (CMV) disease prophylaxis in kidney transplant recipients who were CMV-seronegative and received kidneys from donors who were CMV-seropositive. Genotypic antiviral resistance and CMV glycoprotein B (gB) genotype are reported.

Methods: Plasma samples with detectable CMV DNA were sequenced for the presence of known letermovir and valganciclovir resistance-associated amino acid substitutions (RASs) encoded by CMV gene regions (UL51, UL54, UL56, UL89, UL97) and prevalence of gB (UL55) genotypes (gB1-gB5).

Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients: A Randomized Clinical Trial.

Importance: Valganciclovir for 200 days is standard care for cytomegalovirus (CMV) prophylaxis in high-risk CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor, but its use is limited by myelosuppression.

Objective: To compare the efficacy and safety of letermovir with valganciclovir for prevention of CMV disease in CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor.

Design, Setting, And Participants: Randomized, double-masked, double-dummy, noninferiority, phase 3 trial in adult CMV-seronegative kidney transplant recipients who received an organ from a CMV-seropositive donor at 94 participating sites between May 2018 and April 2021 (final follow-up in April 2022).

The Lung-Liver Axis: A Requirement for Maximal Innate Immunity and Hepatoprotection during Pneumonia.

The hepatic acute-phase response (APR), stimulated by injury or inflammation, is characterized by significant changes in circulating acute-phase protein (APP) concentrations. Although individual functions of liver-derived APPs are known, the net consequence of APP changes is unclear. Pneumonia, which induces the APR, causes an inflammatory response within the airspaces that is coordinated largely by alveolar macrophages and is typified by cytokine production, leukocyte recruitment, and plasma extravasation, the latter of which may enable delivery of hepatocyte-derived APPs to the infection site.

Regulation of acute graft-versus-host disease by microRNA-155.

Acute graft-versus-host disease (aGVHD) remains a major complication of allogeneic hematopoietic stem cell transplant (alloHSCT), underscoring the need to further elucidate its mechanisms and develop novel treatments. Based on recent observations that microRNA-155 (miR-155) is up-regulated during T-cell activation, we hypothesized that miR-155 is involved in the modulation of aGVHD. Here we show that miR-155 expression was up-regulated in T cells from mice developing aGVHD after alloHSCT.

Functional implications of microRNAs in acute myeloid leukemia by integrating microRNA and messenger RNA expression profiling.

Background: The expression of microRNAs (miRNAs) is deregulated in acute myeloid leukemia (AML), but the corresponding functional miRNA-controlled pathways are poorly understood. Integration of messenger RNA (mRNA) and miRNA expression profiling may allow the identification of functional links between the whole transcriptome and microRNome that are involved in myeloid leukemogenesis.

Methods: We integrated miRNA and mRNA expression profiles obtained from 48 newly diagnosed AML patients by using 2 different microarray platforms and performed correlation, gene ontology, and network analysis.

Sp1/NFkappaB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemia.

The biologic and clinical significance of KIT overexpression that associates with KIT gain-of-function mutations occurring in subsets of acute myeloid leukemia (AML) (i.e., core binding factor AML) is unknown.