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Background: Acute graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with significant morbidity and mortality, and efficacy of currently available therapeutics are limited. Acute and chronic GVHD are similar in that both are initiated by antigen presenting cells and activation of alloreactive B-cells and T-cells, subsequently leading to inflammation, tissue damage, and organ failure. One difference is that acute GVHD is mostly attributed to T-cell activation and cytokine release, whereas B-cells are the key players in chronic GVHD. Ibrutinib is an irreversible inhibitor of the Bruton's tyrosine kinase (BTK), which is part of B-cell receptor signaling. Ibrutinib is currently used for treating chronic GVHD, but its efficacy towards acute GVHD is unknown. Besides BTK, ibrutinib also inhibits interleukin-2 inducible T-cell kinase (ITK), which is predominantly expressed in T-cells and a crucial enzyme for activating the downstream pathway of TCR signaling. ITK activates PLCγ2 and facilitates signaling through NF-κB, NFAT, and MAPK, leading to activation and proliferation of T-cells and enhanced cytokine production. Therefore, the TCR signaling pathway is indispensable for development of acute GVHD, and ITK inhibition by ibrutinib would be a rational therapeutic approach., Case Presentation: A 56-year-old male acute myeloid leukemia patient with Myeloid neoplasms with germline DEAD-box RNA helicase 41 ( DDX41 ) mutation underwent cord blood transplantation and developed severe gastrointestinal (GI) acute GVHD which was refractory to steroids and mesenchymal stem cell therapy. While acute GVHD accommodated by multiple life-threatening GI bleeding events persisted, chronic cutaneous GVHD developed, and ibrutinib 420 mg/day was initiated from day 147 of transplant. Although ibrutinib was commenced targeting the chronic GVHD, unexpected and abrupt remission of acute GVHD along with remission of chronic GVHD was observed., Conclusion: Ibrutinib is a promising therapeutic for treating acute GVHD, and further studies are warranted., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

We report a case of bloodstream infection due to Ruminococcus gnavus ( R. gnavus ) associated with pelvic abscess in a 74-year-old female patient undergoing radiotherapy for cervical cancer. Gram staining of positive anaerobic blood cultures revealed short chains of gram-positive cocci. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was performed directly on the blood culture bottle, and 16S rRNA sequencing identified the bacterium as R. gnavus . There was no leakage from the sigmoid colon to rectum on enterography, and R. gnavus was not found in the culture of her pelvic abscess. After the administration of piperacillin/tazobactam, her condition markedly improved. This patient with R. gnavus infection demonstrated no gastrointestinal involvement, whereas past published cases reported diverticulitis or intestinal damage. It is possible that bacterial translocation of R. gnavus occurred from the gut microbiota, due to damage to the intestinal tract caused by radiation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)