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Background Pediatric cardiac surgery is associated with abnormal coagulation, bleeding, and nearly ubiquitous transfusions. With the popularization of patient blood management, attempts are being made to decrease liberal transfusions by administering prothrombin complex concentrates (PCCs). The safety and efficacy of PCCs in adult cardiac surgery has been studied extensively, but only few reports address this in children. We performed an observational study focused on transfusion requirements after off-label use of activated PCC Factor Eight Inhibitor Bypassing Activity (FEIBA) as an adjunct to post-cardiopulmonary bypass (CPB) hemostatic protocol.Methods We reviewed the medical records of children ≤15 kg undergoing cardiac operations with CPB between May 2018 and March 2022. A propensity score (PS) analysis was performed to identify matched pairs of patients who did and did not receive FEIBA.Results Out of 210 patients who met the inclusion criteria, 44 patients received FEIBA. Propensity score-based analysis identified 40 matched pairs of patients with similar baseline characteristics. There was no statistically significant difference in the primary outcome—the volume of transfusion after CPB, which included all allogeneic blood products and salvaged washed red cells administered after protamine. Specifically, FEIBA patients were transfused 28 (22-34) mL/kg and controls were transfused 22 (11-49) mL/kg, P= .989. Upon arrival to ICU, the FEIBA group averaged an 8% lower international normalized ratio, compared with the controls (P= .009) and a 1.08 g/dL higher hemoglobin (P= .050). Neither difference remained significant on POD 1.Conclusions In this exploratory study, we found no change in transfusion requirements after CPB despite FEIBA administration.

Ran-binding protein 3 (RanBP3) is an ∼55-kDa protein that functions as a cofactor for Crm1-mediated nuclear export. RanBP3 stimulates export by enhancing the affinity of Crm1 for Ran·GTP and cargo. However, important additional functions for this cofactor may exist. We now report that RanBP3 associates with the Ran-specific guanine nucleotide exchange factor, regulator of chromosome condensation 1 (RCC1). This interaction was stimulated by the addition of Ran; moreover, Ran·GDP, Ran·GTP, and Ran without nucleotide could all stimulate complex formation between RanBP3 and RCC1 even though binding of Ran·GDP to RanBP3 alone was undetectable. RanBP3 could also promote binding of Crm1 to RCC1 in the presence of Ran. Binding of RanBP3 to RCC1 increased the catalytic activity of RCC1 toward Ran, and importantly, the ability of RanBP3 to stimulate RCC1 was not affected by the presence of Crm1. These data indicate that RanBP3 acts as a scaffold protein to promote the efficient assembly of export complexes. By tethering Crm1 to catalytically enhanced RCC1, RanBP3 may lower the entropic barrier for the loading of Ran·GTP onto Crm1. We propose that this provides an additional mechanism by which RanBP3 facilitates export.

There are few reports of extracorporeal membrane oxygenation (ECMO) therapy for respiratory failure because of Pneumocystis jiroveciipneumonia (PJP) in patients with acquired immunodeficiency syndrome (AIDS). None of the cases reported involvement of immune reconstitution inflammatory syndrome (IRIS), a paradoxical clinical worsening after the initiation of antiretroviral therapy (ART) in ART-naïve patients because of an exaggerated systemic inflammation with cell count recovery. We present a patient with newly diagnosed AIDS and PJP pneumonia that progressed to acute respiratory distress syndrome (ARDS) secondary to probable IRIS for which veno-venous ECMO was initiated. He transitioned to conventional ventilator after 57 days of ECMO therapy. However, he did not survive to hospital discharge. Combined with four previously reported cases of ARDS in human immunodeficiency virus patients secondary to PJP treated with ECMO, three of the five patients survived to ECMO decannulation. Extracorporeal membrane oxygenation is considered an accepted modality for adult patients with respiratory andor cardiac failure refractory to maximal medical therapy. As ECMO becomes increasingly utilized in clinical practice, there is ongoing controversy regarding the appropriate selection of patients. In the past, contraindications to ECMO included immunocompromised states and conditions with known poor prognosis. The cases herein suggest the indications and contraindications warrant further discussion and research.