Refractory cardiogenic shock due to atomoxetine overdose rescued by venoarterial extracorporeal membrane oxygenation: A case report.

Background: Atomoxetine, a selective norepinephrine reuptake inhibitor for attention-deficit hyperactivity disorder, may lead to severe complications, notably cardiac issues, upon overdose. We present a unique case of venoarterial extracorporeal membrane oxygenation (VA-ECMO) rescue for atomoxetine-induced cardiogenic shock. Case Presentation: We report a 30-year-old man who, after ingesting a significant overdose of atomoxetine, experienced seizures and severe cardiogenic shock, necessitating VA-ECMO for resuscitation. While prior reports have noted cardiovascular complications like QTc prolongation and Takotsubo cardiomyopathy following atomoxetine overdose, this case is notable for its life-threatening circulatory failure, which required ECMO intervention. Swift recognition coupled with VA-ECMO initiation, endoscopic medication removal, intravenous lipid emulsion, and activated charcoal may have played a pivotal role in stabilizing the patient and facilitating recovery. Conclusion: Healthcare practitioners should recognize the severe cardiac complications of atomoxetine overdose. Careful monitoring with ECG and echocardiography, along with providing intensive care, is crucial in managing critical cases.

Accuracy of rapid blood coagulation testing device FibCare® in a tertiary emergency department.

Aim: FibCare® is a novel point-of-care testing device enabling prompt evaluation of fibrinogen levels. This study aimed to investigate the accuracy of FibCare® at a tertiary emergency department. Methods: Blood specimens obtained at a tertiary emergency medical center between October 1, 2021, and April 30, 2023, were evaluated. The correlation between the fibrinogen levels assessed via FibCare® and those via the Clauss method was evaluated using the Spearman's test. The discrepancy between the two measurement methods was assessed according to fibrinogen level and diagnosis. Results: A total of 177 specimens from 147 patients were eligible for the analysis. The median age of the patients was 49 years, and 109 (61.6%) were men. The two measurements had statistically significant but moderate correlation (p < 0.001, ρ = 0.76). FibCare® missed 14 out of 35 cases from patients with hypofibrinogenemia (fibrinogen ≤150 mg/dL assessed by the Clauss method). The discrepancy between the two measurements was significantly greater in specimens with lower fibrinogen levels and those obtained from patients following trauma. Conclusions: FibCare®, a novel point-of-care testing device, can be compatible with the Clauss method. However, clinicians should be aware of the risk that FibCare® may underestimate fibrinogen reduction, especially in severe cases and trauma cases.

Myeloid/Lymphoid Neoplasm with PDGFRB Rearrangement with t (5;10) (q33;q22) Harboring a Novel Breakpoint of the CCDC6-PDGFRB Fusion Gene.

Myeloid/lymphoid neoplasms with PDGFRB rearrangement are a distinct type of myeloid neoplasms that occur in association with rearrangement of PDGFRB at 5q32. The hematological features most often show prominent eosinophilia. We herein report a patient with myeloid/lymphoid neoplasms with PDGFRB rearrangement with t (5;10) (q33;q22) who showed atypical chronic myeloid leukemia-like clinical features without eosinophilia and achieved an optimal response to imatinib. A sequence analysis showed a CCDC6-PDGFRB fusion gene with a new break point in the PDGFRB gene. This is the sixth case of myeloid/lymphoid neoplasm with PDGFRB rearrangement harboring a CCDC6-PDGFRB fusion gene, and it has a new breakpoint in the PDGFRB fusion gene.

Integrative genomic and proteomic analyses identifies glycerol-3-phosphate acyltransferase as a target of low-dose ionizing radiation in EBV infected-B cells.

PURPOSE: We sought to gain a better understanding of the low-dose ionizing radiation (LDIR)-induced molecular changes in transformed pre-malignant cells in their microenvironment. MATERIALS AND METHODS: The cellular response to LDIR was compared and contrasted using immortalized human Epstein-Barr virus-infected B-cells (EBV-B) in mono-culture, co-culture with human bone marrow derived stromal cells (MSC), or under the LDIR-induced bystander effect. The resulting alterations in protein and gene expression (including microRNA, miRNA) were evaluated by isobaric tags for relative and absolute quantification (iTRAQ) proteomics assay, western blot, cDNA array and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. RESULTS: The miRNAs let7a, miR-15b, miR-16, and miR-21, and a lipid metabolic miRNA hub miR-23b, were upregulated after LDIR exposure in the mono-cultured EBV-B cells, but were downregulated in EBV-B cells co-irradiated with MSC. A lipid biosynthesis enzyme glycerol-3-phosphate acyltransferase, the common target of these miRNA, was downregulated at the level of protein and mRNA expression in the LDIR-exposed, mono-cultured EBV-B cells and upregulated MSC co-cultured EBV-B cells. CONCLUSIONS: These results suggest a putative miRNA regulatory mechanism controlling the LDIR-induced stress response, and illustrate that LDIR exposure, and the cell's microenvironment, can affect specific gene expression, both directly and indirectly, resulting in altered protein expression.

TGF-ß-Neutralizing Antibody 1D11 Enhances Cytarabine-Induced Apoptosis in AML Cells in the Bone Marrow Microenvironment.

Hypoxia and interactions with bone marrow (BM) stromal cells have emerged as essential components of the leukemic BM microenvironment in promoting leukemia cell survival and chemoresistance. High levels of transforming growth factor beta 1 (TGFß1) produced by BM stromal cells in the BM niche regulate cell proliferation, survival, and apoptosis, depending on the cellular context. Exogenous TGFß1 induced accumulation of acute myeloid leukemia (AML) cells in a quiescent G0 state, which was further facilitated by the co-culture with BM-derived mesenchymal stem cells (MSCs). In turn, TGFß-neutralizing antibody 1D11 abrogated rhTGFß1 induced cell cycle arrest. Blocking TGFß with 1D11 further enhanced cytarabine (Ara-C)-induced apoptosis of AML cells in hypoxic and in normoxic conditions. Additional constituents of BM niche, the stroma-secreted chemokine CXCL12 and its receptor CXCR4 play crucial roles in cell migration and stroma/leukemia cell interactions. Treatment with 1D11 combined with CXCR4 antagonist plerixafor and Ara-C decreased leukemia burden and prolonged survival in an in vivo leukemia model. These results indicate that blockade of TGFß by 1D11 and abrogation of CXCL12/CXCR4 signaling may enhance the efficacy of chemotherapy against AML cells in the hypoxic BM microenvironment.