scholarly journals Etoposide Sensitivity Does Not Predict MLL Rearrangements or Risk of Therapy-Related Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1829-1829
Author(s):  
Jun Yang ◽  
Alessia Bogni ◽  
Cheng Cheng ◽  
Wasim K. Bleibel ◽  
Jean Cai ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Rank Test ◽  
Drug Induced ◽  
Etoposide Treatment ◽  
Signed Rank ◽  
Wilcoxon Signed Rank Test ◽  
Signed Rank Test ◽  
Acute Myeloid

Abstract Therapy-related acute myeloid leukemia (t-AML) can arise from topoisomerase II-directed agents such as etoposide and teniposide, most likely via drug-induced MLL gene fusions. MLL cleavage in its breakpoint cluster region has been linked to apoptosis caused by etoposide and other agents. It has been speculated that the degree of myelotoxicity caused by agents such as etoposide may predispose to t-AML. However, whether drug-induced MLL rearrangements (rMLL) and subsequent leukemogenesis are inextricably linked to the desired drug-induced cytotoxic effects remains a matter of uncertainty. To directly address this question, we compared rMLL in blood samples from and epipodophyllotoxin-related clinical toxicity in children with acute lymphoblastic leukemia (ALL) who did and did not develop t-AML, as well as the level of rMLL in cell lines that were sensitive or resistant to etoposide. In 7 t-AML cases and 7 identically-treated matched controls, rMLL were detectable following etoposide treatment in both cohorts, but at a slightly greater frequency in the former group (P = 0.04, Wilcoxon signed-rank test). However, there was no correlation between the cumulative etoposide dose and the degree of rearrangements (P = 0.5, r2=0.039, Spearman rank correlation). Secondly, etoposide or teniposide-related acute toxicities to the host tissues did not differ between the 14 t-AML cases and the 14 matched controls. The drug-induced reduction in neutrophil and leukocyte counts was not greater among t-AML cases than controls (P>0.17, Wilcoxon signed-rank test), nor was the incidence of infection and gastrointestinal toxicity during epipodophyllotoxin treatment (P>0.22, McNemar’s test). Finally, in 25 human lymphoid cell lines, MLL fusions were more common after etoposide treatment (at equitoxic concentrations) compared to untreated controls (P < 0.0001, paired t test) but did not differ in frequency in etoposide-sensitive versus resistant cell lines (P = 0.91, Mann-Whitney U test). Together, these data indicate that epipodophyllotoxin-mediated leukemogenesis is not directly linked to the cytotoxicity of these agents.

scholarly journals Influence of Bone Marrow Stromal and Leukemic Cells on Cytarabine Chemo-Toxicity in Acute Myeloid Leukemia (AML)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2492-2492
Author(s):  
Liana E Gynn ◽  
Elizabeth Anderson ◽  
Gareth M Robinson ◽  
Sarah Anne Wexler ◽  
Gillian Upstill-Goddard ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Cell Lines ◽  
Stromal Cells ◽  
Myeloid Leukemia ◽  
Stromal Cell ◽  
Leukemic Cells ◽  
Drug Induced ◽  
Acute Myeloid

Mesenchymal stromal cells (MSC) are known to protect leukemic cells from drug-induced toxicity within the bone marrow (BM) niche, however, less is known about leukemic impact on supportive MSC. The nucleoside-analogue, cytarabine (Ara-C), is a front-line therapy for acute myeloid leukemia (AML), entering cells via the human equilibrative nucleoside transporter (hENT1). Over a third of AML patients do not show continued response to Ara-C-based regimens, with chemo-resistance linked with repressed hENT1 availability in some patients, while other mechanisms remain unknown. In addition to chemo-resistance, DNA damage caused by chemotherapeutics such as Ara-C can persist in BM-MSC, which remain of host origin following allogeneic stem cell transplantation. This genotoxicity hinders cellular functionality, and may be implicated in long-term hematopoietic failure and secondary malignancies. This study aimed to further elucidate chemo-resistance mechanisms, with particular focus on the contribution of leukemic cells to stromal cell toxicity; aiming to uncover potentially targetable features of resistant AML and reduce treatment burden on the BM. Primary MSC were isolated from BM aspirates from patients both at diagnosis and post-treatment; following ethical approval and informed consent. MSC cultures were confirmed by immunophenotype (flow cytometry) and differentiation capacity (cytological staining) and used in a similar manner to that of cell lines. AML (HL-60, K562) and stromal (HS-5) cell lines were mono- or co-cultured using trans-well inserts for 24h, prior to 1-24h treatment with 25µM Ara-C (equivalent to in vivo standard dose; 100-200mg/m2). Cytotoxicity was monitored by viability and proliferation (CFSE tracing) assays, and chemo-sensitivity assessed with a drug-efficacy screening tool (bacterial bioluminescent biosensor). Genotoxicity was determined by micronucleus and alkaline comet assays, assessing division abnormalities and DNA fragmentation respectively. Differential cytokine secretion utilised an array, with quantification by ELISA. In co-culture, stromal cells were sensitised to drug-induced cytotoxicity, while leukemic cells were themselves protected from treatment. Genotoxicity was also significantly increased in stromal cells (p=0.0397), while being significantly decreased in leukemic cells when co-cultured (p=0.0089), conferring with cytotoxicity findings. Similarly, BM-MSC from previously treated patients had significantly higher genotoxicity than patients at diagnosis (p=0.0138). While stromal cell proliferation remained unchanged regardless of intervention, data suggest increased proliferation in co-cultured leukemic cells compared to cells cultured alone. Chemo-sensitivity also increased in stromal cells in co-culture, while the opposite was seen for leukemic cells. Seven of 32 cytokines were differentially secreted by cell lines in co-culture compared to combined values from mono-cultured cells; CCL2, CXCL1, G-CSF, GM-CSF, IL-6, MIF and Serpin E1. Of these, the inflammatory cytokine MIF, macrophage migration inhibitory factor, was decreased in co-culture (p<0.0001), and has been implicated in the progression of other malignancies. Separation of cells following co-culture and treatment uncovered opposing MIF secretion profiles in cells with high (HL-60) and low (K562) sensitivity to Ara-C. Despite differential secretion, neither MIF, nor the MIF inhibitor ISO-1, had significant effects on chemo-sensitivity when cells were cultured in each condition for 24 hours. Chemo-resistance is evidently a network of complex, interlinking mechanisms which are not easily identified in vitro. MIF remains a likely candidate for studies into AML chemo-resistance, with research ongoing. This study shows for the first time that the co-culture of AML and MSC alters the genotoxic effect of chemotherapy. Future research utilising larger patient cohorts is required to fully understand how cells in the BM micro-environment can be targeted. This could potentially improve not only the overall outcome for AML patients, but reduce the cytotoxic and long-term genotoxic complications of current therapies. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Pan-Clk/Dyrk Inhibitor Cirtuvivint (SM08502) Exposes Mechanistic Underpinnings of Alternative Splicing As a Therapeutic Vulnerability in Heme Malignancies

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2950-2950
Author(s):  
Carine Bossard ◽  
Elizabeth A. McMillan ◽  
Emily Creger ◽  
Brian Eastman ◽  
Chi-Ching Mak ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Alternative Splicing ◽  
Cell Viability ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Splice Junction ◽  
Mrna Splicing ◽  
Drug Induced ◽  
The Past ◽  
Acute Myeloid

Abstract Mutations in spliceosomal genes are one of the most common classes of somatic alterations in patients with Myelodysplastic Syndrome (MDS) and occur across the entire spectrum of myeloid malignancies, including 10‒25% of patients with acute myeloid leukemia (AML). These mutations occur in higher proportions in AML subjects greater than 60 years of age, or when AML has transformed from an antecedent MDS. Spliceosomal gene mutations are implicated in the production of pathological RNA splicing patterns that block cell differentiation and maintain a myeloid precursor phenotype. This suggests deranged pre-mRNA splicing is a mechanistic determinant of many heme malignancies and, as such, has provoked interest in therapeutic modulation of pre-mRNA splicing as a treatment paradigm. The CLK/DYRK family of protein kinases has been recognized as an integration hub for signal transduction-dependent modulation of alternative pre-mRNA splice junction selection through direct phosphorylation of the serine/arginine-rich splicing factor (SRSF) splice junction enhancer-binding proteins. Thus, these kinases potentially represent a druggable intervention point in alternative splicing-dependent cancers. The isoquinoline SM08502 (cirtuvivint) is a potent ATP-competitive inhibitor of the Cdc2-like kinases (CLK1-4) and the dual specificity tyrosine phosphorylation-regulated kinases (DYRK1-4) with activity against only a minimal number of the remaining members of the CMGC-family kinases and the kinome as a whole. Here the consequence of pan-CLK/DYRK kinase inhibition on cell viability and tumorigenicity was evaluated across a panel of human tumor-derived AML, DLBCL, MCL, myeloma, T-ALL, and CML/CLL models. EC 50s in response to cirtuvivint ranged from 0.014 μM‒0.495 μM in 4-day in vitro cell viability assays, with low-dose responders enriched in subsets of AML, myeloma, DLBCL, MCL and T-ALL. Cell viability EC 50s were associated with induction of programed cell death at drug exposures that inhibited accumulation of phosphorylated SRSF proteins and the anti-apoptotic protein MCL-1. To directly evaluate the contribution of CLK/DYRK kinases to alternative splicing profiles, high-depth RNAseq analysis was performed across 4 cell lines (3 acute myeloid leukemia cell lines and 1 mantle cell lymphoma cell line) +/- a 6-hour exposure to 1µM cirtuvivint. Both baseline and drug-induced changes in alternative splicing events (ASEs) were measured using a multivariate analysis of splicing transcripts (rMATS). The frequency of cirtuvivint-induced ASEs was approximately 20% of total detected ASEs. Concordant drug-induced ASEs among the tested cell lines were in genes enriched in pathways known to drive oncogenesis in hematopoietic lineages, including the MAP kinase and mTOR signaling pathways. Tumor growth inhibition assays in immunocompromised mice showed a range of model-specific responses, including tumor stasis and partial to complete tumor regression at clinically relevant exposures. A cell-based synthetic-lethal screen of cirtuvivint across 36 small molecule inhibitors identified multiple BCL-2 inhibitors among the most prominent synergistic combinations. Consistent with this, combination of the BCL-2 inhibitor venetoclax with cirtuvivint was sufficient to induce tumor regressions in AML xenograft models (KG-1 and HL-60) that were resistant to either single-agent drug at the same concentrations. These observations support further evaluation of CLK/DYRK inhibitors as a therapeutic strategy for heme malignancies dependent upon alternative pre-mRNA splicing. Disclosures Bossard: Biosplice Therapeutics: Current Employment. McMillan: Prizer: Ended employment in the past 24 months. Beaupre: Pfizer: Ended employment in the past 24 months. White: Pfizer: Ended employment in the past 24 months.

PENGARUH TIRAH BARING TERHADAP PENURUNAN RASA MUAL PADA KLIEN GASTRITIS DI PELAYANAN KESEHATAN

2019 ◽  
Vol 3 (1) ◽  
pp. 25
Author(s):  
Dewi Nurhanifah ◽  
Desy Noor Latifah Sari ◽  
Rahmawati Rahmawati
Keyword(s):  
Rank Test ◽  
Purposive Sampling ◽  
Signed Rank ◽  
Wilcoxon Signed Rank Test ◽  
Signed Rank Test

Salah satu masalah kesehatan yang sering dialami adalah penyakit gastritis. Gejala yang sering dikeluhkan oleh penderita gastritis adalah mual. Salah satu penatalaksanaan keperawatan yang dapat mengurangi rasa mual adalah tirah baring. Penelitian ini bertujuan untuk mengetahui pengaruh tirah baring terhadap penurunan rasa mual pada klien gastritis di Pelayanan Kesehatan. Metode penelitian menggunakan eksperimental dengan bentuk penelitian one group pretest-posttest design. Populasi dan sampel adalah klien yang mengalami mual di Wilayah Kerja Puskesmas  yang berjumlah 15 orang. Sampel diambil dengan teknik purposive sampling. Alat pengumpul data menggunakan observasi. Analisa data melalui uji Wilcoxon Signed Rank Test. Hasil penelitian menujukkan klien gastritis sebelum tirah baring mengalami mual ringan sebanyak 7 orang (46,7%), sesudah tirah baring mengalami tidak mual sebanyak 7 orang (46,7%). Ada pengaruh tirah baring terhadap penurunan rasa mual pada klien gastritis di Pelayanan Kesehatan (ρ value = 0,001).

Efektifitas Kompres Jahe Merah Hangat Dan Kompres Serai Terhadap Penurunan Intensitas Nyeri Arthritis Remathoid Pada Lanjut Usia Di Desa Mojoranu Kecamatan Dander Kabupaten Bojonegoro

2017 ◽  
Vol 5 (1) ◽  
Author(s):  
Ferawato Ferawati
Keyword(s):  
Pain Intensity ◽  
Therapy Group ◽  
The Elderly ◽  
Rank Test ◽  
Test Design ◽  
Signed Rank ◽  
Wilcoxon Signed Rank Test ◽  
Post Test ◽  
Signed Rank Test ◽  
Red Ginger

ABSTRAKReumatoid Artritis (RA) merupakan penyakit muscoloskelektal yang sering terjadi pada usia lanjut. Gangguan pada system muscoloskelektal yang ditandai dengan munculnya nyeri sendi dan kekakuan yang mengakibatkan penurunan kemampuan fisiologis atau kualitas hidup lansia. Dampak dari Reumatoid Artritis dapat menimbulkan beberapa keluhan dan dapat menyebabkan kelumpuhan. Untuk menganalisis efektifitas kompres jahe merah hangat dan kompres serai hangat terhadap penurunan intensitas nyeri artitris remauthoid pada lanjut usia.Metode Penelitian: Jenis penelitian adalah quasy experimental dengan two group pre – post test design. Subjek adalah sebagian lansia yang penderita Arthritis Remathoid di Desa Sumberagung Kecamatan Dander Kabupaten Bojonegoro. Subjek dibagi menjadi dua kelompok yaitu kelompok I (n=15) diberi perlakuan kompres jahe hangat dan II (n=15) diberi perlakuan kompres serai hangat. Analisis yang digunakan uji Mann Whitney U Test dan Wilcoxon Signed Ranks Test dengan ingkat kemaknaan α = 0,05.Hasil uji Wilcoxon Signed Rank Test, didapat keduanya mempunyai nilai kemaknaan yaitu ρ value = 0,000. Nilai ρ = 0,031 pada kelompok kompres serai hangat dan kelompok kompres jahe merah ρ value = 0,165. Hasil uji Mann Withney U Test pada Post perlakuan kedua terapi diperoleh selisih nilai nyeri pada kompres jahe ρ= 0,003 dan selisih nilai nyeri kompres serai ρ value = 0,001.Penggunaan kompres jahe merah lebih efektif dibandingkan dengan kompres serai terhadap penurunan intensitas nyeri arthritis remathoid. Kata Kunci: usia lanjut, Reumatoid Artritis (RA), jahe merah, serai, perbedaan efektifitas.    ABSTRACTReumatoid Artritis (RA) is a musculoskeletal which frequently occurs in the elderly. The disorders in the musculoskeletal system are noted by the occurrence of pain in the joints and stiffness which reduces the physiological abilities or life quality of the elderly. The disease causes many such complaints and  consequences of the disease rheumatoid arthritis may experience paralysis. The aims of this study is to analyze the effect of warm red ginger compress therapy and warm lemongrass compress therapy against of  Decreased pain intensity in  the elderly  with  artitris remauthoid. The study was Queasy experimental with two group pre – post test design. Subjects were some elderly people with Arthritis Remathoid in Sumberagung Village, Dander Sub District, Bojonegoro District. Subjects were divided into two groups: group I (n-15) with warm ginger compress therapy, and II (n=15) with warm lemongrass compress therapy. The analyses used in this study were the Mann Whitney U Test and Wilcoxon Signed Ranks Test with α of 0.05. Results of Wilcoxon Signed Rank Test obtained Both have meaning p value of  0.000. ρ value = 0,031 in a warm lemongrass compress therapy group and obtained of warm ginger compress therapy group ρ value = 0,165. The results of Mann Withney U Test on Post treatment second therapy, obtained difference of warm ginger compress therapy with ρ value= 0,003 and difference of warm lemongrass compress therapy with ρ value = 0,001.The use of warm ginger compresses therapy are more effective than a warm lemongrass compress therapy against decreased pain intensity in  the elderly  with  artitris remauthoid.  Keywords: elderly, artitris remauthoid, red ginger, lemongrass, differences in effectiveness

Antitumor Effect of Pomolic Acid in Acute Myeloid Leukemia Cells Involves Cell Death, Decreased Cell Growth and Topoisomerases Inhibition

2019 ◽  
Vol 18 (10) ◽  
pp. 1457-1468
Author(s):  
Michelle X.G. Pereira ◽  
Amanda S.O. Hammes ◽  
Flavia C. Vasconcelos ◽  
Aline R. Pozzo ◽  
Thaís H. Pereira ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Acute Myeloid Leukemia ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Natural Compound ◽  
Dna Topoisomerases ◽  
Human Dna ◽  
Pomolic Acid ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) represents the largest number of annual deaths from hematologic malignancy. In the United States, it was estimated that 21.380 individuals would be diagnosed with AML and 49.5% of patients would die in 2017. Therefore, the search for novel compounds capable of increasing the overall survival rate to the treatment of AML cells is urgent. Objectives: To investigate the cytotoxicity effect of the natural compound pomolic acid (PA) and to explore the mechanism of action of PA in AML cell lines with different phenotypes. Methods: Three different AML cell lines, HL60, U937 and Kasumi-1 cells with different mechanisms of resistance were used to analyze the effect of PA on the cell cycle progression, on DNA intercalation and on human DNA topoisomerases (hTopo I and IIα) in vitro studies. Theoretical experiments of the inhibition of hTopo I and IIα were done to explore the binding modes of PA. Results: PA reduced cell viability, induced cell death, increased sub-G0/G1 accumulation and activated caspases pathway in all cell lines, altered the cell cycle distribution and inhibited the catalytic activity of both human DNA topoisomerases. Conclusion: Finally, this study showed that PA has powerful antitumor activity against AML cells, suggesting that this natural compound might be a potent antineoplastic agent to improve the treatment scheme of this neoplasm.

PENGARUH PEMBACAAN DZIKIR PADA IBU MELAHIRKAN TERHADAP TINGKAT NYERI INTRA NATAL DI RUMAH BERSALIN FAJAR YOGYAKARTA

2010 ◽  
Vol 1 (1) ◽  
Author(s):  
Sri Sumaryani ◽  
Indri Nurasa
Keyword(s):  
Home Delivery ◽  
Labor Pain ◽  
Rank Test ◽  
Control Group ◽  
Pain Level ◽  
Control Group Design ◽  
Signed Rank ◽  
Wilcoxon Signed Rank Test ◽  
Post Test ◽  
Signed Rank Test

PENGARUH PEMBACAAN DZIKIR PADA IBU MELAHIRKAN TERHADAP TINGKAT NYERI INTRA NATAL DI RUMAH BERSALIN FAJAR YOGYAKARTAEffect of Reading Dhikr Women On The Level Of Birth Pain Intra Christmas At Home Delivery Dawn YogyakartaSri Sumaryani1 & Indri Nurasa21, 2)Program Studi Ilmu Keperawatan Fakultas Kedokteran Universitas Muhammadiyah YogyakartaJl. Lingkar Barat Taman Tirto Kasihan Bantul Yogyakarta 55182*)e-mail: [email protected] atau yang biasa disebut dengan proses persalinan merupakan suatu proses membuka dan menipisnya serviks, dan janin turun ke dalam jalan lahir. Gejala awal persalinan akan menimbulkan nyeri yang sangat hebat karena adanya kontraksi uterus dan otot abdomen. Nyeri intra natal adalah suatu nyeri yang dirasakan saat terjadinya proses persalinan (melahirkan). Saat nyeri persalinan muncul, ada baiknya bagi ibu untuk membaca dzikir. Dzikir adalah mengingat Allah SWT dan menghadirkan apa yang tadinya ada di dalam benak untuk kemudian dilafadzkan atau disebut-sebut yang dapat dilakukan secara lisan dengan menggunakan lidah atau bisa juga diucapkan tanpa adanya keterlibatan lidah, yaitu melalui hati. Penelitian ini bertujuan untuk mengetahui pengaruh pembacaan dzikir pada ibu melahirkan terhadap tingkat nyeri intra natal. Teknik pengambilan sampel menggunakan purposive sampling. Desain penelitian pra eksperimen, dengan rancangan pre test-post test tanpa kelompok kontrol. Sampel penelitian berjumlah 30 responden. Pengumpulan data dilakukan dengan observasi langsung kepada responden untuk mengukur tingkat nyeri. Analisa data menggunakan uji statistik wilcoxon signed rank test dan regresi linier dengan menggunakan SPSS 14. Hasil penelitian menunjukkan bahwa hasil uji statistik untuk nilai pre test dan post test tingkat nyeri diperoleh nilai signifikansi 0,02 dengan p < 0,05.Kata kunci: pembacaan dzikir, melahirkan, nyeri intra natal, tingkat nyeriABSTRACTThe delivery or usually called labor process is a process open and thin the cervix, and descent of the fetus into the way of birth. The early symptom of delivery will be appearing very heavy because there are uterus contraction and abdomen muscle. In partum pain is a pain which feel when delivery process happening (labor). When labor pain appears, there is a good for the mother to read dzikir. Dzikir is remembering Allah SWT and make present what before in the mind and then pronounced or make cal can do spoken by tongue or pronounced without there are involving tongue, by heart. The purpose of this research is to know about the influence of reading dzikir to the delivery mother toward in partum level of pain. Technique sampling used purpose sampling. The research of design pre experiment, with pre test-post test without control group design. The sample in this research’s total is 30 respondents. The manner of data was did by direct observation to the respondents to measure pain level. Data analysis used statistic test wilcoxon signed rank test and regression linier in SPSS 14. The results of research showed that results of the statistic pretest and posttest of pain level show significance value 0,02 with p < 0,05.Keywords: reading dzikir, delivery, in partum pain, pain level

scholarly journals Chemotherapy-Induced Survivin Regulation in Acute Myeloid Leukemia Cells

2021 ◽  
Vol 11 (1) ◽  
pp. 460
Author(s):  
Petra Otevřelová ◽  
Barbora Brodská
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Survivin Expression ◽  
Mitotic Cell ◽  
Specific Subset ◽  
Suitable Target ◽  
Acute Myeloid Leukemia Cells ◽  
Almost All ◽  
Acute Myeloid

Survivin is a 16.5 kDa protein highly expressed in centrosomes, where it controls proper sister chromatid separation. In addition to its function in mitosis, survivin is also involved in apoptosis. Overexpression of survivin in many cancer types makes it a suitable target for cancer therapy. Western blotting and confocal microscopy were used to characterize the effect of chemotherapy on acute myeloid leukemia (AML) cells. We found enhanced survivin expression in a panel of AML cell lines treated with cytarabine (Ara-C), which is part of a first-line induction regimen for AML therapy. Simultaneously, Ara-C caused growth arrest and depletion of the mitotic cell fraction. Subsequently, the effect of a second component of standard therapy protocol, idarubicin, and of a known survivin inhibitor, YM-155, on cell viability and survivin expression and localization in AML cells was investigated. Idarubicin reversed Ara-C-induced survivin upregulation in the majority of AML cell lines. YM-155 caused survivin deregulation together with a viability decrease in cells resistant to idarubicin treatment, suggesting that YM-155 might be efficient in a specific subset of AML patients. Expression levels of other apoptosis-related proteins, in particular X-linked inhibitor of apoptosis (XIAP), Mcl-1, and p53, and of the cell-cycle inhibitor p21 considerably changed in almost all cases, confirming the off-target effects of YM-155.

scholarly journals Investigating Dual-Energy CT Post-Contrast Phases for Liver Iron Quantification: A Preliminary Study

Dose-Response ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 155932582110113
Author(s):  
Luca Basso ◽  
Dario Baldi ◽  
Lorenzo Mannelli ◽  
Carlo Cavaliere ◽  
Marco Salvatore ◽  
...  
Keyword(s):  
Temporal Trend ◽  
Dual Energy ◽  
Rank Test ◽  
Liver Iron ◽  
Post Contrast ◽  
Signed Rank ◽  
Wilcoxon Signed Rank Test ◽  
Friedman's Test ◽  
Signed Rank Test ◽  
Time Point

Background and Purpose: Quantification of hepatic virtual iron content (VIC) by using Multidetector Dual Energy Computed Tomography (DECT) has been recently investigated since this technique could offer a good compromise between accuracy and non-invasiveness for liver iron content quantification. The aim of our study is to investigate differences in VIC at different DECT time points (namely baseline and arterial, venous and tardive phases), identifying the most reliable and also exploring the underlying temporal trend of these values. Materials and Methods: Eleven patients who underwent DECT examination and were characterized by low liver fat content were included in this retrospective study. By using the Syngo.via Frontier–DE IronVNC tool, regions of interest (ROI) were placed on the VIC images at 3 hepatic levels, both in left and right liver lobes, at each DECT time point. Friedman’s test followed by Bonferroni-adjusted Wilcoxon signed-rank test for post-hoc analysis was performed to assess differences between DECT timepoints. Page’s L test was performed to test the temporal trend of VIC across the 4 examined timepoints. Results: For both liver lobes, Friedman’s test followed by Bonferroni-adjusted Wilcoxon signed-rank test revealed that VIC values differed significantly when extracted from ROIs placed at the 4 different timepoints. The Page’s L test for multiple comparison revealed a significant growing trend for VIC, from baseline acquisition to the fourth and last time point post-contrast agent injection. Conclusions: The extraction of hepatic VIC in healthy subjects was found to be significantly influenced by the DECT time point chosen for the extrapolation of the VIC values.

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