scholarly journals Similar Survival and Genetic Features between Clonal Cytopenia of Undetermined Significance and Lower-Risk Myelodysplastic Syndrome

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3683-3683
Author(s):  
Eun-Ji Choi ◽  
Young-Uk Cho ◽  
Han-Seung Park ◽  
Jung-Hee Lee ◽  
Kyoo Hyung Lee ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Lower Risk ◽  
Advisory Board ◽  
Red Blood Cell Transfusion ◽  
Genetic Characteristics ◽  
Disease Evolution ◽  
Significant Difference ◽  
Undetermined Significance ◽  
Better Than ◽  
Privately Held

Abstract Background Idiopathic cytopenia of undetermined significance (ICUS) is characterized by a persistent and clinically significant cytopenias which does not meet the diagnostic criteria for myelodysplastic syndrome (MDS). In some patients with ICUS, disease evolution to MDS or acute myeloid leukemia after variable periods of time was observed in several studies. However, the incidence and predictive factors of progression as well as management guidelines for ICUS patients are not well established. We aimed to identify the clinical and genetic characteristics of ICUS in comparison with lower-risk MDS for understanding the pathophysiologic features and providing guidance for treating physicians. Methods We performed targeted deep sequencing including 61 myeloid neoplasm-related genes with a MiSeqDx sequencer (Illumina) using bone marrow (BM) samples obtained from the patients with ICUS (n=139) and MDS (n=226) between May 2009 and December 2019. The cut-off level of variant allele frequency (VAF) was set to 2.0% of mutant allele reads. Cloncal cytopenia of undetermined significance (CCUS) was defined as ICUS with ≥ 2% VAF of mutations and lower-risk MDS was defined as MDS with revised international prognostic scoring system ≤3.5. Results When we compared the overall survival (OS) of the patients according to the disease subtypes, OS of CCUS (77.0% at 5-year) was significantly better than that of higher-risk MDS (41.0%, P<.001) and worse than non-clonal ICUS (94.1%, P=.050), but it was similar to the OS of lower-risk MDS (67.9%, P=.363). Next, we compared the clinical and mutational features between CCUS (n=78) and lower-risk MDS (n=99). As shown in Table, there was no significant difference of patient characteristics between two groups except for higher hemoglobin level (10.5 vs. 9.0 g/dL, P=.008) in CCUS than lower-risk MDS, and the rate of red blood cell transfusion dependency was not different (P=.738). The median number of mutated genes of CCUS and lower-risk MDS were 1 (range, 0-4) and 1 (range, 0-6) (P=.651), and the median mutation numbers were 1 (range, 0-5) in CCUS and 2 (range, 0-7) in lower-risk MDS, respectively (P=.711). The mutational profiles of 61 genes were also similar between CCUS and lower-risk MDS except for SF3B1 (2.6% in CCUS and 18.2% in lower-risk MDS; P=.001) and STAT3 (5.1% in CCUS and 0% in lower-risk MDS; P=.023). Overall, 11 of 78 CCUS and 24 of 99 MDS died, and the causes of death were not different between two groups (P=.861). Conclusion In our study, CCUS and lower-risk MDS showed similar OS which was significantly better than higher-risk MDS and worse than non-clonal ICUS. The clinical and mutational characteristics were also similar except for the degree of anemia and the SF3B1 and STAT3 mutation. Our findings suggest that the patients with CCUS may be regarded and treated as the lower-risk MDS despite a lack of significant dysplasia or MDS-associated definitive chromosomal abnormality. Disclosures Choi: Ingenium Therapeutics, Daejeon, Korea: Consultancy, Current holder of individual stocks in a privately-held company. Lee: Ingenium Therapeutics, Daejeon, Korea: Consultancy, Current holder of individual stocks in a privately-held company. Lee: Korean Society of Hematology: Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Other: Advisory board; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board.

scholarly journals Serum klotho as a marker for early diagnosis of acute kidney injury after cardiac surgery

2019 ◽  
Vol 0 (0) ◽  
Author(s):  
Aleš Jerin ◽  
Osama F Mosa ◽  
Jurij M Kališnik ◽  
Janez Žibert ◽  
Milan Skitek
Keyword(s):  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Early Diagnosis ◽  
Lower Risk ◽  
Kidney Injury ◽  
Tree Model ◽  
Significant Difference ◽  
Better Than

SummaryBackgroundEarly diagnosis of acute kidney injury (AKI) after cardiac surgery is based on serum creatinine which is neither a specific nor a sensitive biomarker. In our study, we investigated the role of serum Klotho in early prediction of AKI after cardiac surgery using cardiopulmonary bypass (CPB).MethodsThe included patients were classified into three groups according to AKI stages using KDIGO criteria. The measurements of creatinine and Klotho levels in serum were performed before surgery, at the end of CPB, 2 hours after the end of CPB, 24 hours and 48 hours postoperatively.ResultsSeventy-eight patients were included in the study. A significant increase of creatinine levels (p<0.001) was measured on the first day after the surgery in both AKI groups compared to the non-AKI group. However, a significant difference between AKI-2 and AKI-1 groups (p=0.006) was not measured until the second day after the operation. Using decision trees for classification of patients with a higher or lower risk of AKI we found out that Klotho discriminated between the patients at low risk of developing more severe kidney injury in the first hours after surgery and the patients at high risk better than creatinine. Adding also the early measurements of creatinine in the decision tree model further improved the prediction of AKI.ConclusionSerum Klotho may be useful to discriminate between the patients at lower and the patients at higher risk of developing severe kidney injury after cardiac surgery using CPB already in the first hours after surgery.

scholarly journals Unique ethnic features of DDX41 mutations in patients with idiopathic cytopenia of undetermined significance, myelodysplastic syndrome, or acute myeloid leukemia

Haematologica ◽  
2021 ◽  
Author(s):  
Eun-Ji Choi ◽  
Young-Uk Cho ◽  
Eun-Hye Hur ◽  
Seongsoo Jang ◽  
Nayoung Kim ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Normal Karyotype ◽  
Hematologic Malignancies ◽  
Genetic Characteristics ◽  
Male Predominance ◽  
Korean Patients ◽  
Acute Myeloid ◽  
Undetermined Significance

DDX41 mutations are associated with hematologic malignancies including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but the incidence in idiopathic cytopenia of undetermined significance (ICUS) is unknown. We investigated the incidence, genetic characteristics, and clinical features of DDX41 mutations in Korean patients with ICUS, MDS, or AML. We performed targeted deep sequencing of 61 genes including DDX41 in 457 patients with ICUS (n=75), MDS (n=210), or AML (n=172). The germline DDX41 mutations with causality were identified in 28 (6.1%) patients, of whom 27 (96.4%) had somatic mutations in the other position of DDX41. Germline origins of the DDX41 mutations were confirmed in all of the 11 patients who performed germline-based testing. Of the germline DDX41 mutations, p.V152G (n=10) was most common, followed by p.Y259C (n=8), p.A500fs (n=6), and p.E7* (n=3). Compared with non-mutated patients, DDX41-mutated patients showed male predominance, old age, normal karyotype, low leukocyte count, and hypocellular marrow at diagnosis. Three of the 4 ICUS patients with germline DDX41 mutations progressed to MDS. DDX41 mutations in Korean patients showed a high incidence and distinct mutation patterns, in that p.V152G was a unique germline variant. ICUS harboring germline DDX41 mutations may be regarded as a hereditary myeloid neoplasm. Germline DDX41 mutations are not uncommon and should be explored when treating the patients with myeloid malignancies.

scholarly journals Recombinant Human Thrombopoietin Accelerates the Recovery of Platelet in Patients With Lower-Risk Myelodysplastic Syndrome: A Proof-of-Concept Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuan Yang ◽  
Zengwei Tang ◽  
Jiang Ji ◽  
Chen Yang ◽  
Miao Chen ◽  
...  
Keyword(s):  
Side Effects ◽  
Myelodysplastic Syndrome ◽  
Lower Risk ◽  
Platelet Transfusion ◽  
Complete Response ◽  
Platelet Response ◽  
Clinical Trial Registration ◽  
Overall Response ◽  
Significant Difference ◽  
Recombinant Human Thrombopoietin

AimThe effect of recombinant human thrombopoietin (rhTPO) is largely unknown in lower-risk myelodysplastic syndrome (LR-MDS). This study aimed at investigating the safety and efficacy of rhTPO in patients with LR-MDS.MethodsLR-MDS patients receiving stanozolol (2 mg, t.i.d.) and supportive care alone (non-rhTPO) or additional rhTPO were enrolled in this study prospectively. rhTPO was given at 15,000 U (q.d.) for 7 days/month for at least 3 months. Patients stopped rhTPO if the platelet count was higher than 50 × 109/L or had no effects after 3 months of treatment. The overall response (OR), complete response (CR), platelet response, side effects, clone evolution, and clinical outcome were evaluated.ResultThirty-five patients were enrolled: 20 (57.1%) patients in the rhTPO group and 15 (42.9%) patients in the non-rhTPO group. The demographic and baseline characteristics were balanced between the two groups. Platelet response was higher at 1 and 2 months as compared with that in the non-rhTPO group (p = 0.006 and p = 0.001, respectively). Meanwhile, the rhTPO group had a shorter time to achieve a platelet transfusion-free state compared with the non-rhTPO group (p = 0.034). Hematologic response was higher at 1 and 2 months compared with that in the non-rhTPO group (p = 0.006 and p = 0.001, respectively). There was no significant difference in the overall response or complete response at 1, 2, 3, 6, and 12 months between the two groups. One patient in the rhTPO group evolved into higher-risk MDS at 9 months. No significant difference in disease progression, infection, gastrointestinal disorders, or drug-related liver/renal injuries was found between the two groups (p &gt; 0.05).ConclusionAdding short-term rhTPO can accelerate the early platelet response and decrease platelet transfusion, with no obvious side effects.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04324060?cond=NCT04324060&amp;draw=2, identifier NCT04324060

scholarly journals DDX41 mutation in Patients with Idiopathic Cytopenia of Undetermined Significance, Myelodysplastic Syndrome, and Acute Myeloid Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3002-3002
Author(s):  
Eun-Ji Choi ◽  
Young-Uk Cho ◽  
Seongsoo Jang ◽  
Chan-jeoung Park ◽  
Han-Seung Park ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Germline Mutation ◽  
Lower Risk ◽  
Myeloid Leukemia ◽  
Novel Mutation ◽  
Myeloid Neoplasms ◽  
Biallelic Mutations ◽  
Acute Myeloid ◽  
Undetermined Significance

Background Following the advances in genetic tests, including next-generation sequencing, there have been new insights into hereditary hematopoietic malignancies. The germline mutation in DDX41 was included in a new category, myeloid neoplasms with germline predisposition, of the updated 2016 WHO classification. Based on the reported data to date, there seem to be racial differences in the mutation variants of DDX41 gene, which were found in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Idiopathic cytopenia of undetermined significance (ICUS) is known to be a precursor lesion of MDS, but the DDX41 mutations have not been evaluated in patients with ICUS. In this study, we aimed to reveal the incidence, genetic characteristics, and clinical features of the DDX41 mutations in patients with ICUS, MDS, and AML. Methods We performed targeted deep sequencing of 141 genes with a MiSeqDx sequencer (Illumina) using bone marrow (BM) samples obtained from the patients with ICUS (n=77), MDS (n=175), and AML (n=148) between May 2009 and June 2019. ICUS was defined by the proposed criteria of 2007 Consensus Group. The cut-off level of variant allele frequency (VAF) was set to 2.0% of mutant allele reads. We divided ICUS into clonal cytopenia of undetermined significance (CCUS), which was defined as ICUS with ≥ 2% VAF of somatic mutations of myeloid malignancy-associated genes and non-CCUS. Results Overall, DDX41 mutations were detected in 6 (7.8%) of 77 ICUS, 19 (10.9%) of 175 MDS, and 8 (5.4%) of 148 AML patients. Thirty-eight (49.4%) of 77 ICUS patients had CCUS. Of 6 DDX41 mutated patients with CCUS, 5 showed biallelic mutations with the median VAF of 44.7% (range, 29.3−50.0) and 10.2% (range, 3.3−25.4), indicating that one germline and one somatic mutation exists. Of 175 MDS patients, 78 were categorized into lower-risk MDS (revised international prognostic scoring system [IPSS-R] < 3.5) and 97 into higher-risk MDS (IPSS-R ≥ 3.5), and DDX41 mutations were identified in 6 (7.7%) of 78 lower-risk MDS and 13 (13.4%) of 97 higher-risk MDS patients. Interestingly, biallelic mutations were found in 16 of 18 DDX41-mutated MDS patients with the median VAF of 47.75% (range, 43.4−55.6) and 13.8% (range, 2.7−35.8). In contrast, only one of 8 DDX41-mutated AML patients had biallelic mutation. Patients with DDX41 mutations typically showed hypocellular marrow (median BM cellularity, 30%; range, 5−95) with significant neutropenia (median neutrophil counts, 607/μL; range, 142−1675), male predominance (29/33, 87.9%), and relatively older age (median age, 64 years; range, 41−79) at diagnosis. In addition, we found novel mutation locations, which were different between presumed germline and somatic variants: V152G in germline, and T227M in somatic (Table 2). During a median follow-up duration of 2.9 years, 1 of 6 ICUS patients progressed to MDS-EB-1 after 17.3 months and 1 to non-severe aplastic anemia after 51.3 months. Conclusion Our data show that a significant proportion of ICUS, MDS, and AML patients had DDX41 mutations, many of which are presumably germline. These findings suggest that careful consideration of the predisposing germline mutation is important when selecting a familial donor for allogeneic HCT. We also found novel mutation locations of DDX41 gene which were different between somatic and germline variants. Further studies are warranted to define the clinical and molecular characteristics of DDX41 mutations and therapeutic implications in myeloid neoplasms. Disclosures No relevant conflicts of interest to declare.

Transplantation of coral fragment, Acropora formosa (Scleractinia)

2014 ◽  
pp. 1
Author(s):  
Hanny Tioho ◽  
Maykel A.J Karauwan
Keyword(s):  
Fragment Size ◽  
Observation Time ◽  
Minimum Size ◽  
Average Growth Rate ◽  
Average Growth ◽  
Significant Difference ◽  
Acropora Formosa ◽  
Survival And Growth ◽  
One Way Anova ◽  
Better Than

The minimum size of coral transplants, Acropora formosa, was assessed to support their survival and growth. For this, 150 coral fragments of different sizes (5, 10, 15 cm) were transplanted close to the donor colony. Their survivorship and growth were observed for 12 months. At the end of the observation time, 90% of 15 cm-transplanted coral fragments survived, while the others (10cm and 5 cm) did 86% and 82% respectively. The average growth rate of 5 cm-coral fragments was 0.860 cm/month, while 10 and 15 cm-fragments were 0.984 cm/month and 1.108 cm/month respectively. One-way ANOVA showed that there was significant difference (p<0.05) among the three (5, 10, 15 cm) transplant initial sizes in which the longest fragment size tended to survive longer than the smaller one.  However, the smaller transplants grew better than the bigger one, 10.318 cm/year (206%) for 5 cm-transplant, 11.803 cm/year (118%) for 10 cm-transplant, and 13.299 cm/year (89%) for 15 cm-transplant, respectively. Ukuran minimal fragmen karang Acropora formosa yang ditransplantasi diduga untuk mendukung ketahanan hidup dan pertumbuhannya. Untuk itu, 150 fragmen karang ditransplantasi ke lokasi yang berdekatan dengan koloni induknya.  Ketahanan hidup dan pertumbuhan semua fragmen karang yang ditransplantasi diamati selama 12 bulan.  Pada akhir pengamatan, 90% dari fragmen karang berukuran 15 cm yang ditransplantasi dapat bertahan hidup, sedangkan yang lainnya (ukuran 10 cm dan 5 cm) masing-masing sebesar 86% dan 82%.  Rata-rata laju pertumbuhan fragmen karang dengan ukuran awal 5 cm adalah 0,860 cm/bulan, sedangkan ukuran fragmen 10 dan 15 cm masing-masing adalah 0,984 cm/bulan and 1,108 cm/bulan. ANOVA satu arah menunjukkan adanya perbedaan yang nyata (p<0.05) antara ketiga ukuran fragmen yang berbeda, di mana ukuran fragmen karang yang lebih panjang cenderung mempunyai ketahanan hidup yang lebih baik. Namun demikian, ukuran transplant yang lebih kecil memiliki pertumbuhan lebih baik dibandingkan dengan ukuran yang lebih besar, yakni10,318 cm/tahun (206%) untuk transplant berukuran 5 cm, 11,803 cm/tahun (118%) untuk 10 cm, dan 13,299 cm/tahun (89%) untuk ukuran 15 cm.

Isolation of an Anti-fatigue Preparation from Cellulase-treated Maca by Hydroalcoholic Extraction

2017 ◽  
Vol 17 (1) ◽  
pp. 93-98
Author(s):  
Zheng Yue ◽  
Zhang Wen-Cheng ◽  
Wu Ze-Yu ◽  
Fu Chuan-Xiang ◽  
Gao Han ◽  
...  
Keyword(s):  
Positive Control ◽  
Glycogen Storage ◽  
Hepatic Glycogen ◽  
Time To Exhaustion ◽  
High Dose ◽  
Hydroalcoholic Extract ◽  
Swimming Time ◽  
Significant Difference ◽  
Pre Treatment ◽  
Better Than

The purpose of this study was to evaluate the anti-fatigue activity of maca hydroalcoholic extract (ME), which mainly contains macamides and polysaccharides. ME was prepared by circumfluence extraction with enzymatic pre-treatment. Anti-fatigue activity of ME was investigated in weight-loaded forced swimming mice, with pure macamides and commercially available maca tablet as positive control. Compared with normal group, pure macamides treatment group could prolong the swimming time to exhaustion, but there was no statistically significant difference (P > 0.05); while ME (middle-dose and high-dose groups) could effectively prolong the swimming durations (P < 0.05). Supplementation with pure macamides significantly decreased blood lactic acid (BLA), whereas ME significantly increased hepatic glycogen (HG), decreased BLA, and blood urea nitrogen (BUN) compared with those in normal control (P < 0.05). The results suggested that the anti-fatigue effect of ME was better than that of pure macamides, which can be explained by the increase of glycogen storage and the reduction of metabolites accumulation.

EMOTIONAL INTELLIGENCE AND ACADEMIC ACHIEVEMENT OF ADOLESCENTS WITH REFERENCE TO GENDER

2017 ◽  
Vol 4 (24) ◽  
Author(s):  
Nisha Chandel ◽  
Seema Chopra
Keyword(s):  
Academic Achievement ◽  
Emotional Intelligence ◽  
Female Adolescents ◽  
Intelligence Scale ◽  
Male And Female ◽  
Male Adolescents ◽  
Significant Difference ◽  
Understanding Emotions ◽  
School Records ◽  
Better Than

The present study was undertaken to find out emotional intelligence and academic achievement of male and female adolescents. The sample consists of 82 students( 41 male and 41 female adolescents) from different schools in Hamirpur district of Himachal Pradesh. Emotional intelligence was assessed with the help of Emotional Intelligence Scale developed by Singh and Narain (2014) and academic achievement score were taken from the school records. The results revealed that there exists a significant difference in emotional intelligence of male and female adolescents. It was found that there existed significant difference in academic achievement of female adolescents and male adolescents. The mean emotional intelligence of female adolescents was better than of male adolescents. On the dimensions of emotional intelligence, it was found that there was no significant difference between male and female adolescents on understanding emotions, empathy and handling relations dimensions of emotional intelligence; while it was reported that there was significant difference between male and female adolescents on understanding motivation dimension of emotional intelligence On the other hand, it was found that there existed significant difference in academic achievement of female adolescents and male adolescents.

scholarly journals Integrated Bimodal Fitting for Unilateral CI Users with Residual Contralateral Hearing

2021 ◽  
Vol 11 (2) ◽  
pp. 200-206
Author(s):  
Gennaro Auletta ◽  
Annamaria Franzè ◽  
Carla Laria ◽  
Carmine Piccolo ◽  
Carmine Papa ◽  
...  
Keyword(s):  
Cochlear Implants ◽  
Hearing Aids ◽  
Speech Intelligibility ◽  
Hearing Aid ◽  
Performance Difference ◽  
Test Conditions ◽  
Significant Difference ◽  
Noisy Conditions ◽  
New Formula ◽  
Better Than

Background: The aim of this study was to compare, in users of bimodal cochlear implants, the performance obtained using their own hearing aids (adjusted with the standard NAL-NL1 fitting formula) with the performance using the Phonak Naìda Link Ultra Power hearing aid adjusted with both NAL-NL1 and a new bimodal system (Adaptive Phonak Digital Bimodal (APDB)) developed by Advanced Bionics and Phonak Corporations. Methods: Eleven bimodal users (Naìda CI Q70 + contralateral hearing aid) were enrolled in our study. The users’ own hearing aids were replaced with the Phonak Naìda Link Ultra Power and fitted following the new formula. Speech intelligibility was assessed in quiet and noisy conditions, and comparisons were made with the results obtained with the users’ previous hearing aids and with the Naída Link hearing aids fitted with the NAL-NL1 generic prescription formula. Results: Using Phonak Naìda Link Ultra Power hearing aids with the Adaptive Phonak Digital Bimodal fitting formula, performance was significantly better than that with the users’ own rehabilitation systems, especially in challenging hearing situations for all analyzed subjects. Conclusions: Speech intelligibility tests in quiet settings did not reveal a significant difference in performance between the new fitting formula and NAL-NL1 fittings (using the Naída Link hearing aids), whereas the performance difference between the two fittings was very significant in noisy test conditions.

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