Publications by authors named "Daisuke Hasegawa"

200 Publications

Recurrence rate and lesions characteristics after cold snare polypectomy of high-grade dysplasia and T1 lesions: A multicenter analysis.

J Gastroenterol Hepatol 2021 Jul 14. Epub 2021 Jul 14.

Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.

Background And Aim: High-grade dysplasia (HGD) and T1 lesions are accidentally resected by cold snare polypectomy (CSP) and the characteristics, and follow-up of them has not been reported. In this study, we analyzed the histopathological findings and recurrence of them.

Methods: This was a multicenter retrospective-cohort study. We collected HGD and T1 lesions of ≤ 10 mm resected by CSP among 15 520 patients receiving CSP from 2014 to 2019 at nine related institutions, and we extracted only cases receiving definite follow-up colonoscopy after CSP of HGD and T1 lesions. We analyzed these tumor's characteristics and therapeutic results such as R0 resection and local recurrence and risk factors of recurrence.

Results: We collected 103 patients (0.63%) and extracted 80 lesions in 74 patients receiving follow-up colonoscopy for CSP scar. Mean age was 68.4 ± 12.0, and male rate was 68.9% (51/80). The mean tumor size (mm) was 6.6 ± 2.5, and the rate of polypoid morphology and rectum location was 77.5% and 25.0%. The rate of magnified observation was 53.8%. The rates of en bloc resection and R0 resection were 92.5% and 37.5%. The local recurrence rate was 6.3% (5/80, median follow-up period: 24.0 months). The recurrence developed within 3 months after CSP for four out of five recurrent cases. Comparing five recurrent lesions to 75 non-recurrent lesions, a positive horizontal margin was a significant risk factor (60.0% vs 10.7%, P < 0.001).

Conclusions: High-grade dysplasia and T1 resected by CSP were analyzed, and the local recurrence rate of them was substantially high.
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http://dx.doi.org/10.1111/jgh.15625DOI Listing
July 2021

Risk Factors of Delayed Bleeding After Cold Snare Polypectomy for Colorectal Polyps: A Multicenter Study.

Dig Dis Sci 2021 Jun 28. Epub 2021 Jun 28.

Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.

Background: Delayed bleeding (DB) rarely occurs after cold snare polypectomy (CSP) for colorectal polyps, but no large-scale studies have investigated this. The present study evaluated the rate, characteristics, and risk factors of DB of CSP.

Methods: We conducted a multicenter retrospective study at 10 Japanese institutions. A total of 18,007 patients underwent CSP for colorectal polyps ≤ 10 mm in size from March 2015 to September 2019, and cases of DB (DB group) were analyzed for the rate, antithrombotic drugs, polyp size, morphology, location, and risk factors. As a control, 269 non-bleeding cases (non-DB group) with 606 polyps who underwent CSP at the same 10 facilities in the 2-week study period were extracted.

Results: We analyzed 26 DB cases with 28 lesions, and the total DB rate was 0.14% (26/18,007). The DB group had significantly higher rates of using antiplatelets (42.3% vs. 13.0%, p < 0.001) and anticoagulants (19.2% vs. 2.6%, p = 0.002), and significantly higher rates of polyp size ≥ 5 mm (67.9% vs. 45.2%, p = 0.015), rectal lesion (25.0% vs. 6.6%, p = 0.003), and polypoid lesion (89.3% vs. 55.3%, p < 0.001) than the non-DB group. A multivariate analysis (odds ratio; 95% confidence interval) for patient characteristics showed antiplatelet use (4.521; 1.817-11.249, p = 0.001) and anticoagulant use (7.866; 20.63-29.988, p = 0.003) as independent risk factors for DB. Polyp size ≥ 5 mm (3.251; 1.417-7.463, p = 0.005), rectal lesion (3.674; 1.426-9.465, p = 0.007), and polypoid lesion (7.087; 20.81-24.132, p = 0.002) were also risk factors for lesion characteristics.

Conclusions: The rate of DB was 0.14% and antithrombotic drug use, polyp size, location, and morphology were related to it.
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http://dx.doi.org/10.1007/s10620-021-07119-7DOI Listing
June 2021

Japanese Rapid/Living recommendations on drug management for COVID-19.

Acute Med Surg 2021 May 4:e664. Epub 2021 May 4.

Department of Anesthesiology and Critical Care Medicine Fujita Health University School of Medicine Toyoake Japan.

The Coronavirus disease 2019 (COVID-19) has spread worldwide since early 2020, and there are still no signs of resolution. The Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock (J-SSCG) 2020 Special Committee created the Japanese Rapid/Living recommendations on drug management for COVID-19 using the experience of creating the J-SSCGs. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of the evidence and strength of the recommendations. The first edition of this guideline was released on September 9, 2020, and this document is the revised edition (ver. 3.1) (released on March 30, 2021). Clinical questions (CQs) were set for the following seven drugs: favipiravir (CQ1), remdesivir (CQ-2), hydroxychloroquine (CQ-3), corticosteroids (CQ-4), tocilizumab (CQ-5), ciclesonide (CQ-6), and anticoagulants (CQ-7). Favipiravir is recommended for patients with mild COVID-19 not requiring supplemental oxygen (GRADE 2C); remdesivir for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 2B); hydroxychloroquine is not recommended for all COVID-19 patients (GRADE 1B); corticosteroids are recommended for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 1B) and severe COVID-19 patients requiring ventilator management/intensive care (GRADE 1A); however, their administration is not recommended for mild COVID-19 patients not requiring supplemental oxygen (GRADE 1B); tocilizumab is recommended for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 2B); and anticoagulant therapy for moderate COVID-19 patients requiring supplemental oxygen/hospitalization and severe COVID-19 patients requiring ventilator management/intensive care (GRADE 2C). We hope that these clinical practice guidelines will aid medical professionals involved in the care of COVID-19 patients.
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http://dx.doi.org/10.1002/ams2.664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209876PMC
May 2021

Effects of Thrombomodulin in Reducing Lethality and Suppressing Neutrophil Extracellular Trap Formation in the Lungs and Liver in a Lipopolysaccharide-Induced Murine Septic Shock Model.

Int J Mol Sci 2021 May 6;22(9). Epub 2021 May 6.

Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Japan.

Neutrophil extracellular trap (NET) formation, an innate immune system response, is associated with thrombogenesis and vascular endothelial injury. Circulatory disorders due to microvascular thrombogenesis are one of the principal causes of organ damage. NET formation in organs contributes to the exacerbation of sepsis, which is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. We have previously reported that recombinant human soluble thrombomodulin (rTM) reduces lipopolysaccharide (LPS)-induced NET formation in vitro. Here, we aimed to show that thrombomodulin (TM)-mediated suppression of NET formation protects against organ damage in sepsis. Mice were injected intraperitoneally (i.p.) with 10 mg/kg LPS. rTM (6 mg/kg/day) or saline was administered i.p. 1 h after LPS injection. In the LPS-induced murine septic shock model, extracellular histones, which are components of NETs, were observed in the liver and lungs. In addition, the serum cytokine (interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), macrophage chemotactic protein-1 (MCP-1), and interleukin-10 (IL-10)) levels were increased. The administration of rTM in this model prevented NET formation in the organs and suppressed the increase in the levels of all cytokines except IL-1β. Furthermore, the survival rate improved. We provide a novel role of TM in treating inflammation and NETs in organs during sepsis.
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http://dx.doi.org/10.3390/ijms22094933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124404PMC
May 2021

Predictive modeling for peri-implantitis by using machine learning techniques.

Sci Rep 2021 May 27;11(1):11090. Epub 2021 May 27.

Department of Prosthodontics, Gerodontology and Oral Rehabilitation, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.

The purpose of this retrospective cohort study was to create a model for predicting the onset of peri-implantitis by using machine learning methods and to clarify interactions between risk indicators. This study evaluated 254 implants, 127 with and 127 without peri-implantitis, from among 1408 implants with at least 4 years in function. Demographic data and parameters known to be risk factors for the development of peri-implantitis were analyzed with three models: logistic regression, support vector machines, and random forests (RF). As the results, RF had the highest performance in predicting the onset of peri-implantitis (AUC: 0.71, accuracy: 0.70, precision: 0.72, recall: 0.66, and f1-score: 0.69). The factor that had the most influence on prediction was implant functional time, followed by oral hygiene. In addition, PCR of more than 50% to 60%, smoking more than 3 cigarettes/day, KMW less than 2 mm, and the presence of less than two occlusal supports tended to be associated with an increased risk of peri-implantitis. Moreover, these risk indicators were not independent and had complex effects on each other. The results of this study suggest that peri-implantitis onset was predicted in 70% of cases, by RF which allows consideration of nonlinear relational data with complex interactions.
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http://dx.doi.org/10.1038/s41598-021-90642-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160334PMC
May 2021

[Diagnosis and treatment of childhood myelodysplastic syndrome].

Authors:
Daisuke Hasegawa

Rinsho Ketsueki 2021 ;62(4):229-238

Department of Pediatrics, St. Luke's International Hospital.

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic disorders characterized by peripheral cytopenia and morphological abnormalities in hematopoietic cells, i.e., myelodysplasia. Aging-related somatic variants acquired in the hematopoietic cells are associated with MDS pathogenesis in adults. However, pediatric MDS often occurs because of germline predispositions. Myelodysplasia can be observed in not only MDS but also other hematopoietic and non-hematopoietic disorders, such as infections and primary immunodeficiencies. Therefore, careful differential diagnosis between MDS and other diseases is necessary. The bone marrow histopathology should be evaluated for accurate differentiation of MDS without excess blasts from aplastic anemia and MDS with excess blasts from acute myeloid leukemia. The treatment strategy for childhood MDS differs based on disease subtypes. The clinical courses of pediatric MDS without excess blasts are heterogeneous; therefore, it is crucial to assess the prognostic values of clinical and cytogenetic findings. In contrast, allogeneic hematopoietic cell transplantation should be considered as the only curative option for pediatric MDS with excess blasts.
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http://dx.doi.org/10.11406/rinketsu.62.229DOI Listing
May 2021

β1-blocker in sepsis.

J Intensive Care 2021 May 8;9(1):39. Epub 2021 May 8.

Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.

Background: The use of ultrashort-acting β1-blockers recently has attracted attention in septic patients with non-compensatory tachycardia. We summarized the metabolic and hemodynamic effects and the clinical evidence of ultrashort-acting β1-blockers.

Main Body: A recent meta-analysis showed that ultrashort-acting β1-blockers reduced the mortality in septic patients with persistent tachycardia. However, its mechanism to improve mortality is not fully understood yet. We often use lactate as a marker of oxygen delivery, but an impaired oxygen use rather than reduced oxygen delivery has been recently proposed as a more reasonable explanation of hyperlactatemia in patients with sepsis, leading to a question of whether β1-blockers affect metabolic systems. While the stimulation of the β2-receptor accelerates glycolysis and lactate production, the role of β1-blocker in lactate production remains unclear and studies investigating the role of β1-blockers in lactate kinetics are warranted. A meta-analysis also reported that ultrashort-acting β1-blockers increased stroke volume index, while it reduced heart rate, resulting in unchanged cardiac index, mean arterial pressure, and norepinephrine requirement at 24 h, leading to an improvement of cardiovascular efficiency. On the other hand, a recent study reported that heart rate reduction using fast esmolol titration in the very early phase of septic shock caused hemodynamic instability, suggesting that ultrashort-acting β1-blockers should be started only after completing initial resuscitation. While many clinicians still do not feel comfortable controlling sinus tachycardia, one randomized controlled trial in which the majority had sinus tachycardia suggested the mortality benefit of ultrashort-acting β1-blockers. Therefore, it still deems to be reasonable to control sinus tachycardia with ultrashort-acting β1-blockers after completing initial resuscitation.

Conclusion: Accumulating evidence is supporting the use of ultrashort-acting β1-blockers while larger randomized controlled trials to clarify the effect of ultrashort-acting β1-blockers are still warranted.
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http://dx.doi.org/10.1186/s40560-021-00552-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105957PMC
May 2021

Clonal evidence for the development of neuroblastoma with extensive copy-neutral loss of heterozygosity arising in a mature teratoma.

Cancer Sci 2021 Jul 6;112(7):2921-2927. Epub 2021 May 6.

Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.

Mature teratomas are usually benign tumors that rarely undergo malignant transformation. We report an advanced neuroblastoma arising in a mature teratoma of the ovary. Whole-exome sequencing identified extensive copy-neutral loss of heterozygosity (LOH) in both neuroblastoma and teratoma elements, suggesting that the neuroblastoma evolved from the teratoma. In addition, several truncating germline heterozygous variants in tumor suppressor genes, including RBL2 and FBXW12, became homozygous as a result of LOH. Collectively, we speculate that extensive LOH in teratoma cells may force heterozygous germline variants to become homozygous, which, in turn, may contribute to the development of neuroblastoma with the acquisition of additional chromosomal changes.
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http://dx.doi.org/10.1111/cas.14931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253283PMC
July 2021

Micro-size plankton abundance and assemblages in the western North Pacific Subtropical Gyre under microscopic observation.

PLoS One 2021 26;16(4):e0250604. Epub 2021 Apr 26.

Fisheries Resources Institute, Japan Fisheries Research and Education Agency, Yokohama, Japan.

While primary productivity in the oligotrophic North Pacific Subtropical Gyre (NPSG) is changing, the micro-size plankton community has not been evaluated in the last 4 decades, prompting a re-evaluation. We collected samples over three years (2016-2018) from depths of 10 to 200 m (n = 127), and the micro-size plankton were identified and counted to understand the heterogeneity of micro-size plankton community structure. The assemblages were consistent to the those of 4 decades ago. Dinophyceae (dinoflagellates) were the most numerically abundant, followed by Cryptophyceae and Bacillariophyceae (diatoms). The other micro-size plankton classes (Cyanophyceae, Haptophyceae, Dictyochophyceae, Euglenophyceae, and Prasinophyceae) were not always detected, whereas only Trichodesmium spp. was counted in the Cyanophyceae. Other unidentified autotrophic and heterotrophic flagellates were also significantly present, and their numeric abundance was higher than or at the same level as was that of the Dinophyceae. In the Dinophyceae, Gymnodiniaceae and Peridiniales were abundant. The chlorophyll a concentration and these class-level assemblages suggested micro-size plankton is not a major primary producer in this area. We applied generalized additive models (GAMs) and principal coordination analyses (PCoAs) to evaluate the habitats of every plankton group and the heterogeneity of the assemblages. The GAMs suggested that every classified plankton abundance showed a similar response to salinity, and we observed differences in habitats in terms of temperature and nitrate concentrations. Based on the PCoAs, we observed unique communities at the 200 m depth layer compared with those at the other sampling layers. The site scores of PCoAs indicated that the micro-size plankton assemblages are most heterogeneous at the 10 m depth layer. At such depth, diazotrophic Cyanophyceae (Trichodesmium spp.) are abundant, particularly in less-saline water. Therefore, nitrogen fixation may contribute to the heterogeneity in the abundance and assemblages in the western NPSG.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250604PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075241PMC
April 2021

Comparison of myoglobin clearance in three types of blood purification modalities.

Ther Apher Dial 2021 Aug 7;25(4):401-406. Epub 2021 May 7.

Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Aichi, Japan.

Myoglobin, which can cause acute kidney injury, has a relatively high molecular weight and is poorly cleared by diffusion. We compared and examined myoglobin clearance by changing the blood purification membrane and modality in patients with a myoglobin blood concentration ≥ 1000 ng/ml. We retrospectively analyzed three patient groups based on the following three types of continuous hemofiltration (CHF): AN69ST membrane, polymethylmethacrylate (PMMA) membrane, and high-flow hemodiafiltration (HDF) with increased dialysate flow rate using the PMMA membrane. There was no significant difference in clearance in CHF between AN69ST and PMMA membranes. However, the high-flow HDF group showed the highest myoglobin clearance (p = 0.003). In the PMMA membrane, changing the treatment modality to high-flow HDF increased clearance above the theoretical value, possibly due to internal filtration. To remove myoglobin by kidney replacement therapy from patients with hypermyoglobinemia, a modality such as high-flow HDF would be desirable.
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http://dx.doi.org/10.1111/1744-9987.13657DOI Listing
August 2021

CT and MRI characteristics of presumptive hypervitaminosis A in a cat.

JFMS Open Rep 2021 Jan-Jun;7(1):2055116921990301. Epub 2021 Mar 15.

Laboratory of Veterinary Radiology, Nippon Veterinary and Life Science University, Musashino, Tokyo, Japan.

Case Summary: A rescued stray cat with an unknown history was examined for non-ambulatory paraparesis in the hindlimbs. Survey radiographs revealed typical findings of hypervitaminosis A, characterised by vertebral exostoses and extensive osteophytes, mainly in the cervicothoracic spine. CT findings were consistent with the radiographic findings, and CT-based volume rendering and virtual endoscopy into the vertebral canal were created for three-dimensional visualisation of the lesion. MRI revealed a focal and mild dilation of the central canal of the spinal cord. Although the clinical diagnosis of hypervitaminosis A is based on an unusual dietary history and characteristic radiographic findings, the history of this cat was unknown and serum concentrations of vitamin A were unremarkable, when measured >1 month after rescue. However, other possible differential diagnoses were thought to be unlikely and clinical signs never worsened, and thus, hypervitaminosis A was presumed.

Relevance And Novel Information: To our knowledge, this is the first report to present the CT and MRI characteristics of a cat with suspected hypervitaminosis A.
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http://dx.doi.org/10.1177/2055116921990301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970248PMC
March 2021

[Management of pediatric hematological diseases during the COVID-19 pandemic].

Rinsho Ketsueki 2021 ;62(2):125-129

Department of Pediatrics St. Luke's International Hospital.

Preventing COVID-19 infection in pediatric patients with hematological disease and cancer is important. Thus, patients and those around them should avoid crowds, wear masks, and perform hand hygiene. It is necessary to try to prevent nosocomial infections during hospitalization. Moreover, determining COVID-19 complications and the condition of patients with hematological disease and cancer, and determining a personalized treatment strategy that prioritizes the treatment of high-risk conditions is necessary when suffering from COVID-19. However, another problem is when the patient refrains from visiting a medical institution due to the fear of contracting COVID-19 infection and becomes seriously ill. Furthermore, the lack of medical resources has affected the treatment of pediatric patients with hematological disease and cancer (e.g., delays and changes in treatment). Thus, appropriate information needs to be provided to children and their parents so that preventive measures can be taken.
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http://dx.doi.org/10.11406/rinketsu.62.125DOI Listing
March 2021

18S rRNA gene sequences of leptocephalus gut contents, particulate organic matter, and biological oceanographic conditions in the western North Pacific.

Sci Rep 2021 Mar 9;11(1):5488. Epub 2021 Mar 9.

Tohoku National Fisheries Research Institute, Japan Fisheries Research and Education Agency, 3-27-5 Shinhama-cho, Shiogama, Miyagi, 985-0001, Japan.

Eel larvae apparently feed on marine snow, but many aspects of their feeding ecology remain unknown. The eukaryotic 18S rRNA gene sequence compositions in the gut contents of four taxa of anguilliform eel larvae were compared with the sequence compositions of vertically sampled seawater particulate organic matter (POM) in the oligotrophic western North Pacific Ocean. Both gut contents and POM were mainly composed of dinoflagellates as well as other phytoplankton (cryptophytes and diatoms) and zooplankton (ciliophoran and copepod) sequences. Gut contents also contained cryptophyte and ciliophoran genera and a few other taxa. Dinoflagellates (family Gymnodiniaceae) may be an important food source and these phytoplankton were predominant in gut contents and POM as evidenced by DNA analysis and phytoplankton cell counting. The compositions of the gut contents were not specific to the species of eel larvae or the different sampling areas, and they were most similar to POM at the chlorophyll maximum in the upper part of the thermocline (mean depth: 112 m). Our results are consistent with eel larvae feeding on marine snow at a low trophic level, and feeding may frequently occur in the chlorophyll maximum in the western North Pacific.
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http://dx.doi.org/10.1038/s41598-021-84532-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930194PMC
March 2021

Post-induction MRD by FCM and GATA1-PCR are significant prognostic factors for myeloid leukemia of Down syndrome.

Leukemia 2021 Feb 15. Epub 2021 Feb 15.

Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.

Myeloid leukemia of Down syndrome (ML-DS) is associated with good response to chemotherapy, resulting in favorable outcomes. However, no universal prognostic factors have been identified to date. To clarify a subgroup with high risk of relapse, the role of minimal residual disease (MRD) was explored in the AML-D11 trial by the Japanese Pediatric Leukemia/Lymphoma Study Group. MRD was prospectively evaluated at after induction therapy and at the end of all chemotherapy, using flow cytometry (FCM-MRD) and GATA1-targeted deep sequencing (GATA1-MRD). A total of 78 patients were eligible and 76 patients were stratified to the standard risk (SR) group by morphology. In SR patients, FCM-MRD and GATA1-MRD after induction were positive in 5/65 and 7/59 patients, respectively. Three-year event-free survival (EFS) and overall survival (OS) rates were 93.3% and 95.0% in the FCM-MRD-negative population, and 60.0% and 80.0% in the positive population. Three-year EFS and OS rates were both 96.2% in the GATA1-MRD-negative population, and 57.1% and 71.4% in the positive population. Adjusted hazard ratios for associations of FCM-MRD or GATA1-MRD with EFS were 10.98 (p = 0.01) and 27.68 (p < 0.01), respectively. Detection of MRD by either FCM or GATA1 after initial induction therapy represents a significant prognostic factor for predicting ML-DS relapse.
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http://dx.doi.org/10.1038/s41375-021-01157-wDOI Listing
February 2021

Prevalence and characteristics of Kawasaki disease before and during the COVID-19 pandemic.

World J Pediatr 2021 04 6;17(2):215-217. Epub 2021 Feb 6.

Department of Pediatrics, St. Luke's International Hospital, 9-1 Akashicho, Chuo-ku, Tokyo, 104-8560, Japan.

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http://dx.doi.org/10.1007/s12519-021-00412-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866965PMC
April 2021

Comparison of Canine and Feline Meningiomas Using the Apparent Diffusion Coefficient and Fractional Anisotropy.

Front Vet Sci 2020 11;7:614026. Epub 2021 Jan 11.

Laboratory of Veterinary Radiology, Nippon Veterinary and Life Science University, Musashino, Japan.

Meningiomas are the most common intracranial tumor in dogs and cats, and their surgical resection is often performed because they are present on the brain surface. Typical meningiomas show comparatively characteristic magnetic resonance imaging findings that lead to clinical diagnosis; however, it is necessary to capture not only macroscopic changes but also microstructural changes to devise a strategy for surgical resection and/or quality of removal. To visualize such microstructural changes, diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) have been used in human medicine. The aim of this retrospective study was to investigate the different characteristics of the apparent diffusion coefficient (ADC) from DWI and fractional anisotropy (FA) from DTI of meningioma between dogs and cats. Statistical analyses were performed to compare ADC and FA values between the intratumoral or peritumoral regions and normal-appearing white matter (NAWM) among 13 dogs (13 lesions, but 12 each in ADC and FA analysis) and six cats (seven lesions). The NAWM of cats had a significantly lower ADC and higher FA compared to dogs. Therefore, for a comparison between dogs and cats, we used ADC and FA ratios that were calculated by dividing the subject (intra- or peritumoral) ADC and FA values by those of NAWM on the contralateral side. Regarding the intratumoral region, feline meningiomas showed a significantly lower ADC ratio and higher FA ratio than canine meningiomas. This study suggested that ADC and FA may be able to distinguish a meningioma that is solid and easy to detach, like as typical feline meningiomas.
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http://dx.doi.org/10.3389/fvets.2020.614026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829344PMC
January 2021

An international retrospective study for tolerability of 6-mercaptopurine on NUDT15 bi-allelic variants in children with acute lymphoblastic leukemia.

Haematologica 2021 07 1;106(7):2026-2029. Epub 2021 Jul 1.

Department of Transplantation and Cell Therapy, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan; Department of Pediatric Hematology and Oncology Research, National Center for Child Health and Development, Tokyo, Japan; Department of Pediatrics, the University of Tokyo, Tokyo.

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http://dx.doi.org/10.3324/haematol.2020.266320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252943PMC
July 2021

Effect of Ultrashort-Acting β-Blockers on Mortality in Patients With Sepsis With Persistent Tachycardia Despite Initial Resuscitation: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Chest 2021 Jun 9;159(6):2289-2300. Epub 2021 Jan 9.

Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Aichi, Japan. Electronic address:

Background: Historically, β-blockers have been considered to be relatively contraindicated for septic shock because they may cause cardiac suppression. On the other hand, there is an increasing interest in the use of β-blockers for treating patients with sepsis with persistent tachycardia despite initial resuscitation.

Research Question: Do ultrashort-acting β-blockers such as esmolol and landiolol improve mortality in patients with sepsis with persistent tachycardia despite initial resuscitation?

Study Design And Methods: This was a systematic review and meta-analysis. We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) that compared the mortality of patients with sepsis and septic shock treated with esmolol or landiolol. We updated our search on April 20, 2020. Two independent reviewers assessed whether titles and abstracts met the following eligibility criteria: (1) RCT, (2) patients with sepsis and septic shock ≥ 18 years of age, and (3) treatment with either esmolol/landiolol or placebo/no interventions. Two authors independently extracted selected patient and study characteristics and outcomes. The results of all analyses are presented using random effect models.

Results: Seven RCTs with a pooled sample size of 613 patients were included. Of these, six RCTs with 572 patients reported 28-day mortality. Esmolol or landiolol use in patients with sepsis and septic shock was significantly associated with lower 28-day mortality (risk ratio, 0.68; 95% CI, 0.54-0.85; P < .001). Unimportant heterogeneity was observed (I = 31%). The absolute risk reduction and number of patients to be treated to prevent one death were 18.2% and 5.5, respectively.

Interpretation: The use of ultrashort-acting β-blockers such as esmolol and landiolol in patients with sepsis with persistent tachycardia despite initial resuscitation was associated with significantly lower 28-day mortality.

Trial Registry: UMIN Clinical Trials Registry; No.: UMIN000040174; URL: https://www.umin.ac.jp/ctr/index.htm.
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http://dx.doi.org/10.1016/j.chest.2021.01.009DOI Listing
June 2021

Multicenter Study of Quantitative SPECT: Reproducibility of Tc Quantitation Using a Conjugated-Gradient Minimization Reconstruction Algorithm.

J Nucl Med Technol 2021 Jun 8;49(2):138-142. Epub 2021 Jan 8.

School of Health Science, International University of Health and Welfare, Ohtawara, Japan.

This multicenter study aimed to determine the reproducibility of quantitative SPECT images reconstructed using a commercially available method of ordered-subset conjugate-gradient minimization. A common cylindric phantom containing a 100 kBq/mL concentration of Tc-pertechnetate solution in a volume of 7 L was scanned under standard imaging conditions at 6 institutions using the local clinical protocol of each. Interinstitutional variation among the quantitative SPECT images was evaluated using the coefficient of variation. Dose calibrator accuracy was also investigated by measuring the same lot of commercially available Tc vials at each institution. The respective radioactivity concentrations under standard and clinical conditions ranged from 95.71 ± 0.60 (mean ± SD) to 108.35 ± 0.36 kBq/mL and from 96.78 ± 0.64 to 108.49 ± 0.11 kBq/mL, respectively. Interinstitutional variation in radioactivity concentration was 4.20%. The bias in the radioactivity concentrations in SPECT images was associated with the accuracy of the dose calibrator at each institution. The reproducibility of the commercially available quantitative SPECT reconstruction method is high and comparable to that of PET, for comparatively large (∼7 L), homogeneous objects.
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http://dx.doi.org/10.2967/jnmt.120.256131DOI Listing
June 2021

Vaginal Transmission of Cancer from Mothers with Cervical Cancer to Infants.

N Engl J Med 2021 01;384(1):42-50

From the Departments of Pediatric Oncology (A.A., T. Kumamoto, M.N., C.O.), Laboratory Medicine (T. Kubo, K. Sunami, H.K.), Diagnostic Pathology (N.M., H.Y.), Breast and Medical Oncology (K. Yonemori, E.N.), Pediatric Surgical Oncology (T.H., N.K.), and Experimental Therapeutics (N. Yamamoto), National Cancer Center Hospital, the Departments of Clinical Genomics (H.I., T. Kubo) and Immune Medicine (K.A.), and the Divisions of Genome Biology (K. Shiraishi, T. Kohno), Cancer Genomics (Y.A., T.S.), and Cancer Immunology (Y.T., H.N.), National Cancer Center Research Institute, the Division of Translational Genomics, Exploratory Oncology Research and Clinical Trial Center (H.I., T. Kubo, T. Kohno), the Children's Cancer Center, National Center for Child Health and Development (T.H.), the Departments of Obstetrics and Gynecology (T. Kuroda, K. Yamada, N. Yanaihara, K. Takahashi, A.O.) and Pathology (T. Kiyokawa), Jikei University School of Medicine, the Departments of Pediatrics (S.H., D.H., A.M.) and Integrated Women's Health (K.O.), St. Luke's International Hospital, and the Department of Pediatrics, Toho University School of Medicine (M.M.), Tokyo, and the Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo (S.H., A.M.) - both in Japan.

Two cases of pediatric lung cancer (in 23-month-old and 6-year-old boys) resulting from mother-to-infant transmission of uterine cervical tumors were incidentally detected during routine next-generation sequencing of paired samples of tumor and normal tissue. Spontaneous regression of some lesions in the first child and slow growth of the tumor mass in the second child suggested the existence of alloimmune responses against the transmitted tumors. Immune checkpoint inhibitor therapy with nivolumab led to a strong regression of all remaining tumors in the first child. (Funded by the Japan Agency for Medical Research and Development and others; TOP-GEAR UMIN Clinical Trials Registry number, UMIN000011141.).
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http://dx.doi.org/10.1056/NEJMoa2030391DOI Listing
January 2021

Risk of lymph node metastasis after endoscopic treatment for rectal NETs 10 mm or less.

Int J Colorectal Dis 2021 Mar 2;36(3):559-567. Epub 2021 Jan 2.

Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.

Purpose: For rectal neuroendocrine tumors (NETs) ≤ 10 mm, endoscopic resection is a standard treatment. However, there is no consensus whether additional surgery should be performed for patients at risk of lymph node metastasis (LNM) after endoscopic resection. The purpose of this study was to analyze the results of endoscopic resection and additional surgery of rectal NETs, thereby clarify the characteristics of cases with LNM.

Methods: This study was a multicenter retrospective cohort study conducted at 12 Japanese institutions. A total of 132 NETs ≤ 10 mm were analyzed regarding various therapeutic results. A comparative analysis was performed by dividing the cases into two groups that underwent additional surgery or not. Furthermore, the relationship between tumor size and LNM was examined.

Results: The endoscopic treatments were 12 endoscopic mucosal resections (EMR), 58 endoscopic submucosal resections with ligation (ESMR-L), 29 precutting EMRs, and 33 endoscopic submucosal dissections (ESD). The R0 resection rates of EMR were 41.7%, and compared to this rate, other three treatments were 86.2% (p < 0.001), 86.2% (p = 0.005), and 97.0% (p < 0.001), respectively. There were 41 non-curative cases (31.1%), and 13 had undergone additional surgery. Then, LNM was observed in 4 of the 13 patients, with an overall rate of LNM of 3.0% (4/132). The rate of positive lymphatic invasion and the rate of LNM by tumor size ≤ 6 mm and 7-10 mm were 9.7 vs. 15.4% (p = 0.375) and 0 vs. 10.3% (p = 0.007).

Conclusions: A multicenter study revealed the priority of each endoscopic resection and the low rate of LNM for rectal NETs ≤ 6 mm.
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http://dx.doi.org/10.1007/s00384-020-03826-1DOI Listing
March 2021

Magnetic Resonance Imaging and Histopathologic Findings From a Standard Poodle With Neonatal Encephalopathy With Seizures.

Front Vet Sci 2020 10;7:578936. Epub 2020 Nov 10.

Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

Neonatal encephalopathy with seizures (NEwS) is an epileptic encephalopathy with an autosomal recessive inheritance pattern found in Standard Poodle puppies. The causal genetic variant for NEwS has been identified as a homozygous missense mutation in (c.152T>G, p.Met51Arg), and a pathological cerebellar change has been reported. Magnetic resonance imaging showed reduced whole-brain size, dilated ventricles, developmental abnormalities of the white matter of the cerebrum, white matter signal abnormalities in the occipital lobe, and abnormal morphology of the cerebellum. Histopathology included previously unrecognized irregular neuronal migration in the subventricular zone around the lateral ventricles in the frontal lobe and white matter rarefaction especially at the level of the occipital lobe in the cerebrum in addition to the cerebellar cortical dysplasia that has been previously described. The findings of this case may highlight the critical role of in neurodevelopmental processes in the canine brain.
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http://dx.doi.org/10.3389/fvets.2020.578936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683776PMC
November 2020

Acquisition of monosomy 7 and a RUNX1 mutation in Pearson syndrome.

Pediatr Blood Cancer 2021 02 16;68(2):e28799. Epub 2020 Nov 16.

Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.

Pearson syndrome (PS) is a very rare and often fatal multisystem disease caused by deletions in mitochondrial DNA that result in sideroblastic anemia, vacuolization of marrow precursors, and pancreatic dysfunction. Spontaneous recovery from anemia is often observed within several years of diagnosis. We present the case of a 4-month-old male diagnosed with PS who experienced prolonged severe pancytopenia preceding the emergence of monosomy 7. Whole-exome sequencing identified two somatic mutations, including RUNX1 p.S100F that was previously reported as associated with myeloid malignancies. The molecular defects associated with PS may have the potential to progress to advanced myelodysplastic syndrome .
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http://dx.doi.org/10.1002/pbc.28799DOI Listing
February 2021

An objection to: "Congenital external hydrocephalus in a dog".

Authors:
Daisuke Hasegawa

J Small Anim Pract 2020 11 3;61(11):714. Epub 2020 Nov 3.

Laboratory of Veterinary Radiology, Nippon Veterinary and Life Science University, Tokyo, 180-8602, Japan.

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http://dx.doi.org/10.1111/jsap.13227DOI Listing
November 2020

Impact of Blood Type O on Mortality of Sepsis Patients: A Multicenter Retrospective Observational Study.

Diagnostics (Basel) 2020 Oct 15;10(10). Epub 2020 Oct 15.

Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.

ABO blood groups have been implicated as potential risk factors for various diseases. However, no study has investigated the association between sepsis mortality and ABO blood types. We aimed to evaluate the impact of these blood types on mortality in patients with sepsis and septic shock. This retrospective observational study was conducted at two general hospitals in Japan. Patients diagnosed with sepsis or septic shock were included and divided into four groups based on blood type (O, A, B, and AB). The association between type O vs. other types and 28- and 90-day mortalities was evaluated using multivariate logistic regression analysis adjusted for age, sex, and Sequential (Sepsis-related) Organ Failure Assessment score. This study included 415 patients, of whom 131 (31.6%), 171 (41.2%), 81 (19.5%), and 32 (7.7%) had type O, A, B, and AB, respectively. Blood type O was not associated with 28-day (odds ratio: 1.7 = 0.08) or 90-day mortality (odds ratio: 1.53, = 0.091). However, type O was significantly associated with higher 90-day mortality (odds ratio: 3.26, = 0.009) in patients with septic shock. The role of ABO blood type in risk stratification for septic shock and the mechanisms that potentially affect the prognosis of sepsis patients need further investigation.
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http://dx.doi.org/10.3390/diagnostics10100826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602578PMC
October 2020

The efficacy and safety of colonoscopy in nonagenarians: A multicenter study.

Indian J Gastroenterol 2020 Dec 15;39(6):557-564. Epub 2020 Oct 15.

Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.

Introduction: The number of colonoscopy (CS) for the elderly is increasing. There are only a few reports focusing on CS among the very elderly aged ≥ 90-y. We aimed to analyze the efficacy of CS and of colorectal cancer (CRC) for patients aged ≥ 90-y.

Methods: We retrospectively analyzed consecutive patients aged ≥ 90-y receiving CS at eight institutions from October 2016 to September 2017. Bowel preparation, complications, and endoscopic diagnosis were analyzed. The non-elderly group aged between 50-y and 64-y and elderly group aged between 65-y and 79-y were compared to very-elderly group aged ≥ 90-y. Through propensity score matching of sex and CS indications (symptomatic or asymptomatic), the number of CRC and the treatment in each group were analyzed.

Results: We analyzed 125 patients receiving 154 colonoscopies (0.9%) in the very-elderly group from among 16,968 cases. Among 92 cases who received bowel-cleansing solution, good preparations were achieved in 94.5%. The rate of CS-related complications was 1.3% (2/154). The rate of CRC in the very-elderly group was 27.2% (34/125), higher than the non-elderly group (7.2%, 9/125, p < 0.01) and elderly group (8.8%, 11/125, p < 0.01). Therapeutic interventions for CRC in the very-elderly group were performed in 73.5% (24/34) patients. The mean survival of 12 patients with CRC resection was 788 days.

Conclusions: CS could be performed safely for the very elderly aged ≥ 90-y with careful considerations. CRC was confirmed to be more frequent in this group with over 70% of patients receiving appropriate therapeutic intervention.
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http://dx.doi.org/10.1007/s12664-020-01066-3DOI Listing
December 2020

The predictive value of airway occlusion pressure at 100 msec (P0.1) on successful weaning from mechanical ventilation: A systematic review and meta-analysis.

J Crit Care 2021 Jun 30;63:124-132. Epub 2020 Sep 30.

Department of Internal Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA; Department of Critical Care Medicine, Kuakini Medical Center, Honolulu, HI, USA.

Purpose: The predictive value of airway occlusion pressure at 100 milliseconds (P0.1) on weaning outcome has been controversial. We performed a meta-analysis to investigate the predictive value of P0.1 on successful weaning from mechanical ventilation.

Materials And Methods: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE, and two authors independently screened articles. The pooled sensitivity, specificity and the summary receiver operating characteristic (sROC) curve were estimated. Diagnostic odds ratio (DOR) was calculated using meta-regression analysis.

Results: We included 12 prospective observational studies (n = 1089 patients). Analyses of sROC curves showed the area under the curve of 0.81 (95% confidence interval (CI): 0.77 to 0.84) for P0.1. The pooled sensitivity and specificity were 86% (95% CI, 72 to 94%) and 58% (95% CI, 37% to 76%) with substantial heterogeneity respectively. DOR was 20.09 (p = 0.019, 95%CI: 1.63-247.15). After filling the missing data using the trim-and-fill method to adjust publication bias, DOR was 36.23 (p = 0.002, 95%CI: 3.56-372.41).

Conclusion: This meta-analysis suggests that P0.1 is a useful tool to predict successful weaning. To determine clinical utility, a large prospective study investigating the sensitivity and specificity of P0.1 on weaning outcomes from mechanical ventilation is warranted.
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http://dx.doi.org/10.1016/j.jcrc.2020.09.030DOI Listing
June 2021

Galápagosization of sepsis management in Japan: a nationwide survey of current practices.

Acute Med Surg 2020 Jan-Dec;7(1):e561. Epub 2020 Sep 2.

Department of Anesthesiology and Critical Care Medicine Fujita Health University School of Medicine Toyoake Japan.

Aim: Sepsis treatment has been standardized in many countries worldwide. However, treatment of sepsis in Japan has developed independently, and how Japanese physicians actually treat sepsis patients nationwide remains uninvestigated. The aim of this study was to clarify the current practice for septic patients in Japan and how it differs from standard care throughout the world.

Methods: This study was designed as a prospective, cross-sectional, self-reported questionnaire- and Web-based electronic survey in Japan. The survey was undertaken to assess respondents' clinical practices and preferences regarding treatment strategies, sepsis assessment, and management in the setting of critical illness. An exploratory factor analysis and a hierarchical cluster analysis were carried out to identify the treatments distinctive to Japan, called "Galápagos therapies".

Results: The final analysis included 295 respondents. According to the factor analysis, we defined anticoagulant therapy for disseminated intravascular coagulation, antimediator renal replacement therapy, and others as Galápagos therapies. These Galápagos therapies were undertaken by approximately two-thirds of the Japanese physicians who responded. We classified Japanese physicians according to three patterns of clinical practice carried out for sepsis: (i) those who do not perform Galápagos therapies but do perform worldwide standardized care, (ii) those who perform Galápagos therapies on top of worldwide standardized care, (iii) those who do not perform worldwide standardized care.

Conclusion: On the basis of a nationwide questionnaire-based survey in Japan, we clarified distinctive sepsis treatments performed in Japan, such as antimediator renal replacement therapy and treatment for sepsis-induced disseminated intravascular coagulation.
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http://dx.doi.org/10.1002/ams2.561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507569PMC
September 2020

The outcomes of relapsed acute myeloid leukemia in children: Results from the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05R study.

Pediatr Blood Cancer 2021 01 29;68(1):e28736. Epub 2020 Sep 29.

Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.

Background: The prognosis of children with acute myeloid leukemia (AML) has improved with the efficacy of hematopoietic cell transplantation (HCT) as a second-line therapy and improvements in supportive care following anthracycline- and cytarabine-based chemotherapy; however, the outcomes of children with relapsed AML still remain unsatisfactory.

Procedure: In order to identify prognostic factors and improve their prognosis, we analyzed 111 patients who relapsed after treatment with the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 protocol and who were registered in the retrospective JPLSG AML-05R study.

Results: The 5-year overall survival rate was 36.1%. The major determinant of survival was duration from the diagnosis to relapse. The mean duration in the nonsurviving group (10.1 ± 4.1 months) was shorter than that in the surviving group (16.3 ± 8.3 months) (P < .01). Moreover, achieving a second complete remission (CR2) prior to HCT was associated with a good prognosis (P < .01). Etoposide, cytarabine, and mitoxantrone (ECM)- or fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG)-based regimens were therefore recommended for reinduction therapy (P < .01). A genetic analysis also revealed the prognostic significance of FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication as a poor prognostic marker (P = .04) and core binding factor-AML, t(8;21), and inv(16) as good prognostic markers (P < .01).

Conclusions: Achieving a CR2 prior to HCT is important in order to improve the prognosis of relapsed pediatric AML. Recent molecular targeted therapies, such as FLT3 inhibitors, may contribute to overcome their prognoses. Larger prospective investigations are necessary to establish individualized treatment strategies for patients with relapsed childhood AML.
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http://dx.doi.org/10.1002/pbc.28736DOI Listing
January 2021
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