Partial replacement of d-glucose with d-allose ameliorates peritoneal injury and hyperglycaemia induced by peritoneal dialysis fluid in rats.

BACKGROUND: Peritoneal dialysis (PD) is a crucial dialysis method for treating end-stage kidney disease. However, its use is restricted due to high glucose-induced peritoneal injury and hyperglycaemia, particularly in patients with diabetes mellitus. In this study, we investigated whether partially replacing d-glucose with the rare sugar d-allose could ameliorate peritoneal injury and hyperglycaemia induced by peritoneal dialysis fluid (PDF). METHODS: Rat peritoneal mesothelial cells (RPMCs) were exposed to a medium containing d-glucose or d-glucose partially replaced with different concentrations of d-allose. Cell viability, oxidative stress and cytokine production were evaluated. Sprague-Dawley (SD) rats were administrated saline, a PDF containing 4% d-glucose (PDF-G4.0%) or a PDF containing 3.6% d-glucose and 0.4% d-allose (PDF-G3.6%/A0.4%) once a day for 4 weeks. Peritoneal injury and PD efficiency were assessed using immuno-histological staining and peritoneal equilibration test, respectively. Blood glucose levels were measured over 120 min following a single injection of saline or PDFs to 24-h fasted SD rats. RESULTS: In RPMCs, the partial replacement of d-glucose with d-allose increased cell viability and decreased oxidative stress and cytokine production compared to d-glucose alone. Despite the PDF-G3.6%/A0.4% having a lower d-glucose concentration compared to PDF-G4.0%, there were no significant changes in osmolality. When administered to SD rats, the PDF-G3.6%/A0.4% suppressed the elevation of peritoneal thickness and blood d-glucose levels induced by PDF-G4.0%, without impacting PD efficiency. CONCLUSIONS: Partial replacement of d-glucose with d-allose ameliorated peritoneal injury and hyperglycaemia induced by high concentration of d-glucose in PDF, indicating that d-allose could be a potential treatment option in PD.

Efficacy and Safety of Single-dose Pegfilgrastim for CD34 + Cell Mobilization in Healthy Volunteers: A Phase 2 Study.

BACKGROUND: Pegfilgrastim, a long-acting form of granulocyte-colony stimulating factor, with a convenient single-injection dosage, is being investigated for peripheral blood stem cell (PBSC) mobilization in healthy volunteers. However, data on the adequate dose of pegfilgrastim for PBSC mobilization are limited. This phase 2, single-arm study evaluated the efficacy and safety of pegfilgrastim for PBSC mobilization in healthy volunteers. METHODS: The study comprised 2 phases: pilot (steps 1-3, dose escalation, a single subcutaneous dose of 3.6, 7.2, and 10.8 mg pegfilgrastim, respectively) and evaluation (step 4, efficacy and safety assessments). The primary endpoint was the proportion of subjects who achieved mobilization of ≥20 × 10 6 /L cluster of differentiation 34 positive (CD34 + ) cells. RESULTS: Thirty-five subjects (6 each in steps 1 and 2 and 23 in step 4) were included. In the pilot phase, step 3 with a 10.8 mg dose was not conducted due to favorable outcomes in step 2 (desired CD34 + cell count), at 7.2 mg pegfilgrastim, which was identified as the optimal dose for the evaluation phase. In the evaluation phase, successful CD34 + mobilization was achieved in all 23 subjects. The mean peripheral blood CD34 + cells count peaked on day 5. Back pain, thrombocytopenia, transient elevations of alkaline phosphatase, and lactate dehydrogenase were the most common adverse events. All adverse events were mild, and none led to study discontinuation. CONCLUSIONS: A single-dose pegfilgrastim successfully mobilized an optimal number of CD34 + cells and was well tolerated. Pegfilgrastim could be an alternative option for PBSC mobilization in healthy volunteers. The trial was registered at www.clinicaltrials.gov (NCT03993639).

Dominant-negative type of IKZF1 deletion showed a favorable prognosis in adult B-cell acute lymphoblastic leukemia.

IKZF1 deletion is a recurrent genomic alteration in B-cell acute lymphoblastic leukemia (B-ALL) and is divided into dominant-negative (DN) and loss of function (LOF) deletions. The prognostic impact of each deletion has not been fully elucidated. We retrospectively analyzed 117 patients with adult B-ALL including 60 patients with BCR::ABL1-positive B-ALL and 57 patients with BCR::ABL1-negative B-ALL by the fluorescence in situ hybridization (FISH) method for IKZF1 deletion and multiplex PCR for the 4 most common IKZF1 deletions (∆4-7, ∆2-7, ∆2-8, and ∆4-8). Samples, in which IKZF1 deletion was detected by FISH but a specific type of deletion was not identified by the PCR, were categorized as "other." Patients were classified into a DN group that had at least 1 allele of ∆4-7 (n = 23), LOF and other group (n = 40), and wildtype group (n = 54). DN type IKZF1 deletions were found in 33.3% of BCR::ABL1-positive cases and 5.2% of BCR::ABL1-negative cases. LOF and other type IKZF1 deletions were found in 43.4% of BCR::ABL1-positive cases and 24.6% of BCR::ABL1-negative cases. Patients with the DN group showed significantly higher overall survival (OS) than that of the LOF and other and WT groups (P = 0.011). Multivariate analysis including age, WBC counts, complex karyotype, and DN type IKZF1 deletion showed that the DN type of IKZF1 deletion (HR = 0.22, P = 0.013) had a positive impact and age ≥ 65 (HR = 1.92, P = 0.029) had a negative impact on OS. The prognostic impact of IKZF1 deletion depends on the type of deletion and DN type of IKZF1 deletion showed better prognosis in adult B-ALL patients.Clinical trial registration This study was part of a prospective observational study (Hokkaido Leukemia Net, UMIN000048611). It was conducted in compliance with ethical principles based on the Helsinki Declaration and was approved by the institutional review board of Hokkaido University Hospital (#015-0344).

Clinical implications of NUP98::NSD1 fusion at diagnosis in adult FLT3-ITD positive AML.

OBJECTIVES: The cryptic fusion oncogene NUP98::NSD1 is known to be associated with FLT3-ITD mutation in acute myeloid leukemia (AML), and an independent poor prognostic factor in pediatric AML. However, there are little data regarding the clinical significance of NUP98::NSD1 in adult cohort. METHODS: We conducted a multicenter retrospective study to investigate the prevalence, clinical characteristics, and prognostic impact of NUP98::NSD1 in adult FLT3-ITD-positive AML patients. RESULTS: In a total of 97 FLT3-ITD-positive AML patients, six cases (6.2%) were found to harbor the NUP98::NSD1 fusion transcript. NUP98::NSD1 positive cases had significantly higher platelet counts and a higher frequency of FAB-M4 morphology than NUP98::NSD1 negative cases. NUP98::NSD1 was found to be mutually exclusive with NPM1 mutation, and was accompanied by the WT1 mutation in three of the six cases. The presence of NUP98::NSD1 fusion at the time of diagnosis predicted poor response to cytarabine-anthracycline-based intensive induction chemotherapy (induction failure rate: 83% vs. 36%, p = .038). Five of the six cases with NUP98::NSD1 underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two of the five cases have successfully maintained remission, with one of them being rescued through a second HSCT. CONCLUSIONS: Detecting NUP98::NSD1 in adult FLT3-ITD-positive AML is crucial to recognizing chemotherapy-resistant group.

Molten salt synthesis of CrMnFeNi alloy nanopowder passivated by TiO x -ZrO y shell used as a superior catalyst support in liquid-phase hydrogenation.

A molten salt method was used to prepare CrMnFeNi alloy nanopowder passivated by TiO x -ZrO y surface shell with a high specific surface area (23 m2 g-1) from the oxide precursors. Analyses by scanning electron microscopy/transmission electron microscopy with energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy revealed the formation of an alloyed Cr-Mn-Fe-Ni-rich core surrounded by an oxide surface shell with a Ti/Zr-rich composition, confirming the formation of TiO x -ZrO y /CrMnFeNi nanopowder. It was speculated that the CrMnFeNi alloy nanoparticles were preferentially formed from the constituent metals by a faster reduction of any oxides of Cr, Mn, Fe, and Ni and a subsequent alloying with Ti and Zr could hardly occur due to the high thermodynamic stability of CrMnFeNi alloy. A Ni-loaded TiO x -ZrO y /CrMnFeNi catalyst exhibited superior catalytic performance to common Ni-loaded TiO2 and ZrO2 in the liquid-phase hydrogenation of p-nitrophenol at room temperature. The enhancement could have originated from an excellent electrical property of CrMnFeNi alloy, promoting the formation of active metallic nickel on the surface during the reaction. Leaching amounts of the constituent elements of Ti-Zr-Cr-Mn-Fe-Ni and loaded Ni was very little in the reaction solution after the reaction; the results confirmed that the prepared CrMnFeNi alloy nanopowder was very stable due to the protection of the Ti/Zr-rich oxide shell. Thus, the potential application of the alloyed powder used as catalyst support was demonstrated.

Subclinical minute FLT3-ITD clone can be detected in clinically FLT3-ITD-negative acute myeloid leukaemia at diagnosis.

Recent advances in next-generation sequencing (NGS) have enabled the detection of subclinical minute FLT3-ITD. We selected 74 newly diagnosed, cytogenetically normal acute myeloid leukaemia (AML) samples in which FLT3-ITD was not detected by gel electrophoresis. We sequenced them using NGS and found minute FLT3-ITDs in 19 cases. We compared cases with clinically relevant FLT3-ITD (n = 37), cases with minute FLT3-ITD (n = 19) and cases without detectable FLT3-ITD (n = 55). Molecular characteristics (location and length) of minute FLT3-ITD were similar to those of clinically relevant FLT3-ITD. Survival of cases with minute FLT3-ITD was similar to that of cases without detectable FLT3-ITD, whereas the relapse rate within 1 year after onset was significantly higher in cases with minute FLT3-ITD. We followed 18 relapsed samples of cases with clinically FLT3-ITD-negative at diagnosis. Two of 3 cases with minute FLT3-ITD relapsed with progression to clinically relevant FLT3-ITD. Two of 15 cases in which FLT3-ITD was not detected by NGS relapsed with the emergence of minute FLT3-ITD, and one of them showed progression to clinically relevant FLT3-ITD at the second relapse. We revealed the clonal dynamics of subclinical minute FLT3-ITD in clinically FLT3-ITD-negative AML. Minute FLT3-ITD at the initial AML can expand to become a dominant clone at relapse.

Prognostic impact of FLT3-ITD, NPM1 mutation and CEBPA bZIP domain mutation in cytogenetically normal acute myeloid leukemia: a Hokkaido Leukemia Net study.

Mutation status of FLT3, NPM1, and CEBPA is used to classify the prognosis of acute myeloid leukemia, but its significance in patients with cytogenetically normal (CN) AML is unclear. We prospectively analyzed these genes in 295 patients with CN-AML and identified 76 (25.8%) FLT3-ITD, 113 (38.3%) NPM1 mutations, and 30 (10.2%) CEBPA biallelic mutations. We found that patients with FLT3-ITD had a poor prognosis at any age, while patients with CEBPA biallelic mutation were younger and had a better prognosis. FLT3-ITD and NPM1 mutations were correlated, and the favorable prognostic impact of being FLT3-ITD negative and NPM1 mutation positive was evident only in patients aged 65 years or more. For CEBPA, 86.7% of the patients with biallelic mutation and 9.1% of patients with the single allele mutation had in-frame mutations in the bZIP domain, which were strongly associated with a favorable prognosis. Multivariate analysis showed that age < 65 years, FLT3-ITD and CEBPA bZIP in-frame mutation were independent prognostic factors. The results suggest that analyzing these gene mutations at diagnosis can inform selection of the optimal intensity of therapy for patients with CN-AML.

Clinical features of complex karyotype in newly diagnosed acute myeloid leukemia.

Complex karyotype acute myeloid leukemia (CK-AML) has been classified as an adverse-risk subtype. Although a few reports have further classified CK-AML as typical (including monosomy of chromosomes 5, 7 and 17 or deletion of 5q, 7q and/or 17p) or atypical, the clinical features of these subtypes in Japanese patients remain unclear. We retrospectively analyzed a total of 115 patients with CK-AML, including 77 with typical CK-AML and 38 with atypical CK-AML. Median overall survival (OS) was significantly shorter in patients with typical CK-AML than atypical CK-AML (143 days vs. 369 days, P = 0.009). Among patients with typical CK-AML, those with monosomy 17 or deletion of 17p had significantly shorter OS than patients without such abnormalities (105 days vs. 165 days, P = 0.033). TP53 mutations were more predominant in patients with typical CK-AML than in patients with atypical CK-AML (69.7% vs. 32.4%, P < 0.001). Patients with typical CK-AML had a poor prognosis regardless of TP53 mutation status. Among patients with atypical CK-AML, however, prognosis was worse for those with the TP53 mutation than those without the mutation. In conclusion, prognosis is extremely poor for both typical CK-AML and atypical CK-AML with TP53 mutation.

Molten Salt Synthesis of Intermetallic Compound TiNi Nanopowder Passivated by TiOx Shell Prepared from NiTiO3 for Catalytic Hydrogenation.

Titanium-nickel alloy is an attractive material due to its unique properties of shape memory effect, superior elasticity, and biocompatibility. Generally, Ti-Ni alloy powders are prepared from pure elemental powders of Ti and Ni as starting materials, but it is an energy-intensive process to obtain pure titanium. In this study, intermetallic compound TiNi powder passivated by TiOx shell was prepared by directly reducing a commercial NiTiO3 using CaH2 reducing agent in a molten LiCl at 650 °C. Analyses by X-ray diffraction, scanning electron microscopy/transmission electron microscopy with energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy revealed that the powder had a core-shell structure, with the core of TiNi and the shell of TiOx-rich composition with scarce metallic Ni nicely catalyzing hydrogenation reactions with good recyclability and stability.

Antiretroviral therapy achieved metabolic complete remission of hepatic AIDS related Epstein-Barr virus-associated smooth muscle tumor.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor which occurs in immunocompromised patients. The immune status is an important factor in the treatment of EBV-SMTs, but the efficacy of antiretroviral therapy (ART) is not elucidated in acquired immune deficiency syndrome (AIDS) related EBV-SMTs. Here, we report the first successful case of a 29-year-old man with hepatic AIDS related EBV-SMT treated with ART solely. Positron emission tomography scan was useful for the evaluation of disease status. Recent advances in ART that enables to restore patient's immune status rapidly may change the treatment strategy in AIDS related EBV-SMT.

High CRP-albumin ratio predicts poor prognosis in transplant ineligible elderly patients with newly diagnosed acute myeloid leukemia.

Acute myeloid leukemia (AML) patients older than 65 years have a poor prognosis. Recently, CAR (C-reactive-protein/albumin ratio) has been actively reported as a prognostic index reflecting the nutritional and inflammatory status of elderly patients with solid tumors, but the usefulness of this index as a prognostic indicator in transplant-ineligible elderly AML patients has not been investigated. We studied genetic alterations and CARs in 188 newly diagnosed AML patients aged 65 years or older who were treated in a multicenter setting and had treated without HSCT. Both NCCN 2017 risk group, reflecting the genetic component of the tumor, and CAR, reflecting the inflammatory and nutritional status of the patient, successfully stratified the overall survival (OS) of the patients (2-year OS; CAR low vs high, 42.3% vs 17.8%, P < 0.001). Furthermore, in multivariate analysis, NCCN 2017 poor group and high CAR were extracted as independent poor prognostic factors predicting 2-year OS in the current study. We found, for the first time, that CAR at diagnosis predicted the prognosis of elderly patients with newly diagnosed AML treated without HSCT.

Perinatal Management in a Pregnant Woman with Ureteropelvic Junction Obstruction: Case Report and Literature Review.

Although giant hydronephrosis (GH) associated with ureteropelvic junction obstruction (UPJO) is extremely rarely detected in pregnant women, diagnostic methods, therapeutic approaches, and perinatal management have not been established. A 31-year-old Japanese primipara had a 15 cm × 12 cm multi-cystic mass in the right abdomen detected by transabdominal ultrasound at gestational week 26. Magnetic resonance imaging revealed that the mass was right renal GH. She underwent serial ultrasound-guided transretroperitoneal drainage as conservative treatment. She delivered vaginally at gestational week 36. Since she had flank pain and a documented non-functional right kidney, laparoscopic nephrectomy was conducted 22 months after delivery. UPJO with fewer smooth muscle cells and fibrosis was histologically diagnosed in the surgical specimen. Her postpartum and postoperative courses were uneventful for 10 months. We performed a literature review of diagnostic methods, clinical characteristics, and perinatal management in pregnant women with GH due to UPJO.

Dynamic change in peripheral blood WT1 mRNA levels within three cycles of azacitidine predict treatment response in patients with high-risk myelodysplastic syndromes.

Azacitidine (AZA) improves overall survival (OS) in patients with high-risk myelodysplastic syndromes (MDS). However, predictive factors for response to AZA remain largely unknown. To elucidate whether dynamic change in peripheral blood (PB) Wilms' Tumor 1 (WT1) mRNA levels could predict response to AZA, we retrospectively identified 75 treatment-naïve patients with high-risk MDS who received at least 3 cycles of AZA. We classified patients into 4 groups, low-increase (LI), low-stable (LS), high-decrease (HD), and high-stable (HS) based on the dynamic change in PB WT1 mRNA levels within 3 cycles of AZA. Cumulative incidence of overall response after 10 cycles of AZA was significantly higher in LS/HD than in HS/LI (75.5% vs 4.5%, P < 0.001). The median OS for LS/HD was 18.2 months (95% CI, 12.8-28.1 months), whereas it was 11.6 months for HS/LI (95% CI, 6.6-14.1 months; P < 0.001). Multivariate analysis demonstrated that poor-/very poor-IPSS-R cytogenetic risk and HS/LI were independently associated with poor OS (poor-/very poor-IPSS-R cytogenetic risk: HR, 2.26; 95% CI, 1.10-4.68, P = 0.03, HS/LI: HR, 2.32; 95% CI, 1.21-4.46, P = 0.01). Patients with HS/LI did not show any further response to continuous AZA, and they should be considered for alternative therapy from earlier cycles.

Non-age-related neoplastic loss of sex chromosome correlated with prolonged survival in real-world CBF-AML patients.

In this real-world clinical study, in which we determined eligibility for allogenic hematopoietic stem cell transplantation by prognostic factors and minimal residual disease status, we retrospectively evaluated cytogenetic, genetic, and clinical features in 96 patients with core-binding factor acute myeloid leukemia (CBF-AML) including 62 patients with RUNX1/RUNX1T1 and 34 patients with CBFß/MYH11. Multivariate analyses for 5-year overall survival (OS) in CBF-AML patients revealed that age of 50 years or older (HR: 3.46, 95% CI 1.47-8.11, P = 0.004) and receiving 2 or more induction cycles (HR: 3.55, 95% CI 1.57-8.05, P = 0.002) were independently associated with worse OS and that loss of sex chromosome (LOS) was independently associated with better OS (HR: 0.09, 95% CI 0.01-0.71, P = 0.022). At the time of complete remission, all 21 karyotyped patients with LOS had a normal karyotype. Furthermore, in all 9 patients with LOS who had a mosaic of metaphase cells with and without t(8;21) or inv(16), the metaphase cells without t(8;21)/inv(16) showed a normal karyotype. These results proved that LOS was not age-related and physiological, but rather a neoplastic chromosomal abnormality.

[Emergence of mutation in the colony-stimulating factor 3 receptor gene during follow-up of unclassifiable myeloproliferative neoplasm].

A 25-year-old male with a medical history of stress polycythemia was admitted to a previous hospital for leukocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed left-shifted myeloid hyperplasia without increased blasts and normal male karyotype. No mutations of JAK2, V617F, and colony-stimulating factor 3 receptor gene (CSF3R) were detected. Fluorescence in-situ hybridization for BCR-ABL1 and FIP1L1-PDGFRA were negative. Based on these findings, a diagnosis of an unclassifiable myeloproliferative neoplasm was made, and he was started on hydroxyurea treatment. He was referred to our hospital in April 2016 for transfusion dependence. Bone marrow examination performed at our hospital revealed granulocytic dysplasia and CSF3R T618I was detected. After induction therapy, CSF3R T618I became undetectable, and he went on to undergo allogeneic stem cell transplantation in October 2016. He has been in remission for >4 years posttransplantation. CSF3R T618I is one of the genes responsible for chronic neutrophilic leukemia and atypical chronic myeloid leukemia, suggesting its involvement in the pathogenesis of this case.

Progression of cervical intraepithelial neoplasia grade 2 lesions among Japanese women harboring different genotype categories of high-risk human papillomaviruses.

Background: This study aimed to examine whether genotype categories of high-risk human papillomaviruses (HR-HPVs), when divided into HPV16/18, HPV 31/33/45/52/58, and HPV35/39/51/56/59/68, had an effect on the time required for and the proportion of cases that progressed to cervical intraepithelial neoplasia (CIN) grade 3 among women with CIN2. Patients: A total of 160 women aged 20-49 years and having CIN2 were recruited between January 2008 and June 2018. The time required for progression to CIN3 was determined by Kaplan-Meier time-to-event analysis. HPV genotypes were determined using the Linear Array HPV genotyping test. Results: During an average follow-up time of 22 months, 62 (39%) women with CIN2 progressed to CIN3, whereas 34 (21%) eliminated HR-HPVs and became cytologically normal. The majority (63%) of the women harboring HPV16/18 progressed to CIN3 with a 50% progression time of 11 months, whereas 26% of those harboring HPV31/33/45/52/58 progressed to CIN3 with a 50% progression time of 70 months. Conclusion: For every patient diagnosed with CIN2, genotyping to distinguish HPV16/18 from other HR-HPVs should be performed. Therefore, electing a surgical treatment, such as conization, should be considered as the primary option for women who are positive for HPV16/18, particularly when they are likely to be lost for follow-up or are 40 years old or older. In contrast, follow-up cytology should be repeated every 12 months for women harboring non-16/18 HR-HPVs. Those who tested negative for HR-HPV may be followed at the maximum interval of 24 months.

Association between physical restraint requirement and unfavorable neurologic outcomes in subarachnoid hemorrhage.

BACKGROUND: Physical restraint has been commonly indicated to patients with brain dysfunction in neurocritical care. The effect of physical restraints on outcomes of critically ill adults remains controversial as no randomized controlled trials have compared its safety and efficacy, and the association between physical restraint requirement and neurological outcome in patients with subarachnoid hemorrhage (SAH) has not been fully examined. The aim of this study was to examine the association between physical restraint requirement and neurological outcomes in patients with SAH. METHODS: A single-center, retrospective study was conducted on patients with acute phase SAH treated for > 72 h in the intensive care unit from 2014 to 2020. Patients were divided into three groups based on the amount of time required for physical restraint during the first 24-72 h after admission: no, intermittent, and continuous use of physical restraint. Unfavorable neurologic outcome, assessed using the modified Rankin scale upon hospital discharge, has been considered as primary end point. RESULTS: Overall, 101 patients were included in the study, with 52 patients (51.5%) having unfavorable neurological outcomes. Among them, 46 patients (45.5%) did not use physical restraint, and 55 (54.5%) patients used physical restraint during the first 24-72 h after admission: 26 (25.7%) intermittent and 29 (28.7%) continuous. Multivariable logistic regression analysis showed that continuous use of physical restraint during the first 24-72 h after admission was significantly associated with unfavorable neurological outcomes in patients with SAH (odds ratio, 3.54; 95% confidence interval, 1.05-13.06; p = 0.042) compared with no physical restraint. CONCLUSIONS: Continuous use of physical restraint during the first 24-72 h after admission was more significantly associated with unfavorable neurological outcomes than no physical restraint among patients with SAH during the acute phase.

A novel nutritional index "simplified CONUT" and the disease risk index independently stratify prognosis of elderly patients with acute myeloid leukemia.

Elderly patients aged 65 or older with acute myeloid leukemia (AML) have poor prognosis. The risk stratification based on genetic alteration has been proposed in national comprehensive cancer network (NCCN) guideline but its efficacy was not well verified especially in real world elderly patients. The nutritional status assessment using controlling nutritional status (CONUT) score is a prognostic biomarker in elderly patients with solid tumors but was not examined in elderly AML patients. We performed prospective analysis of genetic alterations of 174 patients aged 65 or older with newly diagnosed AML treated without hematopoietic stem cell transplantation (HSCT) and developed simplified CONUT (sCONUT) score by eliminating total lymphocyte count from the items to adapt AML patients. In this cohort, both the NCCN 2017 risk group and sCONUT score successfully stratified the overall survival (OS) of the elderly patients. A multivariable analysis demonstrated that adverse group in NCCN 2017 and high sCONUT score were independently associated with poor 2-year OS. Both risk stratification based on NCCN 2017 and sCONUT score predict prognosis in the elderly patients with newly diagnosed AML.

Time Course Changes in Urinary Angiotensinogen and Circulating N-Terminal Pro-B-Type Natriuretic Peptide in Patients Hospitalized with Acute Heart Failure.

Objective Home care is important in patients with heart failure (HF) in order to maintain their quality of life. A biomarker that can be measured noninvasively is needed to optimize the home care of patients with HF. Urinary angiotensinogen (uAGT) is an indicator of the intrarenal renin-angiotensin system activity, which may be augmented in HF. We hypothesized that uAGT might be a urinary biomarker in HF. Methods We measured uAGT by an enzyme-linked immunosorbent assay and uAGT normalized by urinary creatinine (uCr)-designated uAGT/uCr-at admission and discharge in 45 patients hospitalized for HF. Results We found that both uAGT/uCr [median (interquartile range): 65.5 (17.1-127.7) µg/g Cr at admission; 12.1 (6.0-37.0) µg/g Cr at discharge; p<0.01] and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels [5,422 (2,280-9,907) pg/mL at admission; 903 (510-1,729) pg/mL at discharge; p<0.01] significantly decreased between admission and discharge along with an improvement in patient's clinical status [New York Heart Association scores: 3 (3-4) at admission; 1 (1-1) at discharge; p<0.01]. The generalized least squares model revealed that the time course changes in uAGT/uCr also correlated with those in NT-proBNP levels between admission and readmission in five patients readmitted for HF. Conclusion The results indicated that the time course changes in uAGT/uCr correlated with those in the NT-proBNP levels in patients with HF who showed a clinical improvement. Further investigation and development of a kit for the rapid measurement of uAGT are needed to evaluate the clinical utility of uAGT as a biomarker in HF.

Short-term treatment with imetelstat sensitizes hematopoietic malignant cells to a genotoxic agent via suppression of the telomerase-mediated DNA repair process.

Imetelstat is a specific and competitive inhibitor of telomerase enzymatic activity. We demonstrated that imetelstat could interfere with the DNA repair process and enhance the effect of DNA damaging agents using hematological tumor cell lines. Short-term administration of imetelstat enhanced growth suppression by anticancer agents and radiation. It also upregulated γH2AX expression induced by irradiation. Immunofluorescence staining showed that both human telomerase reverse transcriptase (hTERT) and γH2AX were upregulated and co-localized in the nucleus of peripheral blood mononuclear cells after irradiation, suggesting that hTERT was involved in the DNA-DSB repair process. Imetelstat enhanced growth inhibitory effect of cytotoxic agents in short-term culture without shortening of telomeres, indicating that this effect was attributed by telomere length independent mechanism. Our results suggest that the combination of short-term treatment with imetelstat and cytotoxic agent is a promising strategy to treat a wide variety of hematopoietic malignancies.