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Antibody persistence several months after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) mRNA vaccination in allogeneic stem cell transplantation recipients remains largely unknown. We sequentially evaluated the humoral response to two doses of mRNA vaccines in 128 adult recipients and identified the risk factors involved in a poor response. The median interval between stem cell transplantation and vaccination was 2.7 years. The SARS‐CoV‐2 S1 Ab became positive after the second vaccination dose in 87.6% of the recipients, and the median titer was 1235.4 arbitrary units (AU)/ml. In patients on corticosteroid treatment, the corticosteroid dose inversely correlated with Ab titer. Multivariate analysis identified risk factors for poor peak response such as an interval from stem cell transplantation ≤1 year, history of clinically significant CMV infection, and use of >5 mg/day prednisolone at vaccination. Six months after vaccination, the median titer decreased to 185.15 AU/ml, and use of >5 mg/day prednisolone at vaccination was significantly associated with a poor response. These results indicate that early vaccination after stem cell transplantation (<12 months) and CMV infection are risk factors for poor peak response, while steroid use is important for a peak as well as a persistent response. In conclusion, although humoral response is observed in many stem cell transplantation recipients after two doses of vaccination, Ab titers diminish with time, and factors associated with persistence and a peak immunity should be considered separately. [ABSTRACT FROM AUTHOR]

Representative images of male-donor-derived cell (A) and cell with sex chromosome loss in fluorescence in situ hybridization analysis, and microscopic findings of bone marrow in (C) case 1, (D) case 2, (E) case 3 and (F) case 4. In case 2, the transcripts of I TCF3-PBX1 i remained negative even after the appearance of SCL cells, which confirmed that the SCL cells were not derived from relapsed leukemic cells. Recently, chimerism analysis using the SNP-based NGS technique has been developed.14 Using the SNP sequence, we showed the samples including SCL cells did not contain recipient-derived cells. Sex chromosome loss (SCL) in blood cells is often observed in an age-dependent manner.1 The loss of chromosome Y (LOY) in older men was associated with various diseases and shorter survival.2,3 In sex-mismatched allogeneic stem cell transplantation (SCT), sex chromosome fluorescence in situ hybridization (FISH) is the established method for chimerism analysis.4 However, the 45,X karyotype (i.e., loss of an X chromosome in women or LOY in men) can occur after SCT and can be derived from the donor or the recipient. [Extracted from the article]

Gene rearrangements of MLL/KMT2A or RUNX1 are the major cause of therapy‐related leukemia. Moreover, MLL rearrangements are the major cause of infant leukemia, and RUNX1 rearrangements are frequently detected in cord blood. These genes are sensitive to topoisomerase II inhibitors, and various genes have been identified as potential fusion partners. However, fetal exposure to these inhibitors is rare. Therefore, we postulated that even a proliferation signal itself might induce gene rearrangements in hematopoietic stem cells. To test this hypothesis, we detected gene rearrangements in etoposide‐treated or non–treated CD34+ cells cultured with cytokines using inverse PCR. In the etoposide‐treated cells, variable‐sized rearrangement bands were detected in the RUNX1 and MLL genes at 3 hours of culture, which decreased after 7 days. However, more rearrangement bands were detected in the non–treated cells at 7 days of culture. Such gene rearrangements were also detected in peripheral blood stem cells mobilized by cytokines for transplantation. However, none of these rearranged genes encoded the leukemogenic oncogene, and the cells with rearrangements did not expand. These findings suggest that MLL and RUNX1 rearrangements, which occur with very low frequency in normal hematopoietic progenitor cells, may be induced under cytokine stimulation. Most of the cells with gene rearrangements are likely eliminated, except for leukemia‐associated gene rearrangements, resulting in the low prevalence of leukemia development. [ABSTRACT FROM AUTHOR]

Epstein–Barr virus (EBV)‐associated gastric cancer (EBVaGC), whose prognosis remains controversial, is diagnosed by in situ hybridization of EBV‐derived EBER1/2 small RNAs. In The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) project, the EBV molecular subtype was determined through a combination of multiple next‐generation sequencing methods, but not by the gold standard in situ hybridization method. This leaves unanswered questions regarding the discordance of EBV positivity detected by different approaches and the threshold of sequencing reads. Therefore, we reanalyzed the TCGA‐STAD RNA sequencing (RNA‐seq) dataset including 375 tumor and 32 normal samples, using our analysis pipeline. We defined a reliable threshold for EBV‐derived next‐generation sequencing reads by mapping them to the EBV genome with three different random arbitrary alignments. We analyzed the prognostic impact of EBV status on the histopathological subtypes of gastric cancer. EBV‐positive cases identified by reanalysis comprised nearly half of the cases (49.6%) independent from infiltrating lymphocyte signatures, and showed significantly longer overall survival for adenocarcinomas of the 'not‐otherwise‐specified' type [P = 0.016 (log‐rank test); hazard ratios (HR): 0.476; 95% CI: 0.260–0.870, P = 0.016 (Cox univariate analysis)], but shorter overall survival for the tubular adenocarcinoma type [P = 0.005 (log‐rank test); HR: 3.329; 95% CI: 1.406–7.885, P = 0.006 (Cox univariate analysis)]. These results demonstrate that the EBV positivity rates were higher when determined by RNA‐seq than when determined by EBER1/2 in situ hybridization. The RNA‐seq‐based EBV positivity demonstrated distinct results for gastric cancer prognosis depending on the histopathological subtype, suggesting its potential to be used in clinical prognoses. [ABSTRACT FROM AUTHOR]

Abstract: Several studies have investigated the accuracy of cervical auscultation (CA). However, both the sensitivities and the specificities of CA in detecting dysphagic conditions varied widely among these studies. These wide variations of the accuracy of CA might be caused by differences of the targeted sounds, such as the expiratory sound (ES) and/or swallowing sound (SS). Forty‐six dysphagic patients were served as subjects. Patients who had unoccluded tracheostoma and patients who could not follow the instructions were excluded. During the videofluorographic swallowing study (VFSS), the subjects swallowed 3 ml of yogurt containing barium sulfate. The VFSS images were recorded with acoustic signals including both the swallowing and respiratory sounds detected by our method. Classification of the VFSS images was decided by consensus of the three dentists using a penetration‐aspiration scale (PAS). Recorded VFSS images were classified into the following 2 groups based on PAS: “no or minimum risk group”: PAS1–2; and “possible risk group”: PAS3–8. As a result of the classification of VFSS findings, 30 samples were evaluated as no or minimum risk group and 16 as possible risk group. Twelve observers including 10 dentists other than 3 dentists who evaluated VFSS images and 2 speech pathologists auditorily diagnosed “negative” and “positive.” Sensitivity, specificity, and intra‐rater reliability was calculated for the 3 types of acoustic samples. The sensitivity of the intra‐rater reliability was 60.3% for ES, 76.6% for SS, and 89.9% for ES + SS. The sensitivity of intra‐rater reliability of ES + SS samples was significantly higher than that of ES (p < .01) and SS (p < .05). The sensitivity of intra‐rater reliability of SS was significantly higher than that of ES (p < .01). The specificity of the intra‐rater reliability was 53.7% for ES, 50.3% for SS, and 44.5% for ES + SS. ES + SS might be most useful for detecting the presence of material in the airway. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes ( MDS) are defined as stem cell disorders caused by various gene abnormalities. Recent analysis using next-generation sequencing has provided great advances in identifying relationships between gene mutations and clinical phenotypes of MDS. Gene mutations affecting RNA splicing machinery, DNA methylation, histone modifications, transcription factors, signal transduction proteins and components of the cohesion complex participate in the pathogenesis and progression of MDS. Mutations in RNA splicing and DNA methylation occur early and are considered 'founding mutations', whereas others that occur later are regarded as 'subclonal mutations'. RUNX1 mutations are more likely to subclonal; however, they apparently play a pivotal role in familial MDS. These genetic findings may lead to future therapies for MDS. [ABSTRACT FROM AUTHOR]

Background and objective Obesity hypoventilation syndrome ( OHS) prevalence was previously estimated at 9% in patients with obstructive sleep apnoea ( OSA) in Japan. However, the definition of OSA in that study was based on an apnoea-hypopnoea index ( AHI) of ≥ 20/h rather than ≥ 5/h. Therefore, the prevalence of OHS in OSA was not measured in the same way as for Western countries. Our study objectives were to investigate the characteristics of Japanese patients with OHS. Methods Nine hundred eighty-one consecutive patients investigated for suspected OSA were enrolled. At least 90% of them were from urban areas, including 162 with obese OSA (body mass index ( BMI) ≥ 30 kg/m2 and AHI ≥ 5/h). Results The prevalence of OHS ( BMI 36.7 ± 4.9 kg/m2) in OSA and that in obese OSA were 2.3% and 12.3%, respectively. Multiple regression analysis revealed that independent of age and BMI, arterial oxygen pressure (contribution rate (R2) = 7.7%), 4% oxygen desaturation index (R2 = 8.9%), carbon monoxide diffusing capacity/alveolar volume (R2 = 8.3%), haemoglobin concentration (R2 = 4.9%) and waist circumference (R2 = 4.9%) were independently associated with arterial carbon dioxide pressure. After 12.3 ± 4.6 months of CPAP treatment, more than 60% of OHS patients no longer had hypercapnia. Conclusions The prevalence of OHS in OSA in Japan was 2.3%. The mean BMI of patients with OHS in Japan was lower than that in Western countries (36.7 kg/m2 vs 44.0 kg/m2). [ABSTRACT FROM AUTHOR]

Obstructive sleep apnoea is common in patients with diabetes. Recently, it was reported that short sleep duration and sleepiness had deleterious effects on glucose metabolism. Thereafter, several reports showed relationships between glucose metabolism and obstructive sleep apnoea, sleep duration or sleepiness. But the interrelationships among those factors based on recent epidemiological data have not been examined. We analysed data on 275 male employees (age, 44 ± 8 years; body mass index, 23.9 ± 3.1 kg m−2) who underwent a cross-sectional health examination in Japan. We measured fasting plasma glucose, sleep duration using a sleep diary and an actigraph for 7 days, and respiratory disturbance index with a type 3 portable monitor for two nights. Fifty-four subjects (19.6%) had impaired glucose metabolism, with 21 having diabetes. Of those 21 (body mass index, 25.9 ± 3.8 kg m−2), 17 (81.0%) had obstructive sleep apnoea (respiratory disturbance index ≥ 5). Regarding the severity of obstructive sleep apnoea, 10, four and three had mild, moderate and severe obstructive sleep apnoea, respectively. The prevalence of obstructive sleep apnoea was greater in those with than without diabetes ( P = 0.037). Multiple regression analyses showed that the respiratory disturbance index independently related to fasting plasma glucose only in the diabetic subjects. In patients with diabetes, after adjustment for age, waist circumference, etc. sleep fragmentation had a greater correlation with fasting plasma glucose than sleep duration, but without significance ( P = 0.10). Because the prevalence of obstructive sleep apnoea is extremely high in patients with diabetes, sufficient sleep duration with treatment for obstructive sleep apnoea, which ameliorates sleep fragmentation, might improve fasting plasma glucose. [ABSTRACT FROM AUTHOR]

The article offers information on the erythroid hypoplasia or aplasia which is a haematological condition observed in acquired pure red cell aplasia (PRCA) and aplastic anaemia. It discusses the pathogenic mechanisms of erythroid hypoplasia have not been fully elucidated, although T-lymphocyte-mediated inhibition of erythropoiesis which is considered as the most accurate mechanism of pathogenesis.

Summary Obstructive sleep apnoea (OSA) plays a significant role in increasing blood pressure. Significant decreases were reported in blood pressure of hypertensive OSA patients with sleepiness who underwent continuous positive airway pressure (CPAP) treatment, but not in non-sleepy hypertensive OSA patients. More recently, however, significant decreases in blood pressure in non-sleepy hypertensive OSA patients following CPAP were shown. Effects of sleepiness on hypertension in OSA patients have been investigated, but not the effects of hypertension on sleepiness in OSA patients. We investigated the relationships between hypertension and sleepiness in patients with OSA. We analysed data on 275 middle-aged male subjects from a cross-sectional epidemiological health survey. We measured blood pressure and sleep duration objectively using an actigraph for 7 days and the respiratory disturbance index (RDI) with a type 3 portable device for 2 nights, and assessed sleepiness using the Epworth Sleepiness Scale (ESS). The RDI correlated significantly with ESS scores in the 88 hypertensive subjects ( r = 0.33, P = 0.0024), but not in the 187 non-hypertensive subjects ( r = −0.01, P = 0.91). Short sleep duration correlated significantly with ESS scores in both groups. Both the RDI and short sleep duration were related independently to sleepiness in only hypertensive subjects. Furthermore, the RDI was related negatively significantly to sleep duration in hypertensive subjects. Although short sleep duration was related significantly to sleepiness in both groups, hypertension may be important for the sleepiness in OSA patients. Detailed mechanisms of the difference in the relationship between sleepiness and the severity of OSA with or without hypertension should be studied further. [ABSTRACT FROM AUTHOR]

Background and objective: Although non-invasive ventilation (NIV) has been shown to be effective in a wide variety of respiratory diseases, its role in severe asthma attacks remains uncertain. The aim of this study was to clarify the effectiveness of NIV in patients experiencing severe attacks of asthma. Methods: A retrospective cohort study was performed, comparing the periods November 1999–October 2003 (pre-introduction of NIV) and November 2004–October 2008 (post-introduction of NIV). The data and clinical outcomes for patients who experienced severe attacks of asthma, and who fulfilled the inclusion criteria, were retrieved and compared. Results: Fifty events (48 patients) from the pre-NIV period and 57 events (54 patients) from the post-NIV period, which required hospitalization, were included in the analysis. Nine of the 50 pre-NIV events (mean PaO2/fraction of inspired O2 (FiO2) 241 ± 161; PaCO2 79 ± 40) were treated primarily by endotracheal intubation (ETI), while 17 of the 57 post-NIV events (PaO2/FiO2 197 ± 132, P = 0.39; PaCO2 77 ± 30, P = 0.95) were treated primarily by NIV. The rate of ETI decreased in the post-NIV period (2/57 (3.5%) vs 9/50 (18%), P = 0.01). NIV was started earlier than mechanical ventilation (MV) with ETI (mean time interval between arrival and start of MV 171.7 ± 217.9 min vs 38.5 ± 113.8 min for NIV, P < 0.05). In the post-NIV cohort, there was a trend towards a reduction in the duration of MV with ETI or NIV (36.9 ± 38.4 h vs 20.3 ± 35.8 h, P = 0.09), and hospital stay was shortened (12.6 ± 4.2 vs 8.4 ± 2.8 days, P < 0.01). No deaths occurred during this period as a consequence of asthma attacks. Conclusions: The need for ETI in patients with severe attacks of asthma was decreased after introduction of NIV. The ready availability of NIV enabled the rapid commencement of MV and may decrease the need for ETI. NIV is an acceptable and useful method of stabilizing patients experiencing severe attacks of asthma. [ABSTRACT FROM AUTHOR]

AML1/RUNX1 point mutations have been identified in myelodysplastic syndrome (MDS) and MDS-related acute myeloid leukemia (AML), or MDS/AML, and are distributed throughout the full length of AML1/RUNX1. Gene mutation is proposed to be one of the disease-defining genetic abnormalities of MDS/AML. Most of the mutants lose trans-activation potential, which leads to a loss of normal function indicating that AML1/RUNX1 dysfunction is one of the major pathogenic mechanisms of MDS/AML. However, N-terminal in-frame mutations (Ni-type) and C-terminal truncated mutations (Ct-type) of AML1/RUNX1 show a dominant-negative effect on the trans-activation activity, suggesting that these types of mutants may have some oncogenic potential in addition to the loss of normal function. The patients with Ni-type mutations have hypoplastic marrows with other genetic abnormalities, whereas the patients with Ct-type mutations display hyperplastic marrows without other mutations. Although biological analysis using a mouse bone marrow transplantation model transduced with Ni-type of D171N or Ct-type of S291fsX300 mutants has partially confirmed the oncogenic ability of AML1 mutants, it could not explain the mutant specific clinical features of MDS/AML. Biological analysis using human CD34+ cells revealed that the two types exhibited distinct molecular mechanisms. Ni-type shows differentiation block without cell growth, but additional BMI-1-expression resulted in increased blastic cells. In contrast, Ct-type itself has proliferation ability. Thus, AML1/RUNX1 mutants play a central role in the pathogenesis of MDS/AML. Both AML1 mutants are initiating factors for MDS-genesis by inhibiting differentiation of hematopoietic stem cells, and Ni-type mutant requires acquisition of proliferation ability. J. Cell. Physiol. 220: 16–20, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]