Successful Pregnancy and Delivery After Frozen-thawed Embryo Transfer Following the Third Discontinuation of Tyrosine Kinase Inhibitor in a Woman with Chronic Myeloid Leukemia.

Assisted reproductive technology is a viable option for pregnant women with chronic myeloid leukemia. We herein report the case of a patient who underwent successful fertility treatment with frozen embryo preservation at 36 years of age, followed by embryo transfer at 39 years of age, thus resulting in pregnancy and delivery after a third discontinuation of tyrosine kinase inhibitors (TKI). Despite the difficulty of long-term TKI withdrawal, the patient's strong desire for a baby led to a successful pregnancy and delivery with no apparent deformities or abnormalities. Thus, our case highlights the importance of collaboration between reproductive medicine physicians and hematologists.

Comparison of standardized prophylactic high-dose and intrathecal methotrexate for DLBCL with a high risk of CNS relapse.

The efficacy of high-dose methotrexate (HD-MTX) for central nervous system (CNS) relapse prophylaxis in patients with high-risk diffuse large B-cell lymphoma (DLBCL) is controversial. We compared the prophylactic effects of HD-MTX and intrathecal methotrexate (IT-MTX) on CNS relapse in high-risk DLBCL, in a multicenter retrospective study. A total of 132 patients with DLBCL at high risk of CNS relapse who received frontline chemotherapy and IT-MTX from 2003 to 2013 (n = 34) or HD-MTX from 2014 to 2020 (n = 98) were included. After a median follow-up of 52 months (range: 9-174), 11 patients had isolated CNS relapse: six (6.1%) in the HD-MTX group and five (14.7%) in the IT-MTX group. The median time until CNS relapse was 38 months (range: 11-122), and the cumulative incidence of CNS relapse at 3 years was 3.9% in the HD-MTX group and 6.1% in the IT-MTX group (P = 0.93). Similar results were obtained after adjusting for background factors using propensity score-matched analysis (4.5% HD-MTX vs. 7.6% IT-MTX, P = 0.84). The CNS relapse rate in HD-MTX-treated patients was equivalent to that in IT-MTX patients, demonstrating that HD-MTX was not superior to IT-MTX in preventing CNS relapse.

Prognostic significance of the CFA ratio for newly diagnosed acute myeloid leukemia: A multicenter retrospective study.

The CFA ratio, calculated using pretreatment C-reactive protein (CRP), fibrinogen, and albumin levels (CRP × fibrinogen/albumin), was previously reported to be a significant prognostic factor for acute myeloid leukemia (AML). This multicenter retrospective study evaluated the prognostic value of the CFA ratio in 328 adult patients with newly diagnosed AML from April 2000 to March 2018. The median age was 49.5 years (range, 15-75 years), and 60.7% of the population were males. According to the European LeukemiaNet (ELN) risk classification, 67 patients (20.4%) were in the favorable-risk group, 197 patients (60.1%) in the intermediate-risk group, and 58 patients (17.7%) in the adverse-risk group. The median CFA ratio was 1.07 (0-67.69). Based on the calculated cutoff CFA ratio of 1.44, the cohort included 176 and 152 patients with low and high CFA ratios, respectively. At a median follow-up of 91.2 months, the 7-year overall survival (OS) and disease-free survival (DFS) rates were 51.2% and 48.6%, respectively, in the overall cohort. The 7-year OS rates were 61.7% and 39.0% in the low and high CFA ratio groups, respectively (p < 0.001). The 7-year DFS rates were 58.1% and 37.0% in the low and high CFA ratio groups, respectively (p = 0.004). In univariate analysis, age ≥50 years, male sex, ELN risk class, and comorbidities were associated with poor OS. Age, ELN risk class, comorbidities, and high CFA ratio were associated with poor OS in multivariate analysis. Subgroup analysis revealed that the CFA ratio was significant in the intermediate and adverse ELN risk classes. These findings indicate the prognostic significance of the CFA ratio in AML.

[Primary mediastinal large B-cell lymphoma complicated with myotonic dystrophy].

A 39-year-old woman with myotonic dystrophy (DM) presented with syncope and was diagnosed with primary mediastinal large B-cell lymphoma, clinical stage IA. PET-CT revealed an upper mediastinal mass with high FDG uptake (SUVmax, 14.8). She had muscle weakness associated with DM, but her performance status was preserved. She was treated with 6 cycles of dose-adjusted EPOCH-R therapy and localized irradiation for the residual mass, without severe adverse events or recurrence of syncope. Patients with DM should be monitored for cardiac events and muscle weakness when undergoing lymphoma treatment.

[Diffuse large B-cell lymphoma complicated with pancreatic fistula and peritonitis following initial chemotherapy].

A 59-year-old-woman complained of weight loss and abdominal pain. A CT scan revealed a 20 cm large retroperitoneal mass, and she was diagnosed with diffuse large B-cell lymphoma via biopsy of the mass. After 75% CHP therapy, she developed an acute abdomen and CT revealed generalized peritonitis. Amylase in the ascites fluid was elevated, and infiltration into the pancreas was suspected on CT before treatment, suggesting a pancreatic fistula caused by tumor shrinkage. Enterobacteria were found in ascites fluid culture, suggesting a gastrointestinal perforation complication. The patient was refractory to treatment, and death was confirmed due to progression of the primary disease. The pathological autopsy revealed diffuse pancreatic infiltration, suggesting that the pancreatic fistula was caused by pancreatic injury. Pancreatic fistula is a known complication of surgical procedures but is rarely caused by tumor shrinkage due to chemotherapy. Since there is no preventive method for pancreatic injury caused by tumor shrinkage, early diagnosis and early treatment of pancreatic fistula are critical, and ascites fluid analysis, including amylase, was thought to be useful for the diagnosis.

[Immune thrombocytopenia after BNT162b2 mRNA COVID-19 vaccination].

Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic until today, but treatment options remain limited. COVID-19 vaccination is expected to decrease the number of patients with COVID-19 worldwide. In Japan, two types of mRNA COVID-19 vaccine, BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna), have been approved and administered. However, their side effects remain poorly elucidated. This paper presents two cases of immune thrombocytopenia (ITP) after BNT162b2 mRNA COVID-19 vaccination. Whether or not ITP is triggered by the vaccination or not is difficult to identify. Further investigation with a large number of cases is warranted to clarify the side effects of BNT162b2 mRNA COVID-19 vaccination.

The prognostic value of the Fibrinogen-Albumin Ratio Index in patients with myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes treated with azacitidine.

Inflammation is a major hallmark of several cancers. The present study evaluated the prognostic value of the Fibrinogen-Albumin Ratio Index (FARI) at the diagnosis in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) treated with azacitidine (AZA). A retrospective study was conducted in a single cohort of 99 patients with de novo MDS and AML-MRC who were treated with AZA between May 2011 and June 2019 in our hospital. Plasma fibrinogen and serum albumin levels were measured before the start of AZA treatment. A total of 99 patients were included in the analysis. The optimal cut-off value of FARI for predicting the 1-year overall survival (OS) was determined by a receiver operating characteristic (ROC) analysis to be 0.079. A total of 59 (60%) and 40 (40%) patients had an FARI ≥0.079 (high-FARI group) and < 0.079 (low-FARI group), respectively. The high-FARI patients had a significantly shorter OS than low-FARI patients (1-year OS, 35.6% vs. 77.5%, p < 0.001). In a multivariate analysis, parameters with independent adverse significance for the OS were a high FARI (≥0.079) (hazard ratio (HR) 2.41, 95% confidence interval (CI), 1.36-4.29; p = 0.006), and Revised-International Prognostic Scoring System (IPSS-R) very high (HR 1.483, 95% CI, 1.12-1.963, p = 0.006). A high FARI was found to be associated with a poor outcome in MDS and AML-MRC patients treated with AZA, and FARI was an independent prognostic factor for the OS in these patients. Further internal and external validations are needed to clarify the prognostic role of the FARI for MDS and AML-MRC patients.

Prognostic Impact of ABO Blood Group on Survival in Patients With Malignant Lymphoma.

BACKGROUND: The ABO blood group is reported to be associated with survival for several types of malignancy. We conducted a retrospective study to evaluate the prognostic significance of the ABO blood group in patients with malignant lymphoma. PATIENTS AND METHODS: A total of 523 patients with malignant lymphoma were included in this study. The primary outcome measured was the association between the ABO blood group and survival. RESULTS: Patients with blood group B had shorter 5-year overall survival (OS) than patients with non-B blood groups (40.9% vs. 57.3%; P < .01). Among 240 patients with diffuse large B-cell lymphoma (DLBCL), patients with blood group B had shorter 5-year OS in comparison with patients with non-B blood groups (36.3% vs. 56.9%; P < .01). Among male patients with DLBCL, those with blood group B had significantly shorter 5-year OS than those with non-B blood groups (27.5% vs. 55.8%; P = .003). On the other hand, there was no significant difference in the survival between female patients with blood group B and those with non-B blood groups (5-year OS: 49.2% vs. 58.2%; P = .67). A multivariate analysis demonstrated that blood group B (hazard ratio, 1.83; 95% confidence interval, 1.21-2.78; P = .04) was an independent predictor of shorter OS in male patients with DLBCL. CONCLUSION: The ABO blood group is associated with survival in patients with lymphoma. Interestingly, only male patients with DLBCL with blood group B had significantly shorter OS than those male patients with DLBCL with non-B blood groups.

Assessment of genetic diversity and genetic structure of wild rice populations in Myanmar.

To evaluate genetic diversity and genetic structure of wild rice (Oryza rufipogon) populations in Myanmar, seven research sites were selected based on various ecological conditions. A large number of samples under natural growth conditions were collected and studied using six simple sequence repeats (SSRs) and two chloroplast DNA markers. A total of 77 alleles were detected from 1559 samples over six SSR loci. The mean number of alleles per population ranged from 3.167 to 8.667, and the mean expected heterozygosity ranged from 0.140 to 0.701. Wild rice populations survived under various environmental conditions and retained different levels of genetic diversity. The large number of samples was effective to confirm the spatial genetic structure of wild rice populations in a relatively small area. Regarding chloroplast DNA polymorphisms, four populations possessed only one pattern, while the other three showed two or five combinations of haplotypes, even within the same population. Additionally, the existence of a new genotype was revealed. Considerable variations in chloroplast DNA exist in the wild rice populations of Myanmar. A high proportion of genetic variation was detected within, rather than among, populations. To ensure maintenance of allelic diversity, it is advisable to preserve many individuals from a large population.

Factors relating to the feeling of school avoidance among elementary school children: Results from the MEXT (Ministry of Education, Culture, Sports, Science and Education) Super Shokuiku School Project.

Purpose　This study aims to evaluate whether lifestyle factors including media use and social and family environments are associated with elementary school children's feeling of school avoidance.Methods　Total study population for this study was 2,057 children in 5 elementary schools in Takaoka city, Toyama prefecture, which participated in the MEXT Super Shokuiku School Project. A questionnaire survey was conducted in July 2014 and 1,936 students responded (Response rate: 94.1%). Of those who responded, data from 1,698 respondents were relevant for this study. The questionnaire included questions on lifestyle factors (e.g., eating habits, media use, exercise habits, and sleep), health status, and the social and family environments. Children responded to questions on lifestyle factors, health status, and feeling of school avoidance with their parents. Parents were asked to only respond to the questions on social and family environments. Logistic regression analysis was performed to evaluate whether the feeling of avoiding school, as the dependent variable, is associated with the independent variables such as social and family environment factors and lifestyle factors. The odds ratios (OR) and their 95% confidence intervals (95%CI) were calculated.Results　The percentage of children who had the feeling of avoiding school was 32.2% in the study sample. In comparison with the 6th graders, the 1st, 3rd, 4th, and 5th graders were more likely to have this feeling. Relevant adjusted ORs [95%CI] for Grades 1-5 were found to be 1.48 [1.02-2.13], 1.63 [1.10-2.42], 1.60 [1.08-2.39], and 1.56 [1.03-2.35], respectively. Other factors positively correlated with this feeling were skipping breakfast (OR 1.76, 95%CI [1.12-2.75]), daily snacking (OR 1.64, 95%CI [1.21-2.22]), watching TV for 3 hours or longer (OR 1.55, 95%CI [1.05-2.28]), video gaming for 0.5-2 hours (OR 1.37, 95%CI [1.08-1.74]), feeling sleepy (OR 1.51, 95%CI [1.14-1.99]), not feeling well upon waking up (OR 1.64, 95%CI [1.30-2.06]), being unsatisfied with their own health (OR 1.43, 95%CI [1.10-1.87]), and dislike for playing outside (OR 1.62, 95%CI [1.05-2.52]).Conclusions　This study showed that feeling of school avoidance was significantly correlated with several lifestyle factors. School health activities aiming at establishing desirable lifestyles for children could reduce the number of children who have the feeling of school avoidance.

Inconsistent diversities between nuclear and plastid genomes of AA genome species in the genus Oryza.

AA genome species in the genus Oryza are valuable resources for improvement of cultivated rice. Oryza rufipogon and O. barthii were progenitors of two domesticated rice species, O. sativa and O. glaberrima, respectively. We used chloroplast single-nucleotide repeats (RCt1-10) to evaluate genetic diversity among AA genome species. Higher diversity was detected in the American species O. glumaepatula and the Asian species O. rufipogon. Other chloroplast sequences indicated that O. glumaepatula shares high similarity with O. longistaminata. Insertions of retrotransposable elements, however, showed a close relation between O. barthii and O. glumaepatula. To clarify phylogenetic relationships among AA genomes, whole-genome sequences obtained from different species were used to develop chloroplast INDEL markers. The INDEL patterns clearly showed multiple maternal origins of O. glumaepatula. The complicated origins have resulted in high genetic diversity in this species. In contrast, the Australian endemic species O. meridionalis tended to show narrower diversity than the other species. High variation in O. rufipogon, reconfirmed using the chloroplast INDELs, covered the variation in O. meridionalis and part of the variation in O. glumaepatula. Maternal lineages including O. barthii, O. longistaminata and the remainder of O. glumaepatula were phylogenetically close to each other and carried low genetic diversity. They were separated from independent lineages, suggesting that they had diverged from a single ancestral maternal lineage, but diverged later to keep gene flow within respective species, as SSR compositions suggested. Genetic relationships among AA genome species indicate how these species have evolved and become distributed across four continents.

Ethylene is not involved in adaptive responses to flooding in the Amazonian wild rice species Oryza grandiglumis.

The Amazonian wild rice Oryza grandiglumis has two contrasting adaptation mechanisms to flooding submergence: a quiescence response to complete submergence at the seedling stage and an escape response based on internodal elongation to partial submergence at the mature stage. We investigated possible factors that trigger these responses. In stem segments excised from mature O. grandiglumis plants, complete submergence only slightly promoted internodal elongation with increased ethylene levels in the internodes, while partial submergence substantially promoted internodal elongation without increased ethylene levels in the internodes. Incubation of non-submerged stem segments under a continuous flow of humidified ethylene-free air promoted internodal elongation to the same extent as that observed for partially submerged segments. Applied ethylene had little effect on the internodal elongation of non-submerged segments irrespective of humidity conditions. These results indicate that the enhanced internodal elongation of submerged O. grandiglumis plants is not triggered by ethylene accumulated during submergence but by the moist surroundings provided by submergence. The growth of shoots in O. grandiglumis seedlings was not promoted by ethylene or complete submergence, as is the case in O. sativa cultivars possessing the submergence-tolerant gene SUB1A. However, because the genome of O. grandiglumis lacks the SUB1A gene, the quiescence response of O. grandiglumis seedlings to complete submergence may be regulated by a mechanism distinct from that involved in the response of submergence-tolerant O. sativa cultivars.

Evaluation of genetic variation among wild rice populations in Cambodia.

A total of 448 samples in five natural populations of wild rice (Oryza rufipogon) were collected in Cambodia. They were examined using 12 SSR and two chloroplast markers to evaluate the degree of variation among populations and the genetic structure within populations. In the two annual populations, the number of plants with homozygous alleles at all 12 SSR loci were high (66.3% and 79.5%), suggesting that these plants propagate mainly through self-pollination. In the three perennial populations, no individuals had all homozygous genotypes, but redundant genotypes resulted from clonal propagation were observed. Percentages of the redundant genotypes were highly varied (3.6%, 29.2% and 86.0%). This may be due to the different stable levels of environmental conditions. As for chloroplast genome, most of the wild plants showed the same chloroplast types as most Indica-type cultivars have. However, plants with different chloroplast types were maintained, even in the same population. In tropical Asian countries, many wild rice populations were observed under similar ecological conditions examined in this study. Therefore, the present results concerning population structure will be important to further elucidate genetic features of wild rice, and will also give strong clues to utilize and conserve wild natural genetic resources.

Growth promotion and inhibition of the Amazonian wild rice species Oryza grandiglumis to survive flooding.

In Asian cultivated rice (Oryza sativa), distinct mechanisms to survive flooding are activated in two groups of varieties. Submergence-tolerant rice varieties possessing the SUBMERGENCE1A (SUB1A) gene display reduced growth during flash floods at the seedling stage and resume growth after the flood recedes, whereas deepwater rice varieties possessing the SNORKEL1 (SK1) and SNORKEL2 (SK2) genes display enhanced growth based on internodal elongation during prolonged submergence at the mature stage. In this study, we investigated the occurrence of these growth responses to submergence in the wild rice species Oryza grandiglumis, which is native to the Amazon floodplains. When subjected to gradual submergence, adult plants of O. grandiglumis accessions showed enhanced internodal elongation with rising water level and their growth response closely resembled that of deepwater varieties of O. sativa with high floating capacity. On the other hand, when subjected to complete submergence, seedlings of O. grandiglumis accessions displayed reduced shoot growth and resumed normal growth after desubmergence, similar to the response of submergence-tolerant varieties of O. sativa. Neither SUB1A nor the SK genes were detected in the O. grandiglumis accessions. These results indicate that the O. grandiglumis accessions are capable of adapting successfully to flooding by activating two contrasting mechanisms as the situation demands and that each mechanism of adaptation to flooding is not mediated by SUB1A or the SK genes.

Superficial temporal arteriovenous fistula as a complication of rhytidectomy.

A 67-year-old woman who had undergone rhytidectomy 5 years before her presentation experienced increasing pulsatile tinnitus on the left side that had begun 2 years earlier. Angiography revealed a direct arteriovenous fistula between the superficial temporal artery and superficial temporal vein in front of her left ear. There was a scar from the earlier cosmetic surgery at the site. The fistula was embolized with N-butyl cyanoacrylate, and her tinnitus disappeared. We posit that the fistula was a complication of rhytidectomy and that a small arteriovenous fistula formed at the time of surgery and enlarged over time. This case indicates that arteriovenous fistulae can occur as a delayed complication of cosmetic surgery.

Identification and characterization of Australian wild rice strains of Oryza meridionalis and Oryza rufipogon by SINE insertion polymorphism.

Of the rice species with an AA genome, Oryza meridionalis has been identified in northern Australia as a species of the annual type, among those previously classified as Oryza perennis, Oryza rufipogon or Oryza nivara. This notion has, however, led to some confusion to determine which strains belong to O. meridionalis and how different these strains are from the O. rufipogon strains of the annual type. In this paper, we examined Australian wild rice strains for the presence or absence of p-SINE1 members, which have been used for identification of the strains of species with the AA genome, by PCR using primers that hybridize to the sequences flanking each p-SINE1 member. The rice strains examined include perennial and annual strains, which have previously been described as O. rufipogon. We found that all the annual strains and other strains, whose types have not been determined, have p-SINE1 members that are specifically present at the corresponding loci in the standard strains of O. meridionalis, but do not have those which are specifically present at the corresponding loci in the strains of the other species with the AA genome. The perennial strains, however, have p-SINE1 members that are specifically present at the corresponding loci in the standard O. rufipogon strains of either the annual or the perennial type, but do not have those which are specifically present at the corresponding loci in the strains of the other species with the AA genome, including O. meridionalis. These findings support the previous notion that O. meridionalis consists of the annual strains and is a distinct species from O. rufipogon. The p-SINE1 members used in this study appear to be very useful for classification of any wild rice strains of the AA-genome species, even when one has limited knowledge of morphology, taxonomy, physiology, and biochemistry of rice strains.