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Objectives In myelodysplastic syndromes (MDS), neoplastic myeloblast (CD34+CD13+CD33+ cells) numbers often increase over time, leading to secondary acute myeloid leukemia (AML). In recent studies, blasts in some MDS patients have been found to express a megakaryocyte-lineage molecule, CD41, and such patients show extremely poor prognosis. This is the first study to evaluate whether myeloblasts transition to CD41+ blasts over time and to investigate the detailed immunophenotypic features of CD41+ blasts in MDS. Methods We performed a retrospective cohort study, in which time-dependent changes in blast immunophenotypes were analyzed using multidimensional flow cytometry (MDF) in 74 patients with MDS and AML (which progressed from MDS). Results CD41+ blasts (at least 20% of CD34+ blasts expressing CD41) were detected in 12 patients. In five of these 12 patients, blasts were CD41+ from the first MDF analysis. In the other seven patients, myeloblasts (CD34+CD33+CD41- cells) transitioned to megakaryoblasts (CD34+CD41+ cells) over time, which was often accompanied by disease progression (including leukemic transformation). These CD41+ patients were more frequently observed among patients with monosomal and complex karyotypes. CD41+ blasts were negative for the erythroid antigen, CD235a, and positive for CD33 in all cases, but CD33 expression levels were lower in three cases when compared with CD34+CD41- blasts. Among the five CD41+ patients who underwent extensive immunophenotyping, CD41+ blasts all expressed CD61, but two cases had reduced CD42b expression, three had reduced/absent CD13 expression, and three also expressed CD7. Conclusions Myeloblasts become megakaryoblastic over time in some MDS patients, and examining the megakaryocyte lineage (not only as a diagnostic work-up but also as follow-up) is needed to detect CD41+ MDS. The immunophenotypic features revealed in this study may have diagnostic relevance for CD41+ MDS patients.

Cow’s milk allergy (CMA) is one of the most common IgE-dependent food allergies in children. Some children develop severe and persistent CMA, with near-fatal reactions after exposure to trace amounts of cow’s milk (CM). Because milk and dairy products are included in various processed food products, it is difficult to completely remove milk, which negatively affects the quality of life of children with CMA. Oral immunotherapy (OIT) can alleviate food allergen-induced anaphylaxis under continuous ingestion of a little of the causative food. Children with severe CMA may benefit from OIT, but the treatment requires a long time and poses a risk of anaphylaxis. Moreover, in recent years, new therapies, including omalizumab, sublingual immunotherapy, and epicutaneous immunotherapy, have played the role of optional OIT. In this review, we present the current methods of and other attempts at OIT, and discuss OIT for safely treating CMA.

A series of 3 direct-type earthquakes with magnitude ≥6 occurred in the Kumamoto Prefecture, located in the western area of Japan, between April 14 and 16, 2016. Children with food allergies (FA) had difficulty procuring allergen-free meals during this period due to the infrastructure shutdown. We investigated the status of children with FA during the 2016 Kumamoto Earthquake and their behavioral changes after the disaster. We conducted a survey of the parents of 59 children with FA (median: 4 years and 1 month old) who were clinically followed up at our institution. They were questioned about their behavior change to allergen removal and using allergen-free foods during the disaster. Forty-seven (79.7%) children with FA were evacuated immediately after the earthquake and returned to their homes after the restoration of lifelines. Most stayed in their cars, while a few took shelter at public evacuation sites. Thirty-eight children (64.4%) had difficulty obtaining allergen-free food, and 29 children with FA (49.2%) did not have a stockpile at home. Thirty-three children with FA (55.9%) consumed allergen-free foods acquired primarily through relief supplies. Forty-seven guardians (79.7%) insisted that stockpiling allergy-friendly foods at home should be a part of future disaster planning. Stockpiles of allergen-free food were not sufficient in most households. Awareness of self-stockpiling allergen-free foods, reassessing public stockpiling, and establishing a system to provide information regarding relief supplies to evacuees outside evacuation centers are important for disaster planning in children with FA.

Background Oral food challenge (OFC) is the gold standard for diagnosing food allergies (FAs) but carries the risk of anaphylactic reaction. Stepwise OFC, starting with a low dose of allergen and progressing to medium and full doses, is effective in determining a tolerable dose. We retrospectively evaluated the results of a stepwise OFC for hen’s egg (HE) to demonstrate its safety and efficacy. We discuss whether early low-dose administration of HE induces early immune tolerance in HE allergy. Methods We included 2,058 children (median, 2.6 years) who underwent HE-OFC between 2017 and 2021 at two institutes in Japan. The target challenge dose of OFC was classified as low (less than 1/8 of a cooked egg), medium (1/8 or more but less than 1/2), or full (1/2 or more). If the low-dose OFC was negative, subjects were allowed to consume the same dose of HE and underwent medium-dose OFC within 12 months. Even if positive, individuals were recommended to consume previously-tolerated amounts of HE and repeat OFC at the same dose within 12 months. We evaluated the correlation between their OFC results and response. Results A total of 526 (25.6%) children presented positive reactions. There were no cases of anaphylactic shock. Higher serum egg white (EW)- (P < 0.001) and ovomucoid (OVM)- specific IgE (P < 0.001) (sIgE) levels were associated with positive OFC. The low-dose OFC group had more positive reactions ( P  < 0.001), younger children ( P  < 0.001), higher EW-sIgE ( P  < 0.001) and OVM-sIgE ( P  < 0.001), and more histories of anaphylaxis ( P  = 0.014). OFC-positive children were younger than OFC-negative children, particularly in low-dose OFC ( P  = 0.010). OFC results between complete and partial elimination of HE groups across all EW- or OVM-sIgE classes were similar ( P  > 0.05). Conclusions Stepwise OFC is safe and effective in diagnosing HE allergy and facilitates the earlier introduction of HE in children. This study suggests the limited potential of early consumption of lower doses of HE to induce earlier immune tolerance, such that other strategies to induce earlier tolerance in infants with HE allergy should be considered.

Background Cytomorphological examination and classification of bone marrow (BM) cells using a microscope is essential for diagnosing various diseases affecting the haematopoietic system. However, this requires expertise, is effort‐intensive and is inherently subjective. Methods We developed a method for automatically capturing BM cell images at the single‐cell level using an existing cell image analyser designed for peripheral blood. The captured BM cell images were pre‐classified by the same analyser and subsequently viewed on a large screen by cytomorphologists for BM cell classification. The data consistency in BM blast percentages between the digital and conventional optical microscopy (CM) methods was examined. Results During the 3.5‐year study period, 657 (96.2%) of the 683 aspirated samples underwent BM cell classification using the digital method. Digital cell images were captured at 2000× magnification and stored permanently, which allowed high‐quality cell image analysis at any time by anyone. Cell images could be compared side‐by‐side across different cell classes, which improves the cell‐classification accuracy. The detailed cell morphology in some cases differed slightly between the digital images and CM. BM blast percentage was comparable between the developed method and CM when examining patients with myelodysplastic syndromes (MDS) and other conditions that need to be differentiated from MDS. In a multicentre study, cytomorphologists who used this method for the first time could perform cell classification. Conclusion This machine‐assisted and human‐centred approach enhances objectivity in BM cell classification, aligns with the needs of the digital era and facilitates data sharing. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.

Background: The diagnosis of food allergy (FA) is made by oral food challenge tests (OFCs) that occasionally produce serious symptoms in patients; therefore, whether to perform OFCs should be carefully considered. The utility of the histamine release test (HRT) in the diagnosis of childhood FA has not been fully examined. Methods: Sixty-four subjects with suspected hen’s egg allergy, cow’s milk allergy (CMA), and wheat allergy (WA) were enrolled. The diagnosis of FA was made based on the outcomes of OFCs or a convincing history of symptoms after food ingestion within 6 months before or after sample collection. HRT was performed using an HRT Shionogi kit. The threshold of histamine release (HRT threshold), which was defined as the minimum concentration of food antigen to induce a 10% net histamine release, was analyzed in association with FA diagnosis. Results: Receiver operating characteristic analysis showed that the HRT threshold was useful in the diagnosis of heated egg allergy (HEA), raw egg allergy (REA), CMA, and WA. We were able to determine the cutoff value for the HRT threshold in relation to outcomes of OFCs. The cutoff value was 6 ng/ml of egg white antigen in HEA and REA (p < 0.01), 40 ng/ml of milk antigen in CMA (p < 0.01), and 500 ng/ml of wheat antigen in WA (p < 0.05). The efficiency was 70.3% for HEA, 78.0% for REA, 77.6% for CMA, and 70.7% for WA. Conclusions: We conclude that the HRT threshold measurement for egg white, milk, and wheat antigen is related to outcomes of OFCs and is useful in determining when OFCs should be performed.

In triple-negative breast cancer (TNBC), the clinicopathological significance of the expression of a second estrogen receptor, ERβ, remains unclear. Further, although the clinicopathological significance of mutant p53 and androgen receptor (AR) has been investigated in TNBC, they have not been established as therapeutic targets. Experimental studies reported the importance of cross-talk between ERβ and p53 or AR in TNBC. In this study, we immunohistochemically examined ERβ expression in surgical specimens of TNBC obtained from postmenopausal patients who underwent surgery without neoadjuvant therapy and investigated the relationship between ERβ expression and various clinicopathological factors, including clinical outcome, while also considering p53 and AR. No significant difference in clinical outcome was noted according to the ERβ status alone (p = 0.2908). However, the ERβ status did affect the relationship between the clinical outcome and p53 or AR status; p53-positive or AR-positive group exhibited significantly more favorable clinical outcomes than p53-negative or AR-negative group, respectively, in the ERβ-positive group (p53, p = 0.0265; AR, p = 0.0285), but not in the ERβ-negative group (p53, p = 0.7228; AR, p = 0.7734). This may be the result of a functional interaction between ERβ and p53 or AR. The role of ERβ in TNBC will be elucidated in further complex studies considering multiple molecules.