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Responsive liquid marbles (LMs), which can change their shape, stability, and motion by the application of stimuli, attract a growing interest due to their wide range of applications. Our approach to design photo- and thermoresponsive LMs is based on the use of micrometer-sized fatty acid (FA) particles as phase change material covered with polypyrrole (PPy) overlayers with photothermal property. The core-shell particles were synthesized by aqueous chemical oxidative seeded dispersion polymerization. First, we investigated the effect of the alkyl chain length of FA on the resulting FA/PPy core-shell particles by characterizing their size and its distribution, shape, morphology, chemical composition, and photothermal behavior. Then LMs were fabricated by rolling water droplets on the dried FA/PPy particle powder bed and their light and temperature dual stimuli-responsive nature was studied as a function of the FA alkyl chain length. For all FAs studied, LMs disrupted in a domino manner by light irradiation as the first trigger: the temperature of the FA/PPy particles on the LM surface increased by light irradiation, followed by phase change of FA core of the particles from solid to liquid, resulting in disruption of the LM and release of the encapsulated water. The disruption time was closely correlated to the melting point of FA linked to the alkyl chain length and light irradiation power, and it could be controlled and tuned easily between quasi instantaneous and approximately 10 s. Finally, we showed potential applications of the LMs as a carrier for controlled delivery and release of substances and a sensor.

Western countries that were first to administer the COVID-19 vaccination report cases of vaccine-induced axillary lymphadenitis with high FDG uptake. However, no such findings have been reported from any Asian countries. We report here a confusing case of a 31-year-old female cancer survivor with high FDG uptake in her axillary lymph nodes, suggesting recurrence, following mRNA COVID-19 vaccination. Although the value of SUVmax was elevated (12.7), additional imaging revealed that her lymphatic lesions were benign, and they resolved spontaneously. This case of a strong immune reaction to COVID-19 vaccination in regional lymph nodes is the first reported in a Japanese patient. We should be aware of this new mimic and optimize diagnostic imaging methods accordingly in the era of COVID-19.

Acute promyelocytic leukemia (APL) is rare in patients with Down syndrome (DS). Cytotoxic chemotherapy combined with all-trans retinoic acid (ATRA) has been a standard treatment for APL, but is potentially intolerable for DS patients because of their vulnerability to cytotoxic agents. We report here a case of a 10-year-old girl with DS and APL successfully treated with a combination of ATRA and arsenic trioxide, a therapy emerging as a new standard for APL. She achieved molecular remission and completed the therapy without significant toxicities. ATRA/arsenic trioxide combination therapy would be a preferable option for DS patients with APL.

Recently, whole-exome sequencing (WES) has been used for genetic diagnoses of patients who remain otherwise undiagnosed. WES was performed in 177 Japanese patients with undiagnosed conditions who were referred to the Tokai regional branch of the Initiative on Rare and Undiagnosed Diseases (IRUD) (TOKAI-IRUD). This study included only patients who had not previously received genome-wide testing. Review meetings with specialists in various medical fields were held to evaluate the genetic diagnosis in each case, which was based on the guidelines of the American College of Medical Genetics and Genomics. WES identified diagnostic single-nucleotide variants in 66 patients and copy number variants (CNVs) in 11 patients. Additionally, a patient was diagnosed with Angelman syndrome with a complex clinical phenotype upon detection of a paternally derived uniparental disomy (UPD) [upd(15)pat] wherein the patient carried a homozygous DUOX2 p.E520D variant in the UPD region. Functional analysis confirmed that this DUOX2 variant was a loss-of-function missense substitution and the primary cause of congenital hypothyroidism. A significantly higher proportion of genetic diagnoses was achieved compared to previous reports (44%, 78/177 vs. 24–35%, respectively), probably due to detailed discussions and the higher rate of CNV detection.

Various treatments have been used to treat chronic immune thrombocytopenic purpura in children; however, none of it has been established as the standard of care. The administration of thrombopoietin receptor agonists (TPO-RAs) has been approved as a new treatment option in Japan. In this case series, TPO-RAs were administered to 16 patients (eltrombopag, n=9; romiplostim, n=7). Excluding the data of two patients who underwent splenectomy immediately after starting treatment with these medicines, platelet counts increased to ≥50,000/µl in seven patients. The adverse events recorded were grade 2 liver dysfunction (n=1), according to the common terminology criteria for adverse events version 4, and myelofibrosis (classified as MF1 or mild reticulin fibrosis), as observed on bone marrow biopsy (n=2). We continued the administration of TPO-RAs at the same dose in these patients because the complications they experienced were mild. The risk of adverse events associated with long-term use of TPO-RAs in this pediatric population remains unclear, and a prospective evaluation is needed.

Acquired aplastic anemia (AA) is a life-threatening bone marrow aplasia caused by the autoimmune destruction of hematopoietic stem and progenitor cells. There are no existing diagnostic tests that definitively establish AA, and diagnosis is currently made via systematic exclusion of various alternative etiologies, including inherited bone marrow failure syndromes (IBMFSs). The exclusion of IBMFSs, which requires syndrome-specific functional and genetic testing, can substantially delay treatment. AA and IBMFSs can have mimicking clinical presentations, and their distinction has significant implications for treatment and family planning, making accurate and prompt diagnosis imperative to optimal patient outcomes. We hypothesized that AA could be distinguished from IBMFSs using 3 laboratory findings specific to the autoimmune pathogenesis of AA: paroxysmal nocturnal hemoglobinuria (PNH) clones, copy-number–neutral loss of heterozygosity in chromosome arm 6p (6p CN-LOH), and clonal T-cell receptor (TCR) γ gene (TRG) rearrangement. To test our hypothesis, we determined the prevalence of PNH, acquired 6p CN-LOH, and clonal TRG rearrangement in 454 consecutive pediatric and adult patients diagnosed with AA, IBMFSs, and other hematologic diseases. Our results indicated that PNH and acquired 6p CN-LOH clones encompassing HLA genes have ∽100% positive predictive value for AA, and they can facilitate diagnosis in approximately one-half of AA patients. In contrast, clonal TRG rearrangement is not specific for AA. Our analysis demonstrates that PNH and 6p CN-LOH clones effectively distinguish AA from IBMFSs, and both measures should be incorporated early in the diagnostic evaluation of suspected AA using the included Bayesian nomogram to inform clinical application.

Emicizumab reduces bleeding in patients with hemophilia A and inhibitors (PwHA-I). Coagulation potential during the perioperative period in emicizumab-treated PwHA-I undergoing surgery remains to be evaluated. We describe a 14-year-old boy with HA-I receiving emicizumab prophylaxis who experienced arthroscopic synovectomy. He was treated with a bolus infusion of recombinant factor VIIa (rFVIIa; 80 μg/kg) immediately before surgery, and treatment continued at the same dose every 3 h on day 1, every 4 h on day 2, and every 6 h on day 3. Treatment with rFVIIa was discontinued on day 4. No perioperative bleeding or thrombotic events were observed. Coagulation potential throughout the perioperative period was retrospectively assessed with an easy-to-use clot waveform analysis (CWA). Measurements from CWA returned to within or near the normal range, suggesting successful hemostatic management. Coagulation potentials assessed by CWA showed a significant correspondence with those from a thrombin generation assay (TGA) that is already in use. CWA and TGA could both provide useful data for assessing coagulation potential in the perioperative hemostatic management of emicizumab-treated PwHA-I.

Gilteritinib is an FMS-like tyrosine kinase 3 (FLT3) inhibitor that has shown efficacy in patients with refractory or recurrent adult acute myeloid leukemia (AML) with FLT3 mutations. However, there are limited data for pediatric patients treated with this drug. Herein, we report the clinical courses of two children with FLT3-mutated recurrent AML who received gilteritinib. Case 1: An 11-year-old boy with secondary relapsed AML presented with an FLT3 internal tandem duplication (ITD) since the first recurrence. One week after gilteritinib initiation, blasts, which had comprised 90% of the white blood cells before treatment, almost disappeared from the peripheral blood without tumor lysis syndrome. The patient developed multiple adverse effects and died from the disease 2.5 months after gilteritinib initiation. Case 2: A 12-year-old girl diagnosed with AML was positive for FLT3 ITD. She received gilteritinib during her first relapse post-stem cell transplantation. After the drug was administered, the recipient cell counts increased, as determined by molecular tests (i.e., FISH), whereas microscopically, there was a complete response for 5 months with good performance status. Gilteritinib treatment in children with FLT3-mutated recurrent AML is feasible and effective. As a patient experienced several adverse effects with gilteritinib treatment, clinical trials are required to determine the appropriate pediatric dose of this medication.

Kawasaki disease (KD), an acute childhood panvasculitis, presents a variety of ocular complications as well as conjunctival injection among the principal symptoms. However, most pediatricians are unfamiliar with the ophthalmological complications of KD. A 2-year-old girl was referred to us from the ophthalmology department due to injected bulbar conjunctivae and optic disc swelling. She had familial exudative vitreoretinopathy as an underlying disease and the ocular findings had been made by chance while the patient was receiving an eye examination. Although she was afebrile at the time of her first medical interview, KD was diagnosed based on the presence of four of the principal symptoms including fever and dilatation of the coronary arteries. Intravenous immunoglobulin (IVIG) therapy was administered on Day 15 from the onset of fever. After IVIG administration, her laboratory test results showed rapid improvement but her optic disc swelling continued for six months. Eye complications in KD generally occur in the anterior segment, and recovery occurs within two months. Past reports have shown that in three of seven KD cases with optic disc involvement, optic disc swelling lasted over two months. This is the second case in which the condition lasted six months.

Dormant compound buds of grapevines adapt to subfreezing temperatures through a freezing avoidance mechanism. One still-unclear question, however, is whether supercooled water in primordial cells of dormant grape buds are partially dehydrated under subfreezing temperatures. In this study, we used differential thermal analysis (DTA) and cryo-scanning electron microscopy (cryo-SEM) to look for partial dehydration of primordial cells of the freezing-resistant interspecific hybrid cultivar 'Yamasachi'. According to DTA, the freezing temperature of supercooled water in primary buds was not significantly affected by cooling rates between 2 and 5 °C/h; however, maintaining the bud temperature at -15 °C for 12 h followed by cooling at a rate of 5 °C/h depressed the freezing temperature. As revealed by cryo-SEM observation, many wrinkles were present on inner surfaces of walls and outer surfaces of plasma membranes of leaf primordial cells in dormant buds frozen to -15 °C. These results suggest the existence of partial dehydration in dormant-bud primordial cells under subfreezing temperatures. The apparent absence of extracellular ice crystals in bud primordial tissues under subfreezing temperatures suggests that Yamasachi dormant buds adapt to subfreezing temperatures by extraorgan freezing. When we coated primary buds with silicone oil to inhibit freeze dehydration of primordial cells, the freezing temperature of buds was slightly but significantly increased. This result suggests that the partial dehydration of cells promotes bud supercooling capability and has an important role in the freezing adaptation mechanism of grapevines.

Medulloblastoma is one of the most common malignant brain tumors in children. Despite multi-disciplinary treatment for medulloblastoma, including surgery, chemotherapy, and radiation, which have resulted in significant improvement of the prognosis, about 30% of patients still experience recurrence. Most recurrences occur within the first 15 months from diagnosis and late relapse of the tumor is quite rare. We report a case of a 15-year-old female patient with recurrent medulloblastoma 9 years after the primary tumor. At the age of 6, this patient developed a posterior fossa tumor without metastasis and underwent near-total resection. The pathological diagnosis was medulloblastoma with focal desmoplasia. After the surgery, she received multi-agent chemotherapy and radiation therapy consisting of 18 Gy craniospinal irradiation and 51.2 Gy local irradiation. She was in complete remission for 9 years after the treatment. However, gait disturbance began to gradually appear, and magnetic resonance imaging (MRI) showed an intradural lesion in her thoracic spine. The lesion was biopsied, and the pathological findings confirmed the recurrence of medulloblastoma. Currently, we plan to administer local radiation therapy concomitantly with temozolomide to the patient. The case reminds us of the importance of long-term careful follow-up of patients with medulloblastoma. Further studies are warranted for the treatment of relapsed medulloblastomas due to the limited information available at present.

Severe protein C (PC) deficiency leads to purpura fulminans and stroke in newborns. However, the clinical impact of plasma PC activity on the development of neonatal cerebral disease remains elusive. We report a case of hemorrhagic stroke associated with neonatal asphyxia and severe PC deficiency. Plasma PC and protein S activity 7 days after birth was 12% and 43%, respectively. No PROC mutation was found. PC levels did not exceed 20% until 2 months of age, even in the absence of consumption coagulopathy or vitamin K deficiency. Neither thromboembolic nor hemorrhagic events occurred during the infusion of activated PC concentrate (twice weekly, up to 68 days after birth). The PC activity levels gradually increased to the standard value for age by 9 months of age. The present case showed that neonatal PC deficiency without a PROC mutation caused an intracranial hemorrhage before a slow increase in PC activity.