Syndecan-1 as a prognostic biomarker in COVID-19 patients: a retrospective study of a Japanese cohort.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact, with millions of confirmed cases and deaths worldwide. While most cases are mild, a subset progresses to severe respiratory complications and death, with factors such as thromboembolism, age, and underlying health conditions increasing the risk. Vascular endothelial damage has been implicated in severe outcomes, but specific biomarkers remain elusive. This study investigated syndecan-1 (SDC-1), a marker of endothelial damage, as a potential prognostic factor for COVID-19, focusing on the Japanese population, which is known for its aging demographics and high prevalence of comorbidities. METHODS: A multicenter retrospective study of COVID-19 patients in Fukushima Prefecture in Japan who were admitted between February 2020 and August 2021 was conducted. SDC-1 levels were measured along with other clinical and laboratory parameters. Outcomes including thrombosis, 28-day survival, and disease severity were assessed, and disease severity was categorized according to established guidelines. RESULTS: SDC-1 levels were correlated with disease severity. Patients who died from COVID-19 had greater SDC-1 levels than survivors, and the area under the receiver operating characteristic curve (AUC) analysis suggested the potential of the SDC-1 level as a predictor of mortality (AUC 0.714). K‒M analysis also revealed a significant difference in survival based on an SDC-1 cutoff of 10.65 ng/mL. DISCUSSION: This study suggested that SDC-1 may serve as a valuable biomarker for assessing COVID-19 severity and predicting mortality within 28 days of hospitalization, particularly in the Japanese population. However, further investigations are required to assess longitudinal changes in SDC-1 levels, validate its predictive value for long-term survival, and consider its applicability to new viral variants. CONCLUSIONS: SDC-1 is emerging as a potential biomarker for assessing the severity and life expectancy of COVID-19 in the Japanese population, offering promise for improved risk stratification and patient management in the ongoing fight against the virus.

Myeloid sarcoma with plasmacytoid dendritic cell-like proliferation associated with IKZF1, ETV6 and DNMT3A mutations.

The classification of clonal plasmacytoid dendritic cell (pDC) proliferation associated with myeloid neoplasms remains a topic of ongoing debate. Although the fifth edition of the World Health Organization classification classifies clonal pDC proliferation into two categories, it is unclear whether this classification adequately captures the complexities of clonal pDC pathogenesis. We present a clinical case featuring myeloid sarcoma with pDC-like cells in cervical lymph nodes and bone marrow (BM). Analysis of biopsy specimens and BM aspirate revealed two distinct cellular populations expressing myeloid and pDC markers. One population exhibited myeloid leukemia and monocyte markers, including MPO, CD13, CD33, CD11b, and CD14, while the other manifested an immunophenotype reminiscent of pDCs, characterized by expression of CD56 and CD123. Additionally, whole exome sequencing and RNA sequencing of BM mononuclear cells were conducted to explore the pathophysiology of this rare malignancy, and unveiled pDC-like cell proliferation driven by IKZF1 and ETV6 mutations originating from clonal hematopoiesis initiated by a DNMT3A mutation. Notably, venetoclax-based therapy exhibited efficacy for achieving and sustaining complete remission. This case provides pivotal insights into the mechanistic aspects of pDC/pDC-like cell proliferation in myeloid sarcoma, offering valuable perspectives on therapeutic strategies.

Frequency characteristics of an ultrasonic varifocal liquid crystal lens.

Compound lens systems with mechanical actuators are used to focus objects at near to far distances. The focal length of ultrasound varifocal liquid crystal (LC) lenses can be controlled by modulating the refractive index spatial distribution of the medium through the acoustic radiation force, resulting in thin and fast-response varifocal lenses. The frequency characteristics of such a lens are evaluated in this paper, and several axisymmetric resonant vibration modes over 20 kHz are observed. The effective lens aperture decreased with the wavelength of the resonant flexural vibration generated on the lens, meaning that this parameter can be controlled with the driving frequency.

High Efficacy and Safety of Asciminib in a Chronic Myeloid Leukemia Patient with Chronic Kidney Disease Following Renal Transplantation.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by the BCR::ABL1 tyrosine kinase. Tyrosine kinase inhibitors (TKIs) have been established as standard therapies for CML. However, some CML patients experience TKI intolerance. Asciminib was approved for CML patients either intolerant or refractory to TKI therapy. We herein report a 63-year-old CML patient who underwent renal transplantation and exhibited TKI intolerance. He was switched to asciminib, which achieved a deep molecular response without exacerbation of the renal function. Our experience revealed that asciminib is effective and safe for CML patients complicated with chronic kidney disease.

Prognostic Value of Hematogones in Patients With Hematopoietic Disorders After Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to determine whether hematogones in patients with hematopoietic disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with clinical outcomes. We searched the MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform databases from their inception to March 2023. The primary outcome in the summary of findings was three-year relapse-free survival (RFS), and secondary outcomes in the summary of findings included three-year relapse, non-relapse mortality (NRM), overall survival (OS), acute and chronic graft-versus-host disease (GVHD), and infection. The certainty of evidence was determined using the grading of recommendation assessment, development, and evaluation approaches. A systematic review and meta-analysis of outcome measures were conducted using a random-effects model. This study protocol was registered in the Open Science Framework. A total of six studies (including 888 patients) were included in the meta-analysis. Hematogones were related to favorable three-year RFS (risk ratio (RR) = 1.84; 95% confidence interval (CI) = 1.01 to 3.34) and favorable NRM (RR = 0.14; 95% CI = 0.04 to 0.51), OS (RR = 1.51; 95% CI = 1.13 to 2.02), and acute GVHD (RR = 0.44; 95% CI = 0.33 to 0.59). The certainty of the evidence was low for RFS, NRM, OS, and acute GVHD. Evidence regarding the association between hematogones, relapse, and infections is uncertain. Hematogones may be a prognostic factor for long-term prognosis and acute adverse events in patients with hematopoietic disorders after allo-HSCT. Further studies are required to address the long-term life-threatening events.

Quantitative estimation of phospholipid molecules desorbed from a microbubble surface under ultrasound irradiation.

Microbubbles have potential applications as drug and gene carriers, and drug release can be triggered by externally applied ultrasound irradiation while inside blood vessels. Desorption of molecules forming the microbubble shell can be observed under ultrasound irradiation of a single isolated microbubble, and the volume of desorbed molecules can be quantitatively estimated from the contact angle between the bubble and a glass plate. Microbubbles composed of a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) shell and a poorly-soluble gas are created. When the microbubbles are exposed to a pulsed ultrasound, the contact angles increase dramatically; the percentage of DMPC molecules desorbed from the bubble surface reaches 70%. Vibration of a single bubble in the radial direction is measured using a laser Doppler vibrometer. The relationship between the vibrational characteristics and the amount of molecular desorption reveals that a larger vibrational amplitude of the bubble around the resonance size induces a larger amount of molecular desorption. These results support the possibility of controlling molecular desorption with pulsed ultrasound.

Successful allogeneic hematopoietic stem cell transplantation in a patient with type I CD36 deficiency: a case study and literature review.

BACKGROUND: CD36-deficient individuals may produce anti-CD36 antibodies through antigenic exposure to CD36, in situations including blood transfusions. Therefore, allogeneic hematopoietic stem cell transplantation (HSCT) from CD36-positive donors to CD36-negative patients remains a challenge. CASE REPORT: A 64-year-old man with acute myeloid leukemia became refractory to platelet transfusions during chemotherapy. Anti-CD36 antibodies without anti-HLA antibodies were detected in serum, and the absence of CD36 expression on platelets and monocytes confirmed type I CD36 deficiency. The patient achieved complete remission, and received maintenance therapy with CD36-negative platelet transfusions. However, he relapsed soon afterward, and thus underwent peripheral blood stem cell transplantation (PBSCT) from a CD36-positive unrelated donor. The anti-CD36 antibody titer had decreased before the transplant, and the PBSCT-course was uneventful. The patient has been well without any complications associated with CD36 status mismatch. DISCUSSION: The few reports of allogeneic HSCT in patients with CD36 deficiency have suggested that anti-CD36 antibodies could be involved in several post-transplant complications, such as delayed platelet recovery, transfusion refractoriness, and transfusion-related acute lung injury. Our present case confirmed that stem cell transplantation from CD36-positive donors to negative patients is feasible, when it includes careful prior assessment of anti-CD36 antibody titers and interventions to attenuate them.

A case of cold agglutinin syndrome associated with chronic lymphocytic leukaemia harbouring mutations in CARD11 and KMT2D.

Cold agglutinin disease (CAD) is a rare cold autoimmune haemolytic anaemia (cAIHA) caused by IgM antibodies recognizing I antigens on erythrocytes. cAIHA is now mainly classified into two types: primary CAD and cold agglutinin syndrome (CAS). CAS develops in association with the underlying disease, which is most commonly malignant lymphoma. Recent studies have identified gene mutations in CARD11 and KMT2D in a high proportion of patients with CAD, which has led to recognition of CAD as an indolent lymphoproliferative disorder. We herein report a case of cAIHA without lymphocytosis or lymphadenopathy in whom bone marrow was infiltrated by a small population of clonal lymphocytes (6.8%) expressing cell surface markers consistent with chronic lymphocytic leukaemia (CLL). Whole-exome sequencing of bone marrow mononuclear cells revealed mutations in the CARD11 and KMT2D genes. This patient also had somatic hypermutation with overrepresentation of IGHV4-34, which is prevalent in CLL harbouring the KMT2D mutation. These observations suggest that CAS caused by early-phase CLL could be misinterpreted as primary CAD.

Mutated ZRSR2 and CUL3 accelerate clonal evolution and confer venetoclax resistance via RAS signaling pathway in blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive subtype of myeloid malignancy characterized by skin, lymph node and central nervous system (CNS) involvement. Although various regimens are used, a standard therapeutic strategy for BPDCN has not been established. Recent studies revealed that BPDCN patients frequently have a mutation in ZRSR2, which is a minor spliceosome component. However, the association between the clinical features of BPDCN and ZRSR2 mutational status remains unknown. A 70-year-old man was referred to our hospital with skin rash and enlarged lymph nodes, as well as blasts in the peripheral blood. BPDCN was diagnosed based on the immunophenotype of the blasts derived from bone marrow. Whole exome sequencing revealed that BPDCN cells collected at diagnosis had mutations in ZRSR2, ZBTB33, CUL3, TET2 and NRAS. RNA sequencing analysis indicated that U12-type intron retention occurred in LZTR1, caused by ZRSR2 loss. After seven cycles of venetoclax combined with azacitidine therapy, BPDCN cells appeared in the peripheral blood and infiltrated the CNS. Two KRAS mutated clones appeared at BPDCN recurrence. These findings are important for understanding the pathogenesis of BPDCN, which will inform development of novel therapeutic strategies.

Successful allogeneic hematopoietic stem cell transplantation for myelodysplastic neoplasms complicated with secondary pulmonary alveolar proteinosis and Behçet's disease harboring GATA2 mutation.

Myelodysplastic neoplasms (MDS) are defined by cytopenia and morphologic dysplasia originating from clonal hematopoiesis. They are also frequently complicated with diseases caused by immune dysfunction, such as Behçet's disease (BD) and secondary pulmonary alveolar proteinosis (sPAP). MDS with both BD and sPAP is extremely rare, and their prognosis is poor. In addition, haploinsufficiency of the hematopoietic transcription factor gene GATA2 is recognized as a cause of familial MDS and is frequently complicated by sPAP. Herein, we report a case of MDS combined with both BD and sPAP in association with GATA2 deficiency in a Japanese woman. Because she developed progressive leukopenia and macrocytic anemia during BD treatment at the age of 61, she underwent a bone-marrow examination and was diagnosed with MDS. She subsequently developed sPAP. At the age of 63, she underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Since allo-HSCT, she has maintained complete remission of MDS as well as the symptoms of BD and sPAP. Furthermore, we performed whole exome sequencing and identified the GATA2 Ala164Thr germline mutation. These findings suggest that patients with MDS, BD and sPAP should be considered for early allo-HSCT.

Development of evaluation system for cerebral artery occlusion in emergency medical services: noninvasive measurement and utilization of pulse waves.

Rapid reperfusion therapy can reduce disability and death in patients with large vessel occlusion strokes (LVOS). It is crucial for emergency medical services to identify LVOS and transport patients directly to a comprehensive stroke center. Our ultimate goal is to develop a non-invasive, accurate, portable, inexpensive, and legally employable in vivo screening system for cerebral artery occlusion. As a first step towards this goal, we propose a method for detecting carotid artery occlusion using pulse wave measurements at the left and right carotid arteries, feature extraction from the pulse waves, and occlusion inference using these features. To meet all of these requirements, we use a piezoelectric sensor. We hypothesize that the difference in the left and right pulse waves caused by reflection is informative, as LVOS is typically caused by unilateral artery occlusion. Therefore, we extracted three features that only represented the physical effects of occlusion based on the difference. For inference, we considered that the logistic regression, a machine learning technique with no complex feature conversion, is a reasonable method for clarifying the contribution of each feature. We tested our hypothesis and conducted an experiment to evaluate the effectiveness and performance of the proposed method. The method achieved a diagnostic accuracy of 0.65, which is higher than the chance level of 0.43. The results indicate that the proposed method has potential for identifying carotid artery occlusions.

Control of the surface profile of powder using the flexural vibration of a V-shaped plate.

In the pharmaceutical field, a technique to level the surface of powdered medicines is important in the dispensing process because the flatness of the powder surface affects the packaging accuracy directly. This paper investigates a method for leveling of the surface profile of powder using ultrasound vibration on a plate. The system used comprises a V-shaped plate and two ultrasound transducers, and the plate configuration required was determined from the results of simulations performed by finite element analysis. The resonant longitudinal vibration of the transducers generated the resonant flexural vibration mode of the plate at 27.4 kHz, which resulted in transportation and leveling of the powder. The powder was aggregated at the nodal positions of the flexural standing wave, and a correlation was observed between the sound pressure distribution over the plate and the surface profile of the powder. The powder leveling accuracy was investigated by varying the driving phase difference between the transducers, and it was found that a smaller standing wave ratio for the flexural vibration produced higher leveling accuracy. When the input voltage to the transducers was increased, the leveling time decreased and the leveling accuracy improved; the highest leveling accuracy obtained was 2.2 mm at 130 Vpp.

Concentration-Dependent Viscoelasticity of Poloxamer-Shelled Microbubbles.

The oscillation of shelled microbubbles during exposure to ultrasound is influenced by the mechanical properties of the shell components. The oscillation behavior of bubbles coated with various phospholipids and other amphiphiles has been studied. However, there have been few investigations of how the adsorption conditions of the shell molecules relate to the viscoelastic properties of the shell and influence the oscillation behavior of the bubbles. In the present study, we investigated the oscillation characteristics of microbubbles coated with a poloxamer surfactant, that is, Pluronic F-68, at several concentrations after the adsorption kinetics of the surfactant at the gas-water interface had reached equilibrium. The dilatational viscoelasticity of the shell during exposure to ultrasound was analyzed in the frequency domain from the attenuation characteristics of the acoustic pulses propagated in the bubble suspension. At Pluronic F-68 concentrations lower than 2.0 × 10-2 mol L-1, the attenuation characteristics typically exhibited a sharp peak. At concentrations higher than 2.0 × 10-2 mol L-1, the peak flattened. The dilatational elasticity and viscosity of the shell were estimated by fitting the theoretical model to the experimental values, which revealed that both the elasticity and viscosity increased markedly at approximately 2.0 × 10-2 mol L-1. This suggests that the adsorption properties of Pluronic F-68 strongly affect the oscillation characteristics of microbubbles of a size suitable for medical ultrasound diagnostics.

Development of Acute Adult T-cell Leukemia Following PD-1 Blockade Therapy for Lung Cancer.

Immune checkpoint inhibitors (ICIs) are widely used for the treatment of various cancers. However, paradoxical exacerbation of neoplasms, referred to as "hyperprogressive disease," has been reported in a proportion of patients treated with anti-programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1) blockade. We herein report a case of acute adult T-cell leukemia (ATL) that developed shortly after the administration of nivolumab, a PD-1 inhibitor, to treat non-small-cell lung cancer. There were no signs of ATL before the administration of nivolumab, and seropositivity for human T-cell leukemia virus type-1 (HTLV-1) was confirmed after the development of acute ATL. We speculate that nivolumab likely contributed to the development of acute ATL.

Adult paroxysmal cold hemoglobinuria following mRNA COVID-19 vaccination.

Paroxysmal cold hemoglobinuria (PCH) is an extremely rare subtype of autoimmune hemolytic anemia (AIHA) in adults. PCH is caused by the biphasic Donath-Landsteiner (DL) antibody which fixes complement to red blood cells at low temperatures and dissociates at warmer temperatures, leading to complement-mediated intravascular hemolysis. Autoimmune hematological disorders including AIHA and immune thrombocytopenia have been reported to develop following the mRNA COVID-19 vaccination. However, PCH developing subsequent to mRNA vaccination has never been reported. We report a 59-year-old male who developed PCH approximately a month after his second mRNA COVID-19 vaccination.

Varifocal Concave-Convex Lens Using Viscoelastic Gel and Ultrasound Vibration.

A varifocal concave-convex lens using ultrasound and transparent viscoelastic gel is reported. The configuration of the lens is simple and thin, consisting of four pieces of a piezoelectric ultrasound transducer, a glass disk, and a transparent silicone gel film. It uses a combination of the ultrasound resonant flexural standing- and traveling-wave modes excited by in-phase and four-phase drives so that the lens can change its shape to both concave and convex by switching the resonance mode with the same structure. The acoustic radiation force (ARF) originated from the resonant flexural vibration modes changed the surface profile of the gel. Convex and concave deformation were generated at the center of the lens at the resonance frequencies of 38 and 60 kHz, respectively, indicating that a varifocal concave-convex lens could be fabricated by controlling the driving frequency, voltage amplitude, and phase differences among the ultrasound transducers. The deformational displacement on the lens surface and the change in the focal length increased with the input voltage amplitude. The optical microscopic images observed through the lens were enlarged 1.28× (reduced 0.92× ) in the convex (concave) mode with 20 [Formula: see text]. The response time for focusing and the temperature stability under operation were evaluated. By switching the resonance vibration modes of the lens through the input signals to multiple ultrasound transducers, the variable-focus function with both concave and convex lenses was achieved in the same configuration.

Oxidation Mechanisms of Hafnium Overlayers Deposited on an Si(111) Substrate.

The oxidation mechanism of hafnium overlayers on an Si(111) substrate [Hf-Si(111), including the outermost metallic Hf overlayers and interfacial Hf silicides (HfSi and HfSi4)] was investigated via high-resolution synchrotron radiation X-ray photoelectron spectroscopy (SR-XPS) of Hf 4f5/2,7/2, Si 2p1/2,3/2, and O 1s core levels. The atomic-scale interaction of O2 molecules with Hf-Si(111) is discussed by comparing the results obtained following thermal O2 exposures [translational energy (Et) ≈ 0.03 eV] with those obtained following supersonic O2 molecular beam (SOMB) irradiation (Et ≈ 2.2 eV). Metallic Hf and interfacial HfSi were immediately oxidized to HfO2 and Hf (sub)silicates (Hf-O-Si configurations) via trapping-mediated dissociative adsorption. Upon excessive SOMB irradiation, the other interfacial HfSi4 was oxidized via direct dissociation. When oxidation proceeded at the Si(111) substrate via excess SOMB irradiation, volatile Si atoms were emitted from the interfacial SiO2/Si-strained layers. When the volatile Si atoms were trapped in the overlayers, the HfO2 overlayers were converted into completely oxidized Hf silicate layers. However, when the volatile Si atoms passed through the HfO2 overlayers, they reacted with the impinging O2, and the outermost SiO2 deposition layers were formed on HfO2 (or Hf silicate) layers.

Serum IgG and lymphocyte counts are useful for the early detection of infection in patients receiving bendamustine-rituximab therapy.

Bendamustine-rituximab (BR) therapy has been established as a highly effective regimen for indolent non-Hodgkin lymphoma (NHL). However, patients who receive BR therapy exhibit persistent hypogammaglobulinemia and lymphopenia, resulting in an increased incidence of infections. As a sustained immunosuppressive state is a risk factor for infections, early predictive biomarkers for infections related to BR therapy need to be identified. We retrospectively analyzed 61 patients with indolent NHL who were followed up for 2 years after the end of BR therapy. Progression-free survival was significantly influenced by the incidence of infections. Patients with infections related to BR therapy exhibited persistent hypogammaglobulinemia and lymphopenia. In addition, we determined the cutoff values of serum IgG values and lymphocyte counts for infections using receiver operating characteristic curve analysis. Minimum serum IgG and lymphocyte counts at the first BR treatment cycle were significantly associated with the incidence of infections during and after BR treatment. Furthermore, the development of skin reactions during BR therapy was significantly associated with the incidence of infections after BR therapy. Our study suggested that these values and symptom are predictive biomarkers for infections related to BR therapy. Based on these findings, better management of indolent NHL patients will be possible.

Ultrasound liquid crystal lens with a variable focus in the radial direction for image stabilization.

New technologies for adaptive optics are becoming increasingly important for miniature devices such as cell-phone cameras. In particular, motion-free autofocusing and optical image stabilization require sophisticated approaches for alternative lens architectures, materials, and processing to replace multiple solid elements. We discuss a new method, to the best of our knowledge, that provides image stabilization via an annular piezoelectric ceramic that uses ultrasound to drive a liquid crystal layer sandwiched between two circular glass substrates. The piezoelectric ceramic is divided into four quadrants that are independently driven with sinusoidal voltages at the resonant frequency of the lens. The technique is based on ultrasound vibrations with a suitable driving scheme. The lens configuration was modeled via finite-element analysis. Various combinations of the four-channel ultrasound transducer can be used to define the focal point of the liquid crystal lens. Clear optical images could be obtained with the lens. By using two-dimensional fast Fourier transforms, the focal point position was defined and shifted in the radial direction.