CD30 induces Reed-Sternberg cell-like morphology and chromosomal instability in classic Hodgkin lymphoma cell lines.

Classic Hodgkin lymphoma (cHL) is characterized by multinucleated cells called Reed-Sternberg (RS) cells and genetic complexity. Although CD30 also characterizes cHL cells, its biological roles are not fully understood. In this report, we examined the link between CD30 and these characteristics of cHL cells. CD30 stimulation increased multinucleated cells resembling RS cells. We found chromatin bridges, a cause of mitotic errors, among the nuclei of multinucleated cells. CD30 stimulation induced DNA double-strand breaks (DSBs) and chromosomal imbalances. RNA sequencing showed significant changes in the gene expression by CD30 stimulation. We found that CD30 stimulation increased intracellular reactive oxygen species (ROS), which induced DSBs and multinucleated cells with chromatin bridges. The PI3K pathway was responsible for CD30-mediated generation of multinucleated cells by ROS. These results suggest that CD30 involves generation of RS cell-like multinucleated cells and chromosomal instability through induction of DSBs by ROS, which subsequently induces chromatin bridges and mitotic error. The results link CD30 not only to the morphological features of cHL cells, but also to the genetic complexity, both of which are characteristic of cHL cells.

A report on a modified protocol for flow cytometry-based assessment of blood group erythrocyte antigens potentially suitable for analysis of weak ABO subgroups.

BACKGROUND: Flow cytometry (FC) has proven its utility in scrutinizing AB antigen expression in red blood cells (RBCs), cooperating with serological tests for accurate blood group typing. However, technical difficulties may impair the characterization of weak ABO subtypes when background noises appear at non-negligible levels. STUDY DESIGN AND METHODS: We sought to establish an FC method that could prevent antibody-induced hemagglutination and an increase in cellular autofluorescence, two major issues inherent to RBC-FC analysis of AB expression. We optimized fixatives, multicolor-staining protocols, and sequential gating strategies. Blood samples from weak ABO subtype cases, Bm and Ael , were analyzed with the established protocol. RESULTS: The optimized mixture of glutaraldehyde and formaldehyde successfully generated fixed RBCs resistant to agglutination while maintaining low autofluorescence. These features allowed co-staining of leukocyte- and erythrocyte-markers, which enabled sequential gating strategies facilitating the precise AB antigen analysis in purely single RBCs with minimum background noises. By the established FC analysis, we could detect in the Bm sample a small RBC population exhibiting weak B antigen expression. The assay also proved it feasible to identify a small population (0.04%) of RBCs weakly expressing the A antigen in the Ael sample confirmed as harboring a rare c.816dupG ABO variant allele. CONCLUSION: The RBC-FC analysis described here allows the detection of AB antigens weakly expressed in RBCs while achieving minimum background noise levels in negative control samples. Overall, the modified protocol provides a quick and reliable assay valuable in transfusion medicine and is potentially applicable to the characterization of rare weak ABO variants.

B cell-activating factor is involved in thrombocytopenia in patients with liver cirrhosis.

Liver cirrhosis (LC) involves B cells that produce anti-glycoprotein (GP) IIb/IIIa antibodies, found in primary immune thrombocytopenia (ITP). The role of autoimmunity in the pathology of thrombocytopenia in LC was investigated using 25 LC patients with thrombocytopenia, 18 ITP patients, and 30 healthy controls. Anti-GPIIb/IIIa antibody-producing B cells were quantified using enzyme-linked immunospot assay. Platelet-associated and plasma anti-GPIIb/IIIa antibody, plasma B cell-activating factor (BAFF), and a proliferation-inducing ligand (APRIL) levels were measured using enzyme-linked immunosorbent assay. B cell subset fractions and regulatory T cells (Tregs) were quantified using flow cytometry.The number of anti-GPIIb/IIIa antibody-producing B cells was significantly higher in LC patients than in ITP patients and healthy controls (both p < 0.001). Platelet-associated anti-GPIIb/IIIa antibodies were significantly higher in LC patients than in ITP patients and healthy controls (p = 0.002, p < 0.001, respectively). BAFF levels were significantly higher in LC patients than in ITP patients and healthy controls (p = 0.001 and p < 0.001, respectively), and APRIL levels were significantly higher in LC patients than in healthy controls (p < 0.001). Anti-GPIIb/IIIa antibody-producing B cells and platelet-associated anti-GPIIb/IIIa antibodies were positively correlated with BAFF levels in LC patients. LC patients had more naïve B cells and plasmablasts than healthy controls (p = 0.005, p = 0.03, respectively); plasmablasts were positively correlated with BAFF levels. LC patients had similar Tregs levels as ITP patients and healthy controls. Therefore, excessive BAFF production in LC patients with thrombocytopenia is likely associated with autoimmune B cell response, inducing anti-GPIIb/IIIa antibody production.

Artificially Created Reentry Circuit by Laser Irradiation Causes Atrial Tachycardia to Persist in Murine Atria.

BACKGROUND: There is a gradual progression from paroxysmal to persistent atrial fibrillation (AF) in humans. To elucidate the mechanism involved, the creation of an artificial atrial substrate to persist AF in mice was attempted.Methods and Results:This study used wild type (WT) mice, but it is difficult to induce AF in them. A novel antegrade perfusion method from the left ventricle (LV) to enlarge both atria for artificial atrial modification was proposed in this study. Short duration AF was induced by burst pacing under this method. Optical mapping analysis revealed non-sustained focal type and meandering spiral reentrants after short duration AF. A tiny artificial substrate (~1.2 mm in diameter) was added in by laser irradiation to create a critical atrial arrhythmogenic substrate. Burst pacing was performed in a non-laser group (n=8), a circular-shape laser group (n=8), and a wedge-shaped dent laser group (n=8). We defined AF and atrial tachycardia (AT) as atrial arrhythmia (AA). Long-lasting AA was defined as lasting for ≥30 min. Long-lasting AA was observed in 0/8, 0/8, and 6/8 (75%) mice in each group. Optical mapping analysis revealed that the mechanism was AT with a stationary rotor around the irradiated margin. CONCLUSIONS: Regrettably, this study failed to reproduce persistent AF, but succeeded in creating an arrhythmic substrate that causes sustained AT in WT mice.

Efficacy and safety of romiplostim in refractory aplastic anaemia: a Phase II/III, multicentre, open-label study.

A previous dose-finding study has suggested that romiplostim is effective in patients with refractory aplastic anaemia (AA) and 10 µg/kg once weekly was recommended as a starting dose. In this Phase II/III, multicentre, open-label study, romiplostim was administered subcutaneously at a fixed dose of 10 µg/kg once weekly for 4 weeks (weeks 1-4) followed by weekly doses (5, 10, 15 and 20 µg/kg) titrated by platelet response for up to 52 weeks (weeks 5-52). A total of 31 patients with AA who were refractory to immunosuppressive therapy (IST) and thrombocytopenia (platelet count of ≤30 × 109 /l) were enrolled. The primary efficacy endpoint of the proportion of patients achieving any haematological (platelet, neutrophil and erythrocyte) response at week 27 was 84% [95% confidence interval (CI) 66-95%]. Trilineage response was 39% (95% CI 22-58%) at week 53. The most common treatment-related adverse events (AEs) were headache and muscle spasms (each 13%). All AEs were mild or moderate except for three patients with Grade 3 hepatic AEs; no AEs necessitated romiplostim discontinuation. Two patients developed cytogenetic abnormalities, of whom one returned to normal karyotype at last follow-up. High-dose romiplostim is effective and well tolerated in the treatment of patients with AA refractory to IST.

Phase II clinical trial of personalized VCD-VTD sequential therapy using the Vulnerable Elders Survey-13 (VES-13) for transplant-ineligible patients with newly diagnosed multiple myeloma.

The Vulnerable Elders Survey-13 (VES-13) is a well-studied simplified frailty screening tool for elderly patients in the oncology setting. We conducted a prospective clinical trial to evaluate the efficacy and safety of dose-adjusted treatment based on the VES-13 in transplant-ineligible patients with newly diagnosed multiple myeloma (MM). In the Fit group (VES-13 <3), patients were treated with 4 cycles of standard-dose VCD (bortezomib, cyclophosphamide, and dexamethasone) followed by 4 cycles of standard-dose VTD (bortezomib, thalidomide, and dexamethasone). In the Frail group (VES-13 ≥3), patients were treated with 4 cycles of reduced-dose VCD followed by 4 cycles of reduced-dose VTD. The median age was 75 years (66-86 years), and 34% of the cases were classified as PS 3. Among the Fit group (n=16), the overall response rate (ORR) was 87.5%. Among the Frail group (n=31), the ORR was 87.1%. There were no significant differences in progression-free survival (PFS) and overall survival (OS) between the Fit and Frail groups (3-year PFS: 68.8% vs 53.3%, P = 0.658; 3-year OS: 70.0% vs 77.6%, P = 0.919). Personalized VCD-VTD sequential therapy based on the VES-13 was associated with high response rates and showed acceptable safety in elderly frail patients with MM. The study is registered as UMIN000011235.

Impact of Anti-GPIIb/IIIa Antibody-Producing B Cells as a Predictor of the Response to Lusutrombopag in Thrombocytopenic Patients with Liver Disease.

BACKGROUND: To make an accurate estimate of the response to thrombopoietin (TPO) receptor agonists for thrombocytopenia associated with chronic liver disease, we evaluated the influence of antiplatelet autoantibodies on the response to lusutrombopag in thrombocytopenic patients with liver disease. METHODS: A prospective study was conducted at 2 hospitals. Thrombocytopenic patients with liver disease received oral lusutrombopag 3.0 mg once daily for up to 7 days. We analyzed changes in platelet counts from baseline to the maximum platelet count on days 9-14. The definition of clinical response was a platelet count of ≥5 × 104/µL with an increased platelet count of ≥2 × 104/µL from baseline. We assessed the correlation between the response to treatment drug and antiplatelet autoantibodies measured by anti-GPIIb/IIIa antibody-producing B cells. RESULTS: Thirty patients received the trial drug. There were 25 responders and 5 nonresponders. The median change in platelet counts was 3.9 × 104/µL (95% CI 2.8-4.6, p < 0.0001). The correlation between change in platelet counts and the frequency of the anti-glycoprotein IIb/IIIa antibody-producing B cells was moderate (r = 0.414, 95% CI 0.064-0.674, p = 0.023). In multivariate analysis of factors affecting the change in platelet counts, the anti-GPIIb/IIIa antibody-producing B cells were identified as an independent factor (regression coefficient [B] = 0.089; CI 0.021-0.157, p = 0.013). CONCLUSION: Anti-GPIIb/IIIa antibody-producing B cells may be a predictor for TPO receptor agonists in patients with chronic liver disease.

Antithrombotic prophylaxis for surgery-associated venous thromboembolism risk in patients with inherited platelet disorders. The SPATA-DVT Study.

Major surgery is associated with an increased risk of venous thromboembolism (VTE), thus the application of mechanical or pharmacologic prophylaxis is recommended. The incidence of VTE in patients with inherited platelet disorders (IPD) undergoing surgical procedures is unknown and no information on the current use and safety of thromboprophylaxis, particularly of low-molecular-weight-heparin in these patients is available. Here we explored the approach to thromboprophylaxis and thrombotic outcomes in IPD patients undergoing surgery at VTE-risk participating in the multicenter SPATA study. We evaluated 210 surgical procedures carried out in 155 patients with well-defined forms of IPD (VTE-risk: 31% high, 28.6% intermediate, 25.2% low, 15.2% very low). The use of thromboprophylaxis was low (23.3% of procedures), with higher prevalence in orthopedic and gynecological surgeries, and was related to VTE-risk. The most frequently employed thromboprophylaxis was mechanical and appeared to be effective, as no patients developed thrombosis, including patients belonging to the highest VTE-risk classes. Low-molecular-weight-heparin use was low (10.5%) and it did not influence the incidence of post-surgical bleeding or of antihemorrhagic prohemostatic interventions use. Two thromboembolic events were registered, both occurring after high VTE-risk procedures in patients who did not receive thromboprophylaxis (4.7%). Our findings suggest that VTE incidence is low in patients with IPD undergoing surgery at VTE-risk and that it is predicted by the Caprini score. Mechanical thromboprophylaxis may be of benefit in patients with IPD undergoing invasive procedures at VTE-risk and low-molecular-weight-heparin should be considered for major surgery.

Control of the pore size of honeycomb polymer film from micrometers to nanometers via substrate-temperature regulation and its application to photovoltaic and heat-resistant polymer films.

Honeycomb porous polystyrene (PS) films with an aspect ratio of pore depth to pore diameter at approximately 1.0 were fabricated using the breath figure (BF) method. Two modes of water droplet coalescence in the pore growth were observed in real-time by optical microscopy. Pore size significantly increases with the increase in humidity and the decrease in substrate temperature. The porous pattern could emerge even at room temperature under high humidity of 80%. Boiling point and solvent density significantly influence the pore distribution and pore depth. Chloroform and tetrahydrofuran achieve more uniform hexagonal patterns than benzene and dichloromethane. Subsequently, to obtain nanometer porous PS film, the fast-evaporation BF process was designed by regulating the gradient substrate temperature and evaporation time, and porous mesoscopic PS film was obtained. The minimum pore diameter and corresponding pore depth are about 120 nm and 27 nm, respectively. Finally, the fast-evaporation BF process was applied to the honeycomb film formation of photovoltaic polymer poly(3-hexylthiophene) (P3HT), and the heat-resistant polymers polysulfone (PSF) and polyimide (PI).

Two-Dimensional Phonon Polariton Heat Transport.

As is well-known, the phonon and electron thermal conductivity of a thin film generally decreases as its thickness scales down to nanoscales due to size effects, which have dramatic engineering effects, such as overheating, low reliability, and reduced lifetime of processors and other electronic components. However, given that thinner films have higher surface-to-volume ratios, the predominant surface effects in these nanomaterials enable the transport of thermal energy not only inside their volumes but also along their interfaces. In polar nanofilms, this interfacial transport is driven by surface phonon polaritons, which are electromagnetic waves generated at mid-infrared frequencies mainly by the phonon-photon coupling along their surfaces. Theory predicts that these polaritons can enhance the in-plane thermal conductivity of suspended silica films to values higher than the corresponding bulk one, as their thicknesses decrease through values smaller than 200 nm. In this work, we experimentally demonstrate this thermal conductivity enhancement. The results show that the in-plane thermal conductivity of a 20 nm thick silica film at room temperature is nearly twice its lattice vibration counterpart. Additional thermal diffusivity measurements reveal that the diffusivity of a silica film also increases as its thickness decreases, such that the ratio of thermal conductivity/thermal diffusivity (volumetric heat capacity) remains nearly independent of the film thickness. The experimental results obtained here will enable one to build on recent interesting theoretical predictions, highlight the existence of a new heat channel at the nanoscale, and provide a new avenue to engineer thermally conductive nanomaterials for efficient thermal management.

[Acute leukemia developing in the second trimester of pregnancy].

Acute leukemia (AL) during pregnancy poses a substantial risk to both mothers and fetuses. Treatment for leukemia should be initiated promptly; however, the management of AL in pregnant women and fetuses is usually challenging, especially during the second trimester. Here, we report two cases of AL that developed during the second trimester of pregnancy. In one case, chemotherapy was initiated while continuing the pregnancy; in the second case, a cesarean section was performed prior to chemotherapy initiation. As per current medical records, both infants are thriving without any medical problems. The optimal strategy for the treatment of AL during pregnancy typically includes chemotherapy after delivery. However, if fetal development is not sufficient for ex utero survival, the only alternatives available are the initiation of treatment while continuing the pregnancy or treatment after therapeutic abortion (if it is legally allowed). According to previous studies and as per the results from our first case, the initiation of chemotherapy while sustaining the pregnancy may be an acceptable option if it is conducted with appropriate informed consent. The treatment of AL in the second trimester of pregnancy should be carefully decided, while taking into account the medical, legal, and social aspects, such as gestational weeks, maternal and fetal status, and wishes of the patients and their families.

Bleeding risk of surgery and its prevention in patients with inherited platelet disorders.

Excessive bleeding at surgery is a feared complication in patients with inherited platelet disorders. However, very few studies have evaluated the frequency of surgical bleeding in these hemorrhagic disorders. We performed a worldwide, multicentric, retrospective study to assess the bleeding complications of surgery, the preventive and therapeutic approaches adopted, and their efficacy in patients with inherited platelet disorders: the Surgery in Platelet disorders And Therapeutic Approach (SPATA) study. We rated the outcome of 829 surgical procedures carried out in 423 patients with well-defined forms of inherited platelet disorders: 238 inherited platelet function disorders and 185 inherited platelet number disorders. Frequency of surgical bleeding was high in patients with inherited platelet disorders (19.7%), with a significantly higher bleeding incidence in inherited platelet function disorders (24.8%) than in inherited platelet number disorders (13.4%). The frequency of bleeding varied according to the type of inherited platelet disorder, with biallelic Bernard Soulier syndrome having the highest occurrence (44.4%). Frequency of bleeding was predicted by a pre-operative World Health Organization bleeding score of 2 or higher. Some types of surgery were associated with a higher bleeding incidence, like cardiovascular and urological surgery. The use of pre-operative pro-hemostatic treatments was associated with a lower bleeding frequency in patients with inherited platelet function disorders but not in inherited platelet number disorders. Desmopressin, alone or with antifibrinolytic agents, was the preventive treatment associated with the lowest bleedings. Platelet transfusions were used more frequently in patients at higher bleeding risk. Surgical bleeding risk in inherited platelet disorders is substantial, especially in inherited platelet function disorders, and bleeding history, type of disorder, type of surgery and female sex are associated with higher bleeding frequency. Prophylactic pre-operative pro-hemostatic treatments appear to be required and are associated with a lower bleeding incidence.

ACTN1 mutations cause congenital macrothrombocytopenia.

Congenital macrothrombocytopenia (CMTP) is a heterogeneous group of rare platelet disorders characterized by a congenital reduction of platelet counts and abnormally large platelets, for which CMTP-causing mutations are only found in approximately half the cases. We herein performed whole-exome sequencing and targeted Sanger sequencing to identify mutations that cause CMTP, in which a dominant mode of transmission had been suspected but for which no known responsible mutations have been documented. In 13 Japanese CMTP-affected pedigrees, we identified six (46%) affected by ACTN1 variants cosegregating with CMTP. In the entire cohort, ACNT1 variants accounted for 5.5% of the dominant forms of CMTP cases and represented the fourth most common cause in Japanese individuals. Individuals with ACTN1 variants presented with moderate macrothrombocytopenia with anisocytosis but were either asymptomatic or had only a modest bleeding tendency. ACTN1 encodes α-actinin-1, a member of the actin-crosslinking protein superfamily that participates in the organization of the cytoskeleton. In vitro transfection experiments in Chinese hamster ovary cells demonstrated that altered α-actinin-1 disrupted the normal actin-based cytoskeletal structure. Moreover, transduction of mouse fetal liver-derived megakaryocytes with disease-associated ACTN1 variants caused a disorganized actin-based cytoskeleton in megakaryocytes, resulting in the production of abnormally large proplatelet tips, which were reduced in number. Our findings provide an insight into the pathogenesis of CMTP.

High-efficiency generation of pulsed Lyman-α radiation by resonant laser wave mixing in low pressure Kr-Ar mixture.

We report an experimental generation of ns pulsed 121.568 nm Lyman-α radiation by the resonant nonlinear four-wave mixing of 212.556 nm and 845.015 nm radiation pulses providing a high conversion efficiency 1.7x10-3 with the output pulse energy 3.6 µJ achieved using a low pressure Kr-Ar mixture. Theoretical analysis shows that this efficiency is achieved due to the advantage of using (i) the high input laser intensities in combination with (ii) the low gas pressure allowing us to avoid the onset of full-scale discharge in the laser focus. In particular, under our experimental conditions the main mechanism of photoionization caused by the resonant 2-photon 212.556 nm radiation excitation of Kr atoms followed by the 1-photon ionization leads to ≈17% loss of Kr atoms and efficiency loss only by the end of the pulse. The energy of free electrons, generated by 212.556 nm radiation via (2 + 1)-photon ionization and accelerated mainly by 845.015 nm radiation, remains during the pulse below the level sufficient for the onset of full-scale discharge by the electron avalanche. Our analysis also suggests that ≈30-fold increase of 845.015 nm pulse energy can allow one to scale up the L-α radiation pulse energy towards the level of ≈100 µJ.

[A Case of Stage â £ Rectal Cancer with No Evidence of Disease after Neoadjuvant Chemotherapy and Surgery].

A 46-year-old man presented with hematochezia in October 2012. A circumferential type 2 rectal cancer was detected with colonoscopy. Contrast-enhanced CT showed multiple liver and lung metastases. Chemotherapy was administered after the diagnosis of cStage Ⅳ rectal cancer. After 1 course of XELOX plus Bmab, the treatment was changed to XELOX plus Cmab for 21 courses. An infusion reaction occurred during the 21st course. Because a complete response of the liver metastases and a reduction in size of the primary tumor had been achieved, we performed a low anterior resection in April 2014. The final pathological diagnosis was type 2, 10×25 mm, tub1, pMP, int, INF b, pN1 (251). There was no evidence of disease (NED) after the surgery. We are closely following up this patient with no postoperative chemotherapy, and as of July 2015, there is no sign of recurrence. We describe a case of a Stage Ⅳ rectal cancer that was resected with radical surgery after neoadjuvant chemotherapy. We also include a brief review of the literature.

Monoallelic KRAS (G13C) mutation triggers dysregulated expansion in induced pluripotent stem cell-derived hematopoietic progenitor cells.

BACKGROUND: Although oncogenic RAS mutants are thought to exert mutagenic effects upon blood cells, it remains uncertain how a single oncogenic RAS impacts non-transformed multipotent hematopoietic stem or progenitor cells (HPCs). Such potential pre-malignant status may characterize HPCs in patients with RAS-associated autoimmune lymphoproliferative syndrome-like disease (RALD). This study sought to elucidate the biological and molecular alterations in human HPCs carrying monoallelic mutant KRAS (G13C) with no other oncogene mutations. METHODS: We utilized induced pluripotent stem cells (iPSCs) derived from two unrelated RALD patients. Isogenic HPC pairs harboring either wild-type KRAS or monoallelic KRAS (G13C) alone obtained following differentiation enabled reliable comparative analyses. The compound screening was conducted with an established platform using KRAS (G13C) iPSCs and differentiated HPCs. RESULTS: Cell culture assays revealed that monoallelic KRAS (G13C) impacted both myeloid differentiation and expansion characteristics of iPSC-derived HPCs. Comprehensive RNA-sequencing analysis depicted close clustering of HPC samples within the isogenic group, warranting that comparative studies should be performed within the same genetic background. When compared with no stimulation, iPSC-derived KRAS (G13C)-HPCs showed marked similarity with the wild-type isogenic control in transcriptomic profiles. After stimulation with cytokines, however, KRAS (G13C)-HPCs exhibited obvious aberrant cell-cycle and apoptosis responses, compatible with "dysregulated expansion," demonstrated by molecular and biological assessment. Increased BCL-xL expression was identified amongst other molecular changes unique to mutant HPCs. With screening platforms established for therapeutic intervention, we observed selective activity against KRAS (G13C)-HPC expansion in several candidate compounds, most notably in a MEK- and a BCL-2/BCL-xL-inhibitor. These two compounds demonstrated selective inhibitory effects on KRAS (G13C)-HPCs even with primary patient samples when combined. CONCLUSIONS: Our findings indicate that a monoallelic oncogenic KRAS can confer dysregulated expansion characteristics to non-transformed HPCs, which may constitute a pathological condition in RALD hematopoiesis. The use of iPSC-based screening platforms will lead to discovering treatments that enable selective inhibition of RAS-mutated HPC clones.

Incidence and clinical significance of aberrant T-cell marker expression on diffuse large B-cell lymphoma cells.

INTRODUCTION: Aberrant expression of T-cell markers is occasionally observed in B-cell lymphomas. We conducted a retrospective study to establish its incidence and to determine its relationship with clinical features of patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: We reviewed DLBCL patients diagnosed between January 2002 and April 2009. Patients fulfilled the following criteria: (1) age >18 years, (2) HIV negative, (3) B-cell lymphoma confirmed by restricted expression of surface immunoglobulin light chains by flow cytometry (FCM). Aberrant T-cell marker expression (ATCME) was defined as positivity for CD2, CD3, CD4, CD7, and/or CD8 on DLBCL cells by FCM. Phenotyping was also performed by immunohistochemistry (IHC). Patients were grouped according to positive or negative ATCME and their clinical features including survival were compared. RESULTS: Of 150 patients, 11 (7.3%) showed ATCME; CD2 and CD7 were most often expressed. ATCME was less often detected and the signal was weaker using IHC. There were no statistically significant differences in clinical features between the two groups. CONCLUSIONS: FCM may be useful to detect ATCME in a small amount of lymphoma cells. The mechanism responsible for ATCME, and whether it contributes in any way to the pathogenesis of B-cell neoplastic transformation, requires clarification.

Lenalidomide-induced acute lung injury in case of multiple myeloma.

OBJECTIVE: Lenalidomide is now widely used for the treatment of multiple myeloma in virtue of its potent anti-tumor activity and low toxicity. Very few reports stressed the association of this drug with serious pulmonary toxicity. Here we present the case of multiple myeloma who underwent acute respiratory failure caused by non-specific interstitial pneumonia after few days of treatment with lenalidomide. CASE SUMMARY: A 50-year-old man diagnosed as multiple myeloma of IgA κ type, International Staging System III received a combination therapy of lenalidomide (15 mg, Day 1 - 21) with dexamethasone (40 mg, Day 1, 8, 15, 22). After 4 days on chemotherapy, he experienced worsened dyspnea and was urgently hospitalized because of acute respiratory failure. Because serial imaging procedures and thorough laboratory workup strongly suggested that his lung injury was caused by drug-induced interstitial pneumonia, lenalidomide, which was the most suspicious drug, was discontinued immediately, and the glucocorticoid pulse was performed. He showed an excellent response to the therapy. Interstitial pneumonia on the CT scan was resolved dramatically at 12 days after the start of the glucocorticoid pulse. CONCLUSION: We are convinced that our case is so instructive as to arouse attention to clinicians that lenalidomide has an extremely rare but potential adverse effect.

Ab initio calculation for electronic structure and optical property of tungsten carbide in a TiCN-based cermet for solar thermal applications.

We present an ab initio calculation to understand electronic structures and optical properties of a tungsten carbide WC being a major component of a TiCN-based cermet. The TiCN-based cermet is widely used as a cutting tool, and is discarded as usual after use. On the other hand, cermet itself is also a famous ingredient of a solar absorption film. We found that the WC has a fairly low-energy plasma excitation [Formula: see text] 0.6 eV (2 [Formula: see text]m) and therefore can be a good constituent of a solar selective absorber. The evaluated figure of merit for photothermal conversion is prominently high compared to those of the other materials included in the TiCN-based cermet. The imaginary part of the dielectric function is considerably small around the zero point of the real part of the dielectric function, corresponding to the plasma excitation energy. Therefore, a clear plasma edge appeared, ensuring the high performance of the WC as the solar absorber. This is a fascinating aspect, because the wasted TiCN-based cermet cutting tool can be recycled as the solar absorption film after proper treatments and modifications.

Sustained Myocarditis following Messenger RNA Vaccination against Coronavirus Disease 2019: Relation to Neutralizing Antibody and Amelioration by Low-Dose Booster Vaccination.

We recently reported that sub-acute myocarditis occurred following the initial two doses of messenger RNA-based vaccination against coronavirus disease 2019 (0.3 mL Comirnaty®) in elderly Japanese patients with cardiac dysfunction. The present retrospective study of 76 patients revealed that myocarditis following the initial doses persisted for 12 months, was associated with low levels of neutralizing antibodies, and was ameliorated by reducing the third vaccine dose. Low neutralizing antibody levels (<220 U/mL) after the initial doses were an independent predictor of persistent clinical events, defined as death or marked changes in brain natriuretic peptide levels. When the third dose was reduced (0.1 mL), changes in brain natriuretic peptide levels were significantly smaller (p = 0.02, n = 25), no deaths occurred due to heart failure, and neutralizing antibody levels increased 41-fold (p < 0.001) compared with the initial doses. Reduced booster doses could facilitate the worldwide distribution of messenger RNA vaccines.