TAFRO Syndrome: Guidance for Managing Patients Presenting Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis, Renal Insufficiency, and Organomegaly.

TAFRO syndrome is an inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly. Despite great advancements in research on the TAFRO syndrome in the last decade, its diagnosis and treatment are still challenging for most clinicians because of its rarity and severity. Since the initial proposal of the TAFRO syndrome as a distinct disease entity in 2010, two independent diagnostic criteria have been developed. Although these are different in the concept of whether TAFRO syndrome is a subtype of idiopathic multicentric Castleman disease or not, they are similar except for the magnitude of lymph node histopathology. Because there have been no specific biomarkers, numerous diseases must be ruled out before the diagnosis of TAFRO syndrome is made. The standard of care has not been fully established, but interleukin-6 blockade therapy with siltuximab or tocilizumab and anti-inflammatory therapy with high-dose corticosteroids are the most commonly applied for the treatment of TAFRO syndrome. The other immune suppressive agents or combination cytotoxic chemotherapies are considered for patients who do not respond to the initial treatment. Whereas glowing awareness of this disease improves the clinical outcomes of patients with TAFRO syndrome, further worldwide collaborations are warranted.

Mie-Resonant Nanophotonic-Enhancement of Asymmetry in Sodium Chlorate Chiral Crystallization.

Studies on chiral spectroscopy have recently demonstrated strong enhancement of chiral light-matter interaction in the chiral near-field of Mie resonance in high-refractive-index dielectric nanostructures by studies on chiral spectroscopy. This situation has motivated researchers to demonstrate effective chiral photosynthesis under a chiral near-field beyond circularly polarized light (CPL) as a chiral source. However, the effectivity of the chiral near-field of Mie resonance for chiral photosynthesis has not been clearly demonstrated. One major challenge is the experimental difficulty in evaluating enantiomeric excess of a trace amount of chiral products synthesized in the near-field. Here, by adopting sodium chlorate chiral crystallization as a phenomenon that includes both synthesis and the amplification of chiral products, we show that crystallization on a Mie-resonant silicon metasurface excited by CPL yields a statistically significant large crystal enantiomeric excess of ∼18%, which cannot be achieved merely by CPL. This result provides implications for efficient chiral photosynthesis in a chiral near-field.

Chiral Spinodal-like Ordering of Homoimmiscible Water at Interface between Water and Chiral Ice III.

Diversity in structures of water endowed by a hydrogen-bonding network plays crucial roles in wide varieties of phenomena in nature. Chiral ordering of water molecules is an intriguing phenomenon from the viewpoint of bimolecular functions. However, experimental reports on chiral ordering have been limited to the water molecules interacting with biomolecules on the molecular scale. It remains unclear whether pure liquid water forms long-range chiral ordering without any interaction with biomolecules. Here, we show that chiral anisotropy can be observed in the macro/mesoscopic network pattern of an unknown water layer formed via spinodal phase separation-like dynamics at the interface between water and ice III with a chiral crystal structure. We named this unknown water homoimmiscible water. Our observations infer that the unknown water is a chiral liquid crystal. This possibility opens new avenues for a wide variety of research fields such as liquid polymorphism, biology, earth and planetary science, and so forth from the perspective of chirality.

Anisotropy in spinodal-like dynamics of unknown water at ice V-water interface.

Experimentally demonstrating the existence of waters with local structures unlike that of common water is critical for understanding both the origin of the mysterious properties of water and liquid polymorphism in single component liquids. At the interfaces between water and ices Ih, III, and VI grown/melted under pressure, we previously discovered low- and high-density unknown waters, that are immiscible with the surrounding water. Here, we show, by in-situ optical microscopy, that an unknown water appears at the ice V-water interface via spinodal-like dynamics. The dewetting dynamics of the unknown water indicate that its characteristic velocity is ~ 90 m/s. The time evolution of the characteristic length of the spinodal-like undulation suggests that the dynamics may be described by a common model for spinodal decomposition of an immiscible liquid mixture. Spinodal-like dewetting dynamics of the unknown water transiently showed anisotropy, implying the property of a liquid crystal.

Pulmonary Veno-Occlusive Disease after Autologous Stem Cell Transplantation.

Pulmonary veno-occlusive disease (PVOD) is an extremely rare condition in oncology practice. Although PVOD is clinically similar to pulmonary arterial hypertension, the conditions differ in terms of pathophysiology, management, and prognosis. This report discusses the case of a 47-year-old woman who developed dyspnea and fatigue after high-dose cyclophosphamide chemotherapy and autologous hematopoietic stem cell transplantation for relapsed lymphoma. The patient exhibited tachycardia, tachypnea, and hypotension, but other findings in the physical examination were unremarkable. The imaging studies showed no evidence of pulmonary embolism, but multiple ground-glass opacities and bilateral pleural effusions were observed on chest high-resolution computed tomography scans. In the right heart catheterization study, the mean pulmonary artery pressure and pulmonary vascular resistance were 35 mm Hg and 5.93 Wood units, respectively, with a normal pulmonary capillary wedge pressure of 10 mm Hg. Pulmonary function tests revealed a remarkable reduction in the percentage predicted value of diffusing capacity of the lungs for carbon monoxide to 31%. Lymphoma progression, collagen diseases, infectious diseases such as human immunodeficiency virus or parasitic infections, portal hypertension, and congenital heart disease were carefully excluded as these are also capable of causing pulmonary arterial hypertension. Thereafter, we reached a final diagnosis of PVOD. The patient was treated with supplemental oxygen and a diuretic during 1 month of hospitalization, which relieved her right heart overload symptoms. Herein, we present the patient's clinical course and diagnostic workup because misdiagnosis or inappropriate treatment can lead to unfavorable outcomes in patients with PVOD.

Clinical entity of cytomegalovirus disease in patients with malignant lymphoma on bendamustine therapy: a single-institution experience.

We investigated the incidence, risk factors, and clinical outcomes of cytomegalovirus (CMV) disease in patients with B-cell lymphoma treated with a bendamustine-containing regimen. The incidence of CMV disease was analyzed after starting treatment with 139 regimens in 126 patients. Clinically significant CMV disease was observed in seven patients. The median duration between bendamustine initiation and the diagnosis of CMV disease was 69 d (range, 40-233), and the median of cycles completed at onset was 2 (range, 1-6). Furthermore, the incidence of CMV disease was significantly higher in the elderly patients than that in the younger patients. The target organs of CMV disease were the liver, gastrointestinal tract, lungs, and retinas. Antiviral therapy was administered to all patients. However, the recurrence of CMV disease was observed in two patients. This study provides information that could contribute to clinicians' decision-making on lymphoma therapy using bendamustine.

Comparison of the inactivation capacity of various UV wavelengths on SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic. Ultraviolet (UV) is regarded as a very powerful tool against SARS-CoV-2. However, the inactivating effects of different UV wavelengths on SARS-CoV-2 under the same conditions have hardly been compared. Here, we showed that SARS-CoV-2 cultured in Dulbecco's modified Eagle's medium and 2% fetal bovine serum was efficiently inactivated by irradiation with 222, 254, and 265 wavelengths UV, but not at 308 nm. In addition, it was revealed that UV absorption by DMEM-2% FBS is very efficient at 222 nm. Our results present potentially important information for selecting the optimum UV wavelength according to the application.

Clinical impact of central nervous system-directed therapies on intravascular large B-cell lymphoma: A single institution's experience.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of B-cell lymphoma characterized by aggressive disease progression with a high incidence of central nervous system (CNS) involvement. We retrospectively analyzed 16 patients with de novo IVLBCL treated at our hospital between 2004 and 2018 with either standard therapy plus CNS-directed therapy or standard therapy alone. CNS-directed therapy was associated with a significantly better 2-year CNS-free survival (100% vs. 63%, p = 0.0191), despite no significant effects on progression-free or overall survival. Further studies should assess CNS-focused treatment in patients with IVLBCL with or without primary CNS involvement.

Ideal dose intensity of R-CHOP in diffuse large B-cell lymphoma.

INTRODUCTION: The standard of care for diffuse large B-cell lymphoma (DLBCL) is rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, its ideal dose intensity varies among cases. AREAS COVERED: This review provides the latest insights on the dose intensity of R-CHOP for DLBCL patients. Specifically, we discussed the optimal dose intensity for elderly patients, the optimal number of treatment cycles for limited or advanced-stage diseases, and the role of dose-intensified therapies or adding targeted inhibitors. EXPERT OPINION: Performing a comprehensive or simplified geriatric assessment can distinguish elderly DLBCL patients who will likely benefit from curative R-CHOP. Very elderly or medically unfit patients may need dose reduction in R-CHOP; the Age, Comorbidities, and Albumin index may aid decision-making. Four cycles of R-CHOP followed by two rituximab cycles comprise a new standard for low-risk, limited-stage DLBCL patients. Compared to eight cycles, six cycles of R-CHOP have similar efficacy and fewer toxicities for advanced-stage DLBCL. Dose-intensified therapy is not recommended in most DLBCL cases but may be considered for patients with double (or triple)-hit lymphoma. Applying targeted inhibitors and not merely escalating R-CHOP dose intensity through molecular subtyping will improve the treatment outcome for DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is one of the most common blood cancers. Patients with DLBCL are usually treated with a standard (immuno-) chemotherapy called R-CHOP, which stands for rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin, and prednisone. Of these, cyclophosphamide and doxorubicin are particularly toxic but effective. Therefore, the dosages of these drugs are adjusted according to the patient's body size. However, the ideal amounts of these drugs (dose intensity) can vary from case to case. For instance, the regular dose intensity of R-CHOP is too toxic for some people, such as very older patients. Furthermore, ideal total amounts of these drugs, that is, ideal cycle numbers of R-CHOP, are also different between patients with limited disease and advanced disease. Therefore, oncology/hematology researchers have been seeking the optimal dose intensity of R-CHOP in each patient with DLBCL for years. The goal of this review is to provide the latest insights on the ideal dose intensity of R-CHOP in DLBCL treatment. In this article, we discuss: how R-CHOP was established as the standard of care for DLBCL, how to identify candidates for standard R-CHOP among older patients, how to adjust the dose intensity of R-CHOP for patients who are not candidates for standard R-CHOP, optimal cycle number of R-CHOP for limited-disease DLBCL, optimal cycle number of R-CHOP for advanced DLBCL, how to treat patients with a large mass, and the role of more intensive therapies other than R-CHOP in DLBCL treatment. Finally, we demonstrate how experts determined the dose intensity of R-CHOP for some example cases with DLBCL.

Relationship between Carnitine Deficiency and Tyrosine Kinase Inhibitor Use in Patients with Chronic Myeloid Leukemia.

BACKGROUND: Some chemotherapeutic agents cause carnitine deficiency, which causes general fatigue. However, there is no study on carnitine deficiency in patients with chronic myeloid leukemia (CML) during tyrosine kinase inhibitor (TKI) therapy. OBJECTIVE: In this study, we investigated carnitine concentrations in patients with CML receiving TKI therapy. METHOD: This study included patients with well-controlled CML. Total carnitine and free carnitine concentrations were evaluated using the enzyme cycling method. The brief fatigue inventory (BFI) and cancer fatigue scale (CFS) were used to assess general fatigue developed during TKI therapy. RESULTS: Fifty-five patients on TKI therapy were included. Of these, 12 (21.8%) patients had low free carnitine concentrations. Free carnitine concentrations were higher in men than in women. Younger age was closely associated with lower free carnitine concentrations. TKI type, TKI dose, treatment response, or therapy duration were not associated with free carnitine concentrations. None of the scores (the global fatigue score with the BFI and CFS score) correlated with carnitine concentrations. Concentrations of free carnitine in patients in the treatment-free remission group were slightly higher than those in the TKI group, with only 9.1% having a low concentration of free carnitine. CONCLUSION: Carnitine deficiency is probably not a major cause of general fatigue but may occur in patients with CML receiving TKI therapy.

Plastic deformation of synthetic quartz nanopillars by nanoindentation for multi-scale and multi-level security artefact metrics.

Individual authentication using artefact metrics has received increasing attention, as greater importance has been placed on the security of individual information. These artefact metrics must satisfy the requirements of individuality, measurement stability, durability, and clone resistance, in addition to possessing unique physical features. In this study, we proposed that nanostructures of synthetic quartz (SQ) deposited on an SQ plate may provide sophisticated artefact metrics if morphological changes could be intentionally introduced into the SQ nanostructures at certain positions. We fabricated SQ nanopillars using a mass-production method (ultraviolet nanoimprint lithography) and investigated their mechanical deformation using nanoindentation with a spheroid diamond tip through a loading and unloading cycle. The SQ nanopillars with an aspect ratio of 1 (i.e., diameters D of 100 and 200 nm with corresponding heights H of 100 and 200 nm, respectively) could be plastically deformed without collapsing within a specified pillar-array format at programmed positions. The plastically deformed SQ nanopillar arrays demonstrated multi-scale (sub-millimetre, micrometre, and nanometre) and multi-level (shape, area, diameter, and height) individuality authentication and clone resistance. Because SQ is physically and chemically stable and durable, individuality authentication can be a highly reliable tool on Earth and in space.

UVC disinfects SARS-CoV-2 by induction of viral genome damage without apparent effects on viral morphology and proteins.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a pandemic threat worldwide and causes severe health and economic burdens. Contaminated environments, such as personal items and room surfaces, are considered to have virus transmission potential. Ultraviolet C (UVC) light has demonstrated germicidal ability and removes environmental contamination. UVC has inactivated SARS-CoV-2; however, the underlying mechanisms are not clear. It was confirmed here that UVC 253.7 nm, with a dose of 500 µW/cm2, completely inactivated SARS-CoV-2 in a time-dependent manner and reduced virus infectivity by 10-4.9-fold within 30 s. Immunoblotting analysis for viral spike and nucleocapsid proteins showed that UVC treatment did not damage viral proteins. The viral particle morphology remained intact even when the virus completely lost infectivity after UVC irradiation, as observed by transmission electronic microscopy. In contrast, UVC irradiation-induced genome damage was identified using the newly developed long reverse-transcription quantitative-polymerase chain reaction (RT-qPCR) assay, but not conventional RT-qPCR. The six developed long RT-PCR assays that covered the full-length viral genome clearly indicated a negative correlation between virus infectivity and UVC irradiation-induced genome damage (R2 ranging from 0.75 to 0.96). Altogether, these results provide evidence that UVC inactivates SARS-CoV-2 through the induction of viral genome damage.

SARS-CoV-2 Disinfection of Air and Surface Contamination by TiO2 Photocatalyst-Mediated Damage to Viral Morphology, RNA, and Protein.

SARS-CoV-2 is the causative agent of COVID-19, which is a global pandemic. SARS-CoV-2 is transmitted rapidly via contaminated surfaces and aerosols, emphasizing the importance of environmental disinfection to block the spread of virus. Ultraviolet C radiation and chemical compounds are effective for SARS-CoV-2 disinfection, but can only be applied in the absence of humans due to their toxicities. Therefore, development of disinfectants that can be applied in working spaces without evacuating people is needed. Here we showed that TiO2-mediated photocatalytic reaction inactivates SARS-CoV-2 in a time-dependent manner and decreases its infectivity by 99.9% after 20 min and 120 min of treatment in aerosol and liquid, respectively. The mechanistic effects of TiO2 photocatalyst on SARS-CoV-2 virion included decreased total observed virion count, increased virion size, and reduced particle surface spike structure, as determined by transmission electron microscopy. Damage to viral proteins and genome was further confirmed by western blotting and RT-qPCR, respectively. The multi-antiviral effects of TiO2-mediated photocatalytic reaction implies universal disinfection potential for different infectious agents. Notably, TiO2 has no adverse effects on human health, and therefore, TiO2-induced photocatalytic reaction is suitable for disinfection of SARS-CoV-2 and other emerging infectious disease-causing agents in human habitation.

Absolute Lymphocyte Counts After Lenalidomide Initiation may Predict the Prognosis of Patients With Relapsed or Refractory Multiple Myeloma.

Background/Aim: We assessed the prognosis of patients with refractory or relapsed multiple myeloma (RRMM) by focusing on the change in absolute lymphocyte counts (ALCs) after lenalidomide and dexamethasone (Ld) initiation. Patients and Methods: In total, 72 patients with RRMM were treated with Ld. ALCs were evaluated before treatment and at 1, 2, and 3 months after Ld initiation. The median ALCs in the entire cohort before and at 1, 2, 3 months after Ld initiation were 1,131, 1,059, 1,222, and 1,162/µl, respectively. Results: ALCs before Ld initiation did not affect time to next treatment (TNT) or overall survival (OS). However, the patients with ALCs equal to or greater than the median at 3 months showed relatively better TNT than those with lower lymphocyte counts, with a significant difference. OS was also significantly longer in patients with higher ALCs. Conclusion: Immunomodulation by lenalidomide may improve prognosis in patients with RRMM.

Maintenance Therapy With Bortezomib and Dexamethasone for Transplant-ineligible Patients With Multiple Myeloma.

Background/Aim: Here, we investigated whether bortezomib as a maintenance therapy affected outcomes in transplant-ineligible patients with multiple myeloma (MM). Patients and Methods: Following induction therapy with bortezomib, maintenance therapy with bortezomib (1.3 mg/m 2 ) and dexamethasone (20 mg) was administered once or twice every 4 weeks until disease progression. The endpoints of this study were time to next treatment and overall survival. Results: Seventy-six newly diagnosed, transplant-ineligible patients were treated with a bortezomib-based regimen; 28 discontinued induction therapy, 27 did not receive maintenance therapy after induction therapy (the non-maintenance group), and 21 did (the maintenance group). In the three groups, the median times to the next required treatment were 3, 14, and 37 months, respectively. The 3-year overall survival rates were 55%, 69%, and 85%, respectively. There were no significant differences in patient characteristics between the non-maintenance and maintenance groups, except for poorer estimated glomerular filtration rates in the maintenance group. Conclusion: Bortezomib maintenance therapy may be a useful option for transplant-ineligible patients with MM.

Impact of CD56 Continuously Recognizable as Prognostic Value of Acute Promyelocytic Leukemia: Results of Multivariate Analyses in the Japan Adult Leukemia Study Group (JALSG)-APL204 Study and a Review of the Literature.

BACKGROUND: After long-term analysis of the JALSG-APL204 study we recently reported that maintenance therapy with tamibarotene was more effective than all-trans retinoic acid (ATRA) by reducing relapse in APL patients. Here, the clinical significance of other important prognostic factors was evaluated with multivariate analyses. PATIENTS AND METHODS: Newly diagnosed acute promyelocytic leukemia (APL) patients were registered with the study. Induction was composed of ATRA and chemotherapy. Patients who achieved molecular remission after consolidation were randomly assigned to maintenance with tamibarotene or ATRA. RESULTS: Of the 344 eligible patients, 319 (93%) achieved complete remission (CR). After completing consolidation, 269 patients underwent maintenance random assignment-135 to ATRA, and 134 to tamibarotene. By multivariate analysis, overexpression of CD56 in blast was an independent unfavorable prognostic factor for relapse-free survival (RFS) (p = 0.006) together with more than 10.0 × 109/L WBC counts (p = 0.001) and the ATRA arm in maintenance (p = 0.028). Of all phenotypes, CD56 was related most clearly to an unfavorable prognosis. The CR rate, mortality rate during induction and overall survival of CD56+ APL were not significantly different compared with CD56- APL. CD56 is continuously an independent unfavorable prognostic factor for RFS in APL patients treated with ATRA and chemotherapy followed by ATRA or tamibarotene maintenance therapy.

[Transformation of CD5-positive nodal marginal zone lymphoma to diffuse large B-cell lymphoma].

Nodal marginal zone lymphoma (NMZL) is a form of nodal B-cell lymphoma exhibiting proliferation of abnormal lymphocytes at the circumference of the mantle zone in the lymph nodes. Although the outcome of patients with this disease is often favorable, we recently encountered a patient with a CD5-positive NMZL who was resistant to chemotherapy. A 67-year-old woman complaining of systemic lymph node swelling was referred to our hospital. After biopsy of the neck lymph node, she was diagnosed with CD5-positive NMZL. Disease progression was revealed after 16 months, and she was initially treated with chemotherapy consisting of rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP). However, this therapy was ineffective. Subsequent therapy with rituximab and bendamustine also failed to induce remission. A rebiopsy revealed that the NMZL had transformed into a diffuse large B-cell lymphoma. This patient died after 2 years from the initial diagnosis due to lymphoma progression. Cases of CD5-positive NMZL are rare; thus, it is difficult to study the clinical implications of CD5 expression in this disease. Here we describe the current understanding of CD5 expression in NMZL.

Increased Arbekacin Clearance in Patients With Febrile Neutropenia.

BACKGROUND: Arbekacin (ABK) is used to treat infections caused by methicillin-resistant Staphylococcus aureus and is used widely for the treatment of febrile neutropenia (FN). As ABK has a narrow therapeutic concentration window, the dosage must be adjusted via therapeutic drug monitoring. However, the influence of the physiology of patients with FN on the pharmacokinetic (PK) parameters of ABK remains unclear. Therefore, we examined this influence on ABK PK parameters. METHOD: We performed a retrospective cohort study using data from patients with a hematologic malignancy who were ≥18 years and had been administered ABK. We excluded patients who did not receive therapeutic drug monitoring and had an estimated glomerular filtration rate (eGFR) of <30 mL/min, because clinically sufficient data would not be available. RESULT: Of the 99 enrolled patients, 25 did not have FN and 74 had FN. Arbekacin clearance (CLabk) was shown to correlate with eGFR in patients with FN (r = 0.32, P = 0.0062) and without FN (r = 0.50, P = 0.01). CLabk was higher in patients with FN than in those without FN. In addition, in the eGFR of <100 mL/min group (normal renal function), CLabk and CLabk/eGFR were also higher in patients with FN than in those without FN. CONCLUSIONS: CLabk was increased in patients with FN and normal renal function; therefore, we propose an increased ABK dose for patients with FN and normal renal function.

Photoinduced Reorientation in Thin Films of a Nematic Liquid Crystalline Polymer Anchored to Interfaces and Enhancement Using Small Liquid Crystalline Molecules.

The photoinduced reorientation of the side-chain mesogens in nematic liquid crystalline (LC) polymer thin films triggered by the axis-selective photo-Fries rearrangements of side-chain phenyl benzoate moieties is studied to understand the regulation of the anisotropic nanostructures supported by LC polymers. The influence of the substrate surface in anchoring the side-chain mesogens near the interfaces is examined by comparing the reorientation of 30- and 120-nm-thick films. Irradiation with linearly polarized ultraviolet (UV) light and subsequent annealing causes the side-chain mesogen reorientation to align perpendicular to the electric field of the incident UV light. The inplane order in the 30-nm-thick films is lower than that in the 120-nm ones. On the other hand, the annealing period required for mesogen alignment is independent of the film thickness. It is suggested that the substrate surfaces anchor the LC mesogens to fix their orientation, rather than slowing down the reorientational motion. In addition, it is demonstrated that small LC molecules miscible with the nematic LC polymer enhance photoinduced reorientation through cooperative molecular interaction with the side-chain mesogens, remarkably accelerating the orientation and improving the inplane order of the unidirectionally aligned mesogens.