[Pyogenic spondylitis after Corynebacterium striatum blood stream infection following allogeneic hematopoietic stem cell transplantation for malignant lymphoma].

Patient 1 was a 70-year-old woman with refractory diffuse large B-cell lymphoma who received allogeneic peripheral blood stem cell transplantation from an HLA-haploidentical related donor. Upper back pain appeared on day63, and Th8-Th9 pyogenic spondylitis was diagnosed based on magnetic resonance imaging (MRI). Blood culture on day14 identified Corynebacterium striatum as the causative bacteria of blood stream infection (BSI). The pyogenic spondylitis resolved after treatment with daptomycin for 2 months. Patient 2 was a 65-year-old man with relapsed angioimmunoblastic T-cell lymphoma who received bone marrow transplantation from an HLA-DR single-antigen-mismatched unrelated donor. Lower back pain appeared on day30, and L4-L5 pyogenic spondylitis was diagnosed based on MRI. Blood culture was negative. Daptomycin and clindamycin were selected for treatment based on the drug susceptibility of bacteria that had caused pre-engraftment BSI (Escherichia coli on day3 and Corynebacterium striatum on day9), and the pyogenic spondylitis resolved after 6 months of this treatment. Pyogenic spondylitis should be considered in the differential diagnosis of back pain accompanied by BSI before engraftment in allogeneic hematopoietic stem cell transplant recipients.

Investigation of V/III ratio dependencies for optimizing AlN growth during reduced parasitic reaction in metalorganic vapor phase epitaxy.

AlGaN-based ultraviolet (UV) light-emitting diodes (LEDs) are expected to have various applications, including sensing and printing, and light with ultraviolet-C (UVC) wavelengths has a virus inactivation effect. The metalorganic vapor phase epitaxy (MOVPE) method has been used to fabricate LED devices with film control and impurity doping. However, to achieve high luminous efficiency, highly crystalline aluminum nitride (AlN) must be grown in the underlying layer. Although high temperatures are required to grow high-quality AlN for strong migration at the surface, there is a trade-off in the high temperature promoting parasitic reactions. These parasitic reactions are more dominant at a high V/III ratio with more raw material in the case of using the conventional MOVPE. Here, we used jet stream gas flow MOVPE to investigate the effect of V/III ratio dependencies in optimizing AlN growth and without affecting parasitic reaction conditions. As a result, trends of typical AlN crystal growth at V/III-ratio dependencies were obtained. AlN is more stable at a higher V/III ratio of 1000, exhibiting a double atomic step surface, and the crystal orientation is further improved at 1700 °C compared to that at a lower V/III ratio.

High growth temperature for AlN by jet stream gas flow metalorganic vapor phase epitaxy.

Deep ultraviolet light-emitting diodes have attracted considerable attention for realizing virus inactivation applications. The UV-LEDs use the AlN underlying layer and the plane sapphire substrate. However, the low growth temperature in AlN underlying layer is grown by limited growth temperature in conventional MOVPE, and high temperature is preferable for AlN growth. Furthermore, the AlN underlying layer has many dislocations owing to the active layer in the device region when the flat sapphire substrate was used with a dislocation value of > 109 cm-2. We showed the high-temperature crystal growth of AlN with a temperature of 1700 °C by high temperature and gas flow velocity MOVPE. The achieved dislocation density was ~ 4 × 108 cm-2. Additionally, this data means the low dislocation densities in the AlN layer with a growth time of only 15 min and a dislocation density of < 1 × 109 cm-2 are obtained. The AlN growth temperature exceeding 1550 °C decreases the growth rate. These results indicate desorption from the surface of the substrate in a hydrogen atmosphere. Furthermore, the characteristic dislocation behavior of AlN in high-temperature growth at 1700 °C was elucidated from TEM images.

Ultra-thin deep ultraviolet perfect absorber using an Al/TiO2/AlN system.

An ultra-thin perfect absorber for deep ultraviolet light was realized using an Al/TiO2/AlN system. The TiO2 thickness was optimized using the Fresnel phasor diagram in complex space to achieve perfect light absorption. As a result of the calculation almost perfect absorption into the TiO2 film was found, despite the film being much thinner than the wavelength. An optimized Al/TiO2/AlN system was fabricated, and an average absorption greater than 97% was experimentally demonstrated at wavelengths of approximately 255-280 nm at normal light incidence. Our structure does not require nanopatterning processes, and this is advantageous for low-cost and large-area manufacturing.

[FIP1L1::PDGFRA-positive chronic eosinophilic leukemia presenting with multiple ulcers of oral cavity and gastrointestinal tract].

A 66-year-old man developed multiple erosions and pain in the lips and mouth, fever, and black stools. There was persistent bleeding from the lip erosions. When he was admitted to our hospital, his white blood cell count increased to 53,420/µl with 3% eosinophils, and hemoglobin decreased to 3.1 g/dl. Bone marrow biopsy revealed an elevated eosinophil level (24.0%) with markedly toxic granules. Gastrointestinal endoscopy revealed multiple ulcers and erosions in the pharynx, esophagus, stomach, and colon. Histopathological diagnosis indicated nonspecific inflammation with poor infiltration of eosinophils. Bone marrow FISH test was positive for 4q12 deletion (FIP1L1::PDGFRA), leading to the diagnosis of FIP1L1::PDGFRA-positive chronic eosinophilic leukemia. Following initiation of oral administration of imatinib 100 mg/day, the number of eosinophils decreased rapidly, and normalized 2 days after the start of imatinib. The mucosal lesions showed significant improvement and were diagnosed as leukemia-associated lesions. Based on the clinical course of our patient, multiple oral cavity and gastrointestinal ulcers could be the initial presentation in this leukemia.

[Successful alectinib monotherapy for residual disease after brentuximab vedotin combined chemotherapy in ALK-positive anaplastic large cell lymphoma].

A 28-year-old male patient presented with multiple lymphadenopathies and extranodal masses. He was diagnosed with stage IVB ALK-positive anaplastic large cell lymphoma after the right axillary lymph node biopsy. A partial metabolic response with fluorodeoxyglucose accumulation was observed in the residual disease of the upper left hilar lymph node after eight courses of brentuximab vedotin, cyclophosphamide, adriamycin, and prednisolone. We started alectinib at 600 mg daily, which achieved a complete metabolic response (CMR) after three months. The CMR was maintained and alectinib was continuously administered without adverse events at the last follow up. Alectinib showed high efficacy and tolerability, though the optimal period and long-term adverse effects of administration remain unclear. Therefore, further studies are necessary.

Reduction of parasitic reaction in high-temperature AlN growth by jet stream gas flow metal-organic vapor phase epitaxy.

AlGaN-based deep ultraviolet light-emitting diodes (LEDs) have a wide range of applications such as medical diagnostics, gas sensing, and water sterilization. Metal-organic vapor phase epitaxy (MOVPE) method is used for the growth of all-in-one structures, including doped layer and thin multilayers, using metal-organic and gas source raw materials for semiconductor devices. For AlN growth with high crystalline quality, high temperature is necessary to promote the surface migration of Al atoms and Al-free radicals. However, increase in temperature generates parasitic gas-phase prereactions such as adduct formation. In this work, AlN growth at 1500 °C by a stable vapor phase reaction has been achieved by jet stream gas flow metal-organic vapor phase epitaxy. The AlN growth rate increases with gas flow velocity and saturates at ~ 10 m/s at room temperature. Moreover, it is constant at an ammonia flow rate at a V/III ratio from 50 to 220. These results demonstrate the reduction in adduct formation, which is a typical issue with the vapor phase reaction between triethylaluminum and ammonia. The developed method provides the in-plane uniformity of AlN thickness within 5%, a low concentration of unintentionally doped impurities, smooth surface, and decrease in dislocation density because of the suppression of parasitic reactions.

Ultraviolet Light-Emitting Diode (UV-LED) Sterilization of Citrus Bacterial Canker Disease Targeted for Effective Decontamination of Citrus Sudachi Fruit.

A kind of citrus fruit with special flavor, Citrus sudachi harvested in Japan, are exported to various countries. However, the Citrus sudachi needs to be sterilized using aqueous solution of sodium hypochlorite because there is a possibility of the adhesion of citrus bacterial canker (CBC) which is not found in Europe. Due to the sterilization with time-consuming work, a more effective decontamination technique is required. A decontamination method using ultraviolet (UV) light irradiation is thus anticipated. Especially, the use of light emitting diodes (LEDs) wi UV light has many advantages in terms of energy consumption, lifetime, and compactness； although an appropriate method is yet to be established. In this study, we evaluate the fundamental effectiveness of UV-LED decontamination on the basis of the bactericidal ability on CBC in petri dishes, using six kinds of UV-LEDs (265, 280, 285, 300, 310, and 365 nm) . For each irradiation, the resultant bactericidal abilities (BAs) were evaluated precisely taking into account the differences in their optical absorptions. In addition, BAs per unit photon number were also estimated, as a fundamental wavelength-dependence of BA. As a result, the effectiveness of UV-LED irradiation with relatively short wavelengths was demonstrated clearly.

[Successful treatment with cidofovir for disseminated adenovirus infection accompanied by hemophagocytic syndrome and meningitis in an allogeneic hematopoietic stem cell transplantation recipient].

A 65-year-old woman received bone marrow transplantation from an HLA-DRB1 one locus mismatched donor for high-risk myelodysplastic syndrome. On day 237 after transplantation, she developed recurrent acute gastrointestinal graft-versus-host disease and adenoviral hemorrhagic cystitis. Hence, the methylprednisolone (mPSL) dose was increased to 2 mg/kg, and mesenchymal stem cells were administered. After the dose was tapered, she developed high fever, gross hematuria, and progressive pancytopenia. Then, the serum LDH, ferritin, and hepatobiliary enzyme levels of the patient increased, and hemophagocytosis was observed based on bone marrow examination. The adenovirus DNA level in the plasma was 6.3×106 copies/ml on day 278, and the volume of cerebrospinal fluid increased. Hence, the patient was diagnosed with meningitis and disseminated adenovirus infection. On day 288, cidofovir was administered at a dose of 1 mg/kg three times a week for 8 doses. The mPSL dose was again increased to 2 mg/kg for the treatment of hemophagocytic syndrome. Then, the patient's symptoms gradually improved, and the adenovirus viral load became negative on day 369. Based on the clinical course of our patient, cidofovir is useful for severe adenovirus infection.

Quantitative evaluation of SARS-CoV-2 inactivation using a deep ultraviolet light-emitting diode.

Inactivation technology for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is certainly a critical measure to mitigate the spread of coronavirus disease 2019 (COVID-19). A deep ultraviolet light-emitting diode (DUV-LED) would be a promising candidate to inactivate SARS-CoV-2, based on the well-known antiviral effects of DUV on microorganisms and viruses. However, due to variations in the inactivation effects across different viruses, quantitative evaluations of the inactivation profile of SARS-CoV-2 by DUV-LED irradiation need to be performed. In the present study, we quantify the irradiation dose of DUV-LED necessary to inactivate SARS-CoV-2. For this purpose, we determined the culture media suitable for the irradiation of SARS-CoV-2 and optimized the irradiation apparatus using commercially available DUV-LEDs that operate at a center wavelength of 265, 280, or 300 nm. Under these conditions, we successfully analyzed the relationship between SARS-CoV-2 infectivity and the irradiation dose of the DUV-LEDs at each wavelength without irrelevant biological effects. In conclusion, total doses of 1.8 mJ/cm2 for 265 nm, 3.0 mJ/cm2 for 280 nm, and 23 mJ/cm2 for 300 nm are required to inactivate 99.9% of SARS-CoV-2. Our results provide quantitative antiviral effects of DUV irradiation on SARS-CoV-2, serving as basic knowledge of inactivation technologies against SARS-CoV-2.

Kinetics and clinical significance of human herpesvirus 6 DNA shedding in saliva after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Little is known about the kinetics and clinical significance of saliva human herpesvirus-6 (HHV-6) DNA after hematopoietic stem cell transplantation (HSCT). METHODS: In this observational study, we quantified HHV-6 DNA in serially collected plasma and saliva from allogeneic HSCT recipients. Associations between the status of salivary HHV-6 DNA and the development of HHV-6 encephalitis, depression, and oral mucosal graft-versus-host disease (GVHD) were retrospectively analyzed. RESULTS: A total of 787 plasma and 434 saliva samples were collected from 56 patients. The cumulative incidence of HHV-6 DNA in plasma and saliva at 60 days after transplantation was 51.8% and 83.9%, respectively. The peak level of salivary HHV-6 DNA was significantly higher in patients who displayed plasma HHV-6 DNA than in those who did not (median, 51,584 copies/mL vs 587 copies/mL; P < .0001). Salivary HHV-6 DNA levels increased after positive plasma HHV-6 DNA was detected and remained high during observation period. Despite the frequent occurrence of positive salivary HHV-6 DNA, no patient developed depression. Positivity of salivary HHV-6 DNA was not significantly associated with the development of HHV-6 encephalitis (P = 1.00, Fisher's exact test) or oral mucosal GVHD (P = .71, Grey's test). No significant relationship between salivary HHV-6 DNA and these diseases was found even when comparing higher HHV-6 DNA loads in saliva. CONCLUSION: Salivary HHV-6 DNA levels increased after HHV-6 DNA was detected in the blood. However, no epidemiological evidence was shown to support a role of salivary HHV-6 in the development of HHV-6 encephalitis, depression, and oral mucosal GVHD.

[Successful delivery after chemotherapy for acute myeloid leukemia diagnosed in the second trimester].

Development of acute myeloid leukemia (AML) during pregnancy is rare, and the available data are limited to small retrospective reports. Currently, no guidelines exist for the management of AML during pregnancy in Japan. A 26-year-old female was diagnosed with AML at 19 weeks of gestation, received chemotherapy with daunorubicin and cytarabine, and achieved complete remission. Following the first consolidation therapy, she gave birth to a 1964-g female infant by cesarean section at 33 weeks of gestation. One week later, she was initiated on the second consolidation therapy; however, she developed a pelvic abscess during neutropenia. She underwent urgent surgery for open drainage and recovered soon after surgery. She has been in complete remission for eight months, and the daughter is healthy. Chemotherapy delivered after the second trimester rarely causes congenital malformations and may not require the termination of pregnancy. The clinical course of the present case suggests that chemotherapy can be performed safely and effectively in pregnant patients with AML after the trimester and babies.

[Philadelphia chromosome-positive acute lymphoblastic leukemia relapsing with an anterior chamber lesion of the eye].

A 48-year-old Filipino woman underwent umbilical cord blood stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia under non-remission status. Left aqueous humor puncture was performed owing to the development of left eye pain and exacerbation of anterior eye chamber inflammation 72 days after the transplantation; this revealed the relapse of leukemia in the anterior chamber. Subsequently, the patient tested positive for peripheral blood minimal residual disease. Therefore, doctors should take note that anterior chamber disease may appear as a non-typical relapse of leukemia.

[Successful treatment of secondary graft failure in a mixed-phenotype acute leukemia patient with haploidentical hematopoietic stem cell transplantation and post-transplant cyclophosphamide administration].

A 38-year-old woman in the first remission of mixed-phenotype acute leukemia underwent unrelated bone marrow transplantation from an HLA-DR-mismatched donor in the host-versus-graft (HVG) direction with myeloablative conditioning. Neutrophil engraftment was achieved and complete donor chimera was obtained on days 21 and 29 after transplantation, respectively. Subsequently, with delayed blood cell recovery, continuous transfusion was needed to replace platelets. In the CD3 peripheral blood chimerism test, the percentage of recipient cells on days 50, 63, and 80 was 27.3%, 90%, and 95% or higher, respectively. With no relapse of leukemia observed on bone marrow examination, secondary graft failure associated with autologous hematopoietic recovery was diagnosed. Bone marrow transplantation from the patient's HLA-haploidentical sister was performed because of graft failure on day 111 after the initial transplant using post-transplant cyclophosphamide (PTCy). Neutrophil engraftment was achieved and complete donor chimera was obtained on days 14 and 21 after the second transplantation, respectively. With no serious complications or acute graft versus host disease, the patient was discharged with symptomatic improvement. According to our results, retransplant using PTCy obtained from an HLA-haploidentical sibling donor is a potential treatment for graft failure.

Successful Cord Blood Stem Cell Transplantation for an Adult Case of Chronic Active Epstein-Barr Virus Infection.

A 41-year-old man was referred to our hospital for treatment of anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma. Chronic active Epstein-Barr virus (CAEBV) was diagnosed based on the findings of elevated EBV antibody titers and positive EBV-DNA in the peripheral blood, and cord blood stem cell transplantation (CBT) was performed. The EBV-DNA levels in the blood fell below the limit of detection. His lymphoma relapsed on Day 165 with the appearance of eruptions, which disappeared after the withdrawal of tacrolimus. One year after transplantation, there were no signs of recurrence. This encouraging result suggests that CBT should be considered for adult cases of CAEBV with aggressive clinical manifestations.

[Hypofibrinogenemia associated with steroid therapy for the patients who developed GVHD after allogeneic stem cell transplantation].

Hypofibrinogenemia (plasma fibrinogen level <150 mg/dl) is occasionally observed after allogeneic hematopoietic stem cell transplantation, and its etiology is often difficult to determine. We herein report that steroids administered for the treatment of graft-versus-host disease (GVHD) are associated with the development of hypofibrinogenemia. We retrospectively analyzed the plasma fibrinogen (Fg) levels in 15 consecutive patients who had been administered 1 mg/kg/day (1 mg/kg group) or 2 mg/kg/day (2 mg/kg group) methylprednisolone for the treatment of Grade II to IV acute GVHD. Hypofibrinogenemia had developed in 8 of the 15 patients (53%) by day 50 after the start of steroid treatment, and was observed in 2 of 6 patients in the 1 mg/kg group and 6 of 9 in the 2 mg/kg group. A significant decrease in the Fg level was observed in the 2 mg/kg group (the median value before starting steroid treatment and that on the 20th day after starting steroid treatment were 506 mg/dl and 180 mg/dl, respectively, P=0.0013). Other possible causes of hypofibrinogenemia, including liver dysfunction or disseminated intravascular coagulation, were confirmed in only 3 patients during the observation period. In conclusion, hypofibrinogenemia commonly occurs in patients treated with steroids, especially those administered 2 mg/kg/day methylprednisolone for the treatment of GVHD.