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Noise spectroscopy is a key technique to investigate the nature and dynamics of charge carriers in superconductors. The recently discovered superconducting hybrids with Bogoliubov Fermi surfaces exhibit a particularly intriguing and rich charge dynamics, as their charge carriers consist of both Cooper pairs and an extensive number of Bogoliubov quasiparticles. Motivated by this, we compute the noise spectra of Bogoliubov Fermi surfaces and identify their key signatures in the differential conductance and the Fano factor. Specifically, we consider a semiconductor/superconductor hybrid device with an in-plane magnetic field, which exhibits several Bogoliubov Fermi surfaces. The number and orientation of the Bogoliubov Fermi surfaces in this device can be readily controlled by the applied magnetic field, which in turn alters the noise signal. In particular, we find that the Fano factor exhibits a reduced value, substantially lower than two, whenever the charge dynamics is governed by a large number of Bogoliubov quasiparticles. Using experimentally relevant parameters, we make a number of specific predictions for the noise spectra, that can be used as direct evidence of Bogoliubov Fermi surfaces. In particular, we find that the Fano factor as a function of magnetic field and spin-orbit coupling exhibits characteristic discontinuities at the transition lines that separate phases with different number of Bogoliubov Fermi surfaces., Comment: 6 pages, 4 figure, supplemental material

Nodal topological superconductors characterized by $p_x$-wave pairing symmetry host flat-band Majorana bound states causing drastic anomalies in low-energy electromagnetic responses. Nevertheless, the study of flat-band Majorana bound states has been at a standstill owing to a serious lack of candidate materials for $p_x$-wave superconductors. In this paper, by expanding a scheme of planar topological Josephson junctions, we propose a promising device realizing an effective $p_x$-wave superconductor. Specifically, we consider a three-dimensional Josephson junction consisting of a thin-film semiconductor hosting a persistent spin-helix state and two conventional $s$-wave superconductors. We analytically obtain a topological phase diagram and numerically demonstrate the emergence of flat-band Majorana bound states by calculating the local density of states., Comment: 17 pages, 9 figures

The authors propose a tunneling spectroscopy experiment to distinguish possible even-parity superconducting states of strontium ruthenate.

We theoretically study the effects of spin-orbit interactions on symmetry of a Cooper pair in a spin-singlet d-wave superconductor in two-dimension. The pairing symmetry is analyzed in terms of the anomalous Green's function which is obtained by solving the Gor'kov equation analytically. A spin-orbit interaction induces a spin-triplet p-wave pairing correlation in a uniform superconductor. An odd-frequency spin-triplet s-wave pairing correlation appears at a surface of such superconductor as a result of breaking inversion symmetry locally. We also discuss a close relationship among the odd-frequency pairing correlation, chirality of surface bound states at the zero energy, and the anomalous proximity effect. The obtained results enable us to design a superconductor which causes the strong anomalous proximity effect., 14 pages, 5 figures

Despite much effort over the past two decades, the pairing symmetry of a ${\mathrm{Sr}}_{2}{\mathrm{RuO}}_{4}$ superconductor is still unclear. Motivated by the recent rapid progress in fabrication techniques for ${\mathrm{Sr}}_{2}{\mathrm{RuO}}_{4}$ thin films, we propose a promising strategy for identifying the spin-triplet superconductivity in the thin-film geometry by employing an antisymmetric spin-orbit-coupling potential and a Zeeman potential due to an external magnetic field. We demonstrate that a spin-triplet superconducting thin film undergoes a phase transition from a helical state to a chiral state by increasing the applied magnetic field. This phase transition is accompanied by a drastic change in the property of surface Andreev bound states. As a consequence, the helical-chiral phase transition, which is unique to the spin-triplet superconductors, can be detected through a sudden change in a tunneling conductance spectrum of a normal-metal/superconductor junction. Importantly, our proposal is constructed by combining fundamental and rigid concepts regarding the physics of spin-triplet superconductivity.

We study theoretically the Josephson effect between two time-reversal two-band superconductors, where we assume the equal-time spin-singlet $s$-wave pair potential in each conduction band. %as well as the band asymmetry and the band hybridization in the normal state. The superconducting phase at the first band $\varphi_1$ and that at the second band $\varphi_2$ characterize a two-band superconducting state. We consider a Josephson junction where an insulating barrier separates two such two-band superconductors. By applying the tunnel Hamiltonian description, the Josephson current is calculated in terms of the anomalous Green's function on either side of the junction. We find that the Josephson current consists of three components which depend on three types of phase differences across the junction: the phase difference at the first band $\delta\varphi_1$, the phase difference at the second band $\delta\varphi_2$, and the difference at the center-of-mass phase $\delta(\varphi_1+\varphi_2)/2$. A Cooper pairs generated by the band hybridization carries the last current component. In some cases, the current-phase relationship deviates from the sinusoidal function as a result of time-reversal symmetry breaking down., Comment: 6 page, 2 figures

We discuss the minimum value of the zero-bias differential conductance in a normal-metal/unconventional-superconductor junction. A numerical simulation demonstrates that the zero-bias conductance is quantized at $$(4e^2/h) N_\mathrm {ZES}$$ in the limit of strong impurity scatterings in the normal-metal. The integer $$N_\mathrm {ZES}$$ represents the number of perfect transmission channels through the junction. By focusing on the chiral symmetry of Hamiltonian, we prove the existence of $$N_\mathrm {ZES}$$ -fold degenerate resonant states in the dirty normal segment.

The anomalous proximity effect in dirty superconducting junctions is one of most striking phenomena highlighting the profound nature of Majorana bound states and odd-frequency Cooper pairs in topological superconductors. Motivated by the recent experimental realization of planar topological Josephson junctions, we describe the anomalous proximity effect in a superconductor/semiconductor hybrid, where an additional dirty normal-metal segment is extended from a topological Josephson junction. The topological phase transition in the topological Josephson junction is accompanied by a drastic change in the low-energy transport properties of the attached dirty normal-metal. The quantization of the zero-bias differential conductance, which appears only in the topologically nontrivial phase, is caused by the penetration of the Majorana bound states and odd-frequency Cooper pairs into a dirty normal-metal segment. As a consequence, we propose a practical experiment for observing the anomalous proximity effect., Comment: 10 pages, 6 figures

Majorana corner modes appearing in two-dimensional second-order topological superconductors have great potential applications for fault-tolerant topological quantum computations. We demonstrate that in the presence of an in-plane magentic field two-dimensional ($s+p$)-wave superconductors host Majorana corner modes, whose location can be manipulated by the direction of the magnetic field. In addition, we discuss the effects of edge imperfections on the Majorana corner modes. We describe how different edge shapes and edge disorder affect the number and controllability of the Majorana corner modes, which is of relevance for the implementation of topological quantum computations. We also discuss tunneling spectroscopy in the presence of the Majorana corner modes, where a lead-wire is attached to the corner of the noncentrosymmetric superconductor. The zero-bias differential conductance shows a distinct periodicity with respect to the direction of the magnetic field, which demonstrates the excellent controllability of the Majorana corner modes in this setup. Our results lay down the theoretical groundwork for observing and tuning Majoran corner modes in experiments on ($s+p$)-wave superconductors., Comment: 11 pages, 10 figures

Chiral $p$-wave superconductor is the primary example of topological systems hosting chiral Majorana edge states. Although candidate materials exist, the conclusive signature of chiral Majorana edge states has not yet been observed in experiments. Here we propose a smoking-gun experiment to detect the chiral Majorana edge states on the basis of theoretical results for the nonlocal conductance in a device consisting of a chiral $p$-wave superconductor and two ferromagnetic leads. The chiral nature of Majorana edge states causes an anomalously long-range and chirality-sensitive nonlocal transport in these junctions. These two drastic features enable us to identify the moving direction of chiral Majorana edge states in the single experimental setup., Comment: 14 pages, 6 figures

We discuss the symmetry property of a nodal superconductor that hosts robust flat-band zero-energy states at its surface under potential disorder. Such robust zero-energy states are known to induce the anomalous proximity effect in a dirty normal metal attached to a superconductor. A recent study has shown that a topological index ${\cal N}_\mathrm{ZES}$ describes the number of zero-energy states at the dirty surface of a $p$-wave superconductor. We generalize the theory to clarify the conditions required for a superconductor that enables ${\cal N}_\mathrm{ZES}\neq 0$. Our results show that ${\cal N}_\mathrm{ZES}\neq 0$ is realized in a topological material that belongs to either the BDI or CII class. We also present two realistic Hamiltonians that result in ${\cal N}_\mathrm{ZES}\neq 0$., Comment: 9 pages, 3 figures

In the present study, the dosage and duration of rasburicase administration were retrospectively evaluated for the ability to control the serum uric acid (S-UA) level in 13 patients diagnosed with hematological malignancies and tumor lysis syndrome (TLS), or those at risk of developing TLS, at the University of Fukui Hospital. At the time of diagnosis, seven patients already exhibited laboratory TLS, and three demonstrated clinical TLS. All patients received rasburicase in addition to chemotherapy agents. The median dose was 0.19 mg/kg (range, 0.13–0.25 mg/kg), and the median duration was four days (range, 1–7 days). Six patients sequentially received a xanthine oxidase inhibitor, allopurinol or febuxostat. The primary estimate was the normalization of the S-UA level at the end of rasburicase treatment and on treatment day seven. The average S-UA level prior to treatment was 10.4±4.5 mg/dl (mean ±standard deviation), and 11 out of 13 patients demonstrated a S-UA level >7 mg/dl. The S-UA level at the end of rasburicase administration was 0.5±1.5 mg/dl and the S-UA level at day seven was 1.4±1.5 mg/dl. All the patients achieved normalization of the S-UA level. On day seven subsequent to the initiation of treatment, the patients receiving rasburicase for a maximum of three days exhibited an S-UA level of 1.9±1.8 mg/dl, while the patients receiving rasburicase for longer than three days demonstrated an S-UA level of 1.0±1.3 mg/dl (P=0.20; Mann-Whitney test). The administration of 0.13 mg/kg and 0.22 mg/kg resulted in comparable UA level reductions. The administration of allopurinol or febuxostat following rasburicase administration suppressed the re-increase in S-UA level. Therefore, it was concluded that reduced administration of rasburicase successfully controlled the S-UA level in TLS.

Objective We retrospectively compared the clinical efficacy and toxicity of rituximab (R)-THP-COP (pirarubicin, cyclophosphamide, vincristine, and prednisolone) with that of R-CHOP (rituximab, adriamicin, cyclophosphamide, vincristine, and prednisolone) in previously untreated old patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients admitted to our institution between 2004 and 2013 were examined. The patients received either R (375 mg/m2, day 1)-THP-COP (pirarubicin 50 mg/m2 day 1, cyclophosphamide 750 mg/m2 day 1, vincristine 1.4 mg/m2 day 1, and prednisolone 100 mg day 1-5) or R-CHOP (adriamicin 50 mg/m2 day 1, cyclophosphamide 750 mg/m2 day 1, vincristine 1.4 mg/m2 day 1, and prednisolone 100 mg day 1-5). The doses of chemotherapeutic agents were adjusted depending on the patient's age and associated complications. The treatment was performed for 6 to 8 cycles. Results Among 74 patients with DLBCL (median 76, range 65-90 years; male 39, female 35), 29 received R-THP-COP, while 45 received R-CHOP. The overall response rates were 94.6% (complete response 86.4%, partial response 8.1%). The 2-year overall and progression-free survival rates were 77.6% and 68.5% for the R-THP-COP regimen and 79.2% and 78.9% for R-CHOP, respectively. No significant differences were found between these two regimens regarding the clinical efficacies. The most frequent adverse event was neutropenia (72.4% for the R-THP-COP regimen, 88.9% for the R-CHOP regimen). The cardiac function as evaluated by ejection fraction values was not impaired in either regimen. Conclusion R-THP-COP was effective and safe as an alternative to R-CHOP.

We discuss the stability of highly degenerate zero-energy states tha appear at the surface of a nodal superconductor preserving time-reversal symmetry. The existence of such surface states is a direct consequence of the nontrivial topological numbers defined in the restricted Brillouin zones in the clean limit. In experiments, however, potential disorder is inevitable near the surface of a real superconductor, which may lift the high degeneracy at zero energy. We show that an index defined in terms of the chiral eigenvalues of the zero-energy states can be used to measure the degree of degeneracy at zero energy in the presence of potential disorder. We also discuss the relationship between the index and the topological numbers., 12 pages, 7 figures

The primary objective of the present study was to correlate blood cell counts (lymphocyte, monocyte and platelet counts) with early disease relapse following the attainment of complete remission (CR) by the rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP)-like regimen in patients with advanced diffuse large B-cell lymphoma (DLBCL). In total, 30 patients were evaluated, with a median follow-up period of 43 months. All the participating patients attained CR. In total, eight patients experienced relapse within two years of the diagnosis, and the three-year overall survival rate was recorded as 77%. The peripheral counts for lymphocytes, monocytes and platelets, and the lymphocyte-monocyte ratio, all of which have been reported to be prognostic in DLBCL, were assessed. None of these parameters were correlated with the incidence of early relapse or with the prognosis. The lymphocyte count was higher in the patients with durable remission than in those who relapsed, however, no significant differences were identified. Thus, the present study concluded that early disease relapse was not predicted by peripheral blood cell counts in advanced DLBCL that reached CR using the R-CHOP-like regimen.

Background To examine the utility of diffusion-weighted MRI (DW-MRI) for staging and early response to chemotherapy assessment in lymphoma patients as compared with fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). Methods Twenty-eight patients with histologically confirmed malignant lymphoma underwent both MRI and FDG-PET/CT before (pretreatment) and after two courses of chemotherapy (mid-treatment). Staging with MRI (DW-MRI alone and with T2-weighted images) and FDG-PET was compared visually, and the concordance rate (kappa value, κ) was calculated. To evaluate early response to chemotherapy, patients were divided into two groups, lesion-positive (LP) and lesion-negative (LN), based on a proposed original criterion. Progression-free survival (PFS) was compared between the groups using the Kaplan-Meier method. Results The stage diagnosed with DW-MRI alone and with FDG-PET/CT was concordant in 22 patients (κ = 0.71; P

Tetracyclines are administered to cure Japanese spotted fever (JSF) and tsutsugamushi disease (TD). It is generally said that the clinical course of JSF is worse than that of TD despite antibiotic treatment. The precise mechanism underlying the more severe clinical course of JSF is not fully understood. We therefore examined whether the differential cytokine profile between these two infectious diseases contributes to the difference in clinical severity. The serum concentrations of various cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and gamma interferon [IFN-γ]) and chemokines (IL-8, interferon-inducible protein 10 [IP-10], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein 1α [MIP-1α], MIP-1β, and eotaxin) were measured in 32 TD and 21 JSF patients. The results showed that serum levels of TNF-α in the acute phases of TD and JSF were significantly increased, with a higher concentration of TNF-α in patients with JSF (mean, 39.9 pg/ml) than in those with TD (mean, 13.8 pg/ml). Comparatively higher levels of other cytokines and chemokines (IL-6, IFN-γ, IL-8, IP-10, MCP-1, MIP-1α, and MIP-1β) were also observed in the acute phase of JSF. The clinical severity score (3.67 ± 1.71) of JSF patients was higher than that of TD patients (1.47 ± 0.77). Our findings revealed that the cytokine and chemokine levels in the acute phase of JSF were significantly higher than those in the acute phase of TD. The differential cytokine levels may be related to the difference in clinical severity between JSF and TD.

Summary Objectives The rapid diagnosis of bacteremia is crucial for patient management including the choice of antimicrobial therapy, especially in cases of hematological disease, because neutropenia occurs frequently during antineoplastic chemotherapy or disease progression. We describe a rapid detection and identification system that uses universal PCR primers to amplify a variable region of bacterial 16S ribosomal DNA (rDNA), followed by DNA microarray hybridization. Methods Probes for 72 microorganisms including most causal clinical pathogens were spotted onto a microarray plate. The DNA microarray and conventional methods of identification were applied to 335 cultures from patients with hematological diseases. Results Forty-one samples (12.2%) tested positive by conventional blood culture test in a few days, while 40 cases (11.9%) were identified by the new method within 24h. The sensitivity and specificity of this new method were 93% and 99%, respectively, compared with conventional blood culture testing. Conclusions PCR combined with a DNA microarray is useful for the management of febrile patients with hematological diseases.

Plasmablastic lymphoma (PBL) is a rare AIDS-related malignancy with a poor prognosis. Little is known about this entity, and no standard treatment regimen has been defined. To establish an adequate treatment strategy, we investigated 24 cases of PBL arising in human immunodeficiency virus-positive individuals. Most of the patients were in the AIDS stage, with a median CD4 count of 67.5/µL. Lymph nodes (58 %), gastrointestinal tract (42 %), bone marrow (39 %), oral cavity (38 %), and CNS (18 %) were the most commonly involved sites. Histology findings for the following were positive at varying rates, as follows: CD10 (56 %); CD30 (39 %); CD38 (87 %); MUM-1 (91 %); CD138 (79 %); EBER (91 %); and LMP-1 (18 %). There was a marked increase in patients in 2011–12, and the cases found in that period appeared to be more aggressive, showing a higher rate of advanced-stage PBL. Fourteen cases were treated with CHOP, while the others were treated with more intensive regimens, including bortezomib and hematopoietic stem cell transplantation. The overall median survival time was 15 months. A CD4 count of >100/µL at diagnosis and attaining complete remission in the first-line chemotherapy were associated with better outcomes (P = 0.027 and 0.0016, respectively). Host immune status and chemosensitivity are associated with improved prognosis in PBL.

Gemtuzumab ozogamicin (GO) consists of the CD33 antibody linked to calicheamicin. The binding of GO to the CD33 antigen on leukemic cells results in internalization followed by the release of calicheamicin, thereby inducing DNA strand breaks. We hypothesized that the induction of DNA strand breaks would be a surrogate marker of GO cytotoxcity. Here, two GO‐resistant variants (HL/GO‐CSA [225‐fold], HL/GO [200‐fold]) were established by serially incubating human leukemia HL‐60 cells with GO with or without a P‐glycoprotein (P‐gp) inhibitor, cyclosporine A, respectively. The CD33 positivity was reduced in both variants. The HL/GO‐CSA cells showed an increased multidrug resistance protein‐1 (MRP1) transcript, and an MRP1 inhibitor partially reversed GO resistance. The HL/GO cells had neither P‐gp nor MRP1 overexpression. Microarray analysis and Western blotting indicated elevated levels of DNA repair‐associated proteins in both variants. Two other leukemic subclones, showing either P‐gp or MRP1 overexpression, were also GO‐resistant. Using single cell gel electrophoresis analysis, it was determined that GO‐induced DNA strand breaks increased dose‐dependently in HL‐60 cells, whereas the number of breaks was reduced in the GO‐resistant cell lines. The induction of DNA strand breaks was correlated with GO sensitivity among these cell lines. The CD33 positivity and the expression levels of transporters were not proportional to drug sensitivity. Using primary leukemic cells, the induction of DNA strand breaks appeared to be associated with GO sensitivity. Thus, GO‐induced DNA strand breaks as the final output of the mechanism of action would be critical to predict GO cytotoxicity.

We theoretically study the stability of more than one Majorana Fermion appearing in a $p$-wave superconductor/dirty normal metal/$p$-wave superconductor junction in two-dimension by using chiral symmetry of Hamiltonian. At the phase difference across the junction $\varphi$ being $\pi$, we will show that all of the Majorana bound states in the normal metal belong to the same chirality. Due to this pure chiral feature, the Majorana bound states retain their high degree of degeneracy at the zero energy even in the presence of random potential. As a consequence, the resonant transmission of a Cooper pair via the degenerate MBSs carries the Josephson current at $\varphi=\pi-0^+$, which explains the fractional current-phase relationship discussed in a number of previous papers., Comment: 11 pages, 2 figures

An 85-year-old female farmer was admitted to our hospital for fever, general fatigue, and skin rash. Cephalosporin was not effective and minocycline was dramatically effective. An eschar was discovered on her inguinal region after the defervescence. Laboratory examination of serum taken 12 days after onset of the illness showed elevated titers of antibodies against the Shimokoshi strain of Orientia tsutsugamushi. The gene sequence analysis of specimen from the patient's eschar revealed high similarity to the Shimokoshi strain by nested polymerase chain reaction. Therefore, this patient was diagnosed as a case of Shimokoshi-type tsutsugamushi disease, which has not previously been reported in Western Japan. Recently, cases of this type have also been confirmed in northeastern Japan, suggesting the need for further epidemiological studies.

A 69-year-old man with relapsed acute lymphoid leukemia was treated with adriamycin, vincristine, and prednisolone. During this chemotherapy, the patient developed sepsis and meningitis. Although many kinds of antimicrobial drugs, including imipenem, meropenem, amphotericin-B, and gamma-globulin were administered, the patient died of respiratory failure. A positive result for Enterococcus faecalis was obtained in both blood and cerebrospinal fluid culture. Autopsy revealed multiple small erosions in the lower esophagus. Histopathological examination showed multiple nuclear inclusion bodies of herpes simplex virus in the squamous epithelial cells at the edge of the erosions. Moreover, proliferation of micrococci was observed at the base of the erosions and in the lumina of the submucosal small vessels. These findings suggested that E faecalis entered the blood circulation from this lesion. In many patients with febrile neutropenia, the pathogenesis of infection remains unclear. Our case seems significant for clarifying the focus and pathogenesis of febrile neutropenia.

We describe the successful treatment of pyoderma gangrenosum (PG) that developed in a patient with myelodysplastic syndrome (MDS). A 63-year-old Japanese man with MDS was admitted to our hospital because of a large skin ulcer on his neck in November 2001. The initial diagnosis was infectious dermatitis, and antimicrobial therapy was performed, using imipenem/cilastatin, isepamicin, and amphotericin B. However, this therapy was not effective, and the lesion worsened. Cultures of blood, throat swab, and ulcer pus yielded no microorganisms. A biopsy of the skin lesion revealed a severe infiltration of neutrophils in the dermis, without any evidence of infection. The lesion was finally diagnosed as PG, and systemic administration of corticosteroid hormone was started in December 2001. The patient was initially pulsed with 1 g methylprednisolone daily for 3 days. The dose was immediately reduced, and the treatment was maintained with 30 mg prednisolone daily. The skin lesion responded markedly to the therapy, and C-reactive protein became negative. The patient was discharged in February 2002 because the lesion was almost cured. Prednisolone administration was tapered after 6-month maintenance therapy. No recurrence of PG was seen, although his MDS transformed into leukemia in April 2003. Only 31 cases of MDS developing PG have been reported in the past 20 years in Japan. This report describes one such rare patient who was successfully treated with the use of high-dose pulse methylprednisolone and long-term maintenance therapy.

The prognosis of acute myeloid leukemia (AML) in elderly patients remains poor due to their poor general condition and the intrinsic chemotherapy-resistant nature of their leukemia cells. The present retrospective study evaluated the clinical background as well as the response to treatment, of an unselected group of elderly patients with AML who were admitted to our Institution over a period of six years.Patients aged 65 years or older with AML admitted to our Institution between January 2005 and May 2011 were evaluated retrospectively.Forty-six patients were admitted to our Institution, among whom 41 received remission induction chemotherapy. Twenty-four patients received intensive chemotherapy, while 13 received low-dose cytarabine-based chemotherapy. Other modalities were used in four patients. Complete remission was obtained in 20 patients (48.8%). The complete remission rate (50.0%) tended to be higher in patients receiving intensive chemotherapy than in those receiving low-dose cytarabine-based regimens (30.7%; p=0.25). The median survival time for the whole patient group was 12 months and the 2-year overall survival was 18%. The median survival times for patients with complete remission and for non-responding patients were 14 months and 7 months, respectively. The 2-year overall survival in patients with complete remission was 32%, while that of non-responding patients was 6% (p=0.0025, log-rank test).The present study suggests the necessity of achieving complete remission for obtaining better survival for elderly patients with AML.

To examine the utility of diffusion-weighted MRI (DW-MRI) for staging and early response to chemotherapy assessment in lymphoma patients as compared with fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT).Twenty-eight patients with histologically confirmed malignant lymphoma underwent both MRI and FDG-PET/CT before (pretreatment) and after two courses of chemotherapy (mid-treatment). Staging with MRI (DW-MRI alone and with T2-weighted images) and FDG-PET was compared visually, and the concordance rate (kappa value, κ) was calculated. To evaluate early response to chemotherapy, patients were divided into two groups, lesion-positive (LP) and lesion-negative (LN), based on a proposed original criterion. Progression-free survival (PFS) was compared between the groups using the Kaplan-Meier method.The stage diagnosed with DW-MRI alone and with FDG-PET/CT was concordant in 22 patients (κ = 0.71; P 0.05), and by adding T2-weighted images, the number of concordant patients increased to 26 (κ = 0.90; P 0.05). On mid-treatment imaging, 19 patients were diagnosed as LN from both modalities. PFS differed significantly between LP and LN on both DW-MRI (P = 0.0013) and FDG-PET/CT (P = 0.037).DW-MRI is a promising tool for staging and evaluation of early response to chemotherapy in patients with lymphoma.

Hospital-acquired bloodstream infections (BSIs) are significant causes of mortality, and strategies to improve outcomes are needed. We aimed to evaluate the clinical efficacy of a multidisciplinary infection control team (ICT) approach to the initial treatment of patients with hospital-acquired BSI.A before-after quasiexperimental study of patients with hospital-acquired BSI was performed in a Japanese university hospital. The ICT provided immediate recommendations to the attending physician about appropriate antimicrobial therapy and management after reviewing blood cultures, Gram's stain, final organism, and antimicrobial susceptibility results.The sample included 469 patients with hospital-acquired BSI (n = 210, preintervention group; n = 259, postintervention group). There were no significant differences between the groups in background or microbiologic characteristics. The 30-day mortality was significantly lower and significantly more patients received appropriate antimicrobial therapy in the postintervention group (22.9% vs 14.3%; P = .02 and 86.5% vs 69.0%; P.001, respectively). Multivariate analysis confirmed that the ICT intervention was significantly associated with appropriate antimicrobial therapy (odds ratio, 2.22; 95% confidence interval, 1.27-3.89) and 30-day mortality (odds ratio, 0.49; 95% confidence interval, 0.25-0.95).A timely multidisciplinary team approach decreases the delay of appropriate antimicrobial treatment and may improve HABSI patient outcomes.

Uric acid in serum (S-UA) is produced by the breakdown of the cellular nucleic acids of leukemia cells, and may be a marker of disease aggressiveness. S-UA levels were examined for association with clinical outcomes in patients with acute myeloid leukemia (AML). Fifty-six patients with AML admitted to our Institution were evaluated retrospectively. The median S-UA level at diagnosis was 5.0 mg/dl (range 2-13.8 mg/dl). The S-UA levels did not correlate with peripheral lactate dehydrogenase, peripheral white blood cell counts, or peripheral blast counts, and were not proportional to bone marrow blast counts or marrow cellularity. The S-UA levels in the patients who achieved complete remission were slightly lower than those in those who did not. S-UA levels less than, or equal to the median (5.0 mg/dl) were significantly associated with better prognoses, compared with S-UA levels greater than 5.0 mg/dl. Thus, the S-UA level may predict the prognosis of AML, and is a versatile and cost-effective test for such a purpose.

The present retrospective study was conducted to measure Wilms' tumor-1 (WT1) mRNA levels in the peripheral blood of patients with acute myeloid leukemia (AML) in order to examine any association with the clinical outcomes.A total of 58 AML patients were evaluated retrospectively in our institution. WT1 transcripts were determined by real-time reverse transcriptase-polymerase chain reaction in peripheral blood samples.WT1 levels at diagnosis did not vary according to response of induction treatments, and the levels were comparable between the patients with durable remission and the patients with relapse of disease. WT1 levels at the completion of the treatment were higher in the group with relapse of disease than in the group with sustained remission. Detectable WT1 transcripts after the completion of chemotherapy courses were associated with poor prognoses.WT1 mRNA levels at treatment completion may predict for prognosis of AML.

Pancytopenia is caused by acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), aplastic anemia (AA), or by non-hematological diseases. Because Wilms' tumor-1 (WT1) is overexpressed in patients with AML and MDS, its expression level may be helpful for diagnosing these hematological malignancies.We retrospectively investigated the WT1 transcripts in peripheral blood (PB) from 47 patients with decreased blood cell counts.The final diagnoses included AML, MDS, AA, drug poisoning, and non-hematological diseases. PB WT1 mRNA was overexpressed in AML and MDS, whereas the patients with other diseases mostly tested negatively for the transcript. The patients with MDS with higher marrow blast counts had higher PB WT1 mRNA levels. The sensitivity of the PB WT1 transcript in detecting AML and MDS was 78%, and the specificity was 90%.The WT1 mRNA level in PB may help diagnose AML and MDS in patients with pancytopenia.

Minocycline, which is a member of the broad-spectrum bacteriostatic tetracycline antibiotics group, has also recently been shown to have additional effects that are separate from their antimicrobial function; however, the detailed mechanisms involved remain unknown. We examined the effects of minocycline on cytokine and chemokine production and the expression levels of intracellular phosphorylated proteins in a lipopolysaccharide (LPS)-induced cytokine response model in vitro. In the present study, 3 cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and interferon [IFN]-γ) and 7 chemokines (IL-8, interferon inducible protein [IP]-10, monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1α, MIP-1β, regulated upon activation normal T-cell expressed secreted [RANTES], and eotaxin) were suppressed by minocycline in a dose-dependent manner. Moreover, the phosphorylation of inhibitor of nuclear factor-κB alpha (IκBα) and IκB kinase (IKK)α/β, which is located upstream from IκBα, was significantly suppressed by minocycline, whereas the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK), p38, and TGF-β-activated kinase (TAK)1 were not affected. Thus, minocycline appears to inhibit the signaling pathway at the level of IKKα/β phosphorylation. In conclusion, minocycline was found to reduce the production of multiple cytokines and chemokines by inhibiting LPS-induced IKKα/β phosphorylation. That is, minocycline appears to be a potent inhibitor of IKKα/β phosphorylation. From a clinical and translational significance point-of view, these findings suggest that the use of minocycline offers the advantage of providing both antimicrobial and anti-inflammatory effects, which may be key in treating certain types of infectious diseases, particularly those that lead to hypercytokinemia and chronic inflammatory disorders.

In recent years, findings of coagulase-negative Staphylococci (CNS) have been increasing on blood culture tests taken from patients with hematological disorders; however, the diagnosis of true bacteremia is often very difficult because CNS is an indigenous bacterium of the skin. We investigated the relationship between the time from obtaining the blood specimen to the detection of positive culture tests as well as the significance of the pathogen detected. Twenty-three inpatients demonstrated CNS-positive blood culture tests. It was judged that six patients (26%) had contamination, while 17 patients (74%) had true bacteremia. The mean interval until positive culture was 45.3 and 13.9 hours, respectively (p0.005). The cut-off value for predicting true bacteremia was assumed to be 24 h; sensitivity was 94% and specificity was 83%. The interval until blood culture becomes positive will be a useful marker for accurately diagnosing true bacteremia.

Macrolide antibiotics are known to have a variety of immunomodulatory effects in addition to antimicrobial activity, but the mechanisms of immunomodulation are still unclear. We investigated in vitro the effect of azithromycin on tumor necrosis factor alpha (TNF-alpha) production in lipopolysaccharide (LPS)-stimulated THP-1 cells, a human monocytic cell line, and compared the results with those for other macrolides, minocycline and ofloxacin. In the presence of LPS, treatment with azithromycin (AZM) resulted in a significant decrease in LPS-induced TNF-alpha production compared to that with other antimicrobial agents. the results of phosphorylation of three MAPKs, ERK, JNK and p38, indicated that the phospho-p38 level was reduced by AZM. Ikappab-alpha, an inhibitor of NFkappab, was not disrupted by the antibiotics. LPS-induced TNF-alpha release from THP-1 cells was inhibited in the presence of KNK437, a potent 70-kDa heat shock protein (HSP-70) inhibitor. Interestingly, the induction of HSP-70 by LPS was attenuated with the concurrent addition of AZM in the cells. AZM was found to restrain TNF-alpha production by monocytes at least in part by modifying the HSp-70 and p38 related signaling pathways to LPS stimulation.

Pneumonia is a critical issue during the agonal phase, and often becomes lethal in the absence of pathogen detection. Autopsy is a powerful tool for analyzing the cause of a patient's death, progression of the disease, and the therapeutic response. However, it is frequently limited to the identification of bacterial strains. To elucidate the pathogenesis during the agonal phase of pneumonia, intrapulmonary sputum was harvested by directly inserting a swab into a resected lung, and the bacterial composition was analyzed using both pathological and microbiological techniques from 15 patients with hematological malignancies, and the results were compared with those from 25 patients with other medical and surgical diseases. Among the 54 bacteria strains isolated from the 40 patients, multidrug-resistant strains were significantly more prevalent in hematological group than in other diseases (16/21 versus 11/33, P = .002). Enterococcus faecium was preferentially isolated from the hematological patients, whereas the methicillin-resistant Staphylococcus aureus was predominantly found in the nonhematological group. Two coagulase-negative Staphylococcus epidermidis strains in hematological diseases may be diagnosed as causative bacteria of pneumonia by both bacterial and pathological techniques. Although the results of this study may not be directly applicable for clinical diagnosis, this approach has a potential to become not only a diagnostic method for bacterial pneumonia, but may be also useful for the analysis of multidrug-resistant pathogens.

Low-dose cytarabine (ara-C) has been used to treat older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), but has resulted in complete remission for20% of cases. A pilot study of the efficacy of a combination chemotherapy using low-dose ara-C, melphalan (Mel), and mitoxantrone (Mit) was conducted.The treatment comprised ara-C (10 mg/m2) twice daily, melphalan (2 mg/body) every other day, and mitoxantrone (3 mg/m2) every 3 days. The treatment was discontinued if the nuclear cell count was15,000/microl with20% blast count in the bone marrow. The primary end-points were initial response and tolerability.The study comprised 9 patients with AML or high-risk MDS (median age, 75 years). Complete remission was achieved in 3 patients. All the patients displayed grade 4 neutropenia and thrombocytopenia. One patient died from sepsis.The present regimen was more effective and displayed similar safety, compared with low-dose ara-C alone.

Two antibiotics recommended by the guideline of Infectious Diseases Society of America (IDSA) were selected for treatment of febrile neutropenia, and these paired antibiotics were changed periodically three times. The clinical efficacy of each antibiotic was retrospectively evaluated at the end of the final period. There was no significant difference about efficacy rate between two kinds of antibiotics in the same sequential period. However, the efficacy rate has been rising and febrile duration has been shortening by degrees. Only a few drug resistant bacteria were recognized by the surveillance culture during antibiotic cycling. Recently, antibiotic cycling therapy has attracted attention especially in the ICU. However, a clinical study of treatment for febrile neutropenia has not been reported. Our trial suggests that cycling therapy may be useful for febrile neutropenia. However, Some deviation in the patients characteristics of each period may affect the result. It seems that further examination is necessary about usefullness of the cycling therapy for febrile neutropenia.

A 77-year-old man treated with prednisolone for pemphigus developed severe sepsis by Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Several antibiotics were administered. A peripheral blood smear showed growth of a large number of yeast extending pseudohyphae which could be seen both inside and outside of leucocytes. Antifungal agents were added immediately; however, he did not recover. Several days later, blood culture showed Candida albicans septicemia. The autopsy revealed microabscesses in the lung, heart, liver and kidney. A large amount of neutrophil invasion and yeast with pseudohyphae were also detected.

Evidence for nonantibiotic activity displayed by tetracycline has been extensively reported in the field of antiinflammation. Here, we report a growth-inhibitory effect of doxycycline on CCRF-CEM, a T-lymphoblastic human leukemic cell line. Cells were incubated with doxycycline at concentrations ranging from zero to 50 μmol/L. We examined the hypothesis that induction of apoptosis is one of the mechanisms by which doxycycline inhibits CCRF-CEM proliferation. Caspase-3 activity of cells grown in the presence of 10 μmol/L and 50 μmol/L doxycycline increased dose-dependently after 24 hours in culture. The demonstration that doxycycline induces APO 2.7 expression in CCRF-CEM cells in vitro also supports its capacity for induction of apoptosis. The level of matrix metalloproteinase-2 was significantly lower in the medium cultured with 50 μmol/L doxycycline than the control. These phenomena suggest that this well-tolerated oral agent has the potential to be of value in antileukemic therapy. (J Lab Clin Med 2002;140:382-6)

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. The present study assessed retrospectively the clinical significance of the serum soluble interleukin-2 receptor (sIL-2R) level in patients with advanced DLBCL. Twenty-one patients (age; range, 56–87, median, 73-year old, 14 males/7 females) were newly diagnosed as having advanced DLBCL (stages III and IV) based on pathological findings of the biopsy specimen and by using computed tomography and positron emission tomography between 2006 and 2009. All the patients received 6–8 cycles of the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) (R-CHOP) or THP-COP (pirarubicin, cyclophosphamide, vincristine and prednisolone) (R-THP-COP) and attained complete response at the end of the treatment. The follow-up period ranged between 12 and 73 months with the median of 37 months. The serum sIL-2R levels (normal range, 144–518 U/ml) were determined at least before and after the second and the sixth cycles of the chemotherapy were carried out. Although all the patients reached complete remission, six patients experienced the disease relapse within 1 year from the initiation of the treatment. sIL-2R levels before the chemotherapy ranged from 416 to 21300 U/ml (median 2609 U/ml). sIL-2R levels after the second cycle of the chemotherapy ranged from 276 to 1980 U/ml (median 675 U/ml). sIL-2R levels after the sixth cycle of the chemotherapy ranged from 364 to 822 U/ml (median 548 U/ml). The early relapse was significantly associated with the high sIL-2R levels at the sixth cycle of the treatment, while the sIL-2R levels were low in the patients with the durable remission. sIL-2R levels at the disease onset or after the second cycle of the treatment were not correlated to the duration of the remission. Thus, the present study suggested that the sIL-2R levels after the sixth cycle of the chemotherapy might predict the early relapse in patients with advanced DLBCL.

Abstract 4147 Whole-body diffusion-weighted magnetic resonance imaging (DWI-MRI) provides functional information and is able to highlight oncological lesions, but the usefulness has not been established in malignant lymphoma especially for monitoring therapeutic response. Positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) is a useful imaging producer for tumor staging and therapy monitoring that can visualize active tumor tissue including malignant lymphoma. The spatial resolution of FDG-PET is limited, and low accuracy rates in diabetic patients and those with low grade lymphoma have been reported. We prospectively studied the utility of DWI-MRI with T2 imaging and apparent diffusion coefficient (ADC) for staging and monitoring therapeutic responses in patients with malignant lymphoma compared with FDG-PET/CT. Twenty-eight patients with malignant lymphoma (16 patients with diffuse large B cell lymphoma: DLBCL, 7 with follicular Lymphoma: FL, 3 with aggressive T cell lymphoma: TCL and 2 with Hodgkin lymphoma: HL, including one diabetic patient) received both MRI and FDG-PET examination before (n=28), after 2 courses of chemotherapy (n=25) and one month after the end of chemotherapy (n=9). MRI examination was performed with a 3-Tesla MR system (Signa Excite, Generel Electrics). Whole-body DWI-MRI was performed with echo planar imaging sequence with short T1 inversion recovery (STIR) fat suppression. ADC measurement was performed based on the region of interest (ROI) method. ROI was placed on the lesion showing the highest standardized uptake value (SUV) on FDG-PET/CT scanner (Discovery LS, General Electrics) in each patient, and crucial parameters of the ADC and SUV were compared. Based on staging by PET/CT, 4 patients were clinical stage I, 8 were stage II, 7 were stage III and 9 were stage IV. DWI-MRI findings alone matched PET/CT in 22 patients (79%), whereas these findings combined with T2 imaging increased match in 26 patients (93%). Regarding the early response to chemotherapy, 19 of 25 patients (76%) were considered to show CR on PET/CT and the DWI findings matched PET/CT 23 patients (92%). To evaluate the final response after chemotherapy, 7 of 9 patients (78%) were considered to show CR on PET/CT and the DWI findings matched PET/CT in 8 of 9 patients (89%). Of these nine, one patient with DLBCL who did not show a match was a false positive on PET/CT. In all patients with TCL and HL, the DWI-MRI findings combined with T2 imaging matched PET/CT findings for staging and therapeutic response. Interestingly, the ADC values on DWI-MRI did not differ between DLBCL and FL (0.77 +/− 0.23 and 0.70 +/− 0.08, p=0.99, mean +/− SD respectively), whereas the SUV values of DLBCL on PET/CT were higher than those of FL (14.5 +/− 6.97 and 6.09 +/− 2.54, p < 0.0005, mean +/− SD respectively), suggesting the DWI-MRI could detect the lymphoma lesion more accurately than PET/CT in patients with indolent lymphoma such as FL. We conclude that whole-body DWI-MRI combined with T2 imaging and ADC analysis could be promising sensitive method for staging and therapeutic response evaluation in patients with malignant lymphoma. Disclosures: No relevant conflicts of interest to declare.

Abstract 1635 Poster Board I-661 Introduction The rapid diagnosis of bacteremia is important for patient management and the choice of antimicrobial and antifungal therapy, especially in hematological malignancies. We describe a rapid detection and identification system that uses universal PCR primers and DNA microarray hybridization compared to the conventional culture method. This new DNA-microarray method could be performed within only 24 hours. Eighty-four microorganism probes are spotted onto a microarray plate containing most causal clinical pathogens (Patent No.WO2003/106676). We can detect 93% of pathogen of blood culture by the frequency of upper 28 microorganisms. Patients and Methods We used universal PCR primers to amplify a variable region of bacterial 16S ribosomal DNA or fungal ITS (internal transcribed spacer region) of ribosomal DNA, followed by the reverse hybridization of products to a panel of oligonucleotides. Genomic DNA was extracted from blood with a DNA isolation kit (DNeasy; QIAGEN, CA, USA) according to the manufacturer's instructions. The 16S ribosomal ribonucleic acid gene (16S rDNA) was amplified from genomic DNA using broad-spectrum PCR primers; 5'-AGAGTTTGATCCTGGCT-CAG-3', corresponding to Escherichia coli 16S rDNA positions 8 through 27, and 5'-GTATTACCGCGGCTGCTGG-3', corresponding to Escherichia coli 16S rRNA gene positions 517 through 535. On the other hand, the PCR primers; 5'-TCCGTAGGTGAACCTGCGG-3' and 5'-GCTGCGTTCTTCATCGATGC-3' are used to amplify the ITS 1 region. Thirty-five cycles of amplification were performed in a thermal cycler (Gene Amp PCR system 9600, Perkin-Elmer Cetus, CT, USA). The PCR products from samples were labeled by Cy5- primers and applied to the microarray. The microarray was scanned using a ScanArray 4000 (Axon Instruments, CA, USA) to determine the amount of Cy5-labeled PCR products. Fluorescence intensities were calculated with DNASIS Array software (HITACHI Soft Engineering, Japan). This new identification system using DNA microarray hybridization and the conventional blood culture method (BacT/ALERT, bioMerieux and Bactec, Becton-Dickinson, USA) were applied for 336 infectious episodes from 100 patients with hematological malignancy except 2 patients with aplastic anemia retrospectively from May 2004 to February 2007. The hematological malignancies included 152 episodes of acute myeloid leukemia (45.2%), 106 of non-Hodgkin lymphoma (31.5%), 38 of acute lymphoid leukemia (11.3%), 17 of multiple myeloma (5%), 12 of myelodysplastic syndrome (3.6%), 4 of aplastic anemia (1.2%) etc. Results Thirty-nine episodes (11.6%) were positive after a few days of culturing, and 41 episodes (12.2%) were identified by the new microarray method within 24 hours. Both methods yielded positive results 10.7% (36 episodes). Pathogens in most cases were identical at the species level (21/36 episodes 58.3%), some cases were identical at the genus level (6/36 16.7%), in the other cases, several bacteria were detected by each method. A positive DNA microarray and negative blood culture occurred at a rate of 1.5% (5 episodes), with pathogens in these cases being Bacillus cereus, Staphylococcus epidermidis, Chryseobacterium indologenes, and Enterococcus faecium. A negative DNA microarray and positive blood culture occurred at a rate of 0.9% (3 episodes), and with pathogens comprising Staphylococcus aureus, á-Streptococcus, and Pseudomonas aeruginosa. Both methods yielded negative results at a rate of 86.9% (292 episodes). The sensitivity and specificity of this new microarray method were 92.3 and 98.3%, respectively, compared with the conventional blood culture method. Regarding fungal infection, only one episode out of one patient was found to be positive microarray and negative blood culture of Yeast like organism. Conclusion This new DNA microarray method has the potential to diagnose bacteremia quickly and detect pathogens at least at the same rate as the conventional blood culture method. Regarding the possibility of improving the sensitivity and specificity, or application for fungal infection further study should be needed. In conclusion, DNA microarray is a useful method for the management of febrile patients with hematological malignancy. Disclosures Iwasaki: The ministry of Health, Labour and Welfare of Japan: Research Funding.