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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

The proximity effect from a spin-triplet $p_x$-wave superconductor to a dirty normal-metal has been shown to result in various unusual electromagnetic properties, reflecting a cooperative relation between topologically protected zero-energy quasiparticles and odd-frequency Cooper pairs. However, because of a lack of candidate materials for spin-triplet $p_x$-wave superconductors, observing this effect has been difficult. In this paper, we demonstrate that the anomalous proximity effect, which is essentially equivalent to that of a spin-triplet $p_x$-wave superconductor, can occur in a semiconductor/high-$T_c$ cuprate superconductor hybrid device in which two potentials coexist: a spin-singlet $d$-wave pair potential and a spin--orbit coupling potential sustaining the persistent spin-helix state. As a result, we propose an alternative and promising route to observe the anomalous proximity effect related to the profound nature of topologically protected quasiparticles and odd-frequency Cooper pairs., Comment: 6 pages, 4 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.

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.

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.

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.

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.

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.

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.

Background Patients with tsutsugamushi disease sometimes die if they do not receive appropriate chemotherapy. This study measured the concentration of several cytokines both before and after the administration of tetracyclines, and evaluated the changes in cytokine levels in patient serum to investigate the relationship between serum levels of cytokines and disease severity. Methods A total of nine patients were infected with Orientia tsutsugamushi . The diagnosis of tsutsugamushi disease was made using an indirect immunoperoxidase antibody test. The serum concentrations of cytokines were measured using enzyme-linked immunosorbent assays. Results The levels of interleukin (IL)-10 (mean 71.7 pg/ml) and IL-12p40 (mean 588 pg/ml) were elevated in all patients in the acute phase, above the normal upper limits. Tumor necrosis factor-α (TNF-α) levels (mean 9.20 pg/ml) were elevated in 89% and interferon-γ (IFN-γ) levels (mean 41.0 pg/ml) in 44% of patients. The down-regulation of these overproduced cytokines was observed after chemotherapy. There was a significant correlation between the concentrations of TNF-α in the acute phase and the severity of disease ( r =0.918). Conclusion The concentration of TNF-α may predict the severity of tsutsugamushi disease in the acute infectious phase.