Katsunori Tai

Correlation between the concentrations of tumor necrosis factor-α and the severity of disease in patients infected with Orientia tsutsugamushi

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-alpha (TNF-alpha) levels (mean 9.20 pg/ml) were elevated in 89% and interferon-gamma (IFN-gamma) 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-alpha in the acute phase and the severity of disease (r=0.918). CONCLUSION The concentration of TNF-alpha may predict the severity of tsutsugamushi disease in the acute infectious phase.

Utility of PCR amplification and DNA microarray hybridization of 16S rDNA for rapid diagnosis of bacteremia associated with hematological diseases

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 24 h. 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.

Significantly Higher Cytokine and Chemokine Levels in Patients with Japanese Spotted Fever than in Those with Tsutsugamushi Disease

ABSTRACT 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.

Spontaneous spinal epidural hematoma in a patient with acquired Factor X deficiency secondary to systemic amyloid light-chain amyloidosis

Abstract Background Spontaneous spinal epidural hematoma (SSEH) is relatively rare. SSEH with anticoagulants including warfarin and rivaroxaban (Factor Xa inhibitor) have been reported; however, SSEH with Factor X deficiency has not been described yet. Methods Case report. Findings An 82-year-old woman with acquired Factor X deficiency complained of sudden onset of severe posterior neck pain. Magnetic resonance imaging demonstrated an epidural hematoma from C3 to T3 levels. Because she showed tetraparesis on the third hospital day, we performed surgery. Just before surgery, her prothrombin time-international normalized ratio was 2.49, which was immediately reversed by infusion of prothrombin complex concentrate. The patient safely underwent an emergency laminectomy from C3 to T2, in which the epidural hematoma was evacuated. Post-operatively, the patient recovered completely without rebleeding. Hematologists found acquired deficiency of Factor X in this patient with systemic amyloid light-chain amyloidosis. Conclusion To our knowledge, this is the first report of a case of SSEH with Factor X deficiency. A blood coagulation disorder should be considered in patients with SSEH.

Prognostic effect of peripheral blood cell counts in advanced diffuse large B-cell lymphoma treated with R-CHOP-like chemotherapy: A single institution analysis

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.

Fulminant candidemia diagnosed by prompt detection of pseudohyphae in a peripheral blood smear.

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.

3A Comparison between R-THP-COP and R-CHOP Regimens for the Treatment of Diffuse Large B-cell Lymphoma in Old Patients: A Single-institution Analysis

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 patients 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.

Efficacy of aprepitant for CHOP chemotherapy-induced nausea, vomiting, and anorexia

The objective of this study was to evaluate whether aprepitant in addition to 5-HT3 receptor antagonist is useful for preventing chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients receiving CHOP therapy, and to evaluate the relationship between in vivo kinetics of plasma substance P and these adverse events. Patients with malignant lymphoma who received CHOP chemotherapy or THP (THP-ADR)-COP therapy were investigated for CINV and anorexia for 5 days after the start of chemotherapy. With the first course of chemotherapy, all patients received only granisetron on day1 as an antiemetic. Patients who experienced nausea, vomiting, or anorexia exceeding grade 1 in the first course received aprepitant for 3 days in addition to granisetron with the second course of CHOP chemotherapy. Plasma substance P concentrations at 24 and 72 hours after chemotherapy were measured. Nineteen patients were evaluated. Nausea, vomiting, or anorexia was observed with the first course in 7 of 19 patients. During the second course with aprepitant, no patients experienced vomiting, and the toxicity grade of nausea, vomiting, or anorexia was decreased compared with those in the first course. Substance P concentrations showed no differences after chemotherapy, in patients with nausea, vomiting, or anorexia and in patients without. The addition of aprepitant to 5-HT3 receptor antagonist appears effective for CINV or anorexia for patients who received CHOP chemotherapy.