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Vincristine (VCR) is a key drug for treating various malignancies. However, few data are available on the pharmacokinetics of VCR, especially in adult patients. The objective of this study was to clarify the population pharmacokinetics and exposure–response relationships of VCR in adult malignant lymphoma patients. Blood samples were collected from patients who were administered R-CHOP-like regimens, and the VCR plasma concentration was determined using liquid chromatography–mass spectrometry. Using NONMEM software, population pharmacokinetic parameters were estimated, and covariates were evaluated. The relationships between the individual parameters and adverse events or therapeutic effects were also investigated. Plasma concentrations were measured in 30 patients. In the final population pharmacokinetics model, body surface area and age were incorporated into clearance as significant covariates. The inter-individual variations in clearance and volume of distribution in the central and third compartments were 17.0, 26.6, and 66.3%, respectively, and the residual variability in the plasma concentration was 23.8%. Although the variability observed in the volume of distribution was large, good predictability was obtained in the individual estimation. The severity of anemia and peripheral neuropathy was correlated with clearance and peak concentration, respectively (adjusted P = 0.040 and 0.024, respectively). In diffuse large B cell lymphoma patients, those with higher area under the curve and dose experienced longer progression-free survival (P = 0.023 and 0.013, respectively). The population pharmacokinetics of VCR were evaluated in adult malignant lymphoma patients. VCR pharmacokinetic data could explain in part the adverse events and prognosis of these patients.

Despite the importance of a prompt diagnosis to improve cancer patients' survival, little has been reported on diagnostic delay in diffuse large B-cell lymphoma (DLBCL). A single-centre, retrospective study was conducted to examine the association between diagnostic wait time (DWT), the interval from the initial hospital visit to diagnosis, and survival in patients with DLBCL. A total of 193 patients were enrolled from 2007 to 2017 in our institution. A covariate-adjusted Cox proportional hazards model with restricted cubic spline was used to evaluate the impact of DWT on survival, with a subgroup analysis according to the International Prognostic Index (IPI). DWT was not associated with survival in the entire DLBCL population, but the impact of DWT on survival differed between IPI < 3 and ≥ 3; prolongation of DWT steadily exacerbated the prognosis in patients with IPI ≥ 3, whereas there was a patient population with IPI < 3 who had a high mortality rate despite rather early diagnosis. The opposite trend in the effect of DWT on survival between patients with IPI < 3 and ≥ 3 offset survival in all DLBCL patients. DWT had no observable impact on outcomes in the entire DLBCL population, but longer DWT worsened the prognosis, particularly in patients with IPI ≥ 3.

Background The management of severe adverse events (AEs) is important in safely and effectively providing chemotherapy to older adults with diffuse large B-cell lymphoma (DLBCL). However, reports on simple and DLBCL-specific predictive models for treatment-related toxicity in elderly individuals are scarce. The aim of this study was to examine the usefulness of Geriatric 8 (G8) in predicting treatment-related severe AEs, nonhematological toxicity, and febrile neutropenia in older adults with DLBCL in real-world practice. Materials and Methods We conducted a multicenter, retrospective study on 398 consecutive patients with DLBCL (aged ≥65 years) who received standard therapy at three centers in Japan (University of Fukui Hospital, the Fukui Prefectural Hospital, and the Japanese Red Cross Fukui Hospital), between 2007 and 2017. Result Multivariate logistic analysis demonstrated that the G8 score was an independent predictive factor for severe AEs. Moreover, a logistic regression model with restricted cubic spline showed a nonlinear association between the incidence of severe AEs and the G8 score. According to receiver operating characteristic analysis, the most discriminative cutoff value of the G8 for the incidence of severe AEs was 11, with an area under the curve value of 0.670. AEs occurred most often in the first course of chemotherapy and decreased as the course progressed. Conclusion The G8 score, an easy-to-use geriatric assessment tool, can be a useful prediction model of treatment-related severe AEs during standard therapy in older adults with DLBCL. Implications for Practice In older patients with diffuse large B-cell lymphoma (DLBCL), to accurately predict the risk of severe adverse events (AEs) in advance is essential for safe and effective treatment. This study demonstrated that the Geriatric 8 score, a simple and established geriatric assessment tool, indicated a high predictive ability for occurrence of therapy-related severe AEs in elderly patients with DLBCL who were treated with standard treatment.

Reflecting the increasing risk in elderly patients with diffuse large B cell lymphoma (DLBCL), prognostic predictors other than the International Prognostic Index have attracted more attention. This study presents the first analysis of the prognostic utility of the Geriatric Nutritional Risk Index (GNRI) in combination with the Charlson Comorbidity Index (CCI) for overall survival (OS) in elderly DLBCL patients. A multicentre retrospective was conducted on a cohort of 451 patients (≥65 years). The GNRI and CCI were independent predictors in a multivariate Cox proportional hazard model. There was a nonlinear correlation between the GNRI and OS in a Cox model with restricted cubic spline. Multivariate receiver operating characteristic curves showed a significant improvement in prediction accuracy when the GNRI was added to CCI. Adding the GNRI to CCI yielded a significant category-free net reclassification improvement (0·556; 95% CI: 0·378-0·736, P < 0·001) and integrated discrimination improvement (0·094; 95% CI: 0·067-0·122, P < 0·001). The decision curve analysis demonstrated the clinical net benefit associated with the adoption of the GNRI. The GNRI was not only a predictor of OS but also remarkably improved the prognosis prediction accuracy when incorporated with the CCI, having the ability to stratify the prognosis of elderly DLBCL patients.

Rationale and Objectives Severe calcifications of the coronary arteries are still a major challenge in coronary computed tomography (CT) angiography (CCTA). Subtraction CCTA using a 320-detector row CT scanner has recently been introduced for patients with severe calcifications. However, the conventional subtraction CCTA method requires a long breath-holding time of approximately 20–40 seconds. This is a major problem in clinical practice because many patients may not be able to perform such a long breath-hold. We explored a modified subtraction CCTA method with a short breath-holding time to overcome this problem. Materials and Methods This study was approved by our institutional review board, and all patients gave written informed consent. A total of 12 patients with a coronary calcium score of >400 were enrolled in this study. All patients were unable to hold their breath for more than 20 seconds. Modified subtraction CCTA was performed using the bolus-tracking method. The acquisition protocol was adjusted so that the mask scan was acquired 10 seconds after the postcontrast scan during a single breath-hold. The subtraction image was obtained by subtracting the mask image data from the postcontrast image data. The breath-holding times were recorded. Enhancement of the coronary arteries in the subtraction images was assessed. Subjective image quality was evaluated in a total of 32 segments using a 4-point scale. Results The mean breath-holding time was 12.8 ± 0.8 seconds (range, 12–14 seconds). The average CT number in the coronary arteries was 288.6 ± 80.5 Hounsfield units (HU) in the subtraction images. Average image quality was significantly increased from 2.1 ± 0.9 with conventional CCTA to 3.1 ± 0.7 with subtraction CCTA ( P P = 0.001). Conclusions This preliminary study has shown that our modified subtraction CCTA method allows the breath-holding time to be shortened to

Control of serum uric acid (sUA) levels is very important during chemotherapy in patients with malignant tumors, as the risks of tumor lysis syndrome (TLS) and renal events are increased with increasing levels of sUA. We investigated the efficacy and safety of febuxostat, a potent non-purine xanthine oxidase inhibitor, compared with allopurinol for prevention of hyperuricemia in patients with malignant tumors, including solid tumors, receiving chemotherapy in Japan.An allopurinol-controlled multicenter, open-label, randomized, parallel-group comparative study was carried out. Patients with malignant tumors receiving chemotherapy, who had an intermediate risk of TLS or a high risk of TLS and were not scheduled to be treated with rasburicase, were enrolled and then randomized to febuxostat (60 mg/day) or allopurinol (300 or 200 mg/day). All patients started to take the study drug 24 h before chemotherapy. The primary objective was to confirm the non-inferiority of febuxostat to allopurinol based on the area under the curve (AUC) of sUA for a 6-day treatment period.Forty-nine and 51 patients took febuxostat and allopurinol, respectively. sUA decreased over time after initiation of study treatment. The least squares mean difference of the AUC of sUA between the treatment groups was -33.61 mg h/dL, and the 95 % confidence interval was -70.67 to 3.45, demonstrating the non-inferiority of febuxostat to allopurinol. No differences were noted in safety outcomes between the treatment groups.Febuxostat demonstrated an efficacy and safety similar to allopurinol in patients with malignant tumors receiving chemotherapy.http://www.clinicaltrials.jp ; Identifier: JapicCTI-132398.

The microservice architecture is essential for agile development and deployment of the application components; however, designing microservices for a web application is not a straight-forward task. One of the best ways to design microservices is to decompose a monolithic prototype of an application into microservices on the basis of both the complexity in engineering and the component boundaries of the application in the early phase of development. We propose a visualization tool allowing developers to interactively design microservice applications on the basis of the characteristics of source codes and the behaviors of a monolithic prototype. This visualization tool first constructs a calling-context tree from profile data taken in a dry-run of the application. Next, it generates an initial microservice design while considering keyword features in the source codes or amount of function calls between components. Developers can interactively refine this design via this visual interface by taking four-choice actions to revise boundaries of microservices while considering expected communications between them. This interaction will have a significant impact on runtime performance. Case studies of two open-source benchmark applications demonstrate the proposed tool enables interactive design of microservices. The results of the demonstration show that compared to the official microservice designs of the applications, the proposed tool can effectively design microservice applications.

The purpose of this study was to explore the feasibility of subtraction coronary computed tomography angiography (CCTA) by second-generation 320-detector row CT in patients with severe coronary artery calcification using invasive coronary angiography (ICA) as the gold standard. This study was approved by the institutional board, and all subjects provided written consent. Twenty patients with calcium scores of >400 underwent conventional CCTA and subtraction CCTA followed by ICA. A total of 82 segments were evaluated for image quality using a 4-point scale and the presence of significant (>50 %) luminal stenosis by two independent readers. The average image quality was 2.3 ± 0.8 with conventional CCTA and 3.2 ± 0.6 with subtraction CCTA (P

Aim We examined the utility of the neutrophil CD64 level as a rapid and sensitive diagnostic marker for infections in febrile aged patients. Methods The expression level of CD64 per neutrophil was quantitatively measured with flow cytometry using a QuantiBrite kit in samples from febrile (aged >65 years) patients. Information about the presence or absence of infectious disease was retrospectively obtained from each patient's medical record in which attending physicians were obliged to write down a tentative diagnosis after resolution of manifestations. Results With receiver operating characteristic curve evaluation using the results, a CD64 level >2000 molecules per neutrophil was sensitive and specific for detecting infection. Among 102 patients suspected of having infection, 72 patients were diagnosed with infectious diseases, and 30 patients had non-infectious diseases. The sensitivity and specificity of determination of the neutrophil CD64 level were 88% and 63%, respectively. However, considering the high frequency of infections in elderly patients (71% in the present study), the post-test probability reached as high as 93%. The positive likelihood ratio was 2.4, and the negative likelihood ratio was 0.2. Conclusions Considering the frequency of infectious diseases in elderly patients, determination of the neutrophil CD64 level helps detect infectious diseases. Geriatr Gerontol Int 2015; ●●: ●●–●●.

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.

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.

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

Tumor lysis syndrome (TLS) is a life-threatening oncological emergency, in which control of serum uric acid (S-UA) levels is important. S-UA-lowering efficacy of a new xanthine oxidase inhibitor, febuxostat, was retrospectively evaluated in seven patients with hematological malignancies who were at an intermediate risk of developing TLS. A 10-mg dose of febuxostat was initiated and chemotherapy was started within 24 h of administering the first dose of febuxostat. Febuxostat was continued until at least day 7 of chemotherapy treatment. The UA-lowering treatment was considered effective if febuxostat reduced S-UA levels to ≤7.5 mg/dl by day 5. The mean S-UA level at base line was 6.4±2.6 mg/dl and, on day 5, the mean S-UA level was 4.7±1.8 mg/dl. All the patients achieved S-UA levels ≤7.5 mg/dl. Serum creatinine levels decreased from 0.93±0.25 to 0.85±0.25 mg/dl. The estimated glomerular filtration rate values increased from 69.7±24.5 to 76.9±26.2 ml/min. No adverse reactions were noted during the study period and no patients experienced progressive TLS. Successful control of S-UA and improved renal function were obtained in response to febuxostat treatment in cancer patients at a risk of TLS.

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.

Background Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL featured by rapid progression. Given its rapid progression, prompt diagnosis and treatment are essential for achieving long-term survival in DLBCL. In solid cancers, it is known that prolonging diagnostic wait time (DWT), interval from diagnosis to initiation of treatment, could result in stage progression and a worse survival. In DLBCL patients, a prolonged DWT is also expected to be associated with a worse survival, however, little is known about this issue. The purpose of this investigation was to verify the impact of DWT on survival in DLBCL patients using a Cox hazards model with restricted cubic spline (RCS) because this model was more suitable to reflect real-world clinical practice than the linear model. It has been reported a possible association between the International Prognostic Index (IPI) and prognosis, hence the Cox hazards model with RCS was used to examine the differential effects of IPI on survival in association with DWT. Methods We conducted a single center, retrospective study of all consecutive patients seen from 2007 to 2017 at our Hospital. The inclusion criteria were newly diagnosed de novo DLBCL, aged 18 years and older, and treated with standard therapies. We define the standard regimens as R-CHOP [rituximab (RTX), cyclophosphamide (CPA), adriamycin, vincristine (VCR), and prednisolone (PSL)] and R-THP-COP (RTX, CPA, tetrahydropyranyl adriamycin, VCR, and PSL). The primary outcome was overall survival (OS). Exclusion criteria were central nerve system involvement, transformed DLBCL, and receiving non-standard therapies. Furthermore, the subgroup analysis according to IPI was performed. Results Among 179 patients, the median age was 72 (27 - 91) years, the median DWT was 39.5 (0 - 223) days and 53.9% patients had IPI ≥3, the median follow-up time was 29.2 (0.03 - 137.6) months, and 59 (31.3%) patients died during the follow-up period. A multivariate Cox proportional hazards model for OS showed DWT was not associated with worse OS in the entire study population. However, the Cox hazards model with RCS in the all study population revealed that there was nearly U-shaped association between DWT and OS. The Cox hazards model with RCS for each group depending on IPI score (0-5) showed the effect between DWT and OS differed by IPI. The mortality risk increased proportionally as DWT was prolonged in three groups with IPI 3 to 5, but rather negative correlations were seen between in three groups with IPI 0 to 2. Opposite tendencies between IPI ≥3 and Discussion These results demonstrated that the impact of DWT on OS differed depending on the IPI, while DWT did not affect OS of the entire DLBCL patients. DWT steadily increased the risk of mortality in IPI ≥3 group. On the other hand, in IPI 3 at the initial visit should be expedited the diagnosis if there was suspicious of DLBCL, because DWT is a critical predictor determining prognosis in such patients. Moreover, in suspected DLBCL cases, computed tomography, positron emission tomography contributing to identify the IPI, and bone marrow biopsy might be needed immediately when the definitive IPI is uncertain at the initial visit. Conclusions In conclusion, DWT did not associate with survival of entire DLBCL patients who treated with standard therapies, but the impact of DWT on survival differed depending on IPI. Especially in patients with IPI ≥3 at the diagnosis, steadily increased mortality risk was observed. Disclosures Yamauchi: Astellas, AbbVie: Consultancy; Pfizer, Chugai, Teijin, Solasia: Research Funding.

We explore the feasibility of coronary calcium subtraction computed tomography angiography (CCTA) in patients with high calcium scores using invasive coronary angiography as the gold standard. Eleven patients with calcium scores of >400 underwent CCTA using a subtraction protocol followed by invasive coronary angiography. In addition to standard reconstructions, subtracted images were obtained using a dedicated subtraction algorithm. A total of 55 calcified segments were evaluated for image quality [using a 4-point scale ranging from 1 (uninterpretable) to 4 (good)] and the presence of significant (≥50 %) luminal stenosis. Conventional and subtracted CCTA were compared using quantitative coronary angiography (QCA) as the gold standard. The average image quality of conventional CCTA was 2.5 ± 0.6 versus 3.1 ± 0.6 on subtraction CCTA (P

Abdominal computed tomography of a 71-year-old man revealed a 3-cm mass in gastric cardia. Although the mass was widely attached to the gastric wall, no clear contrast enhancement was observed. Abdominal magnetic resonance imaging revealed the mass to have homogenous high intensity on T2W1 images and isointensity on T1W1 images. On diffusion-weighted imaging, no high intensity was observed. However, the mass had a smooth surface and was widely attached to the gastric wall, consistent with computed tomography findings. A gastric submucosal tumor was suspected. Laparoscopic tumor resection was performed. Histopathologic diagnosis of the mass was a bronchogenic cyst derived from the respiratory primordium originating in the foregut of the primitive intestine. Such cysts are mostly found in the mediastinum or thoracic cavity; their occurrence on the gastric wall is extremely rare. Despite this, we think that bronchogenic cysts should be considered in the differential diagnosis of abdominal unilocular cystic diseases.

Background: Hyperuricemia cases (HU) can be classified into four subgroups by combining the two main causes of hyperuricemia, i.e. urate underexcretion and overproduction. These subgroups are as follows: underexcretion-type cases (UE); overproduction-type cases (OP); combined-type cases, and normal-type cases. Since urinary urate excretion (Uua) and urate clearance differ significantly between UE and OP, urate transport in the nephrons and the intratubular urate contents might also differ. Such differences might help clarify the pathophysiology of urate underexcretion in subgroups of hyperuricemia, and thus reveal its underlying mechanisms. Methods: Urate transport coefficients in each subtype of HU were determined employing the previously reported benzbromarone-loading urate clearance tests. The subtype cases of HU were plotted on a graph of urate transport coefficients versus Uua as coordinates. The characteristic features in the distribution of subtype cases on graphs were analyzed in relation to Uua. Results: The mean (±standard error) tubular secretion rate (TSR) in the UE (48.7 ± 1.7 ml/min) was significantly lower and the postsecretory urate reabsorption rate (R2) in the UE (0.904 ± 0.004) was significantly higher than those in the normal controls (78.0 ± 2.1 ml/min and 0.877 ± 0.003) or the OP (61.1 ± 3.2 ml/min and 0.861 ± 0.009). Decrements of TSR and increments of R2 in the UE were largest in the subtypes of the HU, in terms of case numbers and the deviation rate of the group. Conversely, decrements of TSR and increments of R2 were smallest in the OP. A significant correlation was identified between TSR and Uua (r = 0.345, p < 0.0001), and a significant negative correlation was also found between R2 and Uua (r = -0.393, p < 0.0001). Conclusion: In the UE, hyperuricemia is induced mainly by urate underexcretion, which results from the combination of two main causes in urate transporters of the nephron: significantly lower TSR and significantly higher R2. Neither of these was observed in OP. Differences in urate transporters in subtypes of the HU might be important not only for understanding the pathophysiology and mechanisms of urate underexcretion and hyperuricemia, but also for providing a strategic therapy for hyperuricemia.

Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) has been reported to be unreliable for identifying viable myocardium in acute myocardial infarction (AMI), especially in areas with discordance in myocardial blood flow (MBF) and glucose metabolism. In myocardium with decreased FDG uptake but preserved MBF, referred to as exhibiting reverse mismatch, myocardial viability remains controversial and little is known about the metabolic state. The aims of this study were to clarify substrate use and to estimate myocardial viability in infarct areas exhibiting reverse mismatch. Eighteen AMI patients with successful revascularisation were included in this study. Two weeks after onset, 11C-acetate and 18F-FDG PET were performed to evaluate regional oxygen consumption (k mono), MBF and glucose metabolism. Free fatty acid (FFA) metabolism was evaluated with 123I-15-(p-iodophenyl)-3-(R, S)-methylpentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT). To assess wall motion, movement in left ventricular endocardial surface was calculated using ECG-gated 99mTc-tetrofosmin SPECT. The %k mono values in reverse mismatch segments (52.6 ± 13.6 %) were not significantly different from those in non-infarct segments (60.4 ± 12.8 %, p = 0.071) and normal match segments (preserved MBF and FDG uptake) (58.6 ± 11.6 %, p = 0.396), although regional wall motion was more severely impaired (3.06 ± 2.52 mm vs 6.78 ± 3.17 mm, p

Background/Aim: Tumor lysis syndrome (TLS) is a life-threatening complication associated with cancer chemotherapy. We retrospectively evaluated the risk of developing TLS in patients with symptomatic multiple myeloma undergoing chemotherapy. Patients and Methods: Sixty-four patients (median age=71 years, range=48-87 years, 35 males/29 females) who were treated at our Institution between April 2006 and December 2015 were evaluated. Results: A total of 124 chemotherapy courses were administered, of which 63 courses were bortezomib-based regimens and 34 courses were immunomodulatory drug (IMiD)-based regimens. TLS occurred in 13 (10.5%) out of 124 chemotherapy courses with five (4.0%) cases of laboratory TLS and eight (6.5%) cases of clinical TLS. The incidences of TLS were 17.5% for bortezomib-containing regimens and 3.2% for non-bortezomib-based regimens. No TLS occurred in the patients treated with IMiD-containing regimens. TLS occurred more frequently in the patients with elevated uric acid, creatinine, or beta-2-microglobulin levels at baseline. The patients with disease classified as advanced International Staging System also developed TLS more frequently. All the patients who developed clinical TLS received bortezomib-containing regimens (8/63, 12.7%). Among them, patients with elevated values of uric acid or creatinine developed clinical TLS more often than those without such elevation. The incidence of clinical TLS was 33.3% if the patients had renal dysfunction at baseline and were subsequently treated with bortezomib-based regimens (8/24 cases). Conclusion: Patients with renal dysfunction or a high uric acid level receiving bortezomib-based chemotherapy have a high risk of developing TLS.

The microservice architecture is a new framework to construct a Web service as a collection of small services that communicate with each other. It is becoming increasingly popular because it can accelerate agile software development, deployment, and operation practices. As a result, cloud service providers are expected to host an increasing number of microservices that can generate significant resource pressure on the cloud infrastructure. We want to understand the characteristics of microservice workloads to design an infrastructure optimized for microservices. In this paper, we used Acme Air, an open-source benchmark for Web services, and analyzed the behavior of two versions of the benchmark, microservice and monolithic, for two widely used language runtimes, Node.js and Java. We observed a significant overhead due to the microservice architecture; the performance of the microservice version can be 79.2% lower than the monolithic version on the same hardware configuration. On Node.js, the microservice version consumed 4.22 times more time in the libraries of Node.js than the monolithic version to process one user request. On Java, the microservice version also consumed more time in the application server than the monolithic version. We explain these performance differences from both hardware and software perspectives. We discuss the network virtualization in Docker, an infrastructure for microservices that has nonnegligible impact on performance. These findings give clues to develop optimization techniques in a language runtime and hardware for microservice workloads.

To explore the feasibility and diagnostic accuracy of modified subtraction coronary CT angiography (CCTA) with short breath-holding time in patients who have limited breath-hold capability and severe coronary artery calcification.11 patients with a coronary calcium score400 underwent CCTA using a modified subtraction protocol. All patients were unable to hold their breath for more than 20 s. Subjective image quality using a four-point scale and the presence of significant (50%) luminal stenosis were assessed for each calcified or stented segment on both conventional CCTA and modified subtraction CCTA images and compared with invasive coronary angiography (ICA) as the gold standard.The mean breath-holding time was 13.0 ± 0.9 s. A total of 35 calcified or stented coronary segments were evaluated. The average image quality was increased from 2.1 ± 0.9 with conventional CCTA to 3.1 ± 0.7 with subtraction CCTA (p 0.001). The segment-based diagnostic accuracy for detecting significant stenosis according to ICA revealed an area under the receiver-operating characteristic curve of 0.722 for conventional CCTA and 0.892 for subtraction CCTA (p = 0.036).Modified subtraction CCTA allows the breath-holding time to be shortened to15 s. As compared with conventional CCTA, modified subtraction CCTA showed improvement in image quality and diagnostic accuracy in patients with limited breath-hold capability and severe calcification.Modified subtraction CCTA can improve the diagnostic accuracy in patients with a high calcium score and patients who are unable to perform long breath-holds.

Peripheral whole blood cells from normal subjects and from 8 patients with refractory anemia with excess of blasts (RAEB) and one patient with RAEB in transformation (RAEB-t) were studied to ascertain their interferon (IFN)-α-producing capacity. This capacity was determined by time-resolved immuno-fluoroassay 20 hrs after the blood cells had been incubated with 500 HA/ml of Sendai virus. The mean IFN-α-producing capacity in the peripheral whole blood cells of 35 normal males was 8718 ± 4683 IU/ml, while that of 49 normal females was 7549 ± 4731 IU/ml; not a significant difference. All of the RAEB and RAEB-t patients examined showed a significantly low (2500 IU/ml) IFN-α-producing capacity in the peripheral whole blood cells. In addition, the levels of IFN-α-producing capacity in 1 ml cell suspension containing 1 x 10(6) peripheral mononuclear blood cells were markedly lower in all 5 RAEB patients and the RAEB-t patient examined than those in the normal subjects, when 5 HA of Sendai virus was used. The activities of natural killers were lower in the RAEB/RAEB-t patients than those in the normal subjects. These findings suggest that IFN-α-producing capacity is diminished in the peripheral whole blood cells of RAEB and RAEB-t patients, and great care is advised regarding infection by virus and bacteria in treatment of these patients.

症例は51歳の男性で，全身に掻痒を伴う膨疹を主訴に受診した．血液検査でトランスアミナーゼ上昇を認めたため精査したところ，腹部超音波で肝S7，8に3cm大の腫瘤性病変を認めた．CTでは同部に早期から造影されるが内部の造影効果の弱い辺縁高吸収，内部低吸収な結節を指摘された．他に原発巣を認めず，各種腫瘍マーカー・感染症マーカー陰性であったが，CT造影パターンより肝内胆管癌と診断し，肝部分切除術を施行した．病理組織学的診断では，悪性所見は認められず，壊死を伴う肉芽腫性病変であった．異物巨細胞が目立ち，高度な好酸球浸潤により形成されるCharcot-Leyden結晶が認められたことから寄生虫の可能性が考えられたが，虫体，虫卵は指摘できなかった．血清抗体検査で，肝蛭の抗体が高値ではなかったが，ほかの抗体と比べると完全に陰性と判断できるほど低くなく末梢好酸球が高値ではないことから過去に感染した肝蛭症が強く疑われた．

We evaluated the diagnostic utility of peripheral blood neutrophil distribution patterns obtained using the CELL-DYN SAPPHIRE hematology analyzer in patients with myelodysplastic syndrome (MDS). Peripheral blood was obtained from 467 individuals including 32 patients with MDS, and the respective neutrophil distribution patterns were observed using two light scatters [7-degree complexity (7D) and 90-degree lobularity (90D)]. These scattering intensities are shown as median (median neutrophil distribution: MND) and coefficient of variation (neutrophil distribution width: NDW). Generally, MDS patients showed lower 7D MND, higher 7D NDW, lower 90D MND and higher 90D NDW than other comparable groups. Whereas 90D parameters were more diagnostically efficient than 7D ones in patients with MDS. The sensitivity and specificity of 90D MND for MDS patients became 78.1 and 78.9%, respectively (cut-off value = 14,514). 90D NDW was most diagnostically effective with 87.5% sensitivity and 91.0% specificity (cut-off value = 21.2%). Both 90D parameters showed no evident correlation with the degree of either leukocytopenia or peripheral blood dysgranulopoiesis. In conclusion, neutrophil distribution parameters, especially 90D NDW, appear to provide convenient and objective markers for the screening of patients with MDS in routine laboratory hematology.

近年輸血副作用の把握の重要性が認識され，その頻度や重症度について統計をとることが多施設で行われつつある．しかし時に集計の困難さもあり充分な集計ができない場合がある．我々は電子カルテを利用した副作用管理システムを樹立し全輸血における副作用報告を收集できるようになった．その結果バッグ単位ではなく通常報告されていない患者単位の副作用発生頻度の算出を容易にし興味ある結果を得たので報告する． 【対象】2008年1月から2009年12月の期間，輸血を実施した患者を対象とした．【結果】赤血球濃厚液（RCC）は1,154人で5,156バッグ，新鮮凍結血漿（FFP）は261人で1,795バッグ，濃厚血小板血漿（PC）は350人で3,394バッグの輸血が行なわれた．輸血副作用発生実人数はRCC 20人（1.7％），FFP 12人（4.6％），PC 50人（14.2％）であった．PCによる副作用頻度が最も高く診療科別でもPCの使用の多い血液腫瘍内科で22.2％，小児科で23.7％発生していた．患者単位での副作用はバッグ単位の副作用に比較し数倍の頻度が認められ，輸血副作用の評価は両者を比較しつつ行うことが重要であり，電子カルテを利用した副作用管理システムは副作用情報収集に有用と考えられた．

Disseminated intravascular coagulation (DIC) is a life-threatening condition that frequently occurs in patients with hematologic malignancies. Currently, recombinant human soluble thrombomodulin (rTM) is a therapeutic DIC drug that is manufactured and sold in Japan only. We evaluated the efficacy of rTM compared to that of gabexate mesilate (GM), which was previously used routinely for treating DIC in Japan, in patients with acute myeloid leukemia (AML). This retrospective study enrolled 43 AML patients, including 17 with acute promyelocytic leukemia (APL), that was complicated with DIC. DIC resolution rates in non-APL AML and rTM-treated APL patients were 68.4% and 81.8%, respectively. In non-APL AML patients, the duration of rTM administration was significantly shorter than that of GM (7 vs 11 days), suggesting that rTM could improve DIC earlier than GM, although rTM was used in patients with more severe DIC. Moreover, treatment with rTM significantly improved DIC score, fibrinogen, fibrin/fibrinogen degradation product (FDP), and prothrombin time (PT) ratio. Conversely, treatment with GM only improved the DIC score and FDP. In APL patients, the duration of rTM administration was also significantly shorter than that of GM. No severe side effects associated with the progression of bleeding were observed during rTM administration. These findings suggest that rTM is safe, and its anti-DIC effects are more prompt than GM for treating AML patients with DIC.

Myocardial flow reserve (MFR) in the non-infarct-related area (NIRA) has been reported to be impaired after the onset of myocardial infarction (MI). The aim of this study was to determine whether microvascular dysfunction in the NIRA is related to left-ventricular remodeling after MI.We prospectively studied 17 patients who suffered their first single-vessel MI, and who underwent successful revascularization. The MFR in the NIRA was assessed quantitatively using (13)N-ammonia positron emission tomography within 2 weeks after the onset. Peak creatinine kinase and the defect score on (99m)Tc-tetrofosmin myocardial perfusion imaging were used as an index of the severity of MI. The left-ventricular end-diastolic volume index (LVEDVI) was calculated using left ventriculography at 1 month and 6 months after the onset.Patients with severely impaired MFR (2.09) had higher peak creatinine kinase values (6000+/-5485 IU/L vs. 2250+/-1950 IU/L, p=0.0081), defect scores (16.3+/-5.9 vs. 7.9+/-6.5, p=0.0404), and LVEDVI at 1 month (125.6+/-34.4 mL/m2 vs. 82.8+/-17.7 mL/m2, p=0.0036) than those with mildly impaired MFR (or =2.09). Moreover, the differences of LVEDVI between 2 groups persisted over 6 months (133.3+/-43.6 mL/m2 vs. 89.5+/-17.3 mL/m2, p=0.0078). The MFR in the NIRA correlated inversely with the LVEDVI at 1 month and 6 months (r=-0.590, p=0.0127 and r=-0.729, p=0.0031, respectively).These data indicate that microvascular impairment in the NIRA might have contributed to left-ventricular remodeling after MI.

原発性アミロイドーシス7例に対して自己末梢血幹細胞移植併用melphalan大量療法を実施した．顆粒球コロニー刺激因子の単独投与で必要な末梢血幹細胞の確保が可能で，7例中2例（29%）に血液学的寛解が得られた．心アミロイドーシスの存在した2例は移植後それぞれ42日目と159日目に治療関連死亡し，安全性確保の観点から本治療の対象外とする必要性が推測された．非寛解の4例にサルベージ治療が行われ3例に血液学的効果が得られた．Melphalan大量療法またはサルベージ治療で血液学的効果の得られた5例中4例（80%）に臨床症状の改善または安定化が得られた．心アミロイドーシスを除外すればmelphalan大量療法は安全に実施可能と推測されたが有効性には限界がある．心アミロイドーシス例やmelphalan大量療法の無効例には新規治療法を組み込んだ更なる臨床研究が必要である．

Although biological and clinical features differ between B-lineage acute lymphoblastic leukemia (ALL) and T-lineage ALL (T-ALL), there have been few reports that focused on the prognosis for T-ALL in adults, primarily due to its rarity. Here, we studied the long-term outcomes and prognostic factors specific for adult T-ALL by combining patient data from the three prospective trials conducted by the Japan Adult Leukemia Study Group (JALSG). Among 559 patients whose immunophenotypes could be evaluated, 87 (15.6%) were identified as T-ALL. Of them, 66 patients (75.8%) achieved complete remission, and relapse occurred in 41 patients. With a median follow-up for surviving patients of 7.5 years, the probability of overall survival was 35.0% at 5 years. Risk factor analysis revealed that serum albumin levels, initial white blood cell (WBC) counts, and age had independent values for predicting survival. For WBC, not only the high-count group (50 x 10(9)l(-1) or higher), but also the low-count group (less than 3 x 10(9)l(-1)) showed a significantly lower survival rates than the intermediate-count group (p=0.0055 and 0.0037, respectively). Although our findings need confirmation, these results will be helpful in the identification of prognostically distinct subgroups within adult T-ALL.

Background Although diabetes is associated with poor clinical outcomes after acute myocardial infarction, to date there have been no reports focusing on the myocardial oxygen metabolism in these patients. Thus, we evaluated the myocardial oxygen metabolism in patients with and without diabetes suffering from acute myocardial infarction using carbon-11 acetate positron emission tomography. Methods 20 patients (13 diabetic patients [group A] and 7 non-diabetic patients [group B]) underwent carbon-11 acetate positron emission tomography soon after the onset of acute myocardial infarction. The myocardial oxygen metabolism was evaluated within the infarct-related area and in the non infarct-related area. 6 healthy volunteers (group C) and 6 diabetic patients without coronary artery disease (group D) also participated as controls. Results There were no significant differences in gender, age, infarct-related artery, peak level of serum creatine phosphokinase, left-ventricular ejection fraction at onset, or the defect severity on myocardial perfusion images between group A and group B. In group A, the clearance rate (Kmono) of carbon-11 acetate in infarct-related area (0.042±0.010) was not significantly different from that in group B (0.049±0.016). In contrast, Kmono in non infarct-related area in group A (0.059±0.010) was significantly lower than that in group B (0.076±0.009; p =0.002), group C (0.072±0.004; p =0.026) and group D (0.078±0.005; p =0.001). Conclusions These data indicate that the myocardial oxygen metabolism even in non infarct-related area in diabetic patients was impaired after the onset of acute myocardial infarction.

Standardized treatments for indolent B cell lymphoma primarily consisting of follicular lymphoma (FL) and for mantle cell lymphoma (MCL) have yet to be established. Here the Hokuriku Hematology Oncology Study Group conducted a multicenter prospective study to investigate the efficacy and safety of a combination regimen of rituximab, cladribine, mitoxantrone, and dexamethasone (R-CMD) in indolent B cell lymphoma and MCL. A total of 33 CD20-positive patients who received care between January 2008 and August 2011 were investigated. These patients' illnesses were FL (n = 21), nodal marginal zone B cell lymphoma (NMZB, n = 3), MCL (n = 3), splenic marginal zone B cell lymphoma (n = 2), hairy cell leukemia (n = 1), Waldenstrom macroglobulinemia (WM, n = 1), and lymphoplasmacytic lymphoma (LPL, n = 2). Patients received four 21-day cycles of rituximab 375 mg/m(2) (day 1), cladribine 0.10 mg/kg (days 1-3), mitoxantrone 8 mg/m(2) (day 1), and dexamethasone 8 mg/body (days 1-3), with four additional rituximab doses at 4-week intervals. Of the 33 patients, 26 achieved complete response/unconfirmed complete response, and six achieved a partial response (4 with FL, 1 with NMZB, 1 with WM). One had progressive disease (FL), and four relapsed after remission (1 with FL, 2 with MCL, 1 with LPL). R-CMD therapy was relatively convenient and effective in indolent B cell lymphoma and MCL. Nonetheless, to suppress the number and function of both B cells and T cells, comprehensive infection prevention and follow-up are necessary in the future.

We assessed the efficacy and adverse effects of febuxostat in male hyperuricemia patients.This was a 12-week, multicenter, open-label, uncontrolled study. The enrolled subjects were 89 hyperuricemic male patients (12 overexcretors, 56 normal excretors, and 21 underexcretors). The endpoint was percent change in serum urate level.The concentration of urate in serum before and 12 weeks after beginning administration of febuxostat in the overexcretors was 9.34 ± 1.48 and 5.59 ± 1.17 mg/dl, respectively, while those were 8.59 ± 1.24 and 5.41 ± 1.35 mg/dl, respectively, in the normal excretors, and 8.29 ± 1.01and 5.11 ± 1.71 mg/dl, respectively, in the underexcretors. After 12 weeks, the rate of change in serum urate after beginning administration of febuxostat was - 0.384 ± 0.186 in the overexcretors, - 0.368 ± 0.128 in the normal excretors, and - 0.365 ± 0.217 in the underexcretors, with no significant differences among them. A common adverse event related to febuxostat was gout flare.Febuxostat effectively reduced the concentration of urate in serum in hyperuricemic patients regardless of the level of uric acid excreted in urine without severe adverse effects.

In the treatment of heart failure, the effects of therapeutic agents on life prognosis remains unclear. We investigated the effects of long-term oral administration of a nonpeptide, selective, vasopressin V2 receptor antagonist, OPC-31260, on Sprague-Dawley rats that were treated with adriamycin to induce progressive water retention.Intraperitoneal saline was administered to 14 rats as a control (Group 1). A total cumulative dose of 15 mg/kg of adriamycin was administered intraperitoneally in six equal doses over a period of 2 weeks to another 52 rats. Adriamycin-treated rats were further divided into Group 2, which received saline (p.o.), and Group 3, which received 50 mg/kg (p.o.) of V2 antagonist. Oral administration continued every day for 6 weeks. Group 1 rats also received saline (p.o.) for 6 weeks.The V2 antagonist decreased urine osmolality and increased diuresis of rats in Group 3. Urinary excretion of electrolytes was not increased by the V2 antagonist in Group 3. Serum osmolality was likewise unchanged by the V2 antagonist in Group 3. Plasma concentrations of vasopressin were significantly higher in Group 3 than in the other groups (Group 1, 4.0+/-1.1 pg/ml; Group 2, 4.2+/-1.5 pg/ml; Group 3, 8.5+/-1.0 pg/ml; p0.05). During the experimental period, survival rate was higher in Group 3 than in Group 2 (Group 1, 100%; Group 2, 59%; Group 3, 83%).Our data show that administration of orally active V2 antagonist did not reduce the survival of adriamycin-treated rats through continuous aquaretic action, despite elevated plasma levels of vasopressin.

We have already shown that the antileukemic activity of daunorubicin that had been reported to be dependent on the area under the concentration - time curve (AUC) was actually peak concentration (Cmax) dependent. The antitumor activity of doxorubicin (DXR) has also been reported to be dependent on AUC, whereas its cumulative cardiotoxicity has been reported to be Cmax dependent. In this study, we evaluated whether the antileukemic and cardiotoxic effects of DXR were AUC or Cmax dependent, and compared their cytotoxic effects, utilizing the computer-controlled in vitro pharmacokinetic simulation system or a conventional culture system for a leukemic cell line and measuring the intracellular ATP amount or the proportion of beating cells for the cardiotoxicity. In leukemic cells, the cytotoxic rate decreased as the simulated infusion time or exposure time increased with the same AUC value in the simulation and conventional culture system (P0.05 and0.01, respectively). The intracellular ATP and proportion of beating cells also increased with prolonged DXR exposure time with the same constant concentration - time product value (P0.05 and0.0001, respectively) in heart cells. These results indicated that both the antileukemic effects and the cardiotoxicity were Cmax dependent. However, a comparison of the two showed that cardiotoxicity was more Cmax dependent than the antileukemic effect. These results suggested that the continuous infusion treatment schedule of DXR may have the clinical advantage of reducing cardiotoxicity more markedly than the antileukemic effect.

Matrix metalloproteinase (MMP) may contribute to myocardial remodeling after myocardial infarction. The goal of this study was to characterize the effects of pravastatin on circulating levels of MMP and on left ventricular dilatation after acute myocardial infarction (AMI).Thirty-four consecutive patients with successful reperfusion following AMI were assigned to either pravastatin group (group P, n=12) or non-pravastatin group (group NP, n=22). Serum MMP-2 and tissue inhibitor of MMP (TIMP)-2 were measured immediately after reperfusion, on days 2, 3, 7, 30, and at 6 months after MI. Left ventriculography was performed after reperfusion and at 4 weeks and 6 months.MMP-2 levels were higher in patients with MI than control on days 1, 30, and at 6 months. Left ventricular end-diastolic volume index (LVEDVI) at 6 months correlated with MMP-2 levels on day 30 (r=0.47, p0.01) and at 6 months (r=0.56, p0.001). MMP-2 levels at 6 months were significantly lower in group P than group NP. Further, LVEDVI at 6 months tended to be smaller and DeltaLVEDVI was significantly smaller in group P when compared with group NP.Serum MMP-2 varied in a time-dependent manner following AMI and correlated with late changes in LVEDVI. Serum MMP-2 levels were significantly lower in treatment group than in non-treatment group and DeltaLVEDVI was significantly smaller in treatment group after long-term pravastatin administration. Use of statins in AMI patients may provide beneficial effects in terms of preventing heart failure over and above its lipid-lowering effects.

The successful treatment of an elderly patient with primary central nervous system lymphoma is described. A 74-year-old Japanese man with left hemiplegia and consciousness disturbance presented in December 2001. His performance status was Grade 4. Computed tomography of the brain revealed a tumor in the right paraventricle. A biopsy of the brain confirmed the diagnosis of non-Hodgkin lymphoma (diffuse large, B cell type). Radiographic examinations did not detect any other lesions outside the brain. Primary central nervous system lymphoma was diagnosed. Chemotherapy was initiated in January 2002 using intravenous administration of methotrexate (600 mg/m2, 6-h infusion, day 1) combined with etoposide (25 mg/m2, continuous infusion, day 2–5), doxorubicin (5 mg/m2, continuous infusion, day 2–5), vincristine (0.2 mg/m2, continuous infusion, day 2–5), cyclophosphamide (350 mg/m2, 2-h infusion, day 6) and dexamethazone (6 mg/body, 1-h infusion, day 1–6), with intrathecal administration of methotrexate (15 mg/body, day 8) and prednisolone (10 mg/body, day 8). Four courses of chemotherapy were completed without severe toxicities, followed by whole-brain radiotherapy (25 Gy). Complete remission was achieved, and the patient became alert with normalized movement of the left extremities. Despite poor prognostic factors (old age, low performance status), the patient was successfully treated as such and was still in remission without neurotoxicity in May 2004. The combination of methotrexate-based chemotherapy and radiotherapy with appropriate dose modification may improve the outcome in elderly patients with this disease since supportive therapy; CHOP, a combination of cyclophosphamide, doxorubicin, vincristine and prednisolone; and solo radiotherapy are usually not effective.

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.