Summary
Pegfilgrastim is a pegylated form of the granulocyte‐colony stimulating factor, filgrastim. Herein, we report the results of a multicentre, randomized, double‐blind phase III trial comparing ...the efficacy and safety of pegfilgrastim with filgrastim in patients with malignant lymphoma. Patients were randomized to receive either a single subcutaneous dose of pegfilgrastim or daily subcutaneous doses of filgrastim on day 4 after the completion of cyclophosphamide, cytarabine, etoposide and dexamethasone ± rituximab (CHASE(R); day 1–3) chemotherapy. The primary endpoint was the duration of severe neutropenia (DSN), defined as the number of days with neutrophil count <0·5 × 109/l in the first cycle of chemotherapy. A total of 111 lymphoma patients were randomized to either the pegfilgrastim or filgrastim group. 109 patients received either pegfilgrastim (n = 54) or filgrastim (n = 55). Efficacy data were available for 107 patients (pegfilgrastim: n = 53, filgrastim: n = 54). Both groups were well balanced in terms of gender, age, performance status and other variables. The mean DSN (±S.D.) was 4·5 (±1·2) and 4·7 (±1·3) d in the pegfilgrastim and filgrastim groups. No significant difference in safety was observed. This trial verified the non‐inferiority of a single subcutaneous dose of pegfilgrastim compared with daily subcutaneous doses of filgrastim, considering DSN as an indicator.
The effect of alcohol consumption on the liver is controversial. Recent reports have suggested that moderate alcohol consumption decreases the prevalence of elevated alanine aminotransferase levels. ...The role of alcohol consumption in the development of fatty liver (FL), however, has not been studied definitively. The aim of this study was to examine the association between alcohol consumption and FL in a large Japanese population.
A total of 7,431 asymptomatic male subjects who underwent a complete medical survey in our institute between May 2007 and July 2008 were recruited. Cases positive for hepatitis B or C viruses, potential hepatotoxic drug intake, or under treatment for metabolic disorders were excluded. FL was defined by ultrasonography. Visceral and subcutaneous adipose tissues (VAT and SAT) were measured by computed tomography. Independent and significant predictors associated with FL were determined by multiple logistic regression analysis.
Of the initial study candidates, 130 (1.7%) were positive for hepatitis B and 66 (0.8%) were positive for hepatitis C. On the basis of the inclusion and exclusion criteria, 5,599 men (50.9+/-8.1 years) were studied cross-sectionally. Light (40-140 g/week) and moderate (140-280 g/week) alcohol consumption significantly and independently reduced the likelihood of FL (odds ratio=0.824 and 0.754, 95% confidence interval=0.683-0.994 and 0.612-0.928, P=0.044 and 0.008, respectively) by multivariate analysis after adjusting for potential confounding variables. VAT, SAT, low-density lipoprotein, triglycerides, and fasting blood glucose were significant predictors of the increased prevalence of FL, whereas age was a predictor of the decreased prevalence of FL.
The prevalence of FL was significantly and independently decreased by light and moderate alcohol consumption in men of an asymptomatic Japanese population.
Background
The impact of obesity on gastroesophageal reflux disease remains controversial. We undertook this study, with a large sample size, to investigate risk factors for endoscopic erosive ...esophagitis by multivariate analysis, including visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) as covariates.
Methods
Japanese males who visited our institute for a comprehensive medical survey between 2007 and 2010 were enrolled. All subjects voluntarily participated in a self-paid health check-up program including blood test screening, physical examinations, and esophagogastroduodenoscopy. VAT and SAT were measured by computed tomography at the navel level. Independent and significant predictors of erosive esophagitis were determined by multivariate analysis.
Results
Of 9840 eligible subjects, 1831 (18.6%) were diagnosed with erosive esophagitis. Body mass index and triglyceride were predictors of an increased prevalence of erosive esophagitis (odds ratios ORs = 1.063 and 1.001; 95% confidence intervals CIs = 1.020–1.108 and 1.001–1.002;
p
= 0.004 and <0.001, respectively). Heavy alcohol consumption, heavy smoking, and hiatal hernia were also associated with an increased prevalence of erosive esophagitis (ORs = 1.276, 1.399, and 2.758; 95% CIs = 1.085–1.501, 1.220–1.605, and 2.474–3.075;
p
< 0.001 for all).
Helicobacter pylori
infection significantly and independently decreased the prevalence of erosive esophagitis (OR = 0.346, 95% CI = 0.299–0.401,
p
< 0.001). Central obesity, as determined by VAT and waist girth, did not confer an increased risk of erosive esophagitis after adjusting for confounders.
Conclusions
Lifestyle factors including heavy alcohol consumption, heavy smoking, metabolic disorders, and hiatal hernia increased the risk of erosive esophagitis, but central obesity did not.
Background: Helicobacter pylori infection has been shown to contribute to atherosclerosis and cardiovascular diseases. Insulin resistance is the pathophysiologic background of the clinical features ...of atherosclerosis and cardiovascular diseases. We examined the association between H. pylori infection and insulin resistance in a large Japanese population.
Materials and Methods: Fifteen hundred ninety‐eight consecutive asymptomatic subjects that underwent a complete medical survey in our institute between May 2007 and July 2008 were recruited. Cases under medication for hypertension, hyperlipidemia, diabetes mellitus, hyperuricemia, or cardiovascular diseases were excluded from the study. Cases suffering from chronic renal or liver failure were also excluded. The homeostasis model assessment of insulin resistance (HOMA‐IR) score was used to quantitatively estimate insulin resistance. Visceral and subcutaneous adipose tissues (SAT) were measured by computed tomography. The association between H. pylori serostatus and HOMA‐IR score was investigated by multivariate regression analysis.
Results: A total of 988 men and 119 women were eventually eligible for this cross‐sectional survey. Helicobacter pylori seropositivity was significantly higher in 99 cases with insulin resistance (HOMA‐IR ≥2.5) compared with 1008 cases without insulin resistance (HOMA‐IR <2.5) (39.4 vs 28.7%, p = .027). There was a significant association between H. pylori serostatus and HOMA‐IR score by multiple linear regression analysis (coefficients = 0.152, 95% CI = 0.058–0.246, p = .001), after adjusting for sex, age, body mass index, waist girth, visceral and subcutaneous adipose tissues, smoking status, alcohol consumption, dietary habits, and physical activity.
Conclusions: Helicobacter pylori infection significantly and independently contributed to promoting insulin resistance in a large asymptomatic population.
Pregnancy with paroxysmal nocturnal hemoglobinuria (PNH) is associated with significant risk of complications, such as life-threatening thrombosis. Recently, eculizumab has come into clinical use and ...revolutionized the treatment of PNH. However, clinical information regarding eculizumab use for PNH during pregnancy is limited. The present report describes pregnancies with PNH treated with eculizumab that were registered with the Japan PNH study group and reviews the literature. In case 1, the patient received eculizumab throughout pregnancy and delivered a healthy neonate at term, although breakthrough hemolysis occurred at 20 weeks of gestation. In case 2, the patient discontinued eculizumab before pregnancy and developed preeclampsia at 27 weeks of gestation. She received eculizumab and delivered a preterm, but healthy, neonate by cesarean section. In case 3, the patient received eculizumab from 18 weeks of gestation and delivered a healthy neonate at term without any complications. Reports of 11 pregnant women treated with eculizumab were identified in the literature. Of 14 pregnancies, including our own cases, breakthrough hemolysis and preeclampsia occurred in five and two cases, respectively. There were no thrombotic complications, maternal or neonatal deaths, or fetal structural abnormalities. Thus, eculizumab appears to be safe and effective for managing PNH during pregnancy.
Large granular lymphocyte leukemia-associated pure red cell aplasia accounts for a significant portion of secondary pure red cell aplasia cases. However, because of its rarity, long-term responses ...and relapse rates after immunosuppressive therapy are largely unknown. We conducted a nationwide survey in Japan and collected 185 evaluable patients. Fourteen patients with large granular lymphocyte leukemia-associated pure red cell aplasia were evaluated. Cyclophosphamide, cyclosporine A and prednisolone produced remissions in 6/8, 1/4 and 0/2 patients respectively. Seven and 5 patients were maintained on cyclophosphamide or cyclosporine A respectively. Two patients relapsed after stopping cyclophosphamide, and 2 patients relapsed during maintenance therapy with cyclosporine A. The median relapse-free survival in the cyclophosphamide - and the cyclosporine A groups was 53 and 123 months respectively. Large granular lymphocyte leukemia-associated pure red cell aplasia showed a good response to either cyclophosphamide or cyclosporine A. Most patients continued to receive maintenance therapy and it remains uncertain whether cyclophosphamide or cyclosporine A can induce a maintenance-free hematologic response in large granular lymphocyte leukemia-associated pure red cell aplasia.
Thymoma-associated pure red cell aplasia (PRCA) accounts for a significant proportion of cases of secondary PRCA and immunosuppressive therapy has been reported to be useful in this condition. ...However, because of its rarity, the long-term response and relapse rates after immunosuppressive therapy are largely unknown, and optimal management of this disorder remains unclear. The aim of this study was to collect more information on the outcome of patients with thymoma-associated PRCA.
We conducted a nationwide survey in Japan. From a total of 185 patients, comprising 73 with idiopathic and 112 with secondary PRCA, 41 patients with thymoma were evaluated for this report. End-points of this study were the response rate, duration of the response after immunosuppressive therapy and overall survival.
Surgical removal of thymoma was reported in 36 patients, 16 of whom developed PRCA at a median of 80 months post-thymectomy. First remission induction therapy was effective in 19 of 20 patients treated with cyclosporine, 6 of 13 patients treated with corticosteroids and 1 of 1 treated with cyclophosphamide. No cyclosporine-responders relapsed within a median observation period of 18 months (range; 1 to 118 months). Relapse of anemia was observed in three corticosteroid-responders who did not receive additional cyclosporine. Only two patients were in remission after stopping therapy for 19 and 67 months. The estimated median overall survival time of all patients was 142 months.
Thymoma-associated PRCA showed an excellent response to cyclosporine and cyclosporine-containing regimens were effective in preventing relapse of anemia. It does, however, remain uncertain whether cyclosporine can induce a maintenance-free hematologic response.
Cyclosporine A (CsA) has become one of the leading agents for the treatment of pure red cell aplasia (PRCA). However, further studies are necessary to determine the relapse-free survival (RFS) and ...overall survival (OS) of patients treated with this drug, the minimum duration of therapy for induction of remission, and whether or not there is need for maintenance treatment.
We conducted a nationwide survey in Japan. From a total of 185 patients (with 73 primary idiopathic PRCA and 112 with secondary PRCA), we evaluated 62 patients with primary idiopathic PRCA for this report.
The remission induction therapy for these patients included CsA (n=31), corticosteroids (CS) (n=20) or other drugs (n=11). CsA and CS produced remissions in 23 (74%) and 12 (60%) patients, respectively. The salvage treatment produced remissions in 58 patients (94%). Forty-one and 15 patients were maintained on CsA+/-CS (CsA-containing group) or CS alone (CS group), respectively. The median RFS in the CsA-containing group was 103 months, longer than that seen in the CS group (33 months) (p<0.01). Of 14 patients whose CsA was discontinued, 12 patients (86%) relapsed after a median of 3 months (range 1.5 to 40 months), while only 3 of 27 patients (11%) relapsed during CsA-containing maintenance therapy. Thus, the discontinuance of maintenance therapy was strongly correlated with relapse (p<0.001). Four patients in the CsA-containing group died; however, the OS of this group was not significantly different from that of the CS-groups (p=0.104).
CsA-containing regimens sustain prolonged RFS more effectively than CS in primary idiopathic PRCA and seem to be important to prevent relapse.
Abstract We conducted an open-label, randomized study to evaluate the clinical efficacy of cefozopran, meropenem or imipenem–cilastatin using cefepime as a control in febrile neutropenia (FN) ...patients. Three hundred and seventy-six patients received cefepime, cefozopran, meropenem or imipenem–cilastatinas initial therapy for FN. The primary endpoint was the non-inferiority of response rates including modification at day 7 in cefozopran, meropenem or imipenem–cilastatin patients compared with cefepime in the per-protocol population (delta = 10%). The response rates for cefozopran, meropenem and imipenem–cilastatin were not significantly different compared with cefepime (cefozopran: 54/90 (60%), meropenem: 60/92 (65%), and IPM/CS: 63/88 (72%) versus cefepime: 56/85 (66%) ( p = 0.44, 1.0 and 0.51, respectively)), and the differences in treatment success for cefozopran, meropenem and imipenem–cilastatin compared with cefepime were −5.9% (95% confidence interval (CI): −20.1–8.4), −0.7% (95% CI: −14.6–13.3), and 5.7% (95% CI: −8.1–19.4), respectively. The same tendency was seen in the modified intention-to-treat population. Based on the evaluation of initial drug efficacy performed on days 3–5, there was no significant difference between the four drugs. In the subgroup with an absolute neutrophil count ≤100 × 106 /L for longer than seven days, there was significantly better efficacy in the carbapenem arm compared to 4th generation beta-lactams (52% versus 27% at days 3–5, p = 0.006, and 76% versus 48% at day 7, p = 0.002). Our results suggest that the effects of these four drugs as empiric therapy were virtually the same for adult FN patients, although non-inferiority was shown only in imipenem–cilastatin compared with cefepime (clinical trial number: UMIN000000462 ).
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