Serum level of oxidative stress marker is dramatically low in patients with rheumatoid arthritis treated with tocilizumab

Regarding the pathobiology of rheumatoid arthritis, oxidative stress induced by reactive oxygen species is an important mechanism that underlies destructive and proliferative synovitis. Abundant amounts of reactive oxygen species have been detected in the synovial fluid of inflamed rheumatoid joints. It is reported that drugs that block tumor necrosis factor-?? reduce the oxidative stress marker levels in patients with rheumatoid arthritis. In this study, we measured reactive oxygen species using a free radical analytical system in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs, tumor necrosis factor-??-blocking drugs (infliximab, etanercept), and an interleukin-6-blocking drug (tocilizumab). The serum level of oxidative stress was drastically low in patients with rheumatoid arthritis treated with tocilizumab, suggesting that interleukin-6 blocking therapy reduces not only joint damage, but also vascular degeneration in patients with rheumatoid arthritis. We believe that such a drastic effect would reduce the incidence of cardiovascular events and mortality in patients with rheumatoid arthritis.     

Long-term effect of lamivudine treatment on the incidence of hepatocellular carcinoma in patients with hepatitis B virus infection

Background

Nucleotide analogues have recently been approved for the treatment of patients with hepatitis B virus (HBV) infection. However, it is still controversial whether the decrease of HBV-DNA amount induced by treatment with nucleotide analogues can reduce the risk of hepatocellular carcinoma (HCC) development in HBV patients.

Methods

A total of 293 HBV patients without HCC who were treated with lamivudine (LAM) were enrolled in a multicenter trial. The incidence of HCC was examined after the start of LAM therapy, and the risk factors for liver carcinogenesis were analyzed. The mean follow-up period was 67.6?±?27.4?months.

Results

On multivariate analysis for HCC development in all patients, age ≥50?years, platelet count <14.0?×?10⁴/mm³, cirrhosis, and median HBV-DNA levels of ≥4.0?log copies/ml during LAM treatment were significant risk factors. The cumulative carcinogenesis rate at 5?years was 3% in patients with chronic hepatitis and 30% in those with cirrhosis. For the chronic hepatitis patients, the log-rank test showed the significant risk factors related to HCC development to be age ≥50?years, platelet count <14.0?×?10⁴/mm³, and hepatitis B e antigen negativity, but median HBV-DNA levels of <4.0?log copies/ml (maintained viral response, MVR) did not significantly suppress the development of HCC. In cirrhosis patients, however, the attainment of MVR during LAM treatment was revealed to reduce the risk of HCC development.

Conclusions

These results suggest that the incidence of HCC in HBV patients with cirrhosis can be reduced in those with an MVR induced by consecutive LAM treatment.     

Lamivudine-to-entecavir switching treatment in type B chronic hepatitis patients without evidence of lamivudine resistance

Purpose  A considerable number of chronic hepatitis B (CH-B) patients remain under continuous lamivudine treatment, although switching treatment to entecavir could be beneficial. We investigated the antiviral efficacy of switching treatment to entecavir in CH-B patients without apparent evidence of lamivudine resistance during the preceding lamivudine treatment. Methods  Forty-four CH-B patients, who underwent lamivudine treatment for more than 6 months and showed no evidence of lamivudine resistance, switched to entecavir. Serial changes in hepatitis B virus (HBV) DNA were correlated with the patients' baseline HBV DNA at the commencement of entecavir administration. The entecavir-resistant substitution was examined by PCR-direct sequencing. The median follow-up period of entecavir treatment was 20 (10–23) months. Results  All 31 patients with baseline HBV DNA <2.6 logcopies/ml maintained HBV DNA-negative status during entecavir treatment. Of seven patients having HBV DNA of 2.6–<4.0 logcopies/ml, all achieved undetectable HBV DNA at the end of follow-up. As for six patients having HBV DNA ≥4.0 logcopies/ml, three patients achieved undetectable HBV DNA, whereas virological breakthrough was observed in one patient at month 15. An entecavir-resistant virus having rtM204V, rtL180M and rtS202G substitutions was detected in this patient. Conclusions  The lamivudine-to-entecavir switching treatment may be generally recommendable in CH-B patients without evidence of lamivudine resistance during the preceding lamivudine treatment. However, great care should be taken with respect to the emergence of entecavir-resistance, especially in patients who do not respond well to the preceding lamivudine treatment.     

Risk factors for hepatocellular carcinoma in hepatitis C patients with normal alanine aminotransferase treated with pegylated interferon and ribavirin

Pegylated interferon (Peg‐IFN) plus ribavirin combination therapy is effective in patients with hepatitis C virus (HCV) infection and normal alanine aminotransferase levels (NALT). However, it remains unclear whether the risk of hepatocellular carcinoma (HCC) incidence is actually reduced in virological responders. In this study, HCC incidence was examined for 809 patients with NALT (ALT ≤ 40 IU/mL) treated with Peg‐IFN alpha‐2b and ribavirin for a mean observation period of 36.2 ± 16.5 months. The risk factors for HCC incidence were analysed by Kaplan–Meier method and Cox proportional hazards model. On multivariate analysis among NALT patients, the risk of HCC incidence was significantly reduced in patients with sustained virological response (SVR) or relapse compared with those showing nonresponse (NR) (SVR vs NR, hazard ratio (HR): 0.16, P = 0.009, relapse vs NR, HR: 0.11, P = 0.037). Other risk factors were older age (≥65 years vs <60 years, HR: 6.0, P = 0.032, 60–64 vs <60 years, HR: 3.2, P = 0.212) and male gender (HR: 3.9, P = 0.031). Among 176 patients with PNALT (ALT ≤ 30 IU/mL), only one patient developed HCC and no significant risk factors associated with HCC development were found. In conclusion, antiviral therapy for NALT patients with HCV infection can lower the HCC incidence in responders, particularly for aged and male patients. The indication of antiviral therapy for PNALT (ALT ≤ 30 IU/mL) patients should be carefully determined.     

A new prognostic system for hepatocellular carcinoma including recurrent cases: a study of 861 patients in a single institution

OBJECTIVE: To manage hepatocellular carcinoma (HCC) patients surviving for a long term, the treatment strategy for recurrent cancer is as important as that for the initial treatment. However, no prognostic scoring system has been available for patients with HCC recurrence. The purpose of this study was to develop a new staging system for deciding the treatment strategy not only for first-time diagnosed patients but also for recurrent patients. METHODS: A total of 861 cases diagnosed at our single institution from 1993 to 2003 were included. Overall survival was the only end point. The Cox model was used for multivariate analyses. RESULTS: As of August 2004, 344 cases (59%) had died. Overall median survival time was 41 months. For multivariate Cox regression analysis, independent predictive factors of survival were the number of recurrences, the Child-Pugh score, 3 nodules less than 3 cm and none of vascular invasion, and the alpha-fetoprotein level. A simple scoring system was thus developed, assigning scores (0/1) to the 4 covariates of the final model. Compared with the other scoring systems, the new scoring system has a greater discriminant ability. CONCLUSIONS: We concluded that our scoring system can serve as a new prognostic system that reflects the spread of HCC, treatment response, and liver function. It should be very useful as the only method which can be applied for patients with recurrence.     

Favorable response of heavily treated wilms' tumor to Paclitaxel and Carboplatin

Background: Heavily treated Wilms' tumor responding to the combination of paclitaxel and carboplatin has not yet been reported. Case Report: A 17-year-old man presented with hematuria. He received a diagnosis of Wilms' tumor with multiple lung metastases and was treated with preoperative chemotherapy including vincristine, dactinomycin, and doxorubicin, a right nephrectomy, and adjuvant chemotherapy, followed by pulmonary metastasectomy. During the next 8 years, he suffered from 4 relapses and has been treated with multiple anticancer agents including high-dose chemotherapy with autologous peripheral blood stem cell transplantation. Finally, the disease progressed due to peritoneal and pleural metastases. With opioid administration for left shoulder pain due to pleural metastasis, he received combination chemotherapy with carboplatin (area under the curve = 4) and paclitaxel (175 mg/m(2)) on day 1. After 2 cycles, he achieved a partial response with mild toxicity. He received 7 cycles of the chemotherapy and the time to progression was 200 days. Conclusion: In a refractory case after intensive treatments, we succeeded to control the disease for a while.     

Studies on health hazards among cooks providing school lunch service. Report 1. The influence of working conditions in central and school kitchens prevalence of health hazards

Since the School Lunch Law was enacted in 1954, the school lunch program in Japan has seen rapid development, mainly in compulsory schools. Eighty-four percent of all pupils in compulsory schools are fed lunch, and nearly half of the meals are provided by the central kitchen system. There has been much criticism of the central kitchen system concerning the quality of the meals. Recently, it has been demonstrated that many cooks suffer from musculo-skeletal symptoms in their necks, shoulders, arms and lower backs. This paper discusses the relationship between the cooking work load and health hazards by comparing the tasks of cooks in the central kitchen system with those of cooks in individual school kitchens. All the female cooks in one prefecture were queried by a mail survey method. The respondents totalled 1,428 (response rate 68%). Of this number, 186 work in 15 central kitchens (group C) and the other 1,242 work in 401 school kitchens (group S). In addition physical examinations were carried out on cooks who registered serious complaints in the questionnaires and on those who wanted to undergo the examination. The results are as follows: The work load in the central kitchens is greater than that in the school kitchens. Both groups C and S complained of cervicobrachial symptoms and low-back pain as frequently as other workers already reported to be in a high risk of these hazards. Group C suffer from these hazards more frequently and seriously than group S. Group C assigned "carrying heavy objects" as a cause of low-back pain and cervicobrachial symptoms more frequently than group S. This was related to the difference in numbers of meals served by groups C and S. As a result of the physical examination, serious cases of cervicobrachial disorders and/or low-back pain were found more frequently among cooks who had serious complaints than among other examinees. It was concluded that these results demonstrated a positive relationship between the cooking work load and the development of health hazards. Therefore, if we wish to protect cooks from these hazards, it is not advisable to maintain the current central kitchen system.