ITPA gene variant protects against anemia induced by pegylated interferon‐α and ribavirin therapy for Japanese patients with chronic hepatitis C

Aim: Host genetic variants leading to inosine triphosphatase (ITPA) deficiency, a condition not thought to be clinically important, protect against hemolytic anemia in chronic hepatitis C patients receiving ribavirin. In this study, we evaluated the clinical significance of ITPA variants in Japanese hepatitis C patients who were treated with pegylated interferon plus ribavirin. Methods: In this multicenter retrospective cross‐sectional study, 474 hepatitis C patients were enrolled who were treated with pegylated interferon plus ribavirin in four geographically different hospitals in Japan. Patients were grouped according to hemoglobin decline of more than 3 g/dL at week 4. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs6051702, rs1127354) were genotyped. Results: A functional SNP, rs1127354, within the ITPA exon was strongly associated with protection against anemia with only one (0.8%) in 129 patients with the ITPA minor variant A developing severe anemia (P = 5.9 × 10^?20). For rs6051702, which had significant association in European‐Americans, significant but weak association with severe hemoglobin reduction was found in Japanese (P = 0.009). In patients excluding genotype 1b and high viral load, those with the ITPA minor variant A achieved significantly higher sustained viral response rate than those with the major variant (CC) (96% vs 70%, respectively, P = 0.0066). Conclusion: ITPA SNP, rs1127354, is confirmed to be a useful predictor of ribavirin‐induced anemia in Japanese patients. Patients with the ITPA minor variant A (～27%) have an advantage in pegylated interferon plus ribavirin‐based therapies, due to expected adherence of ribavirin doses, resulting in a higher viral clearance rate.     

High sensitivity assay using serum sample for IL28B genotyping to predict treatment response in chronic hepatitis C patients

Aim: Recent human genome‐wide association studies (GWAS) revealed a strong association between IL28B gene variation and the pegylated interferon‐α with ribavirin (PEG‐IFN‐α/RBV) treatment response in chronic hepatitis C patients. Two single nucleotide polymorphisms (SNP), rs8103142 and rs11881222 located in the IL28B gene, were found in significant association with the viral clearance. The present study employed these SNPs to develop a new accessible screening method allowing identification of potential non‐responders before starting the therapy. Methods: Primer sets were designed to amplify rs8103142 and rs11881222 fragments from genomic DNA extracted from serum samples. This method was validated using microarray typing (GWAS) and applied for genotyping of 68 hepatitis C virus‐infected patients with PEG‐IFN‐α/RBV treatment at baseline. Results: In comparison with GWAS, the screening method showed 100% and 95.6% accuracy in typing of rs8103142 and rs11881222, respectively, indicating incomplete specificity but 100% of sensitivity in both. Genotyping by both SNP showed that 53 (77.9%), 14 (20.6%) and one (1.5%) of the patients were of major homozygous, heterozygous and minor homozygous type, respectively. The majority (85%) of homozygous patients exhibited response to therapy in contrast to heterozygous patients (29%). Among all genotyped only one case was found with the minor homozygous genotype which had late virological response to therapy before relapsing. Conclusion: This study described a highly sensitive assay that can be useful in determining SNP genotypes as well as in predicting the response to IFN‐based treatment.     

Acupuncture needle-associated prosthetic knee infection after total knee arthroplasty

The case of a patient who previously had permanent acupuncture needles placed in the knee joint and had been doing well, with no evidence of infection, but who eventually underwent a revision total knee arthroplasty due to acupuncture needle-associated prosthetic infection is presented. The microorganism responsible for the infection was Enterococcus faecalis, a bacterium which rarely causes infection following arthroplasty. This case should be highlighted to increase the awareness of healthcare providers to acupuncture-associated subclinical infection that may be exacerbated by surgical manipulation.     

PCI using a 4‐Fr “child” guide catheter in a “mother” guide catheter: Kyushu KIWAMI® ST registry

Objectives: With the development of PCI techniques, the indications for stents have been expanding as well. On the other hand, we often encounter the situations where deploying a stent/stents by the conventional method is technically challenging. We report a novel stent delivery system using a newly developed 4Fr. straight catheter with Mother‐and‐Child method. Methods and results: We collected the data on coronary angioplasty in which we experienced the difficulty to deliver coronary stents and used 4Fr. KIWAMI ST01. The case number amounts to 32 cases over a six‐month period from October 2009 through March 2010;76:919‐–923. The angioplasty was performed for lesions in the RCA in 9 patients (28%), lesions in the LAD in 15 patients (47%), lesions in the LCX in 5 patients (16%), lesions in the saphenous vein grafts in 2 patients (6%), and lesions in the internal thoracic artery (LITA) grafts in 1 patient (3%). And the reasons for the difficult stent delivery by the conventional methods were as follows: severe calcification in 12 patients (37%), intense tortuosity in 7 patients (22%), poor backup support for guide catheter in 8 patients (25%), and trapping of the stent proximal to the target lesion in 5 patients (16%). The dislodgment of stent did not happened in all cases. Conclusions: KIWAMI® ST01 stent delivery system is feasible, safer, and effective in cases where stent delivery is difficult by the conventional method. © 2010 Wiley‐Liss, Inc.     

Identification of potential serum markers for endometrial cancer using protein expression profiling

Objectives

Screening method of endometrial cancer (EC) has not been established yet. Our study was to explore serum biomarkers of EC patients using surface-enhanced laser desorption and ionization-time-of-flight mass spectrometry (SELDI-TOF MS).

Methods

Serum samples from 65 EC patients and 40 controls were analyzed by SELDI-TOF MS (training set). Single- and multi-variant analyses were performed to compare protein profiles in serum of EC patients and healthy controls. Subsequently, blind test set including 40 EC patients and 40 controls were analyzed for validation.

Results

A panel of four biomarker candidates were selected in training set analysis. These markers could also distinguish stage I patients from controls. Among them, two biomarkers were purified and identified as apolipoprotein A1 and a modified form of apolipoprotein C1. Screening for blind test set using dual-biomarker analysis yielded a sensitivity of 82% and a specificity of 86%.

Conclusions

Involvement of apolipoproteins with EC is first suggested in this study. In addition to possibility of screening method for EC, findings of these new biomarkers might be related with carcinogenesis or predisposition to EC.     

Multiple cognitive functional assessments used to modify the disturbed behavior of an elderly woman with dementia from the viewpoint of psychoeducation for the patient and her family

We report a case of a patient with dementia for whom a psychoeducational intervention based on a cognitive functional assessment by multiple cognitive functional tests was useful. She was an 82-year-old woman with hypertension and hyperlipidemia. She often asked about the date, scorched pans several times, and bought large amounts of the same items over 2 years. Her family worried that she might have dementia and hospitalized her. Mixed type dementia was diagnosed from the results of a cognitive functional assessment and magnetic resonance imaging findings. A psychoeducational program was conducted based on the findings of retained and impaired cognitive abilities derived from the above assessment. Her daily life disturbances were modified by an external compensation method. For example, her son told her repeatedly when it was not necessary to make supper, and made use of a block calendar. To consider how to cope appropriately with daily life disturbances derived from the symptoms of dementia, it is important to understand retained and impaired cognitive abilities, by comparing multiple cognitive functional assessments with the type of disturbances, and to deepen understanding of patients' psychological profiles, from the viewpoint of psychoeducation for the patient and family.     

Reactivation of hepatitis B virus in HBsAg-negative patients with multiple myeloma: two case reports

It was recently reported that hepatitis B virus (HBV) reactivation had occurred in HBsAg-negative lymphoma patients who received rituximab plus steroid combination chemotherapy. HBV reactivation in myeloma patients have not been reported extensively. We describe here two cases of HBV reactivation in HBsAg-negative myeloma patients receiving systemic chemotherapy: one from the medical records of 40 patients and another from 61 patients with prospective HBV-DNA monitoring. In the first case positive for anti-HBs, HBV reactivation was diagnosed when hepatitis developed during conventional chemotherapy such as MP and MCP regimen in a relapsed patient after autologous stem cell transplantation (APBSCT); in the second case positive for anti-HBc and anti-HBs, elevation of HBV-DNA was recognized by serial HBV-DNA monitoring performed prospectively following APBSCT. Interestingly, these two cases had the reduction of the titer of anti-HBs during the treatment, followed by HBV reactivation. These clinical data suggest that the HBV-DNA monitoring is necessary for not only HBsAg-positive but also HBsAg-negative myeloma patients with anti-HBc-positive and/or anti-HBs-positive following transplantation and after conventional chemotherapy in the salvage setting. Establishment of a standard strategy to prevent HBV reactivation is important for myeloma patients receiving systemic chemotherapy.     

Multidisciplinary therapeutic approach for maintaining long-term nutritional status for patient with advanced esophageal carcinoma confounded by dermatomyositis

We report a patient with advanced esophageal carcinoma associated with dermatomyositis who successfully maintained long-term good nutritional status by chemoradiation therapy and continuous enteral nutrition. A 64-year-old Japanese man was admitted to our hospital because of dysphagia and systemic edema. Because of debilitated status and malnutrition, intravenous corticosteroid infusion was first performed. Continuous enteral nutrition was performed through percutaneous endoscopic gastrostomy, and chemoradiation therapy was then performed. Although the endoscopic examination revealed complete regression of esophageal carcinoma, an esophagobronchial fistula was formed. The patient was periodically followed up by a multidisciplinary team for appropriate nutritional management; as a result, nutritional status was markedly improved and well maintained. A covered, selfexpandable metallic stent was placed in the esophagus to conceal the esophagobronchial fistula. This case highlights the importance of multidisciplinary therapeutic approach for maintaining good nutritional status and quality of life in patients with advanced esophageal carcinoma confounded by debilitating disorders.