Fatal Cytomegalovirus Pneumonia and Associated Herpes Virus Infection in a Relapsed/Refractory Multiple Myeloma Patient Treated with Bortezomib plus Dexamethasone

Multiple myeloma (MM) remains a largely incurable disease in the long term despite positive responses to first-line chemotherapy. Herein we report the case of a 68-year-old woman who died following treatment with bortezomib plus dexamethasone for refractory MM. The combination was associated with significant antitumor activity, but bacterial pneumonia/sepsis was followed by bilateral cytomegalovirus pneumonia with herpes simplex co-infection, and this was almost certainly the cause of death. Physicians need to pay careful attention when treating patients with refractory MM with bortezomib plus dexamethasone, and to be mindful that antiviral therapy may be needed in some cases

Pathogenesis of Metastatic Calcification due to Hypercalcemia in Adult T-cell Leukemia-Lymphoma

Two cases of metastatic calcification due to hypercalcemia in adult T-cell leukemia-lymphoma (ATLL)associated with osteolytic change for activation of osteoclasts are reported. These cases of serum calcium were at a high level, 16.2 and 19.4mg/dl (normal range 8.4-10.4mg/dl). In our cases, metastatic calcification was detected in the tubules of kidneys, in the pulmonary alveolar septa of lungs, in the myocardium, in the muscular layer of stomach, in the lower portion of media of aorta, in the mucosa of stomach, in the tubules of testis, and in the liver by von Kossa\u27s silver nitrate method for calcium. Scattered osteoclasts were seen around the cortex of the bone. Roentgenograms showed osteolytic change in the skull, in the bilateral ulna, in the radius, in the humerus, in the tibia, and in the fibula. Therefore, hypercalcemia in ATLL may be caused by bone resorption-stimulating factors which promote the differeniation of osteocalast cells, resulting in calcium increases in the serum

Dorsal Column Degeneration after Bortezomib Therapy in a Patient with Multiple Myeloma

We present here a case of dorsal column degeneration in a female patient with multiple myeloma following exposure to bortezomib. Two days after intravenous administration of a first course of bortezomib 1 mg/m2, the patient developed rapidly-progressive numbness, pain and muscle weakness in the bilateral upper and lower limbs. Following gancyclovir treatment of subsequent cytomegalovirus viremia, the patient went on to receive a course of EPOCH (etoposide 50 mg/m2/day on days 1–4, vincristine 0.4 mg/m2/day on days 1–4, doxorubicin 10 mg/m2/day on days 1–4, cyclophosphamide 750 mg/m2/day on day 6, and prednisolone 60 mg/m2/day on days 1–6). Shortly thereafter, the patient developed bilateral Aspergillus pneumonia. Despite treatment with appropriate antifungal agents, the patient died from respiratory failure due to bilateral diffuse alveolar damage of the lungs and without recovery of severe sensory and motor neuropathy prior to her death. Post mortem examination revealed spongy degeneration of the dorsal column from the medulla oblongata to the cervical spinal cord. Bortezomib-associated peripheral neuropathy in patients with multiple myeloma has been commonly reported but appears to resolve in a majority of these patients after dose reduction or discontinuation. We believe this to be the first report of spinal cord abnormalities in a patient with multiple myeloma treated with bortezomib. Further investigation is required to ascertain the exact mechanism of this central neurotoxic effect and to identify appropriate neuroprotective strategies

Predictive scoring model of mortality after surgical or endovascular revascularization in patients with critical limb ischemia

ObjectiveThe latest guideline points to life expectancy of <2 years as the main determinant in revascularization modality selection (bypass surgery [BSX] or endovascular therapy [EVT]) in patients with critical limb ischemia (CLI). This study examined predictors and a predictive scoring model of 2-year mortality after revascularization.MethodsWe performed Cox proportional hazards regression analysis of data in a retrospective database, the Bypass and Endovascular therapy Against Critical limb ischemia from Hyogo (BEACH) registry, of 459 consecutive CLI patients who underwent revascularization (396 EVT and 63 BSX cases between January 2007 and December 2011) to determine predictors of 2-year mortality. The predictive performance of the score was assessed with the area under the time-dependent receiver operating characteristic curve.ResultsOf 459 CLI patients (mean age, 72 ± 10 years; 64% male; 49% nonambulatory status, 68% diabetes mellitus, 47% on regular dialysis, and 18% rest pain and 82% tissue loss as treatment indication), 84 died within 2 years after revascularization. In a multivariate model, age >75 years (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.10-2.85), nonambulatory status (HR, 5.32; 95% CI, 2.96-9.56), regular dialysis (HR, 1.90; 95% CI, 1.10-3.26), and ejection fraction <50% (HR, 2.49; 95% CI, 1.48-4.20) were independent predictors of 2-year mortality. The area under the time-dependent receiver operating characteristic curve for the developed predictive BEACH score was 0.81 (95% CI, 0.76-0.86).ConclusionsPredictors of 2-year mortality after EVT or BSX in CLI patients included age >75 years, nonambulatory status, regular dialysis, and ejection fraction <50%. The BEACH score derived from these predictors allows risk stratification of CLI patients undergoing revascularization

1-Year Results of the ZEPHYR Registry (Zilver PTX for the Femoral Artery and Proximal Popliteal Artery) Predictors of Restenosis

AbstractObjectivesThis study sought to assess the rate and predictors of 1-year restenosis after drug-eluting stent implantation for femoropopliteal (FP) lesions in patients with peripheral arterial disease.BackgroundZilver PTX, a paclitaxel-eluting stent for FP lesions, provides superior outcomes to angioplasty and bare-metal stents in clinical trials. However, its real-world outcomes and the associated features remain unclear.MethodsThis was a prospective multicenter study enrolling 831 FP lesions (797 limbs, 690 patients) treated by Zilver PTX implantation. The primary endpoint was 1-year restenosis. Secondary endpoints included major adverse limb event and stent thrombosis.ResultsMean lesion length was 17 ± 10 cm. One-year restenosis, major adverse limb event, and stent thrombosis rates were 37%, 22%, and 2%, respectively. The generalized linear mixed model showed that lesion length ≥16 cm assessed by angiography and distal external elastic membrane area ≤27 mm2 and minimum stent area ≤12 mm2 assessed by intravascular ultrasound were independent risk factors for restenosis. One-year restenosis rates were 15% in cases with none of these risk factors and 50% in those with ≥2 risk factors.ConclusionsThe current study demonstrated 1-year real-world outcomes after drug-eluting stent treatment for FP lesions, including challenging ones in clinical practice. Lesion length, external elastic membrane area, and minimum stent area were independent predictors for restenosis. (Zilver PTX for the Femoral Artery and Proximal Popliteal Artery—Prospective Multicenter Registry [ZEPHYR]; UMIN000008433

Association of dietary fiber intake with subsequent fasting glucose levels and indicators of adiposity in school-age Japanese children

Abstract Objective: To evaluate the relationships of fiber intake with subsequent body mass index SD-score, waist-to-height ratio, and serum fasting glucose levels among school-age Japanese children. Design: A prospective study of school-age Japanese children. Participants were followed from 6–7 to 9–10 years of age (follow-up rate: 92.0%). Fiber intake was assessed using a validated food frequency questionnaire. Serum fasting glucose was measured by a hexokinase enzymatic method. Using a general linear model, the associations between dietary fiber intake at baseline and body mass index SD-score, waist-to-height ratio, and serum levels of fasting glucose at follow-up were evaluated after considering potential confounding factors. Setting: Public elementary schools in a city in Japan Participants: A total of 2,784 students. Results: The estimated means for fasting glucose at 9–10 years of age were 86.45, 85.68, 85.88, and 85.58 mg/dl in the lowest, second, third, and highest quartile of fiber intake at 6–7 years of age, respectively (p= 0.033, trend p= 0.018). Higher fiber intake at 6–7 years of age was associated with lower waist-to-height ratio at 9–10 years of age (trend p= 0.023). The change in fiber intake was inversely associated with concurrent change of body mass index SD-score (trend p= 0.044). Conclusion: These results suggest that dietary fiber intake may be potentially effective to limit excess weight gain and lower glucose levels during childhood

Multicenter retrospective and comparative study of 5-minute versus 15-second endoscopic papillary balloon dilation for removal of bile duct stones

Background and study aims Endoscopic papillary balloon dilation (EPBD) is a method of bile duct stone removal that has a better long-term outcome but a high risk of post-ERCP pancreatitis (PEP). Recent studies have suggested that 5-minute EPBD can reduce the incidence of PEP. This study aimed to examine the safety and effectiveness of longer duration EPBD compared with shorter duration EPBD (5 minutes vs. 15 seconds after disappearance of the waist of a dilation catheter). Patients and methods Patients without a history of endoscopic sphincterotomy or EPBD who underwent EPBD to remove bile duct stones were selected retrospectively from five centers. The incidence of PEP, other early adverse events, and outcomes of EPBD were compared between the groups. A multivariable analysis of risk factors for PEP was performed. Results: A total of 607 patients (157 and 450 in the 5-minute and 15-second EPBD groups, respectively) were included. There were no statistically significant differences between the groups in terms of the incidence of PEP (8.3 % and 8.9 % in the 5-minute and 15-second EPBD groups, respectively; P = 0.871) and the incidence of overall early adverse events ( P = 0.999). Although 5-minute EPBD elongated the procedure time (45 vs. 37 minutes, P < 0.001), it increased the rate of complete stone removal during a single session ( P < 0.001) and decreased the use of lithotripsy ( P < 0.001). Conclusions: Compared with 15-second EPBD, 5-minute EPBD did not reduce the incidence of PEP

Analysis of mRNA expression for steroidogenic enzymes in the remaining adrenal cortices attached to adrenocortical adenomas.

DESIGN AND METHODS: We have recently demonstrated that the adrenal cortices attached to aldosterone-producing adenoma (APA) contained microscopic subcapsular micronodules suggestive of active aldosterone production. In this study, we used in situ hybridization to investigate the mRNA expression of steroidogenic enzymes in the adrenal cortices attached to cortisol-producing adenoma (CPA) and clinically silent adenoma (non-functioning adenoma; NFA), in addition to APA. RESULTS: Microscopic subcapsular micronodules, which were several hundreds of micrometers in size and spheroid in shape, were observed in the cortices attached to CPA and NFA, as well as APA, at high frequency. Most of the cortical nodules in zona fasciculata to zona reticularis showed a suppressed steroidogenesis in the cortices attached to adenoma, but some expressed intensely all necessary steroidogenic enzyme mRNAs for cortisol synthesis. CONCLUSIONS: It is thus necessary to keep in mind, on the occasion of subtotal adrenalectomy, that lesions with the potential to later develop into functional adrenocortical nodules may be present in other parts of the ipsilateral or contralateral adrenal cortices

特別支援教育におけるライフキャリアの支援

In this study, we reviewed the history and relevant literature of career education and life career education. At the same time, we clarified the essential points of education by viewing and discussing guidance for children with intellectual disabilities, guidance for children with high-functioning developmental disabilities, and guidance at University Attached School for Special Needs Education for intellectual disabilities through the perspective of life career. The main results of our research are as follows. 1)Education and practices related to life career are undoubtedly progressing. In special needs education, it is vital to nurture career adaptability and life career resilience. 2)If teachers share the perspective of life career education, they can have a qualitative and quantitative influence on the relationships among children by setting up learning activities (meetings) that are open to participation of children of different grades and continuously guiding children with intellectual disabilities. 3)For young children with high-functioning developmental disabilities, life career development support from early childhood and the setting up of opportunities for young children to become aware of each other and act altruistically are particularly important. 4)In life career education for young students with intellectual disabilities or autism, the three concepts of "work, life, and leisure" are of importance. Further, by incorporating a systematic teaching model in education, the quality of lessons increases, leading to transformation in the children. 5)In life career education, it is necessary to expand on experiences helpful for choosing a fitting way of life in the future. For this purpose, for example, leisure — especially the participation in recreation and sports — is of importance. 6)It is important to educate and train teachers to provide adequate guidance based on the key concepts of career education and life career education in special needs education