Cost-effectiveness of primary prophylaxis of febrile neutropenia with pegfilgrastim in docetaxel, cisplatin and 5-fluorouracil therapy for esophageal cancer.

Objective: The efficacy of docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy in treating esophageal cancer has been reported. However, febrile neutropenia (FN) is a potentially serious adverse event of DCF therapy with an incidence of 10 to 40%. Pegfilgrastim, a granulocyte colony-stimulating factor (G-CSF), has been shown to have a primary prophylactic role in FN. However, it has been suggested that excessive use of expensive G-CSF should be avoided. Therefore, we performed a cost-utility analysis of primary prophylaxis with pegfilgrastim. Design: Cost-effectiveness analysis using decision tree modelling. Methods: We used a decision tree analysis model based on the report of primary prophylaxis with pegfilgrastim. Based on a previous study, the FN incidence rate was set at 40.0% (95% confidence interval (CI): 11.9-68.1) for the pegfilgrastim group and 43.5% (95%CI: 21.6-65.4) for the no pegfilgrastim group. The FN treatment cost was US$726.63, and the duration of FN was 3.65±1.20 days. The utility value of patients who received DCF therapy was 0.643, and the change in utility value at FN onset was -0.15. Expected cost, quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER) were calculated, and cost-utility analysis was performed. Results: The ICER of pegfilgrastim was 184,976.75 USD/QALY. As a result of sensitivity analysis, the utility of FN had the greatest impact on the cost-effectiveness analysis, followed by the drug cost of pegfilgrastim. Conclusion: Primary prophylaxis of FN with pegfilgrastim might not be cost-effectiveness. In determining whether to administer pegfilgrastim it is necessary to consider patient factors, not just the incidence of FN.

Primary Lymphangiosarcoma of the Urinary Bladder in a Dog.

Abdominal ultrasonographical and computed tomography examinations of a 12-year-old neutered female toy poodle revealed a protruding mass, approximately 2 cm in diameter, at the apex of the bladder. The mass was firm and haemorrhagic with a homogeneously brownish-yellow cut surface. Microscopically, it was unencapsulated and located in the muscle layer with invasion of the extra-muscular layer. It was composed of spindloid to oval neoplastic cells that formed irregular clefts and diffuse sheets that dissected bundles of collagen. Immunohistochemically, the neoplastic cells were positive for vimentin and lymphatic vessel endothelial hyaluronan receptor 1 antigens, but negative for cytokeratin AE1/AE3, factor VIII-related antigen, CD31, CD34, Prox-1, S100, desmin, α-smooth muscle actin and MyoD1. Negative immunolabelling for laminin antigen supported the absence of evidence of a basal lamina on ultrastructural examination. Based on these findings, this tumour was identified as a lymphangiosarcoma. To the best of our knowledge, this case is the first report of lymphangiosarcoma arising from the bladder in a dog.

Diffuse Pulmonary Meningotheliomatosis with Sarcomatous Transformation in a Shiba Dog.

A 2-year-old neutered female Shiba dog exhibited laboured breathing for 1 month. Computed tomography of the thoracic cavity revealed multiple nodules (2-5 mm diameter) in the lungs. Grossly, the lungs were firm and normal in shape. The nodules were grey-white in colour. Microscopically, the nodules were non-encapsulated and exhibited an irregular shape. They were composed of polygonal or spindle cells with indistinct cell borders arranged in sheets. The cells had large, round, hyperchromatic nuclei and abundant pale eosinophilic cytoplasm with no atypia. Intrapulmonary arterial emboli and infiltration into the bronchioles were observed. Immunohistochemically, the cells were positive for vimentin and negative for cytokeratin, glial fibrillary acidic protein and α-smooth muscle actin. Ultrastructurally, the cells displayed cytoplasmic processes, desmosomes and intermediate filaments. These findings led to a diagnosis of diffuse pulmonary meningotheliomatosis with sarcomatous transformation. To the best of our knowledge, this is the first report of diffuse pulmonary meningotheliomatosis in a dog.

Malignant Oestrogen-producing Teratoma in a Cat.

A 5-year-old female domestic shorthair cat was presented with abdominal distension and serum biochemical evaluation indicated a high concentration of oestradiol (32.81 pg/ml). Exploratory laparotomy revealed a large cystic mass in the right ovary with cystic fluid containing a high level of oestradiol (18.80 pg/ml). The tumour was composed of immature neuroectodermal tissue, mature cartilage, smooth muscle, adipose tissue and aggregated, poorly differentiated mesenchymal cells. It contained cysts of various sizes that were lined by epithelium of different types. The basal layer of the lining epithelium was shown to express aromatase by immunohistochemistry. The findings suggest that this was a novel, malignant, oestrogen-secreting teratoma and that the aromatase-positive, neoplastic cells may have been the source of elevated levels of serum oestrogen.

Subacute sarcoid myositis with ocular muscle involvement; a case report and review of the literature.

Sarcoidosis is a chronic granulomatous disease that can affect multiple organs. The lungs, eyes, and skin are known to be highly affected organs in sarcoidosis. There have been reports based on random muscle biopsy that 32-80% of systemic sarcoidosis comprises noncaseating granulomas; however, muscle involvement in sarcoidosis is generally asymptomatic and has an unknown frequency. We describe a case of acute to subacute sarcoid myositis of the skeletal and extraocular muscles. Typical ophthalmic involvement (manifested by infiltration of the ocular adnexa, intraocular inflammation, or infiltration of the retrobulbar visual pathways) and extraocular sarcoid myositis (as with the present case) is infrequently reported. It is important to keep in mind the rare yet perhaps underestimated entity of sarcoid myositis, and to utilize muscle biopsy and imaging tests for appropriate diagnosis and management of patients with sarcoidosis.

Thermal Conductivity through the Quantum Critical Point in YbRh_{2}Si_{2} at Very Low Temperature.

The thermal conductivity of YbRh_{2}Si_{2} has been measured down to very low temperatures under field in the basal plane. An additional channel for heat transport appears below 30 mK, both in the antiferromagnetic and paramagnetic states, respectively, below and above the critical field suppressing the magnetic order. This excludes antiferromagnetic magnons as the origin of this additional contribution to thermal conductivity. Moreover, this low temperature contribution prevails a definite conclusion on the validity or violation of the Wiedemann-Franz law at the field-induced quantum critical point.

Effects of conversion from a twice-daily tacrolimus to a once-daily tacrolimus on glucose metabolism in stable kidney transplant recipients.

INTRODUCTION: The adverse effects of tacrolimus are known to play major roles in new-onset diabetes after transplantation. The purpose of this study was to investigate the effects of conversion from a twice-daily tacrolimus (Tac-BID) to a once-daily tacrolimus (Tac-OD) on glucose metabolism in stable kidney transplant recipients. PATIENTS AND METHODS: Twenty-six patients were converted from Tac-BID to Tac-OD on a 1:1 mg basis and examined for its effects on glucose metabolism. Unless rejection or tacrolimus toxicity was suspected, we did not perform dose adjustments of Tac-OD or reconversion to Tac-BID until 4 weeks after conversion. Subsequent dose adjustments were allowed to maintain tacrolimus target trough concentration within the. Changes in clinical parameters were compared between baseline and 24 weeks after conversion. RESULTS: Conversion from Tac-BID to Tac-OD on a 1:1 mg basis resulted in a significant decrease in tacrolimus trough level at 4 weeks after conversion. Because dose adjustments were performed, the trough level did not differ significantly between baseline and 24 weeks after conversion. At 4 and 24 weeks after conversion, the homeostasis model assessment of pancreas ß-cell function (HOMA-ß) increased significantly. CONCLUSIONS: Although there was no change in tacrolimus trough level between baseline and 24 weeks after transplantation, HOMA-ß at 24 weeks after conversion was significantly higher than that at baseline. These results indicated that conversion from Tac-BID to Tac-OD may improve pancreas ß-cell function in kidney transplant recipients.

Glucose intolerance is associated with increased intimal-medial thickness of the carotid artery and increased pulse-wave velocity in renal transplant recipients.

BACKGROUND: Although new-onset diabetes after transplantation has been demonstrated to have a significant negative impact on allograft and patient survival, the role of glucose intolerance (impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT], as asymptomatic hyperglycemia and borderline diabetes, has not been identified in renal transplant recipients. METHODS: We enrolled 32 renal transplant recipients (at least 1 year after transplantation) without prior evidence of diabetes at our institution in this study. Transplant recipients were divided into 2 groups (normal glucose tolerance group and glucose intolerance group) according to the results of their oral glucose tolerance test with 75 g of glucose. Glucose intolerance included IFG, IGT, and IFG/IGT. Normal glucose tolerance was detected in 19 patients, and glucose intolerance in 13: had 6 IGT, 2 IFG, and 5 IGT/IFG. Bilateral brachial-ankle pulse-wave velocity (baPWV) and intimal-media thickness (IMT) measured as markers of atherosclerosis were compared between the 2 groups. Insulin resistance was estimated with the homeostasis model assessment of insulin resistance (HOMA-R), and pancreatic ß-cell function evaluated by the homeostasis model assessment of ß-cell function and insulinogenic index. RESULTS: The patients in the glucose intolerance group showed significantly greater baPWV and IMT than those in the normal glucose tolerance group. HOMA-R in the glucose intolerance patients was significantly higher than in the normal glucose tolerance patients. Linear regression analysis showed the increased IMT in the renal transplant recipients to be significantly correlated with HOMA-R. CONCLUSIONS: Renal transplant recipients with glucose intolerance had increased IMT and baPWV, suggesting that glucose intolerance in renal transplant recipients may induce atherosclerosis and that the rise in insulin resistance may contribute to the increased IMT in renal transplant recipients.

Insulin resistance and insulin secretion in renal transplant recipients with hepatitis C.

BACKGROUND: Several reports have suggested an association between hepatitis C virus (HCV) infection and new-onset diabetes after transplantation (NODAT). NODAT is a common complication after renal transplantation, and it has been associated with increased long-term morbidity and mortality. HCV-positive recipients may have abnormal glucose metabolism, even though NODAT has never been previously diagnosed. The aim of this study was to analyze the pathogenic factors responsible for glucose metabolism in a series of HCV-positive renal transplant recipients. METHODS: The study population comprised 16 renal transplant patients who received their grafts from deceased or living donors with anti-HCV antibodies. HCV-negative transplant recipients were individually matched with these HCV-positive recipients by year of transplantation, sex, age, serum creatinine levels, and type of calcineurin inhibitors. None of the patients had been diagnosed with diabetes. Insulin secretion and insulin resistance were determined by a 75-g oral glucose tolerance test (OGTT) and compared between the 2 groups. Categories of glucose tolerance were defined according to World Health Organization criteria. RESULTS: Glucose intolerance (impaired fasting glucose, impaired glucose tolerance, diabetes mellitus) as assessed by OGTT was detected in 7 of the HCV-positive recipients (43.8%) and 3 of the HCV-negative recipients. The homeostasis model assessment of insulin resistance was greater in the HCV-positive recipients than in the HCV-negative recipients. The homeostasis model assessment of ß-cell function was higher in the HCV-positive recipients than in the HCV-negative recipients. CONCLUSIONS: The frequency of glucose intolerance tended to be higher in HCV-positive recipients. Furthermore, insulin resistance was greater and insulin secretion higher in HCV-positive recipients, which indicated that the increase in insulin secretion compensated for insulin resistance observed in these patients. However, HCV-positive renal transplant recipients may ultimately develop NODAT as this compensation diminishes with time.

Verification of the Wiedemann-Franz law in YbRh2Si2 at a quantum critical point.

The thermal conductivity measurements are performed on the heavy-fermion compound YbRh(2)Si(2) down to 0.04 K and under magnetic fields through a quantum critical point (QCP) at B(c)=0.66 T∥c axis. In the limit as T→0, we find that the Wiedemann-Franz law is satisfied within experimental error at the QCP despite the destruction of the standard signature of Fermi liquid. Our results place strong constraints on models that attempt to describe the nature of the unconventional quantum criticality of YbRh(2)Si(2).

Diagnostic performance of fluorodeoxyglucose-positron emission tomography/computed tomography combined with ultrasonography-guided fine needle aspiration cytology for identifying axillary lymph node status in patients with breast cancer.

AIM: The aim of this study was to assess the diagnostic performance of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in combination with ultrasonography-guided fine needle aspiration cytology (US-guided FNAC) for the preoperative diagnosis of axillary lymph node (ALN) metastases in patients with breast cancer. MATERIALS AND METHODS: A total of 318 patients with breast cancer were recruited retrospectively. Some of the cases that underwent neoadjuvant chemotherapy (NAC) were included. The sensitivity and specificity of FDG-PET/CT were calculated. We assessed the relationship between the combined results for US-guided FNAC with FDG-PET/CT and the pathological ALN status. RESULTS: A total of 271 patients underwent FDG-PET/CT. Of these patients, 41 underwent US-guided FNAC. The sensitivity and the specificity of FDG-PET/CT for the cases without NAC were 18.5%, 97.1%, respectively. The sensitivity in cases with NAC was 68.2%. As a whole, the sensitivity was 40.8%. ALN metastasis was detected using US-guided FNAC in a case with a negative FDG uptake in the ALN. The T stage was T2 in the case and the FDG uptake at the primary site was poor. CONCLUSION: FDG-PET/CT has a good specificity for ALN metastasis, although its sensitivity is limited, especially in early-stage cases. In cases with a negative FDG uptake in the ALN, US-guided FNAC may play a role in the detection of lymph node metastasis when the primary tumor size is large and the FDG uptake in the primary tumor is low.

Thermoelectric response near a quantum critical point of ß-YbAlB4 and YbRh2Si2: a comparative study.

The thermoelectric coefficients have been measured down to a very low temperature for the Yb-based heavy-fermion compounds ß-YbAlB4 and YbRh2Si2, often considered as model systems for the local quantum criticality case. We observe a striking difference in the behavior of the Seebeck coefficient S in the vicinity of their respective quantum critical point (QCP). Approaching the critical field, S/T is enhanced in ß-YbAlB4, but drastically reduced in YbRh2Si2. The ratio of thermopower to specific heat remains constant for ß-YbAlB4, but it is significantly reduced near the QCP in YbRh2Si2. In both systems, on the other hand, the Nernst coefficient shows a diverging behavior near the QCP. The interplay between valence and magnetic quantum criticality and the additional possibility of a Lifshitz transition crossing the critical field under magnetic field are discussed as the origin of the different behaviors of these compounds.

Twofold spontaneous symmetry breaking in the heavy-fermion superconductor UPt3.

The field-orientation dependent thermal conductivity of the heavy-fermion superconductor UPt3 was measured down to very low temperatures and under magnetic fields throughout the distinct superconducting phases: B and C phases. In the C phase, a striking twofold oscillation of the thermal conductivity within the basal plane is resolved reflecting the superconducting gap structure with a line of node along the a axis. Moreover, we find an abrupt vanishing of the oscillation across a transition to the B phase, as a clear indication of a change of gap symmetries. We also identify extra two line nodes below and above the equator in both B and C phases. From these results together with the symmetry consideration, the gap function of UPt3 is determined as a E(1u) representation characterized by a combination of two line nodes at the tropics and point nodes at the poles.

Conversion of stable kidney transplant recipients from a twice-daily prograf to a once-daily tacrolimus formulation: a short-term study on its effects on glucose metabolism.

BACKGROUND: The adverse effects of tacrolimus are known to play major roles in posttransplantation diabetes mellitus (PTDM). In the present study, we investigated the effects of conversion from a twice-daily (Tac BID) to a once-daily prolonged release of tacrolimus formulation (Tac OD) on glucose metabolism in stable kidney transplant recipients. PATIENTS AND METHODS: In this prospective study, 26 patients converted from Tac BID to the same milligram-milligram daily dose of Tac OD were examined for the effects on renal function, drug trough levels, and glucose metabolism over a 4-week period. RESULTS: Conversion from Tac BID to Tac OD on a 1:1 mg basis resulted in a significant decrease in tacrolimus trough levels, but no significant changes in renal function. At 4 weeks after conversion, a homeostasis model assessment of ß-cell function, and hemoglobin A1c (HbA1c) decreased significantly. CONCLUSIONS: This study demonstrated a significant reduction in tacrolimus trough levels after switching from Tac BID to Tac OD, which increased insulin secretion and decreased HbA1c, suggesting that it may decrease the frequency of PTDM among stable renal transplant recipients.

Excellent outcomes of ABO-incompatible kidney transplantation: a single-center experience.

INTRODUCTION: Due to the severe shortage of deceased donors in Japan, ABO-incompatible living donor kidney transplantation has been performed since the late 1980s. Excellent long-term outcomes have been achieved; the rates of graft survival among these patients are currently similar to those of recipients of ABO-compatible grafts. Our single-center experience describing the immunosuppressive protocols, complications, and grafts survivals is documented in this study. PATIENTS AND METHODS: Among 123 patients with end-stage renal disease who underwent living donor kidney transplantation between January 1999 and December 2010, 25 cases were ABO-incompatible grafts. All of these patients were followed until August 2011. Analyzing these patients, we focused on their immunosuppressive protocols, complications, and graft survivals. RESULTS: Patient and graft survival rates were 100%. One patient experienced antibody-mediated rejection and an intractable acute cellular rejection episode, 1 patient an antibody-mediated rejection, and 6 patients had acute cellular rejection episodes. However, there were no severe complications. CONCLUSION: Although ABO-incompatible kidney transplantation is a high-risk procedure, a short-term graft survival rate of 100% may be expected due to recent significant improvements in desensitization and recipient management.

Anisotropic hysteretic Hall effect and magnetic control of chiral domains in the chiral spin states of Pr2Ir2O7.

We uncover a strong anisotropy in both the anomalous Hall effect (AHE) and the magnetoresistance of the chiral spin states of Pr(2)Ir(2)O(7). The AHE appearing below 1.5 K at a zero magnetic field shows hysteresis which is most pronounced for fields cycled along the [111] direction. This hysteresis is compatible with the field-induced growth of domains composed by the 3-in 1-out spin states which remain coexisting with the 2-in 2-out spin ice manifold once the field is removed. Only for fields applied along the [111] direction, we observe a large positive magnetoresistance and Shubnikov-de Haas oscillations above a metamagnetic critical field. These observations suggest the reconstruction of the electronic structure of the conduction electrons by the field-induced spin texture.

Enhanced quasiparticle heat conduction in the multigap superconductor Lu2Fe3Si5 .

Thermal transport measurements have been made on the Fe-based superconductor Lu2Fe3Si5 (T(c) ∼ 6 K) down to a very low temperature T(c)/120. The field and temperature dependences of the thermal conductivity confirm the multigap superconductivity with fully opened gaps on the whole Fermi surfaces. In comparison to MgB2, Lu2Fe3Si5 reveals a remarkably enhanced quasiparticle heat conduction in the mixed state. The results can be interpreted as a consequence of the unequal weight of the Fe 3d-electron character among the distinct bands.

Desensitization protocol in highly HLA-sensitized and ABO-incompatible high titer kidney transplantation.

BACKGROUND: A positive crossmatch indicates the presence of donor-specific alloantibodies and is associated with a graft loss rate of >80%; anti-ABO blood group antibodies develop in response to exposure to foreign blood groups, resulting in immediate graft loss. However, a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation has not yet been established. METHODS: We treated 6 patients with high (≥1:512) anti-A/B antibody titers and 2 highly HLA-sensitized patients. Our immunosuppression protocol was initiated 1 month before surgery and included mycophenolate mofetil (1 g/d) and/or low-dose steroid (methylprednisolone 8 mg/d). Two doses of the anti-CD20 antibody rituximab (150 mg/m(2)) were administered 2 weeks before and on the day of transplantation. We performed antibody removal with 6-12 sessions of plasmapheresis (plasma exchange or double-filtration plasmapheresis) before transplantation. Splenectomy was also performed on the day of transplantation. Postoperative immunosuppression followed the same regimen as ABO-compatible cases, in which calcineurin inhibitors were initiated 3 days before transplantation, combined with 2 doses of basiliximab. RESULTS: Of the 8 patients, 7 subsequently underwent successful living-donor kidney transplantation. Follow-up of our recipients showed that the patient and graft survival rates were 100%. Acute cellular rejection and antibody-mediated rejection episodes occurred in 1 of the 7 recipients. CONCLUSIONS: These findings suggest that our immunosuppression regimen consisting of rituximab infusions, splenectomy, plasmapheresis, and pharmacologic immunosuppression may prove to be effective as a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation.

Comparison of physical properties and drug-releasing characteristics of white petrolatums.

White petrolatums of Japanese Pharmacopoeia grade and Sun white marketed as a cosmetic were characterized by measuring their physical properties and drug-releasing characteristics. White petrolatums of Japanese Pharmacopoeia grade available commercially in Japan were Perfecta, White 1S, Ultima, Snow, Snow V and Regent (Propeto). Penetrating stress, shear stress and spreading properties were measured as physical properties of the white petrolatums. The physical properties of white petrolatums varied, and Regent was the softest and the most spreadable ointment base. In vitro release test was performed using flow-through Franz diffusion cells. Fluorescein isothiocyanate and tetracycline hydrochloride were used as drug models. Their release characteristics varied among the tested white petrolatums, and Regent had the best release properties. Among the white petrolatums, with the exception of Regent, the release properties should depend on the distribution of drugs between white petrolatum and the receiver solution. Considerations of usability and characteristics of theprincipal agent are needed when choosing white petrolatums.

[Descending necrotizing mediastinitis].

We treated of 3 patients with descending necrotizing mediastinitis that is often to be fatal. There are 3 important issues regarding the treatment of this disease. First, the precise sites of abscess should be determined by computed tomography (CT) scans from the neck to diaphragm. Second, effective drainage of the neck and mediastinal abscess should be carried out immediately when the sites of abscess are determined. Third, drainage under video-assisted thoracic surgery (VATS) is an appropriate treatment because VATS is less invasive and provides an easier placement of the drainage tubes at abscess sites.