Comparison of three different anti-Xa assays in major orthopedic surgery patients treated with direct oral anticoagulant

Background

Measurement of edoxaban plasma concentration has been gathering attention in major orthopedic surgery patients receiving edoxaban for the prevention of venous thromboembolism (VTE).

Methods

The anti-Xa activity was measured one hour after edoxaban intake using 3 different assays in 200 patients after major orthopedic surgery.

Results

The anti-Xa activities on Day 8 were significantly higher than those on Day 4 and those on Day 4 were significantly higher than those on Day 1. The anti-Xa activities in two assays closely correlated with each other, but the other anti-Xa assay did not correlated with other two assays. The anti-Xa activities as detected in the three Xa assays were significantly higher in the patients without deep vein thrombosis (DVT) than in those with DVT on Day 4. Additionally, there were no significant differences in the anti-Xa activities of assays A, B and C between patients with and without massive bleeding (MB) on Days 1, 4, 8 and 15.

Conclusion

The results of this study suggest that anti-Xa level could be predictive of the risk of VTE, but not of the risk of massive bleeding.

     

Acute Renal Failure Caused by Hyperuremic Acidemia in ABO-Incompatible Kidney Transplant Maintained With Cyclosporine and High-Dose Mizoribine: A Case Report

Introduction

The shortage of cadaver organs has led to expansion of living donor kidney transplantations with, 30% increase among ABO-incompatible cases in Japan and the use of marginal extended donors. Herein we have reported the outcome after an ABO-incompatible kidney transplantation from an aged living-related donor who suffered from mild diabetes mellitus and hypertension.

Case Report

A 48-year-old man underwent ABO-incompatible kidney transplantation from his 76-year-old father, using anti-CD20 antibody induction, followed by cyclosporine (CsA), mycophenolate mofetil (MMF), and prednisolone. After the operation, MMF was switched to high-dose mizoribine (MZ). He was discharged from the hospital on postoperative day (POD) 28 with a serum creatinine (sCr) of 1.47 mg/dL. On POD 34 when the sCr was 8.14 mg/dL, his urine examination showed uric acid crystals with serum uric acid of 24.6 mg/dL. Biopsy findings showed no evidence of acute rejection but mild tubulointerstitial injury. Hemodialysis performed twice to reduce uric acid was accompanied by hydration. CsA/MZ was switched to tacrolims/MMF; benzbromarone, to febuxostat to treat hyperuric acidemia. On POD 58, sCr reduced to 1.75 mg/dL he was discharged. On POD 416, graft function was stable with sCr of 1.70 mg/dL.

Conclusion

Common side effect of MZ is hyperuricemia which presumably caused acute renal failure of this aged marginal donor kidney.     

Effects of granulocyte-colony stimulating factor on cardiac remodeling after myocardial infarction

BACKGROUND: Recent studies suggest that granulocyte colony-stimulating factor (G-CSF) may be beneficial in the treatment of myocardial infarction (MI). However, the effects of G-CSF on MI are still controversial and the molecular mechanism of G-CSF treatment for repair of the infarcted heart is not fully understood. METHODS: Mice were divided into three groups: Control, MI and MI treated with G-CSF. Four weeks after MI, we examined cardiac function by Doppler echocardiography and measured non-infarcted myocardial mRNA expression by northern blot analysis. RESULTS: Cardiac function decreased significantly in the MI groups compared with the sham-operated groups. Additionally, the ratios of E wave to A wave peak velocity (E/A) in the MI groups were higher than in the control group. E/A in G-CSF MI mice was significantly lower than in control MI mice (p<0.01). Matrix metalloproteinase-2 (MMP-2) mRNA expression was significantly increased in the MI groups compared with the control group (p<0.01). Furthermore, mRNA expression in the G-CSF MI group was significantly higher than in the Control MI group (p<0.05). CONCLUSIONS: G-CSF can prevent the LV remodeling process after MI that accompanies progressive cardiac dysfunction. One of the mechanisms of G-CSF treatment for cardiac remodeling after MI may be overexpression of MMP-2 in non-infarcted myocardium.     

NT5E mutation in sisters who underwent aortic valve replacements for aortic stenosis

Mutations of the NT5E gene encoding the cluster of differentiation 73 (CD73) protein have been found in patients with characteristic calcification of joints and arteries (CALJA). CD73 plays a protective role against aortic valve calcification; therefore, its deletion results in aortic valve calcification. However, to date, there are no reports of a patient with CALJA with aortic stenosis. In this study, we describe 2 extremely rare cases of sisters with identical NT5E gene mutation patterns, both of whom developed late-onset severe aortic stenosis and limb ischaemia. Both patients underwent aortic valve replacement and bilateral distal arterial bypass surgeries successfully. They were genetically diagnosed with CALJA based on the NT5E mutation. Our report suggests that NT5E mutations should be considered in patients requiring aortic valve replacement for a calcified aortic valve and bypass surgery for specific calcified and occluded arteries.     

Unruptured aneurysm of the sinus of valsalva with Beh?et's disease.

A 52-year-old Japanese man who had suffered from Beh?et's disease since the age of 45 years was admitted to hospital for evaluation of syncope and heart murmur. Echocardiography and aortography revealed severe aortic regurgitation and cystic masses under the right coronary cusp and the left ventricular outflow tract, but no shunt jet. He was diagnosed with unruptured aneurysm of the sinus of Valsalva, and surgical closure of the orifice of the aneurysm was performed. The diameter of the orifice was 11 mm and the aneurysm was 15 mm in depth, and consisted of 2 chambers. Because the aortic regurgitation was reduced after patch closure of the orifice, aortic valve replacement was not performed. Unruptured aneurysm of the sinus of Valsalva is a rare clinical lesion, but patients with active inflammatory disease of the aorta, such as in Beh?et's disease, should have periodic echocardiography for early detection of an aneurysm or valvular involvement, even if there are not any symptoms.     

Neither homeostasis model assessment nor quantitative insulin sensitivity check index can predict insulin resistance in elderly patients with poorly controlled type 2 diabetes mellitus

To clarify whether homeostasis model assessment (HOMA IR) and quantitative insulin sensitivity check index (QUICKI) may be indicators of insulin resistance in elderly patients with type 2 diabetes mellitus, their relationship with the glucose infusion rate during the euglycemic hyperinsulinemic clamp study (clamp IR) was assessed. This study comprised 56 Japanese patients with type 2 diabetes mellitus; of these, 28 were 70 yr of age or older (group 1) and 28 were less than 70 yr of age (group 2). Their blood sugars were in poor control (fasting plasma glucose levels: group 1, 9.0 +/- 2.6 mmol/liter; group 2, 8.9 +/- 2.3 mmol/liter; hemoglobin A1c: group 1, 9.5 +/- 2.0%; group 2, 9.2 +/- 1.7%). Log-transformed HOMA IR was significantly correlated with the clamp IR in group 2 patients (r = -0.51, P < 0.01), but not in group 1 patients (r = -0.28, P = 0.15). There was a significant positive correlation between QUICKI and clamp IR in group 2 patients (r = 0.50, P < 0.01). However, no significant correlation was observed between QUICKI and clamp IR in group 1 patients (r = 0.31, P = 0.12). There was a significant correlation between log-transformed HOMA IR (r = -0.37, P < 0.01) or QUICKI (r = 0.37, P < 0.01) and clamp IR when both groups were combined. In conclusion, neither HOMA IR nor QUICKI should be used as an index of insulin resistance in elderly patients with poorly controlled type 2 diabetes mellitus. The results of this study suggest the need for developing a new noninvasive method for evaluating insulin resistance in those patients.     

A case of aggressive myeloma recognized shortly after the remission following high-dose chemotherapy with autologous peripheral blood stem cell transplantation

A 45-year-old woman was referred to our hospital with acute renal failure and pyrexia. In August 2005, the patient was diagnosed with IgA-λ type multiple myeloma with chromosome 13 deletion, and received three cycles of vinclistine, adriamycin and dexamethasone followed by high-dose melphalan-based autologous peripheral stem cell transplantation: this resulted in remission 2 months before admission to our hospital. Serum IgA concentration was within the normal limit, but an excess of myeloma cells in bone marrow was confirmed. Immunoelectrophoresis revealed BJP-λ production with no IgA-λ. The patient received several courses of chemotherapy with mechanical ventilation and regular hemodialysis. The progression of the illness was rapid: multiple organ failure promptly developed and the patient died 2 months after admission. Autopsy revealed deposition of light chain λ protein in multiple organs. We report this unusual case of aggressive myeloma recognized shortly after successful autologous transplantation.     

Tyrosine-kinase dependent TGF-beta and extracellular matrix expression by mechanical stretch in vascular smooth muscle cells.

Vascular hypertrophy, which is characterized by proliferation of vascular smooth muscle cells (VSMC) and accumulation of extracellular matrix (ECM), is a major pathological change in blood vessels after chronic exposure to hypertension. Blood pressure is transmitted to the arterial walls and counterbalanced by mechanical stress, leading to stretching of circumferentially oriented VSMC, which may play some role in the pathogenesis of vascular hypertrophy. The present study was designed, therefore, to investigate the effect of mechanical stretch on the expression of ECM components and transforming growth factor-beta (TGF-beta), a potent stimulator for ECM production, and to examine the signal transduction mechanisms of the induction of TGF-beta in cultured rat VSMC. VSMC were subjected to cyclic stretch to provide a maximal elongation of 20% at a rate of 60 cycles per minute for up to 24 h. Mechanical stretch stimulated TGF-beta1 mRNA expression in a time- and elongation-dependent manner. Indeed, the secretion of TGF-beta proteins into the culture media was increased after stretch. Stretch also stimulated mRNA expression of the ECM components, type I and type IV collagen, and fibronectin, which was largely inhibited by addition of neutralizing antibody against TGF-beta. The tyrosine kinase inhibitors genistein and herbimycin A blocked the induction of TGF-beta1 and type I collagen by stretch, while protein kinase C inhibitors, the calcium channel blockers nitrendipine and gadolinium, or Ca removal from the media had no effect. These results suggest that stretch-induced, tyrosine kinase-mediated autocrine/paracrine production of TGF-8 may play a critical role in the progression of vascular remodeling associated with high blood pressure.     

SEN virus: response to interferon alfa and influence on the severity and treatment response of coexistent hepatitis C

The SEN virus (SENV) is a recently identified single-stranded, circular DNA virus. A strong association between 2 SENV variants (SENV-D and SENV-H) and transfusion-associated non-A-to-E hepatitis has been reported. To clarify the effect of SENV infection on coexisting chronic hepatitis C and the effect of interferon alfa (IFN-alpha) therapy on SENV replication, SENV DNA was quantitated by polymerase chain reaction in serum samples from 186 patients with chronic hepatitis C. Thirty-nine of 186 (21%) patients with chronic hepatitis C were positive for SENV DNA. There were no differences in the clinical, virologic and histologic features between patients with and without SENV infection. Eighteen of 102 patients with chronic hepatitis C who received IFN-alpha were positive for SENV DNA. The sustained response rate for hepatitis C virus (HCV) clearance after IFN-alpha treatment did not differ significantly between patients with SENV (28%) and without SENV infection (39%). SENV DNA levels decreased during therapy in 15 of 16 patients, and 11 of the 16 patients (69%) had a sustained loss of SENV DNA in response to IFN-alpha. In coinfected patients, SENV responses to IFN-alpha were significantly better in those who failed to clear HCV RNA than in those who lost HCV RNA (P =.013). In conclusion, SENV infection was frequently found in patients with chronic hepatitis C. SENV infection had no apparent influence on the severity of HCV-related liver disease or the HCV response to IFN-alpha. SENV was sensitive to IFN-alpha therapy and the majority of patients had a sustained virologic response.     

Improvement of regional cerebral blood flow after treatment with branched-chain amino acid solutions in patients with cirrhosis

OBJECTIVE: The administration of solutions rich in branched-chain amino acids leads to mental recovery from acute hepatic encephalopathy in patients with liver cirrhosis. However, the mechanism of action of branched-chain amino acids remains unclear. The purpose of this study was to evaluate the effect of intravenous infusion of branched-chain amino acids on brain perfusion in patients with liver cirrhosis. METHODS: Single photon emission computed tomography scans were performed in 14 patients with liver cirrhosis before and after the administration of branched-chain amino acids in a single-day split-dose protocol. The per cent change in regional brain perfusion was calculated in high frontal, parietal, temporal, occipital lobes and cerebellum. Thereafter, statistical parametric mapping was performed to identify brain regions with abnormal cerebral perfusion. RESULTS: Intravenous infusion of solutions enriched with branched-chain amino acids induced a 13-20% increase in regional cerebral blood flow. Cirrhotic patients had regions of significant hypoperfusion, as determined by statistical parametric mapping, in the left superior parietal and posterior cingulate as compared to the control group. This hypoperfusion of parietal and cingulate regions was not detected after treatment with solutions of branched-chain amino acids. CONCLUSIONS: The results of the present study suggest that administration of solutions enriched with branched-chain amino acids improves cerebral perfusion in patients with cirrhosis.