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BackgroundAllogeneic hematopoietic stem cell transplantation is a potentially curative treatment for acute myeloid leukemia. However, extramedullary relapse of acute myeloid leukemia can occur after hematopoietic stem cell transplantation, causing treatment failure. Extramedullary relapse rarely involves the peripheral nerves, and it is not influenced by the effect of the graft on leukemia.Case presentationWe report a case of extramedullary relapse of acute myeloid leukemia in the brachial plexus of a 41-year-old woman treated with allogeneic hematopoietic stem cell transplantation (HSCT). Complete hematological remission was confirmed by bone marrow examination 1 month after HSCT, and she developed no major complications immediately after HSCT. The immunosuppressant was discontinued 5 months later. However, 2 weeks after immunosuppressant withdrawal, the patient developed left arm pain and paresthesia, with subsequent development of a mass in the left brachial plexus. She was initially diagnosed with brachial plexus neuropathy because of concomitant graft-versus-host disease. Despite the administration of immunosuppressive agents, the mass continued to enlarge. The biopsy of the lesion revealed leukemic relapse. Thus, the patient was diagnosed with extramedullary relapse and underwent radiotherapy, resulting in tumor shrinkage.ConclusionExtramedullary relapse should be considered a differential diagnosis in post-transplant patients with leukemia presenting with paresthesia.

A patient with underlying Hashimoto's thyroiditis developed amiodarone-induced thyrotoxicosis type 1 that was successfully treated using methimazole in combination with potassium iodide. A 35-year-old woman admitted for perinatal care of twin-to-twin transfusion syndrome was given amiodarone for 7 days for paroxysmal ventricular contraction following pulseless ventricular tachycardia 1 day after delivery. She developed thyrotoxicosis one month after the discontinuation of amiodarone therapy and was negative for thyroid-stimulating hormone receptor antibody. An increased peak velocity of the superior thyroid artery suggested amiodarone-induced thyrotoxicosis type 1. Her thyroid function recovered after combination therapy with methimazole and potassium iodide.

Background: The Gait Exercise Assist Robot (GEAR) has been developed to support gait training for stroke patients. The GEAR can assist paretic lower limb swing and stance stability, which make it p...

Primary graft failure can be a cause of early morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), as it leads to a high risk of severe infections and bleeding. Splenomegaly is associated with primary graft failure in patients of myelofibrosis, but the association between splenomegaly and outcomes after HSCT in patients with myeloid malignancies has not been previously evaluated. The aim of this study was to investigate the effect of spleen volume on engraftment kinetics in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We enrolled 85 patients. The median spleen volume was 146 cm3 (quartile 88–201 cm3). The adjusted hazard ratios for neutrophil and platelet engraftments were 0.17 (0.07–0.40, p

Background Patients with relapsed or refractory peripheral T-cell lymphoma, not otherwise specified (R/R-PTCL-NOS) usually have short survival with conventional salvage chemotherapies. Prediction of poor survival in patients who undergo conventional salvage chemotherapies might help identify candidates for novel therapies that have been recently available for R/R-PTCL-NOS. However, no prognostic marker other than the second-line International Prognostic Index (sIPI) has been reported. We aimed to investigate the prognostic value of serum soluble interleukin-2 receptor (sIL-2R) level in patients with R/R-PTCL-NOS. Patients and Methods We retrospectively analyzed 37 patients with R/R-PTCL-NOS who underwent salvage chemotherapy. Serum sIL-2R level was measured within a week before salvage chemotherapy initiation. We determined the cutoff level of serum sIL-2R as 4.03 times the upper limit of normal by using receiver operating characteristic curve analysis. Results The 3-year overall survival (3yOS) was 5.2% and 37.5% in high sIL-2R and low sIL-2R groups, respectively (P = .005). In multivariate analysis, high sIL-2R level was independently associated with lower 3yOS (hazard ratio, 2.30; 95% confidence interval, 1.04-5.11; P = .040). In subgroup analysis, high sIL-2R level did not affect 3yOS in patients with high-risk sIPI (NA [not available] vs. 7.1%; P = .354), but was significantly associated with poor 3yOS in patients with low-risk sIPI (NA vs. 60.0%; P = .037). Conclusion Serum sIL-2R is a useful prognostic marker for patients with R/R-PTCL-NOS. In particular, high sIL-2R level can identify groups of patients with low-risk sIPI who have poor prognosis. Our results suggest that novel therapeutic approaches might be necessary for patients with high-risk sIPI and/or high sIL-2R level.

Leukemic stem cells (LSCs) play a crucial role in chemotherapy resistance in acute myeloid leukemia (AML). Although the association between the expression of individual LSC markers and poor prognosis has been reported, few studies have evaluated the prognostic effect of multiple LSC markers in patients with AML. Herein, we examined three LSC markers (CD25, CD96, and CD123) and the combined effect of their expression on clinical outcome. We retrospectively analyzed 80 adult patients with de novo AML who received intensive chemotherapy. Multiple LSC marker expression was significantly associated with shorter three-year overall survival (OS), compared with single or no LSC marker expression (18.2 vs. 65.0%, p

Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have a poor prognosis, even in the rituximab era. Several studies have reported the clinical importance of the peripheral blood lymphocyte-to-monocyte ratio (LMR) in various malignancies, including lymphoma. However, the prognostic value of the LMR in relapsed/refractory DLBCL has not been well evaluated. The purpose of the present study was to investigate whether the LMR at relapse can predict clinical outcomes for relapsed/refractory DLBCL patients treated with rituximab.We analyzed data on 74 patients with relapsed/refractory DLBCL, who were initially treated with R-CHOP (rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone) or an R-CHOP-like regimen.There was a significant association between a low LMR (≤ 2.6) and shorter overall survival (OS; P .001) and progression-free survival (PFS; P .001) compared with the high LMR group (2.6). Multivariate analysis showed that LMR was an independent prognostic factor for OS (P .001) and PFS (P .001), as was the international prognostic index (IPI) at relapse for OS. In addition, the LMR had an incremental value for OS and PFS compared with the IPI at relapse.The LMR predicts OS and PFS outcomes in relapsed/refractory DLBCL patients treated with rituximab, and might facilitate better stratification among patients in low- and intermediate-risk IPI groups.

Objective Coronary spasm as well as atherosclerosis plays an important role in the pathogenesis of coronary heart disease. However, the relationship between coronary spasm and atherosclerosis is not well known. The purpose of the present study was to examine the differences and interactions between risk factors for coronary spasm and atherosclerosis and thereby explore the pathogenesis of coronary spasm. Methods The study subjects consisted of 938 patients with chest discomfort (522 men and 416 women, mean age 65.2±11.0) who underwent intracoronary-acetylcholine provocation tests for coronary spasm. Coronary risk factors, including age, gender, body mass index, blood pressure, high-sensitivity C-reactive protein (hsCRP), white blood cells, glucose, lipid profiles, and other laboratory chemistries were examined. Results Four hundred and ninety-six patients (315 men and 181 women, mean age: 65.1±11.4) were diagnosed with coronary spastic angina (CSA), while the remaining 442 patients (207 men and 235 women, mean age: 65.3±10.7) were diagnosed with non-CSA. A multiple logistic regression analysis revealed men, smoking, hsCRP, and low diastolic blood pressure (DBP) to be predictors (p=0.001, p=0.009, p=0.034, and p=0.041, respectively) for CSA, while age, diabetes mellitus, low high-density lipoprotein-cholesterol, systolic blood pressure (SBP), uric acid and male gender were found to be predictors (p

Coronary spasm plays an important role in the pathogenesis of ischemic heart disease. Endothelial function is impaired in patients with coronary spasm. Exercise training has been shown to improve endothelial function.We examined the effects of aerobic interval exercise training (AIT) on attacks in conjunction with endothelial function in patients with coronary spastic angina.The study participants were 26 patients with rest angina (19 men and 7 women, mean age 61.7±11.7 years) in whom coronary spasm was documented and no severe organic lesions were found. The numbers of attacks and of individuals with attacks were examined in conjunction with endothelial function, oxidative stress, inflammation, and insulin resistance before and after 3 successive days of AIT.The number of attacks/patient and the ratio of patients with attacks/5 days decreased [from 2 (1, 7) to 0 (0, 2), P0.001, and from 23/26 (88.5%) to 10/26 (38.5%), P0.001] in conjunction with the improvement in endothelial function assessed by improved flow-mediated dilatation (4.8±2.7 vs. 6.9±2.8%, P0.001), plasma levels of diacron-reactive oxygen metabolites (363±58 vs. 349±61 U.CARR, P=0.001), interleukin-6[1.63 (1.33, 2.22) vs. 1.39 (1.09, 2.02) pg/ml, P=0.012], high-sensitivity C-reactive protein [0.087 (0.041, 0.136) vs. 0.063 (0.028, 0.085) mg/dl, P=0.028], and homeostasis model assessment-insulin resistance [1.79 (1.41, 2.39) vs. 1.54 (1.17, 1.79) mg/dl µU/ml, P=0.005] after AIT.AIT in the afternoon suppressed the attacks in conjunction with improvement in endothelial function, oxidative stress, inflammation, and insulin resistance in patients with coronary spastic angina.

B-type natriuretic peptide (BNP) is produced by the heart and its plasma level is increased with the severity of left ventricular (LV) dysfunction/hypertrophy. The normal heart preferentially utilizes fatty acids as energy substrates. Plasma BNP levels are reported to be lower in obese individuals. We examined the relationship between BNP production and plasma free fatty acids (FFA), homeostasis model assessment of insulin resistance (HOMA-IR), and LV dysfunction/ hypertrophy. We examined the plasma BNP levels and FFA at the aortic root (AO) and coronary sinus (CS) as well as hemodynamic parameters in 62 patients (38 men and 24 women, 62.5±11.7 yrs) who underwent cardiac catheterization. Log BNP (AO) had a significant positive correlation with log BNP (CS-AO) (r=0.877, P

SummaryBackground Aldosterone is reported to be associated with obesity and is a risk factor for metabolic syndrome. Metabolic abnormalities are more strongly associated with visceral adipose tissue (VAT) than with subcutaneous adipose tissue (SAT). Objective We examined whether aldosterone is more closely associated with VAT area than with SAT area in obese individuals. Methods We enrolled 81 Japanese patients (46 men, mean age 43 ± 13 years and 35 women, mean age 53 ± 10 years) suspected of metabolic disorders and measured plasma and 24-h urinary aldosterone, as well as SAT and VAT areas. SAT and VAT areas were measured at the umbilical level by computed tomography. Results Spearman's rank correlation analysis showed that urinary aldosterone was significantly and positively correlated with body mass index, waist circumference, SAT area, alanine aminotransferase, C-reactive protein, plasma immune-reactive insulin, plasma renin activity and estimated glomerular filtration rate, and negatively correlated with age and blood glucose. Urinary aldosterone was not correlated with VAT area (r = 0·013, P = 0·906). Multivariate regression analyses revealed that log SAT area, age and diastolic blood pressure were significant (P = 0·001, 0·001 and 0·032, respectively) predictors of log urinary aldosterone excretion rate. Conclusion Our results indicate that urinary aldosterone excretion is positively associated with SAT but not with VAT area in the middle-aged obese individuals.Urinary aldosterone is also negatively correlated with age.

Objectives Coronary spasm is implicated in the pathogenesis of acute coronary syndromes including acute myocardial infarction (AMI). Stent implantation in the primary percutaneous coronary intervention is the first choice of treatment for patients with AMI. However, the relationship between coronary spasm and stent implantation after AMI and its clinical implications remain unknown. We examined the incidence and clinical implications of provoked coronary spasm after stent implantation in patients with AMI. Methods Fifty-seven patients (43 men and 14 women with a mean age of 65.1±12.5 years) with ST elevation AMI who had undergone a stent implantation were the participants of this study. They underwent a provocation test for coronary spasm by intracoronary injection of acetylcholine 2-5 weeks after the attack. The patients with provoked spasms were given calcium channel blockers, and all the participants of the study were followed up for an average of 35.0±26.9 months. Results Coronary spasm was induced in 40 (70.2%) and multivessel spasm in 17 (29.8%) of the 57 patients. Spasms occurred in 31 (55.4%) of the infarct-related arteries (IRAs) and 33 (30.6%) of the non-IRAs. There was no significant difference (χ=1.01, P=0.314) in the major cardiac events between the spasm group and nonspasm group during the follow-up. Conclusion Coronary spasm was provoked with a high frequency in both the IRAs and non-IRAs after stent implantation in patients with AMI. Calcium channel blockers may be useful to improve the prognosis in patients with AMI after stent implantation by suppressing coronary spasm.

Tenascin C (TNC) is an extracellular matrix glycoprotein up-regulated in solid tumors. Higher TNC expression is shown in invading fronts of breast cancer, which correlates with poorer patient outcome. We examined whether TNC induces epithelial-mesenchymal transition (EMT) in breast cancer. Immunohistochemical analysis of invasive ductal carcinomas showed that TNC deposition was frequent in stroma with scattered cancer cells in peripheral margins of tumors. The addition of TNC to the medium of the MCF-7 breast cancer cells caused EMT-like change and delocalization of E-cadherin and β-catenin from cell-cell contact. Although amounts of E-cadherin and β-catenin were not changed after EMT in total lysates, they were increased in the Triton X-100-soluble fractions, indicating movement from the membrane into the cytosol. In wound healing assay, cells were scattered from wound edges and showed faster migration after TNC treatment. The EMT phenotype was correlated with SRC activation through phosphorylation at Y418 and phosphorylation of focal adhesion kinase (FAK) at Y861 and Y925 of SRC substrate sites. These phosphorylated proteins colocalized with αv integrin-positive adhesion plaques. A neutralizing antibody against αv or a SRC kinase inhibitor blocked EMT. TNC could induce EMT-like change showing loss of intercellular adhesion and enhanced migration in breast cancer cells, associated with FAK phosphorylation by SRC; this may be responsible for the observed promotion of TNC in breast cancer invasion.

Background Although a decrease in serum potassium level has been suggested to be a fairly common observation in acute coronary syndrome (ACS), there have so far been no definitive reports directly demonstrating the transient potassium decrease (the potassium dip) during ischemic attack of ACS compared to stable phase in individual patients. To understand the pathophysiological significance of the potassium dip, we examined the changes in serum potassium level throughout ischemic attack and evaluated the clinical factors affecting it. Methods The degree of the potassium dip during ischemic attack (as indicated by ΔK, ΔK = K at discharge − K on admission) was examined in 311 consecutive patients with ACS who required urgent hospitalization in our institution. Results Serum potassium level during ischemic attack was significantly decreased compared to that during stable phase (P Conclusions We have clearly demonstrated that there is a transient decrease in serum potassium level during ischemic attack of ACS compared to stable phase. The degree of the potassium dip was tightly correlated with glucose level, which overwhelmed the diabetic condition, and it also indicates the disease severity. The present study therefore promotes awareness of the significance of monitoring potassium level in parallel with glucose level in patients with ACS.