Retroperitoneal Bronchogenic Cyst Presenting Paraadrenal Tumor Incidentally Detected by 18F-FDG PET/CT

A follow-up ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT scan of a 57-year-old asymptomatic male who had undergone total thyroidectomy for thyroid cancer revealed a 5.0 × 4.0-cm, well-defined, ovoid-shaped mass around the left adrenal gland without definite FDG uptake. On the adrenal CT scan, the left paraadrenal tumor showed high attenuation on the precontrast scan without enhancement. The average Hounsfield unit (HU) was 58.1 on the precontrast scan and 58.4 on the postcontrast scan. The patient underwent laparoscopic adrenalectomy for resection of the left paraadrenal tumor. The final histopathologic examination revealed a bronchogenic cyst. Although retroperitoneal bronchogenic cysts are rare, they should be considered in the differential diagnosis of retroperitoneal cystic tumors. The preoperative diagnosis is difficult, but a contrast-enhanced CT scan or ¹⁸F-FDG PET/CT scan may be useful for differentiating hyperattenuated cysts from other soft tissue masses.     

Repositioning Potential of PAK4 to Osteoclastic Bone Resorption

Drug repositioning is a rational approach for expanding the use of existing drugs or candidate drugs to treat additional disorders. Here we investigated the possibility of using the anticancer p21‐activated kinase 4 (PAK4)‐targeted inhibitor PF‐3758309 to treat osteoclast‐mediated disorders. PAK4 was highly expressed in bone marrow cells and was phosphorylated during their differentiation into osteoclasts, and osteoclast differentiation was significantly inhibited by the dominant negative form of PAK4 and by PF‐3758309. Specifically, PF‐3758309 significantly inhibited the fusion of preosteoclasts, the podosome formation, and the migration of preosteoclasts. PF‐3758309 also had in vivo antiresorptive activity in a lipopolysaccharide‐induced bone erosion model and in vitro antiosteoclastogenic activity in the differentiation of human bone marrow–derived cells and peripheral blood mononuclear cells into osteoclasts. These data demonstrate the relevance of PAK4 in osteoclast differentiation and the potential of PAK4 inhibitors for treating osteoclast‐related disorders. © 2015 American Society for Bone and Mineral Research © 2015 American Society for Bone and Mineral Research.     

Effects of the calcineurin dependent signaling pathway inhibition by cyclosporin A on early and late cardiac remodeling following myocardial infarction

BACKGROUND: The calcineurin-mediated signaling pathway has been implicated as one of the crucial pathways in cardiac hypertrophy. However, the role of calcineurin pathway on cardiac remodeling after myocardial infarction (MI) has not been well defined. METHODS: Infarcted rats (n = 45) were randomized into calcineurin inhibitor, cyclosporin A (CsA) or vehicle groups, 3 days after MI and treated for 2 weeks (early post-MI cardiac remodeling stage), or randomized 17 days after MI and treated for 2 weeks (late remodeling stage). RESULTS: Calcineurin pathway inhibition during the early cardiac remodeling stage attenuated the myocardial hypertrophy after MI (P < 0.05). However, left ventricular dimensions were further increased and fractional shortening deteriorated with calcineurin inhibition during this stage (P < 0.05, each). During late remodeling stage, CsA treatment did not affect myocardial hypertrophy and cardiac dilation following MI. CONCLUSION: Our results strongly support the hypothesis that calcineurin pathway mediates compensatory myocardial hypertrophy during the early remodeling stage after MI. However, the calcineurin pathway does not seem to affect the late remodeling after MI.     

High prevalence and little change in TSH receptor blocking antibody titres with thyroxine and antithyroid drug therapy in patients with non-goitrous autoimmune thyroiditis

OBJECTIVE We have reevaluated the prevalence and pathogenetic importance of TSH receptor blocking antibodies (TRBAb) in autoimmune hypothyroidism, and investigated the changes in TRBAb activities during thyroxine and antithyroid drug treatment. DESIGN Serum TSH binding inhibitor immunoglobulin (TBII) and thyroid stimulation blocking antibody (TSBAb) were measured serially in all patients with non-goitrous autoimmune thyroiditis (AT) and measured monthly during methimazole treatment in 6 patients. PATIENTS Ninety patients with non-goitrous AT and 95 patients with goitrous AT were entered consecutively into this study. All patients with non-goitrous AT were treated with thyroxine and followed at intervals of 6 months for 2 years initially and then yearly intervals. The duration of follow-up was 1–8 years. Six patients from the TRBAb-positive non-goitrous AT group who were treated with thyroxine were randomly selected and given additional treatments with methimazole (40 mg per day) for 6 months. MEASUREMENTS Serum TBII was measured by 8 radioreceptor assay, TSBAb by using FRTL-5 cells, and antithyroid peroxidase and antithyroglobulin antibodies by radioimmunoassay. RESULTS The prevalences of TBII and TSBAb in non-goitrous AT were 47–8 and 58.9%, respectively, which were significantly higher than those in goitrous AT (6.3% for TBII, 10.5% for TSBAb). All but one patient showed persistent TBII and TSBAb activities during the thyroxine treatment for up to 8 years. A high dose of methimazole (40 mg per day) did not affect the titres of TBII and TSBAb in 5 out of 6 patients with non-goitrous AT tested. However, antithyroid peroxidase and antithyroglobulin antibodies activities were significantly decreased during the methimazole treatment. CONCLUSION The high prevalence of TSH receptor blocking antibodies (TRBAb) suggests that TRBAb may play a major role in the development of hypothyroidism and thyroid atrophy in the vast majority of patients with non-goitrous autoimmune thyroiditis. Most TRBAb activities are stable for at least 8 years and are not affected by thyroxine and antithyroid drug treatment.     

Effects of continuous administration of clopidogrel before off-pump coronary artery bypass grafting in patients with acute coronary syndrome.

BACKGROUND: Clopidogrel has become standard treatment after urgent percutaneous coronary revascularization. Due to its enhanced and irreversible platelet inhibition, patients undergoing urgent surgical revascularization have a higher risk of bleeding complications and transfusions. Therefore, the effect of preoperative continuous administration of clopidogrel on the incidence of hemorrhagic complications in patients undergoing off-pump coronary artery bypass surgery with acute coronary syndrome was evaluated. METHODS AND RESULTS: From March 2004 to September 2006, 172 patients with acute coronary syndrome underwent isolated off-pump coronary artery bypass surgery; 70 (40.7%) and 102 (59.3%) of these patients did or did not take clopidogrel before surgery respectively. Seventy patients in each group were matched using propensity scores and associations between preoperative continuous administration of clopidogrel and postoperative bleeding, hemostatic reoperation, blood products received, the need for multiple transfusions and early graft patency by coronary computed tomography were assessed. Univariate analysis showed the continuous clopidogrel group had similar levels of postoperative bleeding for 24 h (601.4+/-312.6 ml vs 637.2+/-452.4 ml, p=0.616) and rates of reexploration (1.4% vs 1.4%), perioperative blood transfusion (33.3% vs 34.3%, p>0.05) and platelet transfusion (2.9% vs 7.1%, p=0.44) compared with the non-continuous group. CONCLUSIONS: Preoperative continuous administration of clopidogrel did not increase the risk of hemorrhagic complications in patients with acute coronary syndrome undergoing isolated off-pump coronary artery bypass surgery. These findings indicate that surgery after clopidogrel treatment in patients with acute coronary syndrome should not be delayed until platelet function returns to normal because they may have a higher risk of recurrent myocardial ischemic events.     

Close correlation of p53 mutation to microvascular invasion in hepatocellular carcinoma

Mutation of p53 is a poor prognostic indicator of hepatocellular carcinoma (HCC). Although poor histologic differentiation of HCC has been associated with p53 mutations, the exact reasons for unfavorable clinical outcomes in patients with HCC remain to be clarified. In this study, we evaluate the association between p53 mutation and histopathologic features of HCCs, as well as tumor recurrences and survival. We examined 20 HCCs and surrounding liver tissues from patients who underwent surgical resection, and we performed direct sequencing of p53 gene. p53 mutations were found in 9 of 20 HCCs; none were found in the surrounding liver tissue. p53 mutations were frequent in large, multinodular, and poorly differentiated HCCs. Five of 9 with p53 mutation (in contrast, none of 11 with wild-type mutation) showed microvascular invasions. Hepatocellular carcinoma recurred in 6 of 9 with p53 mutation, in contrast to only 2 of 11 with wild-type mutation. The 1-year survival rate with p53 mutation was significantly lower than that with wild-type. In conclusion, it is suggested that p53 mutations tend to be commonly associated with microvascular invasions, which may result in micrometastasis, followed by frequent recurrences.     

Effects of robot-assisted gait training on the balance and gait of chronic stroke patients: focus on dependent ambulators

[Purpose] The purpose of this study was to confirm the effect of robot-assisted gait training on the balance and gait ability of stroke patients who were dependent ambulators. [Subjects and Methods] Twenty stroke patients participated in this study. The participants were allocated to either group 1, which received robot-assisted gait training for 4 weeks followed by conventional physical therapy for 4 weeks, or group 2, which received the same treatments in the reverse order. Robot-assisted gait training was conducted for 30 min, 3 times a week for 4 weeks. The Berg Balance Scale, Modified Functional Reach Test, Functional Ambulation Category, Modified Ashworth Scale, Fugl-Meyer Assessment, Motricity Index, and Modified Barthel Index were assessed before and after treatment. To confirm the characteristics of patients who showed a significant increase in Berg Balance Scale after robot-assisted gait training as compared with physical therapy, subgroup analysis was conducted. [Results] Only lateral reaching and the Functional Ambulation Category were significantly increased following robot-assisted gait training. Subscale analyses identified 3 patient subgroups that responded well to robot-assisted gait training: a subgroup with hemiplegia, a subgroup in which the guidance force needed to be decreased to needed to be decreased to ≤45%, and a subgroup in which weight bearing was decreased to ≤21%. [Conclusion] The present study showed that robot-assisted gait training is not only effective in improving balance and gait performance but also improves trunk balance and motor skills required by high-severity stroke patients to perform activities daily living. Moreover, subscale analyses identified subgroups that responded well to robot-assisted gait training.Key words: Stroke, Robotics, Gait