Clinical efficacy of infrapopliteal endovascular procedures for hemodialysis patients with critical limb ischemia.

PURPOSE: To investigate 5-year clinical outcomes after infrapopliteal endovascular therapy (EVT) for critical limb ischemia (CLI) patients on or not on hemodialysis (HD), and compare the clinical efficacy of EVT between the 2 groups. METHODS: The subjects were 1091 CLI patients (1310 limbs) who underwent EVT for isolated infrapopliteal lesions from 2004 to 2012, and were classified into 2 groups for comparative study: the patients on HD group (670 patients, 830 limbs) and not on HD group (421 patients, 480 limbs). RESULTS: The HD group had a significantly lower rate of freedom from major adverse limb events or perioperative death (HD 78.4% vs. non-HD 86.0% at 1 year, HD 70.3% vs. non-HD 82.4% at 5 years, P = 0.01), or amputation-free survival (AFS) rate (HD 65.7% vs. non-HD 78.7% at 1 year, HD 34.4% vs. non-HD 59.8% at 5 years, P < 0.01) after EVT compared with the non-HD group. Independent predictors of AFS in HD patients were nonambulatory, diabetes mellitus, albumin <3.0 g/dL, ejection fraction ≤0.48, and no patent pedal arch arteries before EVT. AFS at 1 year was 81% in patients with 0 or 1 predictor, surpassing the suggested AFS objective performance goal (OPG) end points of 68%, but AFS in patients with 2 or more predictors failed to reach the OPG. CONCLUSIONS: In comparison with non-HD patients, the clinical efficacy of infrapopliteal EVT for HD patients was poor. Preoperative risk stratification based on AFS predictors can be used as an index for predicting the prognosis.

Stable knockdown of S100A4 suppresses cell migration and metastasis of osteosarcoma.

S100A4, a 10-12 kDa calcium-binding protein, plays functional roles in tumor progression and metastasis. The present study aimed to investigate the function of S100A4 in osteosarcoma (OS) metastasis, using a loss-of-function approach. Our previous expression profiling analysis revealed that S100a4 was preferentially expressed in the highly metastatic mouse OS cell line, LM8. Introducing a short hairpin ribonucleic acid (shRNA) targeting S100a4 using a newly established vector containing insulators and transposons, we established stable LM8 subclones with almost 100% silencing of endogenous S100a4 protein. These transfectants showed a significant suppression of cell migration in vitro as well as a marked reduction in their ability to colonize the lung and form pulmonary metastases in vivo following intravenous inoculation, whereas there was no significant change in cell proliferation or cell attachment to fibronectin, laminin, and type I collagen. Expression and phosphorylation of ezrin, an emerging OS metastasis-associated factor, and expression of MMPs, remained the same in S100a4-shRNA clones. In 61 human OS, immunohistochemical analysis showed that lesional cells in 85.2% samples expressed S100A4 protein, and the immunoreactivity was primarily cytoplasmic, but it also showed occasional nuclear localization. Chondroblastic and osteoblastic OS subtypes expressed more S100A4 than fibroblastic subtypes. The causative role of S100A4 in OS lung metastasis shown in the murine xenograft model, together with the high proportion of primary human OS expressing S100A4, suggest that S100A4 protein represents an important potential target for future OS therapy.

Open-loop, clockwise QT-RR hysteresis immediately before the onset of torsades de pointes in type 2 long QT syndrome.

Delay of QT interval adaptation to sudden heart rate change causes hysteresis in dynamic QT-RR relationship. We analyzed QT-RR plotting during and after exercise in a patient with genetically identified type 2 long QT syndrome before and after starting oral propranolol. Blunted QT shortening by exercise and augmented postexercise QT prolongation resulted in an open-loop, clockwise QT-RR hysteresis immediately before the onset of torsades de pointes before propranolol. However, this hysteresis was eliminated by propranolol. QT-RR analysis provided insight into the mechanisms of the onset of torsades de pointes at least in this case of type 2 long QT syndrome.

Case of atrial tachycardia originating from giant coronary sinus connected to persistent left superior vena cava: successful catheter ablation guided by noncontact mapping.

Radiofrequency (RF) catheter ablation is widely applied to tachyarrhythmia associated not only with structurally normal hearts but also with relatively mild cardiac anomalies. We present a case of 35 year-old female complaining of exercise-induced frequent palpitations caused by atrial tachycardia (AT) originating from giant coronary sinus (CS) connected to persistent left superior vena cava. AT was sensitive to intravenous ATP administration. Electrophysiological study partly using noncontact balloon of EnSite system clarified that two foci of AT were located at the orifice and the distal inner lumen of giant CS. After repetitive applications of RF energy to these origins, AT was not induced by drip infusion of isoproterenol. AT was not evoked by exercise without antiarrhythmic drugs 15 months after the RF ablation. This case indicates that RF ablation guided by noncontact mapping technique should be considered as a therapeutic regimen for AT associated with mild cardiac malformations.