Characteristics and Clinical Outcomes of Cancer Patients who Developed Constrictive Physiology After Pericardiocentesis.

BACKGROUND AND OBJECTIVES: This study aimed to identify the characteristics and clinical outcomes of cancer patients who developed constrictive physiology (CP) after percutaneous pericardiocentesis. METHODS: One-hundred thirty-three cancer patients who underwent pericardiocentesis were divided into 2 groups according to follow-up echocardiography (CP vs. non-CP). The clinical history, imaging findings, and laboratory results, and overall survival were compared. RESULTS: CP developed in 49 (36.8%) patients after pericardiocentesis. The CP group had a more frequent history of radiation therapy. Pericardial enhancement and malignant masses abutting the pericardium were more frequently observed in the CP group. Fever and ST segment elevation were more frequent in the CP group, with higher C-reactive protein levels (6.6±4.3mg/dL vs. 3.3±2.5mg/dL, p<0.001). Pericardial fluid leukocytes counts were significantly higher, and positive cytology was more frequent in the CP group. In baseline echocardiography before pericardiocentesis, medial e' velocity was significantly higher in the CP group (8.6±2.1cm/s vs. 6.5±2.3cm/s, p<0.001), and respirophasic ventricular septal shift, prominent expiratory hepatic venous flow reversal, pericardial adhesion, and loculated pericardial fluid were also more frequent. The risk of all-cause death was significantly high in the CP group (hazard ratio, 1.53; 95% confidence interval,1.10-2.13; p=0.005). CONCLUSIONS: CP frequently develops after pericardiocentesis, and it is associated with poor survival in cancer patients. Several clinical signs, imaging, and laboratory findings suggestive of pericardial inflammation and/or direct malignant pericardial invasion are frequently observed and could be used as predictors of CP development.

D-dimer/troponin ratio in the differential diagnosis of acute pulmonary embolism from non-ST elevation myocardial infarction.

BACKGROUND/AIMS: The aim of this study was to investigate useful cardiac biomarkers in the differential diagnosis of acute pulmonary embolism (APE) with troponin elevation from acute non-ST elevation myocardial infarction (NSTEMI). METHODS: A total of 771 consecutive NSTEMI patients with D-dimer measurements and 90 patients with troponin-I (TnI) elevation out of 233 APE patients were enrolled, and cardiac biomarkers were compared. RESULTS: D-dimer elevation was noted in 382 patients with NSTEMI (49.5%), and TnI elevation was noted 90 out of 233 APE patients (38.6%). Unnecessary coronary angiography was performed in 10 patients (11.1%) among 90 APE patients with TnI elevation. D-dimer was significantly elevated in APE than in NSTEMI (9.9 ± 11.6 mg/L vs. 1.8 ± 4.3 mg/L, p < 0.001), whereas TnI was significantly elevated in NSTEMI (22.4 ± 41.5 ng/mL vs. 0.7 ± 1.4 ng/mL, p < 0.001). D-dimer/TnI ratio was significantly higher in APE than in NSTEMI (50.6 ± 85.3 vs. 1.6 ± 5.7, p < 0.001). On receiver operation characteristic curve analysis, the optimal cut-off value for differentiating APE from NSTEMI was 1.12 mg/L for D-dimer (sensitivity 81.1%, specificity 70.2%), 0.72 ng/mL for TnI (sensitivity 80.6%, specificity 78.9%), and 1.82 for D-dimer/TnI ratio (sensitivity 93.3%, specificity 86.6%). CONCLUSION: D-dimer/TnI ratio would be a simple and useful parameter for differentiating APE with cardiac troponin elevation from NSTEMI. Optimal cardiovascular imaging to identify APE should be considered in patients with D-dimer/ TnI ratio > 1.82 before performing coronary angiography to avoid unnecessary invasive procedure.

Predictors of reversible severe functional tricuspid regurgitation in patients with atrial fibrillation.

BACKGROUND: Atrial remodeling associated with atrial fibrillation (AF) is known to be a risk factor for significant tricuspid regurgitation (TR), but the predictor of reversible TR in patients with severe functional TR and AF has been poorly studied. The aim of this study was to investigate the predictors of reversible TR in patients with severe functional TR and AF. METHODS: Among 232 patients with severe TR, a total of 71 patients with severe functional TR and AF were enrolled and divided into 2 groups: reversible TR group (n=16, 70.1±15.5 years, 7 males) vs. non-reversible TR group (n=55, 72.3±11.8 years, 20 males). Improvement of TR to moderate or lesser degree on follow-up (FU) echocardiography was considered as reversible TR in the present study. RESULTS: During 38.9±26.7 months of FU period, reversible TR was observed in 16 patients (22.5%). The presence of left ventricular (LV) systolic dysfunction was significantly prevalent (43.8% vs. 20.0%, p=0.03) and the improvement in LV ejection fraction (EF) more than 10% on FU echocardiography was more significantly frequent (62.5% vs. 23.3%, p=0.003) in the reversible TR group than in the non-reversible TR group. However, the other echocardiographic parameters, including right ventricular function were not different between the groups. In multivariate analysis using Cox proportional hazard model, the improvement of LVEF more than 10% was the only independent predictor of reversible TR (HR=7.39, 95%CI 1.80-30.28, p=0.005). Nine patients died only in patients with non-reversible TR (12.7%), but the reversibility of TR was not associated with mortality. CONCLUSIONS: The improvement of LV systolic function was the only independent predictor of reversible TR. Appropriate medical therapy including management for heart failure should be considered before performing surgery in patients with severe functional TR and AF, especially in patients with LV dysfunction.

Chemotherapy-Induced Left Ventricular Dysfunction in Patients with Breast Cancer.

PURPOSE: As the numbers of cancer cases and survivors increase, the incidence and natural history of chemotherapy-induced cardiotoxicities in patients with breast cancer may also be expected to change. The present study aimed to investigate the incidence and predictors of chemotherapy-induced left ventricular dysfunction (LVD) in patients with breast cancer. METHODS: From 2003 to 2010, 712 female patients with breast cancer (55.7±10.7 years) were enrolled and divided into the LVD group (n=82, 56.7±10.1 years) and the non-LVD group (n=630, 55.6±10.8 years). Baseline clinical and treatment-related variables were compared. RESULTS: Chemotherapy-induced LVD developed in 82 cases (11.4%). Low body mass index (BMI), low triglyceride level, advanced cancer stage, and the use of doxorubicin, paclitaxel, trastuzumab, or radiotherapy were significant predictors of LVD in a univariate analysis. In a multivariate analysis, low BMI, advanced cancer stage, and the use of target therapy with trastuzumab were independent predictors of chemotherapy-induced LVD. Chemotherapy-induced LVD was recovered in 53 patients (64.6%), but left ventricular function was not recovered in 29 patients (35.4%). CONCLUSION: Chemotherapy-induced LVD was not uncommon and did not reduce in many of our patients with breast cancer. Low BMI, advanced cancer stage, and the use of trastuzumab were independent predictors of chemotherapy-induced LVD in patients with breast cancer. The development of chemotherapy-induced LVD should be carefully monitored in patients with breast cancer who are receiving trastuzumab therapy, have poor nutritional status, and advanced cancer stage.

Impaired Diastolic Recovery after Acute Myocardial Infarction as a Predictor of Adverse Events.

BACKGROUND: To investigate the impact of left ventricular (LV) diastolic functional recovery on major adverse cardiac events (MACE) 6 months after acute myocardial infarction (AMI) in patients with preserved LV systolic function. METHODS: A total 463 patients with preserved LV systolic function at 6 months after an AMI were divided into two groups based on the extent of diastolic recovery assessed by echocardiography: group I (n = 241) showed improving diastolic function and group II (n = 222) did not. MACE included death, recurrent myocardial infarction, and rehospitalization due to heart failure, and these events were compared with the patients' characteristics at baseline. RESULTS: Compared with group I, the patients in group II were older and had a higher prevalence of hypertension and diabetes. Blood levels of hemoglobin and triglyceride were lower in group II, whereas the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and of high-sensitivity C-reactive protein were higher in this group than in group I. MACE were significantly more frequent in group II than in group I. Age, elevated NT-proBNP, and impaired diastolic recovery were significant independent predictors of MACE. CONCLUSION: Despite improvement in LV systolic function, LV diastolic function had not improved in 222 patients (47.9%) by the 6-month follow-up after the index AMI, and impaired diastolic functional recovery was found to be an independent predictor of MACE. Evaluation of diastolic function would be a useful way to stratify risk in patients discharged after an index AMI.

Bee Venom Mitigates Cisplatin-Induced Nephrotoxicity by Regulating CD4(+)CD25(+)Foxp3(+) Regulatory T Cells in Mice.

Cisplatin is used as a potent anticancer drug, but it often causes nephrotoxicity. Bee venom (BV) has been used for the treatment of various inflammatory diseases, and its renoprotective action was shown in NZB/W mice. However, little is known about whether BV has beneficial effects on cisplatin-induced nephrotoxicity and how such effects might be mediated. In the present study, the BV-injected group showed a significant increase in the population of Tregs in spleen. Although there was no significant difference in the numbers of Tregs 3 days after cisplatin injection between the BV- and PBS-injected groups, more migration of Tregs into the kidney was observed 6 hours after cisplatin administration in BV group than in PBS group. In addition, BV-injected mice showed reduced levels of serum creatinine, blood urea nitrogen, renal tissue damage, proinflammatory cytokines, and macrophage infiltration into the kidney 3 days after cisplatin administration. These renoprotective effects were abolished by the depletion of Tregs. The anticancer effect of repeated administrations of cisplatin was not affected by BV injection. These results suggest that BV has protective effects on cisplatin-induced nephrotoxicity in mice, at least in part, through the regulation of Tregs without a big influence on the antitumor effects of cisplatin.

Therapeutic strategy for in-stent restenosis based on the restenosis pattern after drug-eluting stent implantation.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the outcomes of repeated percutaneous coronary intervention (PCI) based on the restenosis pattern in drug-eluting stent (DES) failure. SUBJECTS AND METHODS: From April 2003 to March 2006, all 67 patients (67 lesions) at our 3 centers who had DES in-stent restenosis (ISR) were enrolled. The patients were divided into 3 groups: group I had focal edge restenosis, group II had focal body restenosis, and group III had non-focal restenosis. All patients were treated with conventional PCI including plain old balloon angioplasty (POBA), cutting balloon angioplasty (CBA), and repeated DES implantation (Re-DES). Angiographic and clinical one year follow-up results for the 3 groups were evaluated. RESULTS: Sixteen patients were enrolled in group I, 36 in group II, and 15 in group III. Baseline clinical and angiographic characteristics and the proportion of patients in each group receiving each type of treatment strategy were not significantly different among the groups. Within each group, a comparison of angiographic and clinical outcomes for each therapeutic modality revealed that restenosis rates were not statistically different. Although rates of major adverse cardiac events (MACE) were not statistically different between groups I and II, in group III, MACE were 3-fold higher for the POBA (4/4, 100.0%) and CBA (4/4, 100.0%) subgroups than for Re-DES (1/3, 33.3%) (p=0.06), but the differences did not reach statistical significance. CONCLUSION: THE PRESENT STUDY SUGGESTS THAT TREATMENT OF DES ISR SHOULD BE INDIVIDUALIZED ACCORDING TO RESTENOSIS PATTERN: any PCI strategy appears appropriate for focal ISR patterns, while Re-DES might be a better choice for non-focal ISR patterns.

Comparison of triple anti-platelet therapy (aspirin, clopidogrel, and cilostazol) and double anti-platelet therapy (aspirin and clopidogrel) on platelet aggregation in type 2 diabetic patients undergoing drug-eluting stent implantation.

BACKGROUND AND OBJECTIVES: Triple anti-platelet therapy may produce more potent inhibition of platelet aggregation in patients undergoing coronary stent implantation. We tested whether this effect could be maintained in diabetic patients, where platelet reactivity is increased and the risk of stent thrombosis is higher. SUBJECTS AND METHODS: Fifty five type 2 diabetic patients who had undergone drug-eluting stent (DES) implantation and chronic anti-platelet therapy (>1 month) were stratified according to the status of anti-platelet therapy. Platelet aggregation after adenosine diphosphate (ADP; 10 micromol/L and 20 micromol/L) stimulation was compared using light transmittance aggregometry between dual (aspirin plus clopidogrel, n=34) and triple therapy (aspirin, clopidogrel plus cilostazol, n=21) groups. RESULTS: The 2 groups had similar clinical and procedural characteristics. Maximal ADP-induced platelet aggregation was significantly lower in the triple therapy group than the dual therapy group (ADP 10 micromol/L, 37.1+/-15.4 vs. 28.3+/-11.8, p=0.03; ADP 20 micromol/L, 63.1+/-15.0 vs. 49.1+/-15.1, p=0.01), but there were no differences in diabetic treatment (oral hypoglycemic agent vs. insulin) or diabetic control {hemoglobin Alc (HbA1c) 7}. CONCLUSION: Triple anti-platelet therapy showed more potent inhibition of maximal ADP induced platelet aggregation in type 2 diabetic patients receiving chronic anti-platelet therapy. This finding suggests that triple antiplatelet therapy may be more effective in preventing thrombotic complications after DES implantation in type 2 diabetic patients.

Disc size regulation in the brood cell building behavior of leaf-cutter bee, Megachile tsurugensis.

The leaf-cutter bee, Megachile tsurugensis, builds a brood cell in a preexisting tunnel with leaf discs that she cuts in decreasing sizes and assembles them like a Russian matryoshka doll. By experimentally manipulating the brood cell, it was investigated how she regulates the size of leaf discs that fit in the brood cell's internal volume. When the internal volume was artificially increased by removing a bulk of leaf discs, she decreased the leaf disc size, although increasing it would have made the leaf disc more fitting in the increased internal volume. As a reverse manipulation, when the internal volume was decreased by inserting a group of inner layers of preassembled leaf discs to a brood cell, she decreased the leaf disc size, so that the leaf disc could fit in the decreased internal volume. These results suggest that she uses at least two different mechanisms to regulate the disc size: the use of some internal memory about the degree of building work accomplished in the first and of sensory feedback of dimensional information at the construction site in the second manipulation, respectively. It was concluded that a stigmergic mechanism, an immediate sensory feedback from the brood cell changed by the building work, alone cannot explain the details of the bee's behavior particularly with respect to her initial response to the first manipulation. For a more complete explanation of the behavior exhibited by the solitary bee, two additional behavioral elements, reinforcement of building activity and processing of dimensional information, were discussed along with stigmergy.

Tea polyphenol inhibits allostimulation in mixed lymphocyte culture.

Green tea polyphenols are known to protect allogenic donor tissues from acute rejection by their recipients. This immunosuppressive effect may be generated by a unique chemical property of the major component, epigallocatechin-o-gallate (EGCG), which can block specific cell surface molecules of the donor tissues. To test this hypothesis, we examined the effects of EGCG on the murine mixed lymphocyte reactions. EGCG treatment of stimulator cells significantly attenuated the proliferation of responder T cells. The proliferation did not recover upon the secondary stimulations by fresh untreated cells or exogenous IL-2. Flow cytometric analyses showed that EGCG treatment decreased the staining intensities of various cell surface molecules including MHC II, which plays a major role in antigen presentation, and B7.1, B7.2, and their ligand, CD28, which are required for costimulatory signals in T-cell activation. These results suggest that an anergic state of alloreactive T cells may be induced by either weakening of antigen signaling or blockage of costimulatory signals with EGCG. Other possible mechanisms behind the immunosuppressive effect and a potential use of EGCG treatment of donor tissues in transplantation medicine are discussed.

Hibernation, reversible cell growth inhibition by epigallocatechin-3-O-gallate.

Epigallocatechin-3-O-gallate (EGCg) and related polyphenolic compounds found in tea are known to have antioxidative activities. However, they also have pro-oxidative activities such as generation of hydrogen peroxide. In this report, we investigated the effect on cells and showed the potential usage of EGCg in cell preservation. H(2)O(2) was generated from EGCg at concentrations of more than 300 microg/mL for 6 h at 37 degrees C, and high cytotoxicity for L929 cells were shown. In contrast, in the presence of 1 microg/mL catalase, the amount of generated H(2)O(2) was significantly low and cytotoxicity decreased markedly. This indicates that catalase eliminated H(2)O(2) generated by degradation of EGCg. Although H(2)O(2) generation was prevented, L929 cell proliferation was slightly inhibited in proportion to the concentrations of EGCg. L929 was exposed able to be 300 microg/mL to EGCg and 1 microg/mL catalase for maximum 18 days. EGCg inhibited the growth of L929 cells, and cell proliferation was restarted immediately after medium change for removing EGCg. We concluded that EGCg had a reversible growth inhibition when H(2)O(2) was eliminated from cell cultures.

Maternal investment and size-number trade-off in a bee, Megachile apicalis, in seasonal environments.

Maternal investment in offspring size and number differed between spring- and summer-emerging individual females of Megachile apicalis, a solitary multivoltine bee. Data from experimentally initiated female populations indicated that spring-emerging females produced a relatively large number of progeny but allocated a small amount of food to each, resulting in small progeny. Adult females of larger body sizes provisioned food at a greater rate than did smaller females, and this body-size effect was significant in spring-emerging females. The large body size of these females allowed them to increase the number of progeny produced under the abundant floral resources that occurred during the spring. Conversely, summer-emerging females produced fewer progeny under the diminishing resources for brood production, but allocated each with more food, producing larger progeny, most of which emerged in the spring of the following year. Field data using trap-nests also indicated the same pattern of seasonal offspring size allocation found in the experimental populations. This maternal investment strategy entails a trade-off between the size and number of progeny, so that the daughters upon emergence can best perform in their brood production under the seasonally variable environments where they reproduce.