Combined percutaneous coronary atherectomy and coronary angioplasty: Experience in 19 consecutive patients

AbstractAmong 82 patients undergoing coronary atherectomy, 19 (23%) underwent this procedure in combination with coronary angioplasty. The most frequently involved vessel was the left anterior descending coronary artery. In 11 patients (58%), attempted atherectomy preceded coronary angioplasty. In 6 of the 11, angioplasty was used after the atherectomy catheter could not be positioned across the lesion; 4 patients underwent “rescue” angioplasty after developing vessel occlusion related to atherectomy and 1 patient had an unsatisfactory result of atherectomy. The success rate of the combined intervention was 82% for these 11 patients.In eight patients (42%), atherectomy was performed after initial angioplasty. In four of the eight, atherectomy was a rescue procedure to manage vessel occlusion by thrombus or intimal dissection and was successful in three. In the other four, angioplasty was performed to establish an easier passage for the atherectomy catheter and was successful in three. Thus, the success rate of the combined intervention was 75% for these eight patients.The overall success rate for all 19 patients was 79%; there was one in-hospital death and one non-Q wave infarction, and one patient required immediate coronary artery surgery. Two other patients underwent coronary artery surgery before hospital discharge. Combined intervention with coronary angioplasty and atherectomy seems to be a relatively safe and effective approach in selected patients when either of these procedures alone is unsuccessful or is accompanied by acute coronary complications

República: Año III Número 346 - (10/08/33)

BACKGROUND: Biomedical knowledge graphs have become important tools to computationally analyse the comprehensive body of biomedical knowledge. They represent knowledge as subject-predicate-object triples, in which the predicate indicates the relationship between subject and object. A triple can also contain provenance information, which consists of references to the sources of the triple (e.g. scientific publications or database entries). Knowledge graphs have been used to classify drug-disease pairs for drug efficacy screening, but existing computational methods have often ignored predicate and provenance information. Using this information, we aimed to develop a supervised machine learning classifier and determine the added value of predicate and provenance information for drug efficacy screening. To ensure the biological plausibility of our method we performed our research on the protein level, where drugs are represented by their drug target proteins, and diseases by their disease proteins. RESULTS: Using random forests with repeated 10-fold cross-validation, our method achieved an area under the ROC curve (AUC) of 78.1% and 74.3% for two reference sets. We benchmarked against a state-of-the-art knowledge-graph technique that does not use predicate and provenance information, obtaining AUCs of 65.6% and 64.6%, respectively. Classifiers that only used predicate information performed superior to classifiers that only used provenance information, but using both performed best. CONCLUSION: We conclude that both predicate and provenance information provide added value for drug efficacy screening

Changing experience with dual chamber (DDD) pacemakers

Dual chamber (DDD) or “universal” pacemakers have had a significant impact on the advancement of artificial pacemakers by providing a more physiologic approach to cardiac pacing. However, with the early generation of DDD pacemakers (pacemakers that sense and pace in both the atrium and the ventricle), a significant number of patients experienced pacemaker-mediated tachycardia because intact ventriculoatrial conduction was sensed in the atrium and a reentrant tachycardia was induced. Newer generation DDD pacemakers have provided longer atrial refractory periods, which should correct this problem.In this study the first and second years of a 2 year experience with DDD pacemakers were compared to determine if the newer generation devices have allowed maintenance of pacing in the DDD mode as opposed to reprogramming to some alternate mode because of pacemaker-mediated tachycardia or other pacing problems. The results showed a significant decrease in pacemaker-mediated tachycardia during the second year and continuation of pacing in the DDD mode in a higher percent of patients. This improvement is attributed to improvement in the pulse generator as well as better patient selection

Discovering information from an integrated graph database

The information explosion in science has become a different problem, not the sheer amount per se, but the multiplicity and heterogeneity of massive sets of data sources. Relations mined from these heterogeneous sources, namely texts, database records, and ontologies have been mapped to Resource Description Framework (RDF) triples in an integrated database. The subject and object resources are expressed as references to concepts in a biomedical ontology consisting of the Unified Medical Language System (UMLS), UniProt and EntrezGene and for the predicate resource to a predicate thesaurus. All RDF triples have been stored in a graph database, including provenance. For evaluation we used an actual formal PRISMA literature study identifying 61 cerebral spinal fluid biomarkers and 200 blood biomarkers for migraine. These biomarkers sets could be retrieved with weighted mean average precision values of 0.32 and 0.59, respectively, and can be used as a first reference for further refinements

Effect of external beam irradiation on neointimal hyperplasia after experimental coronary artery injury

AbstractHuman coronary artery restenosis after percutaneous revascularization is a response to mechanical injury. Smooth muscle cell proliferation is a major component of restenosis, resulting in obstructive neointimal hyperplasia. Because ionizing radiation inhibits cellular proliferation, this study tested in a porcine coronary injury model the hypothesis that the hyperplastic response to coronary artery injury would be attenuated by X-irradiation.Deep arterial injury was produced in 37 porcine left anterior descending coronary artery segments with overexpanded, percutaneously delivered tantalum wire coils. Three groups of pigs were irradiated with 300-kV X-rays after coil injury: Group I (n = 10), 400 cGy at 1 day; Group II (n = 10), 400 cGy at 1 day and 400 cGy at 4 days and Group III (n = 9), 800 cGy at 1 day. Eight pigs in the control group underwent identical injury but received no radiation. Treatment efficacy was histologically assessed by measuring neointimal thickness and percent area stenosis.Mean neointimal thickness in all irradiated groups was significantly higher than in the control groups and thickness was proportional to X-ray dose.X-irradiation delivered at these doses and times did not inhibit proliferative neointima. Rather, it accentuated the neointimal response to acute arterial injury and may have potentiated that injury

Restenosis after directional coronary atherectomy: Differences between primary atheromatoes and restenosls lesions and influence of subintimal tissue resection

AbstractRates of restenosis were evaluated in 70 patients (74 lesions) after successful directional coronary atherectomy. The extent of vascular tissue resection was correlated with restenosis rates for coronary (n = 59) and vein bypass graft (n = 15) lesions.After 6 months, the overall restenosis rate was 50% (37 of 74 lesions); it was 42% (15 of 36 lesions) when intima alone was resected, 50% (7 of 14 lesions) when media was resected and 63% (15 of 24 lesions) when adventitia was resected. Subintimal tissue resection increased the restenosis rate for vein grafts (43% with intimal resection versus 100% with subintimal resection, p = 0.01) but not for coronary arteries (50% versus 48%). There was no overall difference in restenosis rates after atherectomy between primary lesions and restenosis lesions that occurred after balloon angioplasty (46% versus 54%). Among postballoon angioplasty restenosis lesions, a higher rate of restenosis after atherectomy was found with subintimal than with intimal resection (78% versus 32%, p = 0.01).Tissues from patients undergoing a second atherectomy for restenosis after initial atherectomy (n = 8) demonstrated neointimal hyperplasia that appeared histotogically identical to restenotic tissue developing after balloon angioplasty (n = 37).These data suggest that the cellular response to directional coronary atherectomy is characterized by neointimal proliferation similar to that which may develop after balloon angioplasty. The extent of fibrous hyperplasia appears to be related to the depth of tissue resection in vein graft lesions and coronary artery restenosis lesions that occur after balloon angioplasty but not in primary atheromatous coronary artery lesions

Automated extraction of potential migraine biomarkers using a semantic graph

Problem Biomedical literature and databases contain important clues for the identification of potential disease biomarkers. However, searching these enormous knowledge reservoirs and integrating findings across heterogeneous sources is costly and difficult. Here we demonstrate how semantically integrated knowledge, extracted from biomedical literature and structured databases, can be used to automatically identify potential migraine biomarkers. Method We used a knowledge graph containing more than 3.5 million biomedical concepts and 68.4 million relationships. Biochemical compound concepts were filtered and ranked by their potential as biomarkers based on their connections to a subgraph of migraine-related concepts. The ranked results were evaluated against the results of a systematic literature review that was performed manually by migraine researchers. Weight points were assigned to these reference compounds to indicate their relative importance. Results Ranked results automatically generated by the knowledge graph were highly consistent with results from the manual literature review. Out of 222 reference compounds, 163 (73%) ranked in the top 2000, with 547 out of the 644 (85%) weight points assigned to the reference compounds. For reference compounds that were not in the top of the list, an extensive error analysis has been performed. When evaluating the overall performance, we obtained a ROC-AUC of 0.974. Discussion Semantic knowledge graphs composed of information integrated from multiple and varying sources can assist researchers in identifying potential disease biomarkers

Sorafenib decreases proliferation and induces apoptosis of prostate cancer cells by inhibition of the androgen receptor and Akt signaling pathways

Antihormonal and chemotherapy are standard treatments for nonorgan-confined prostate cancer. The effectivity of these therapies is limited and the development of alternative approaches is necessary. In the present study, we report on the use of the multikinase inhibitor sorafenib in a panel of prostate cancer cell lines and their derivatives which mimic endocrine and chemotherapy resistance. 3H-thymidine incorporation assays revealed that sorafenib causes a dose-dependent inhibition of proliferation of all cell lines associated with downregulation of cyclin-dependent kinase 2 and cyclin D1 expression. Apoptosis was induced at 2 μM of sorafenib in androgen-sensitive cells, whereas a higher dose of the drug was needed in castration-resistant cell lines. Sorafenib stimulated apoptosis in prostate cancer cell lines through downregulation of myeloid cell leukemia-1 (MCL-1) expression and Akt phosphorylation. Although concentrations of sorafenib required for the antitumor effect in therapy-resistant sublines were higher than those needed in parental cells, the drug showed efficacy in cells which became resistant to bicalutamide and docetaxel respectively. Most interestingly, we show that sorafenib has an inhibitory effect on androgen receptor (AR) and prostate-specific antigen expression. In cells in which AR expression was downregulated by short interfering RNA, the treatment with sorafenib increased apoptosis in an additive manner. In summary, the results of the present study indicate that there is a potential to use sorafenib in prostate cancers as an adjuvant therapy option to current androgen ablation treatments, but also in progressed prostate cancers that become unresponsive to standard therapies

Long distance transport of magnon spin information in a magnetic insulator at room temperature

The transport of spin information has been studied in various materials, such as metals, semiconductors and graphene. In these materials, spin is transported by diffusion of conduction electrons. Here we study the diffusion and relaxation of spin in a magnetic insulator, where the large bandgap prohibits the motion of electrons. Spin can still be transported, however, through the diffusion of non-equilibrium magnons, the quanta of spin wave excitations in magnetically ordered materials. Here we show experimentally that these magnons can be excited and detected fully electrically in linear response, and can transport spin angular momentum through the magnetic insulator yttrium iron garnet (YIG) over distances as large as 40 micrometer. We identify two transport regimes: the diffusion limited regime for distances shorter than the magnon relaxation length, and the relaxation limited regime for larger distances. With a model similar to the diffusion-relaxation model for electron spin transport in (semi)conducting materials, we extract the magnon relaxation length lambda = 9.4 micrometer in a 200 nm thin YIG film at room temperature