Determinants of enhanced thromboxane biosynthesis in renal transplantation

Background. Despite great improvement in patient and graft survival, the long-term morbidity and mortality in renal transplant recipients (RTRs) are still significant, with a high incidence of cardiovascular disease-related deaths. Methods. We investigated thromboxane (TXA2) biosynthesis and endothelial and coagulative activation in 65 patients who received a renal transplant. Results. The rate of TXA2 biosynthesis (urinary 11-dehydro-TXB2 excretion largely reflects platelet TXA2 production in vivo) was significantly (P < 0.0001) higher in RTRs than in healthy subjects. Plasma von Willebrand factor (vWF) and thrombin-antithrombin (TAT) complexes were significantly higher (P < 0.001) in RTRs compared with controls. Urinary 11-dehydro-TXB2 directly correlated with plasma vWF and cholesterol. We next examined the relative influence of cyclosporine A (CsA) on TXA2 biosynthesis and endothelial activation, comparing a group of RTRs not receiving CsA with an age- and sex-matched group of patients treated with CsA. Urinary excretion of 11-dehydro-TXB2 and plasma levels of vWF were significantly increased in RTRs who received CsA compared with those who did not. After an overall follow-up of 120 months, RTRs who experienced cardiovascular events had a higher frequency of abnormal plasma levels of vWF than patients who remained event free. Conclusion. Renal transplantation is associated with in vivo platelet activation highly related to endothelial activation. This is particularly evident in CsA-treated patients. Administration of drugs that are able to reduce or eliminate thromboxane-dependent platelet activation in vivo may be beneficial to reduce the risk of cardiovascular events in RTRs

Argon plasma coagulation in the treatment of post-radiotherapy rectal bleeding

Introduction: Chronic radiation proctitis is often associated to radiotherapy for treatment of pelvic cancer. The most common side effect of this pathological condition is rectal bleeding but despite the great number of clinical approaches and techniques that have been employed no consensus for the management of it is available. Although prospective randomized trials about hemorrhagic radiation proctitis are still lacking, endoscopic approach delivering an Argon Plasma Coagulation (APC) seems to be a successful and available option. Patients and Methods: Sixteen patients suffering from post-radiotherapy rectal bleeding were followed. In the nine cases presenting a rectum ulcerative colitis (RUC) like endoscopic picture a 5-ASA therapeutic approach was chosen initially, followed by an APC treatment of areas of telangectasias. The other cases, presenting only areas of telangectasias, were treated only with APC. Results: 5-ASA therapy led to an improvement of inflammation state related to RUC but recurrence of rectal bleeding caused by telangectasias was observed. In these cases an additional APC treatment gave a total remission of the problem. Also in the other cases, presenting only areas of telangectasias, a remission of rectal bleeding was achieved through APC application. Conclusions: In the cases of radiation proctitis characterized by a severe compromission of rectal mucosa integrity an anti-inflammatory pharmacological therapy is necessary but not sufficient to abrogate rectal bleeding which is often caused by the presence of areas of telangectasias. In these cases a remission of the problem could be achieved through a combination of anti-inflammatory therapy (5-ASA) and APC

MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer : The hOrmone and Diet in the ETiology of breast cancer prospective study

report was to investigate whether many years before the diagnosis of breast cancer miRNA expression is already disregulated. In order to test this hypothesis, we compared miRNAs extracted from leukocytes in healthy women who later developed breast cancer and in women who remain healthy during the whole 15-year follow-up time. Accordantly, we used a case-control study design nested in the hOrmone and Diet in the ETiology of breast cancer (ORDET) prospective cohort study addressing the possibility that miRNAs can serve as both early biomarkers and components of the hormonal etiological pathways leading to breast cancer development in premenopausal women. We compared leukocyte miRNA profiles of 191 incident premenopausal breast cancer cases and profiles of 191 women who remained healthy over a follow-up period of 20 years. The analysis identified 20 differentially expressed miRNAs in women candidate to develop breast cancer versus control women. The upregulated miRNAs, miR-513-a-5p, miR- 513b-5p and miR-513c-5p were among the most significantly deregulated miRNAs. In multivariate analysis, miR-513a-5p upregulation was directly and statistically significant associated with breast cancer risk (OR = 1.69; 95% CI 1.08-2.64; P = 0.0293). In addition, the upregulation of miR-513-a-5p displayed the strongest direct association with serum progesterone and testosterone levels. The experimental data corroborated the inhibitory function of miR-513a-5p on progesterone receptor expression confirming that progesterone receptor is a target of miR-513a-5p. The identification of upregulated miR-513a-5p with its oncogenic potential further validates the use of miRNAs as long-term biomarker of breast cancer risk

miR-181c associates with tumor relapse of high grade osteosarcoma

High-grade osteosarcoma (OS) is characterized by low incidence, high aggressiveness and moderate 5-years survival rate after aggressive poly-chemotherapy and surgery. Here we used miRNA profiling as a tool to possibly predict and monitor OS's development and therapeutic outcome. First, we evaluated the altered expression of selected miRNAs from a case of Giant Cell Tumor (GCT) apparently evolved into an OS. We found that most of modulated miRs were associated with pathways of bone resorption and osteogenesis. miRNA expression also revealed that GCT and OS were distinct tumors. Second, we validated the observed miRNA profile in two independent casuistries of ten GCT (not evolved into malignant tumors) and sixteen OS patients. Interestingly, we found that miR-181c and other three miRNAs identified in the first step of the study were also consistently de-regulated in all OS patients. Ectopic expression of miR-181c reduced cell viability and enhanced chemotherapeutic-induced cell death of U2OS and SAOS2 cells. These findings indicate that: i) miRNAs aberrantly modulated in GCT could be predictive of its development into OS and ii) miRNAs expression could be useful to monitor the OS therapeutic outcome

Evidence-Based Cognitive Rehabilitation: Systematic Review of the Literature From 2009 Through 2014

Objective To conduct an updated, systematic review of the clinical literature, classify studies based on the strength of research design, and derive consensual, evidence-based clinical recommendations for cognitive rehabilitation of people with TBI or stroke. Data Sources Online Pubmed and print journal searches identified citations for 250 articles published from 2009 through 2014. Study Selection 186 articles were selected for inclusion after initial screening. 50 articles were initially excluded (24 healthy, pediatric or other neurologic diagnoses, 10 non-cognitive interventions, 13 descriptive protocols or studies, 3 non-treatment studies). 15 articles were excluded after complete review (1 other neurologic diagnosis, 2 non-treatment studies, 1 qualitative study, 4 descriptive papers, 7 secondary analyses). 121 studies were fully reviewed. Data Extraction Articles were reviewed by CRTF members according to specific criteria for study design and quality, and classified as providing Class I, Class II, or Class III evidence. Articles were assigned to 1 of 6 possible categories (based on interventions for attention, vision and neglect, language and communication skills, memory, executive function, or comprehensive-integrated interventions). Data Synthesis Of 121 studies, 41 were rated as Class I, 3 as Class Ia, 14 as Class II, and 63 as Class III. Recommendations were derived by CRTF consensus from the relative strengths of the evidence, based on the decision rules applied in prior reviews. Conclusions CRTF has now evaluated 491 papers (109 Class I or Ia, 68 Class II, and 314 Class III) and makes 29 recommendations for evidence-based practice of cognitive rehabilitation (9 Practice Standards, 9 Practice Guidelines and 11 Practice Options). Evidence supports Practice Standards for attention deficits after TBI or stroke; visual scanning for neglect after right hemisphere stroke; compensatory strategies for mild memory deficits; language deficits after left hemisphere stroke; social communication deficits after TBI; metacognitive strategy training for deficits in executive functioning; and comprehensive-holistic neuropsychological rehabilitation to reduce cognitive and functional disability after TBI or stroke

Complications of mechanical thrombectomy for acute ischemic stroke: Incidence, risk factors, and clinical relevance in the Italian Registry of Endovascular Treatment in acute stroke

BACKGROUND: There are limited data concerning procedure-related complications of endovascular thrombectomy for large vessel occlusion strokes. AIMS: We evaluated the cumulative incidence, the clinical relevance in terms of increased disability and mortality, and risk factors for complications. METHODS: From January 2011 to December 2017, 4799 patients were enrolled by 36 centers in the Italian Registry of Endovascular Stroke Treatment. Data on demographic and procedural characteristics, complications, and clinical outcome at three months were prospectively collected. RESULTS: The complications cumulative incidence was 201 per 1000 patients undergoing endovascular thrombectomy. Ongoing antiplatelet therapy (p < 0.01; OR 1.82, 95% CI: 1.21-2.73) and large vessel occlusion site (carotid-T, p < 0.03; OR 3.05, 95% CI: 1.13-8.19; M2-segment-MCA, p < 0.01; OR 4.54, 95% CI: 1.66-12.44) were associated with a higher risk of subarachnoid hemorrhage/arterial perforation. Thrombectomy alone (p < 0.01; OR 0.50, 95% CI: 0.31-0.83) and younger age (p < 0.04; OR 0.98, 95% CI: 0.97-0.99) revealed a lower risk of developing dissection. M2-segment-MCA occlusion (p < 0.01; OR 0.35, 95% CI: 0.19-0.64) and hypertension (p < 0.04; OR 0.77, 95% CI: 0.6-0.98) were less related to clot embolization. Higher NIHSS at onset (p < 0.01; OR 1.04, 95% CI: 1.02-1.06), longer groin-to-reperfusion time (p < 0.01; OR 1.05, 95% CI: 1.02-1.07), diabetes (p < 0.01; OR 1.67, 95% CI: 1.25-2.23), and LVO site (carotid-T, p < 0.01; OR 1.96, 95% CI: 1.26-3.05; M2-segment-MCA, p < 0.02; OR 1.62, 95% CI: 1.08-2.42) were associated with a higher risk of developing symptomatic intracerebral hemorrhage compared to no/asymptomatic intracerebral hemorrhage. The subgroup of patients treated with thrombectomy alone presented a lower risk of symptomatic intracerebral hemorrhage (p < 0.01; OR 0.70; 95% CI: 0.55-0.90). Subarachnoid hemorrhage/arterial perforation and symptomatic intracerebral hemorrhage after endovascular thrombectomy worsen both functional independence and mortality at three-month follow-up (p < 0.01). Distal embolization is associated with neurological deterioration (p < 0.01), while arterial dissection did not affect clinical outcome at follow-up. CONCLUSIONS: Complications globally considered are not uncommon and may result in poor clinical outcome. Early recognition of risk factors might help to prevent complications and manage them appropriately in order to maximize endovascular thrombectomy benefits

The GRAVITY young stellar object survey: VIII. Gas and dust faint inner rings in the hybrid disk of HD141569

Stars and planetary system

The GRAVITY young stellar object survey: IX. Spatially resolved kinematics of hot hydrogen gas in the star-disk interaction region of T Tauri stars

Stars and planetary system