Antithrombotic treatment of retinal vein occlusion: a position statement from the Italian Society on Thrombosis and Haemostasis (SISET).

Retinal vein occlusion (RVO) represents a common cause of visual impairment and blindness. RVO may be associated with both local (e.g., hyperopia, glaucoma) and systemic (e.g., hypertension, diabetes, smoking, obesity, and dyslipidaemia) risk factors. The association with thrombophilia remains controversial. Data on the use of antithrombotic therapy for RVO are poor and inconsistent with most of the information being derived from observational studies. Here we provide a position statement from the Italian Society on Thrombosis and Haemostasis (SISET) to guide the clinical and therapeutic management of patients with RVO based on the available evidence and expert opinion.

Eltrombopag to allow chemotherapy in a patient with MYH9-related inherited thrombocytopenia and pancreatic cancer.

Chemotherapy is the mainstay of treatment for advanced pancreatic cancer however, due to possible myelotoxicity, it is used with caution in patients with thrombocytopenia, especially when severe. TPO-receptor agonists have been employed for chemotherapy-induced thrombocytopenia, however treatment with TPO-receptor agonists to allow chemotherapy in patients with inherited thrombocytopenia has not been reported so far. We report the first successful use of eltrombopag to prevent chemotherapy-induced thrombocytopenia in a patient with MHY9-related disorder and pancreatic cancer. Treatment with eltrombopag allowed to attain a safe and stable platelet count for several months sufficient to permit chemotherapy and to allow the patient to undergo endoscopic placement of a biliary stent with no bleeding complications.

Antithrombotic prophylaxis for surgery-associated venous thromboembolism risk in patients with inherited platelet disorders. The SPATA-DVT Study.

Major surgery is associated with an increased risk of venous thromboembolism (VTE), thus the application of mechanical or pharmacologic prophylaxis is recommended. The incidence of VTE in patients with inherited platelet disorders (IPD) undergoing surgical procedures is unknown and no information on the current use and safety of thromboprophylaxis, particularly of low-molecular-weight-heparin in these patients is available. Here we explored the approach to thromboprophylaxis and thrombotic outcomes in IPD patients undergoing surgery at VTE-risk participating in the multicenter SPATA study. We evaluated 210 surgical procedures carried out in 155 patients with well-defined forms of IPD (VTE-risk: 31% high, 28.6% intermediate, 25.2% low, 15.2% very low). The use of thromboprophylaxis was low (23.3% of procedures), with higher prevalence in orthopedic and gynecological surgeries, and was related to VTE-risk. The most frequently employed thromboprophylaxis was mechanical and appeared to be effective, as no patients developed thrombosis, including patients belonging to the highest VTE-risk classes. Low-molecular-weight-heparin use was low (10.5%) and it did not influence the incidence of post-surgical bleeding or of antihemorrhagic prohemostatic interventions use. Two thromboembolic events were registered, both occurring after high VTE-risk procedures in patients who did not receive thromboprophylaxis (4.7%). Our findings suggest that VTE incidence is low in patients with IPD undergoing surgery at VTE-risk and that it is predicted by the Caprini score. Mechanical thromboprophylaxis may be of benefit in patients with IPD undergoing invasive procedures at VTE-risk and low-molecular-weight-heparin should be considered for major surgery.

Choice and Outcomes of Rate Control versus Rhythm Control in Elderly Patients with Atrial Fibrillation: A Report from the REPOSI Study.

BACKGROUND: Among rate-control or rhythm-control strategies, there is conflicting evidence as to which is the best management approach for non-valvular atrial fibrillation (AF) in elderly patients. DESIGN: We performed an ancillary analysis from the 'Registro Politerapie SIMI' study, enrolling elderly inpatients from internal medicine and geriatric wards. METHODS: We considered patients enrolled from 2008 to 2014 with an AF diagnosis at admission, treated with a rate-control-only or rhythm-control-only strategy. RESULTS: Among 1114 patients, 241 (21.6%) were managed with observation only and 122 (11%) were managed with both the rate- and rhythm-control approaches. Of the remaining 751 patients, 626 (83.4%) were managed with a rate-control-only strategy and 125 (16.6%) were managed with a rhythm-control-only strategy. Rate-control-managed patients were older (p = 0.002), had a higher Short Blessed Test (SBT; p = 0.022) and a lower Barthel Index (p = 0.047). Polypharmacy (p = 0.001), heart failure (p = 0.005) and diabetes (p = 0.016) were more prevalent among these patients. Median CHA2DS2-VASc score was higher among rate-control-managed patients (p = 0.001). SBT [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94-1.00, p = 0.037], diabetes (OR 0.48, 95% CI 0.26-0.87, p = 0.016) and polypharmacy (OR 0.58, 95% CI 0.34-0.99, p = 0.045) were negatively associated with a rhythm-control strategy. At follow-up, no difference was found between rate- and rhythm-control strategies for cardiovascular (CV) and all-cause deaths (6.1 vs. 5.6%, p = 0.89; and 15.9 vs. 14.1%, p = 0.70, respectively). CONCLUSION: A rate-control strategy is the most widely used among elderly AF patients with multiple comorbidities and polypharmacy. No differences were evident in CV death and all-cause death at follow-up.

Reduced survival in patients with early-stage non-small-cell lung cancer is associated with high pleural endothelial progenitor cell levels.

OBJECTIVES: Endothelial progenitor cells are capable of contributing to neovascularization in tumours. In patients with either malignant or transudative pleural effusion, we tested the presence of pleural endothelial progenitor cells. We also measured the number of endothelial progenitor cells in post-surgery pleural drainage of either patients with early non-small-cell lung cancer or control patients with benign lung disease undergoing pulmonary resection. The prospective influence of post-surgery pleural-drainage endothelial progenitor cells on cancer recurrence/survival was investigated. METHODS: Pleural endothelial progenitor cell levels were quantified by fluorescence-activated cell sorting analysis in pleural effusion of 15 patients with late-stage non-small-cell lung cancer with pleural involvement and in 15 control patients with congestive heart failure. Also, pleural-drainage endothelial progenitor cells were measured in pleural-drainage fluid 48 h after surgery in 64 patients with early-stage non-small-cell lung cancer and 20 benign lung disease patients undergoing pulmonary resection. Cancer recurrence and survival was evaluated in patients with high pleural-drainage endothelial progenitor cell levels. RESULTS: The number of pleural endothelial progenitor cells was higher in non-small-cell lung cancer pleural effusion than in transudative pleural effusion. Also, pleural-drainage endothelial progenitor cell levels were higher in patients with non-small-cell lung cancer than in patients with benign lung disease undergoing pulmonary resection (P < 0.05). Non-small-cell lung cancer patients with high pleural-drainage endothelial progenitor cell levels had a significantly 4.9 higher rate of cancer recurrence/death than patients with lower pleural-drainage endothelial progenitor cell levels, irrespective of confounders. CONCLUSIONS: Endothelial progenitor cells are present in the pleural effusion and are higher in patients with late-stage non-small-cell lung cancer with pleural involvement than in congestive heart failure patients. Endothelial progenitor cell levels are higher in the post-surgery pleural drainage of patients with non-small-cell lung cancer than in non-neoplastic pleural-drainage fluid. High pleural-drainage endothelial progenitor cell levels in patients undergoing pulmonary resection for early non-small-cell lung cancer predict an increased risk of cancer recurrence and death.

Long noncoding RNAs: new insights into non-small cell lung cancer biology, diagnosis and therapy.

Recent advances in tiling array and high throughput analyses revealed that at least 87.3 % of the human genome is actively transcribed, though <3 % of the human genome encodes proteins. This unexpected truth suggests that most of the transcriptome is constituted by noncoding RNA. Among them, high-resolution microarray and massively parallel sequencing analyses identified long noncoding RNAs (lncRNAs) as nonprotein-coding transcripts. lncRNAs are largely polyadenylated and >200 nucleotides in length transcripts, involved in gene expression through epigenetic and transcriptional regulation, splicing, imprinting and subcellular transport. Although lncRNAs functions are largely uncharacterized, accumulating data indicate that they are involved in fundamental biological functions. Conversely, their dysregulation has increasingly been recognized to contribute to the development and progression of several human malignancies, especially lung cancer, which represents the leading cause of cancer-related deaths worldwide. We conducted a comprehensive review of the published literature focusing on lncRNAs function and disruption in nonsmall cell lung cancer biology, also highlighting their value as biomarkers and potential therapeutic targets. lncRNAs are involved in NSCLC pathogenesis, modulating fundamental cellular processes such as proliferation, cell growth, apoptosis, migration, stem cell maintenance and epithelial to mesenchymal transition, also serving as signaling transducers, molecular decoys and scaffolds. Also, lncRNAs represent very promising biomarkers in early-stage NSCLC patients and may become particularly useful in noninvasive screening protocols. lncRNAs may be used as predictive biomarkers for chemotherapy and targeted therapies sensitivity. Furthermore, selectively targeting oncogenic lncRNAs could provide a new therapeutic tool in treating NSCLC patients. lncRNAs disruption plays a pivotal role in NSCLC development and progression. These molecules also serve as diagnostic, prognostic and predictive biomarkers. Characterization of lncRNA genes and their mechanisms of action will enable us to develop a more comprehensive clinical approach, with the final goal to benefit our patients.

Baseline and post-surgery endothelial progenitor cell levels in patients with early-stage non-small-cell lung carcinoma: impact on cancer recurrence and survival.

OBJECTIVES: Endothelial progenitor cells (EPCs) are believed to play a role in promoting abnormal vascularization in neoplastic sites. We measured the number of circulating EPCs in treatment-naïve patients with early non-small-cell lung cancer (NSCLC) and healthy controls. The prospective influence of baseline and post-surgery EPC levels on cancer recurrence and survival was investigated. METHODS: Circulating EPCs were quantified by FACS analysis in 34 patients with Stage I-II NSCLC and 68 healthy age- and sex-matched controls. Measurement of EPCs was repeated 48 h after thoracic surgery and at the hospital discharge. Cancer recurrence and survival was evaluated after 446 ± 106 days of follow-up (range 182-580 days). RESULTS: The base 10 logarithmic [log] number of circulating EPCs was comparable between patients with NSCLC and controls [mean ± standard deviation (SD): 2.3 ± 0.32 vs 2.3 ± 0.26 n/ml, P = 0.776]. In regression analysis, smoking status [standardized coefficient beta (ß) = -0.26, 95% confidence interval (CI) for B -0.29/-0.03, P = 0.014] and systolic blood pressure [ß = -0.23, 95% CI for B -0.011/-0.001, P = 0.018] were independent predictors of the number of EPCs, irrespective of the NSCLC status. The mean number of EPCs did not change after surgical treatment. However, a post-surgery EPC increase was observed in 44% patients. Patients with a 48 h post-surgery EPC increase had a higher rate of cancer recurrence/death than patients with either stable or decreased post-surgery EPC levels [hazard ratio (HR) 4.4, 95% CI 1.1-17.3; P = 0.032], irrespective of confounders. CONCLUSIONS: Circulating EPC levels are comparable between patients with early-stage NSCLC and healthy controls. Overall, surgical cancer resection was not associated with a significant early EPC change. However, an early post-surgery EPC increase is able to predict an increased risk of cancer recurrence and death.