Retinoids and cancer: antitumoral effects of ATRA, 9-cis RA and the new retinoid IIF on the HL-60 leukemic cell line.

Objective: To compare the antitumoral effects of all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA) with those of 5-OH,11-O-hydrophenanthrene (IIF), a new derivative of retinoic acid. Materials and Methods: The effect of retinoids was tested on cell line HL-60. Cell differentiation and apoptosis were evaluated by morphological and biochemical analysis as bcl-2 protein and by DNA fragmentation assay. The ability to activate retinoic acid receptors (RAR) and/or retinoid X receptors (RXR) and to modulate gene expression was determined by transactivation assay. Results: With cell line HL-60, the antiproliferative effect of IIF was stronger than that of ATRA and 9-cis RA. Following retinoid treatment, cells appeared to differentiate and apoptotic cells were observed. The appearance of DNA laddering and a decrease in the amount of bcl-2 protein confirmed apoptosis. IIF transcriptionally activated RXR-γ more than RAR-α. Conclusion: The findings indicate that IIF transcriptionally activates RXR-γ preferentially, induces apoptosis and has a more antiproliferative activity than ATRA and 9-cis RA on cell line HL-60

Incidence and prevalence analysis of non-small-cell and small-cell lung cancer using administrative data

Treatment of lung cancer depends on the stage of the tumor and the histological type. In recent years, the histological confirmation of lung non-small-cell lung cancer has become crucial since the availability of selective target therapeutic approaches. The aim of the study was to develop a validated procedure to estimate the incidence and prevalence of non-small-cell and small-cell lung cancer from healthcare administrative data. A latent class model for categorical variables was applied. The following observed variables were included in the analysis: ICD-9-CM codes in the Hospital Discharge Registry, ATC codes of medications dispensed present in the Drugs Prescriptions Registry, and the procedure codes in the Outpatient Registry. The proportion of non-small-cell lung cancer diagnoses was estimated to be 85% of the total number of lung cancer on the cohort of incident cases and 89% on the cohort of prevalent cases. External validation on a cohort of 107 patients with a lung cancer diagnosis and histological confirmation showed a sensitivity of 95.6% (95%CI: 89–98.8%) and specificity of 94.1% (95%CI: 71.3–99.9%). The procedure is an easy-to-use tool to design subpopulation-based studies on lung cancer and to better plan resource allocation, which is important since the introduction of new targeted therapies in non-small-cell lung carcinoma

A generalized truncated logarithm

We introduce a generalization $G^{(\alpha)}(X)$ of the truncated logarithm $\pounds_1(X)=\sum_{k=1}^{p-1}X^k/k$ in prime characteristic $p$, which depends on a parameter $\alpha$. The main motivation of this study is $G^{(\alpha)}(X)$ being an inverse, in an appropriate sense, of a parametrized generalization of the truncated exponential given by certain Laguerre polynomials. Such Laguerre polynomials play a role in a {\em grading switching} technique for non-associative algebras, previously developed by the authors, because they satisfy a weak analogue of the functional equation $\exp(X)\exp(Y)=\exp(X+Y)$ of the exponential series. We also investigate functional equations satisfied by $G^{(\alpha)}(X)$ motivated by known functional equations for $\pounds_1(X)=-G^{(0)}(X)$

Definition of indicators of appropriateness in the management of neovascular age-related macular degeneration: An expert opinion

Wet age-related macular degeneration is a chronic condition culminating, in most cases, in blindness. The introduction of anti-angiogenic agents in 2006 has represented a major breakthrough in the treatment of the disease, but timely and effective treatment with regular follow-up and monitoring is mandatory to stabilize and preserve visual acuity. In clinical practice, however, appropriate therapy provision is frequently challenged by economic and organizational issues that result in suboptimal visual outcomes and increased incidence of legal blindness. International Guidelines have defined a diagnostic and therapeutic pathway to ensure the best practice in wet age-related macular degeneration management, but reference parameters to evaluate and compare the performance of Retina Centers are lacking. To address the appropriateness of wet age-related macular degeneration management in Italy, a multidisciplinary panel of ten experts gathered in three meetings. They defined three sets of indicators and relative benchmark values that each Center should comply with to ensure patients optimal care already from the first access: (a) clinical intervention indicators, to determine the possible Center\u2019s deviation from the diagnostic and therapeutic pathway; (b) outcome indicator, to evaluate the socioeconomic impact of the healthcare systems\u2019 performance; (c) management indicators, to test the size of the gap between the Center\u2019s supply and demand. Once the indicators have been analyzed, healthcare systems can plan actions to improve appropriateness and monitor their effects. However, to put this in practice, a concerted effort by all parts involved in healthcare provision is required, together with adequate systems to analyze clinical and administrative documentation

The Mediterranean island states : Malta and Cyprus

The 2004 European Union enlargement also included the Mediterranean island-states of Cyprus and Malta, two former British colonies and members of the British Commonwealth. The islands share a number of similarities but they are also dissimilar in uniquely distinct ways. The membership applications of both states initially presented the EU with a number of political difficulties. With respect to Cyprus, many member states would have preferred to see the island join the Union after the ‘Cyprus Problem’ had been settled. As for Malta, the island showed a very high degree of Euroskepticism. It froze its application in 1996 but reactivated it in 1998. Apart from this skepticism the island’s neutral status, enshrined in the Constitution could present insurmountable problems.peer-reviewe

Efficacy of Three Different Prophylactic Treatments for Postoperative Nausea and Vomiting after Vitrectomy: A Randomized Clinical Trial

Postoperative nausea and vomiting (PONV) after vitreoretinal surgery may potentially be associated with severe complications, such as suprachoroidal hemorrhage. The purpose of the present multicenter clinical trial (NCT02386059) was to assess the efficacy of three different prophylactic treatments for PONV after vitrectomy under local anesthesia. Patients undergoing primary vitrectomy were randomized to the control arm or to one of the treatment arms (4 mg ondansetron, 4 mg dexamethasone, combination of the two drugs). The primary outcome measure was the proportion of complete response (no nausea, no vomiting, no retching, and no use of antiemetic rescue medication) during 24 h after vitrectomy. Secondary outcomes included the severity standardized score of PONV, postoperative pain standardized score, and rate of ocular and non-ocular adverse events. Baseline demographics of the 1287 patients were comparable between the four arms. The combined therapy group showed a statistically significant lower incidence of PONV compared to the placebo and monotherapy (p < 0.001). PONV severity was also reduced in the combination group compared to the others (p < 0.001). Postoperative pain scores and adverse events were comparable among the four groups. Combined therapy with dexamethasone and ondansetron was the most effective treatment for reducing the incidence and severity of PONV in patients undergoing vitrectomy under local anesthesia

Characterization of the pathophysiological role of CD47 in uveal melanoma

Uveal melanoma (UM) represents the most frequent primary intraocular tumor, however, limited therapeutic options are still available. We have previously shown that cluster of differentiation 47 (CD47) is significantly upregulated in UM cells following inflammatory stimuli and that it represents a predictor of disease progression. Here, we aimed to better characterize the pathophysiological role of CD47 in UM. We show that CD47 is not modulated at different cancer stages, although patients with the lowest expression of CD47 show significant better progression-free survival, after correcting for the presence of BAP1, GNAQ, and GNA11 mutations. By stratifying patients based on the expression of CD47 in the tumor, we observed that patients with high levels of CD47 have a significant increase in immune score as compared to patients with low levels of CD47. In particular, deconvolution analysis of infiltrating immune cell populations revealed that a significantly higher number of CD4+ and CD8+ T cells can be found in patients with high CD47 levels, with the most enriched populations being the Th2, Treg, and CD8+ Tcm cells. We also show that a large number of transcripts are significantly modulated between the groups of patients with high and low levels of CD47, with a significant enrichment of interferon IFN-alpha regulated genes. The results from this study may propel the development of anti-CD47 therapies for UM patients

Pain Following the Use of Anesthesia Formulation Among Individuals Undergoing Cataract Surgery: A Randomized Controlled Trial

Purpose: To assess the pain intensity of two intracameral anesthetic solutions in patients undergoing cataract surgery and evaluate the factors influencing the patients’ postoperative activities. Methods: Sixty-two patients undergoing cataract surgery were randomized to receive the study drug – a manufactured solution of 0.02% tropicamide/0.31% phenylephrine/1% lidocaine (Mydrane) or a traditional anesthetic formulation - solution of 1% lidocaine/0.025% adrenaline as an intraocular anesthetic. The pain intensity was assessed by Visual Analog Scale for Pain (VAS Pain) and Brief Pain Inventory-short form (BPI) on the next day after the surgery. Results: The mean pain score measured preoperatively with VAS Pain was 0.34 in Mydrane group and 0.09 in the reference group (p = 0.51). There were no statistically significant differences between the two anesthetic methods with respect to pain intensity during the surgery (p = 0.94) and the influence of pain during the last 24 h on activity (p = 0.79), mood (p = 0.31), social contacts (p = 0.29), sleep (p = 0.5) and the joy of life (p = 0.39). Additionally, there was no statistically significant influence of age, sex, lateralization, co-existing ophthalmological diseases (p = 0.98) and post-operative complications (p = 0.4) on the experienced pain measured during the surgery and in the last 24 h. Conclusions: New commercially available intraocular anesthetic solution (Mydrane™) seems to be as effective as off-label traditional anesthetic formulation, in reducing the pain experienced during cataract surgery under topical anesthesia