Plasma miRNA-based signatures in CRC screening programs

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607–0.682), 0.670 (0.626–0.714) and 0.682 (0.580–0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.     

Impact of new technologies on diabetes care

Technologies for diabetes management, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems, have improved remarkably over the last decades. These developments are impacting the capacity to achieve recommended hemoglobin A1c levels and assisting in preventing the development and progression of micro- and macro vascular complications. While improvements in metabolic control and decreases in risk of severe and moderate hypoglycemia have been described with use of these technologies, large epidemiological international studies show that many patients are still unable to meet their glycemic goals, even when these technologies are used. This editorial will review the impact of technology on glycemic control, hypoglycemia and quality of life in children and youth with type 1 diabetes. Technologies reviewed include CSII, CGM systems and sensor-augmented insulin pumps. In addition, the usefulness of advanced functions such as bolus profiles, bolus calculators and threshold-suspend features will be also discussed. Moreover, the current editorial will explore the challenges of using these technologies. Indeed, despite the evidence currently available of the potential benefits of using advanced technologies in diabetes management, many patients still report barriers to using them. Finally this article will highlight the importance of future studies tailored toward overcome these barriers to optimizing glycemic control and avoiding severe hypoglycemia.     

Ethmoido-orbital tumors: our experience

No data in the literature report the specific invasion of the orbit from ethmoidal tumors, although such a pattern of involvement of the orbit frequently occurs because of the thin lamina papyracea separating the two structures. From January 1986 to January 2003, 38 patients with untreated primary ethmoidal malignancies were observed at the Unit of Maxillo-Facial Surgery of the University "La Sapienza" in Rome. Personal data were obtained from review of the personal clinical file of each. Orbital invasion was present in 24 patients with ethmoidal malignancy. Three stages of orbital invasion were identified. The average overall survival, with the Kaplan-Meyer method, was 61.4% after 1 year and 51.1% at 5 and 10 years. Intracranial involvement is the main element for short-term negative prognosis. Orbital exenteration is fundamental if grade III orbital invasion occurs because it ensures an improvement of the disease-free survival.     

Barriers and Facilitators to Engagement and Retention in Care among Transgender Women Living with Human Immunodeficiency Virus

Background

Transgender women have 49 times the odds of human immunodeficiency virus (HIV) infection compared to other groups, yet they are disproportionately underserved by current treatment efforts.

Purpose

This study aimed to examine culturally unique barriers and facilitators to engagement and retention in HIV care and strengthen efforts to mitigate health disparities, guided by the Models of Gender Affirmation and Health Care Empowerment.

Methods

Through 20 interviews and five focus groups (n?=?38), transgender women living with HIV discussed their experiences and life contexts of engagement in and adherence to HIV care and treatment.

Results

Our participants faced substantial challenges to adhering to HIV care and treatment, including avoidance of healthcare due to stigma and past negative experiences, prioritization of hormone therapy, and concerns about adverse interactions between antiretroviral treatment for HIV and hormone therapy. Receiving culturally competent, transgender-sensitive healthcare was a powerful facilitator of healthcare empowerment.

Conclusions

Recommendations are offered to inform intervention research and guide providers, emphasizing gender affirming HIV care that integrates transition-related healthcare needs.     

Enhanced repertoire of brain dynamical states during the psychedelic experience

The study of rapid changes in brain dynamics and functional connectivity (FC) is of increasing interest in neuroimaging. Brain states departing from normal waking consciousness are expected to be accompanied by alterations in the aforementioned dynamics. In particular, the psychedelic experience produced by psilocybin (a substance found in “magic mushrooms”) is characterized by unconstrained cognition and profound alterations in the perception of time, space and selfhood. Considering the spontaneous and subjective manifestation of these effects, we hypothesize that neural correlates of the psychedelic experience can be found in the dynamics and variability of spontaneous brain activity fluctuations and connectivity, measurable with functional Magnetic Resonance Imaging (fMRI). Fifteen healthy subjects were scanned before, during and after intravenous infusion of psilocybin and an inert placebo. Blood‐Oxygen Level Dependent (BOLD) temporal variability was assessed computing the variance and total spectral power, resulting in increased signal variability bilaterally in the hippocampi and anterior cingulate cortex. Changes in BOLD signal spectral behavior (including spectral scaling exponents) affected exclusively higher brain systems such as the default mode, executive control, and dorsal attention networks. A novel framework enabled us to track different connectivity states explored by the brain during rest. This approach revealed a wider repertoire of connectivity states post‐psilocybin than during control conditions. Together, the present results provide a comprehensive account of the effects of psilocybin on dynamical behavior in the human brain at a macroscopic level and may have implications for our understanding of the unconstrained, hyper‐associative quality of consciousness in the psychedelic state. Hum Brain Mapp 35:5442–5456, 2014. © 2014 Wiley Periodicals, Inc .     

Using Protamine Can Significantly Reduce the Incidence of Bleeding Complications after Carotid Endarterectomy without Increasing the Risk of Ischemic Cerebral Events

Background

Controversy persists regarding the use of protamine sulfate (PS) during carotid endarterectomy (CEA), chiefly because of conflicting experiences reporting both less bleeding and a higher stroke risk. The goal of the present study was to test the hypothesis that reversing heparin with PS after CEA significantly reduces the incidence of bleeding complications without increasing the risk of postoperative stroke.

Methods

From January 2010 to December 2012 all consecutive patients undergoing CEA under general anesthesia at our institution received 5,000 U of heparin prior to carotid clamping, which was partially (half-dose) reversed with PS 25 mg immediately after declamping (group I). Heparinization had never been reversed with PS in earlier CEAs performed from 1998 to 2009 at the same institution (group II). All patients were assessed preoperatively and postoperatively by a neurologist, and cerebral magnetic resonance imaging was performed in all group I patients to exclude any silent cerebral infarction. End points of the study were bleeding complications, perioperative (30-day) stroke, and death.

Results

Overall, 219 CEAs (201 patients) were performed in group I, and 1,458 CEAs (1,294 patients) in group II. Demographics, risk factors, and preoperative antiplatelet medication were comparable in the two groups. The incidence of adverse events (group I vs group II) was as follows: stroke (0 vs 0.5 % [8/1,458], p = 0.27); death (0 vs 0 %); neck bleeding (0 vs 8.2 % [120/1,458], p < 0.001).

Conclusions

The results of the present study demonstrate that (1) partially neutralizing heparin with PS after CEA can significantly reduce the risk of bleeding complications, and (2) there is no association between the administration of PS and the incidence of postoperative stroke.