Histologic Features with Predictive Value for Outcome of Patients with Ulcerative Colitis

Ulcerative colitis is an inflammatory bowel disease with variable evolution, in which is difficult to establish patient’s outcome. Histology is an important part of diagnosis of ulcerative colitis and has an increasing role in patients’ management, since increasingly more histologic features with predictive value are being identified and validated. This chapter presents the most important histologic prognostic factors that should be included in histologic reports of patients with ulcerative colitis. Basal plasmacytosis and histologic healing are the most significant validated factors of prognosis in ulcerative colitis, while dysplasia is important since colorectal carcinoma is a severe complication of the disease

Direct isolation of small extracellular vesicles from human blood using viscoelastic microfluidics

Small extracellular vesicles (sEVs; <200 nm) that contain lipids, nucleic acids, and proteins are considered promising biomarkers for a wide variety of diseases. Conventional methods for sEV isolation from blood are incompatible with routine clinical workflows, significantly hampering the utilization of blood-derived sEVs in clinical settings. Here, we present a simple, viscoelastic-based microfluidic platform for label-free isolation of sEVs from human blood. The separation performance of the device is assessed by isolating fluorescent sEVs from whole blood, demonstrating purities and recovery rates of over 97 and 87%, respectively. Significantly, our viscoelastic-based microfluidic method also provides for a remarkable increase in sEV yield compared to gold-standard ultracentrifugation, with proteomic profiles of blood-derived sEVs purified by both methods showing similar protein compositions. To demonstrate the clinical utility of the approach, we isolate sEVs from blood samples of 20 patients with cancer and 20 healthy donors, demonstrating that elevated sEV concentrations can be observed in blood derived from patients with cancer

Oligohydramnios: A review of etiology and management options

Oligohydramnios is both a consequence of fetal malformations and of uteroplacental insufficiency. Its existence is associated with a high rate of both antepartum and intrapartum complications. It is vital that its occurrence is detected as early as possible so that we can manage it correctly. The main causes of its occurrence are identified and described in this review. The management of oligohydramnios is most often expectant, the timing of delivery also being determined by Doppler examination and changes in parameters measuring fetal growth and development

Open Problems in Extracellular RNA Data Analysis: Insights From an ERCC Online Workshop.

We now know RNA can survive the harsh environment of biofluids when encapsulated in vesicles or by associating with lipoproteins or RNA binding proteins. These extracellular RNA (exRNA) play a role in intercellular signaling, serve as biomarkers of disease, and form the basis of new strategies for disease treatment. The Extracellular RNA Communication Consortium (ERCC) hosted a two-day online workshop (April 19-20, 2021) on the unique challenges of exRNA data analysis. The goal was to foster an open dialog about best practices and discuss open problems in the field, focusing initially on small exRNA sequencing data. Video recordings of workshop presentations and discussions are available (https://exRNA.org/exRNAdata2021-videos/). There were three target audiences: experimentalists who generate exRNA sequencing data, computational and data scientists who work with those groups to analyze their data, and experimental and data scientists new to the field. Here we summarize issues explored during the workshop, including progress on an effort to develop an exRNA data analysis challenge to engage the community in solving some of these open problems

Right ventricle to pulmonary artery coupling after transcatheter aortic valve implantation—Determinant factors and prognostic impact

IntroductionRight ventricular (RV) dysfunction and pulmonary hypertension (PH) have been previously associated with unfavorable outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI), but little is known about the effect of right ventricle (RV) to pulmonary artery (PA) coupling. Our study aimed to evaluate the determinant factors and the prognostic value of RV-PA coupling in patients undergoing TAVI.MethodsOne hundred sixty consecutive patients with severe AS were prospectively enrolled, between September 2018 and May 2020. They underwent a comprehensive echocardiogram before and 30 days after TAVI, including speckle tracking echocardiography (STE) for myocardial deformation analysis of the left ventricle (LV), left atrium (LA), and RV function. Complete data on myocardial deformation was available in 132 patients (76.6 ± 7.5 years, 52.5% men) who formed the final study population. The ratio of RV free wall longitudinal strain (RV-FWLS) to PA systolic pressure (PASP) was used as an estimate of RV-PA coupling. Patients were analyzed according to baseline RV-FWLS/PASP cut-off point, determined through time-dependent ROC curve analysis, as follows: normal RV-PA coupling group (RV-FWLS/PASP ≥0.63, n = 65) and impaired RV-PA coupling group (RV-FWLS/PASP &lt; 0.63, n = 67).ResultsA significant improvement of RV-PA coupling was observed early after TAVI (0.75 ± 0.3 vs. 0.64 ± 0.3 before TAVI, p &lt; 0.001), mainly due to PASP decrease (p &lt; 0.001). LA global longitudinal strain (LA-GLS) is an independent predictor of RV-PA coupling impairment before and after TAVI (OR = 0.837, p &lt; 0.001, OR = 0.848, p &lt; 0.001, respectively), while RV diameter is an independent predictor of persistent RV-PA coupling impairment after TAVI (OR = 1.174, p = 0.002). Impaired RV-PA coupling was associated with a worse survival rate (66.3% vs. 94.9%, p-value &lt; 0.001) and emerged as an independent predictor of mortality (HR = 5.97, CI = 1.44–24.8, p = 0.014) and of the composite endpoint of death and rehospitalization (HR = 4.14, CI = 1.37–12.5, p = 0.012).ConclusionOur results confirm that relief of aortic valve obstruction has beneficial effects on the baseline RV-PA coupling, and they occur early after TAVI. Despite significant improvement in LV, LA, and RV function after TAVI, RV-PA coupling remains impaired in some patients, it is mainly related to persistent pulmonary hypertension and is associated with adverse outcomes

Biogenesis, delivery, and function of extracellular RNA

The Extracellular RNA (exRNA) Communication Consortium was launched by the National Institutes of Health to focus on the extent to which RNA might function in a non-cell-autonomous manner. With the availability of increasingly sensitive tools, small amounts of RNA can be detected in serum, plasma, and other bodily fluids. The exact mechanism(s) by which RNA can be secreted from cells and the mechanisms for the delivery and uptake by recipient cells remain to be determined. This review will summarize current knowledge about the biogenesis and delivery of exRNA and outline projects seeking to understand the functional impact of exRNA

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Obstacles and opportunities in the functional analysis of extracellular vesicle RNA - An ISEV position paper

The release of RNA-containing extracellular vesicles (EV) into the extracellular milieu has been demonstrated in a multitude of different in vitro cell systems and in a variety of body fluids. RNA-containing EV are in the limelight for their capacity to communicate genetically encoded messages to other cells, their suitability as candidate biomarkers for diseases, and their use as therapeutic agents. Although EV-RNA has attracted enormous interest from basic researchers, clinicians, and industry, we currently have limited knowledge on which mechanisms drive and regulate RNA incorporation into EV and on how RNAencoded messages affect signalling processes in EV-targeted cells. Moreover, EV-RNA research faces various technical challenges, such as standardisation of EV isolationmethods, optimisation of methodologies to isolate and characteriseminute quantities of RNA found in EV, and development of approaches to demonstrate functional transfer of EV-RNA in vivo. These topics were discussed at the 2015 EV-RNA workshop of the International Society for Extracellular Vesicles. This position paper was written by the participants of the workshop not only to give an overview of the current state of knowledge in the field, but also to clarify that our incomplete knowledge – of the nature of EV(-RNA)s and of how to effectively and reliably study them – currently prohibits the implementation of gold standards in EV-RNA research. In addition, this paper creates awareness of possibilities and limitations of currently used strategies to investigate EV-RNA and calls for caution in interpretation of the obtained data