Fluoroscopy Time as a New Predictor of Short-Term Outcomes after Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an almost totally cine-fluoroscopic guided procedure. The amount of radiation used during the procedure is strictly related to the fluoroscopy time (FT), that has already been demonstrated to be associated with outcomes and complexity of coronary procedures. The aim of our study is to demonstrate the relationship between FT and the short-term outcomes after TAVR defined by to the Valve Academic Research Consortium (VARC)-2 and -3 consensus documents. METHODS: After splitting 1797 consecutive patients into tertiles of FT, the composite endpoint early safety (ES) was adjudicated according to VARC-2 and VARC-3 definitions, whereas the composite endpoints device success (DS) and technical success (TS) according to VARC-3 criteria. RESULTS: The absence of all these outcomes (VARC-2 ES amd VARC-3 TS, DS, and ES) was significantly associated with longer FT: this association was independent from both intraprocedural complications and other intraprocedural factors linked to longer FT, and still persisted after propensity score matching analysis. Notwithstanding, after receiver operating characteristic analysis, FT had adequate diagnostic accuracy in identifying the absence of only VARC-3 TS and VARC-2 ES. CONCLUSION: Longer FT is related with periprocedural and short-term outcomes after the procedure, especially in those that are more challenging. A FT duration of more than 30 min has an adequate accuracy in identifying VARC-3 technical failure (TS and DS) and absence of VARC-2 ES, selecting patients who are likely to take advantage from more careful in-hospital follow-up.

CardioMotion: identification of functional and structural cardiotoxic liabilities in small molecules through brightfield kinetic imaging.

Cardiovascular toxicity is an important cause of drug failures in the later stages of drug development, early clinical safety assessment, and even postmarket withdrawals. Early-stage in vitro assessment of potential cardiovascular liabilities in the pharmaceutical industry involves assessment of interactions with cardiac ion channels, as well as induced pluripotent stem cell-derived cardiomyocyte-based functional assays, such as calcium flux and multielectrode-array assays. These methods are appropriate for the identification of acute functional cardiotoxicity but structural cardiotoxicity, which manifests effects after chronic exposure, is often only captured in vivo. CardioMotion is a novel, label-free, high throughput, in vitro assay and analysis pipeline which records and assesses the spontaneous beating of cardiomyocytes and identifies compounds which impact beating. This is achieved through the acquisition of brightfield images at a high framerate, combined with an optical flow-based python analysis pipeline which transforms the images into waveform data which are then parameterized. Validation of this assay with a large dataset showed that cardioactive compounds with diverse known direct functional and structural mechanisms-of-action on cardiomyocytes are identified (sensitivity = 72.9%), importantly, known structural cardiotoxins also disrupt cardiomyocyte beating (sensitivity = 86%) in this method. Furthermore, the CardioMotion method presents a high specificity of 82.5%.

Surgical Mortality Risk Scores in Transcatheter Aortic Valve Implantation: Is Their Early Predictive Value Still Strong?

BACKGROUND: Surgical mortality risk scores, even if not properly designed and rarely tested in the transcatheter aortic valve implantation (TAVI) setting, still guide the heart team in managing significant aortic stenosis. METHODS: After splitting 1763 consecutive patients retrospectively based on their mortality risk thresholds, the composite endpoint early safety (ES) was adjudicated according to Valve Academic Research Consortium (VARC)-2 and -3 consensus documents. RESULTS: ES incidence was higher if VARC-2 rather than VARC-3 defined. Despite only patients showing VARC-2 ES had significantly lower absolute values of all three main risk scores, these last still failed to foresee both VARC-2 and -3 ES in intermediate-risk patients. The receiver operating characteristic analysis also showed a significant correlation, but with poor diagnostic accuracy, among the three scores and only VARC-2 ES; moreover, the absence of VARC-2 ES and low-osmolar contrast media administration were identified as independent predictors of 1-year mortality and absence of VARC-3 ES, respectively. Finally, even a single complication included in the ES definition could significantly affect 1-year mortality. CONCLUSION: Currently, the most used mortality risk scores do not have adequate diagnostic accuracy in predicting ES after TAVI. The absence of VARC-2, instead of VARC-3, ES is an independent predictor of 1-year mortality.

Fe3O4@uio66 core-shell composite for detection of electrolyte leakage from lithium-ion batteries.

Fe3O4is an environmentally friendly gas sensing material with high response, but the cross-response to various analytes and poor thermal stability limit its practical applications. In this work, we prepared Fe3O4@uio66 core-shell composite via a facile method. The selective response to volatile organic compounds, especially to electrolyte vapors of lithium-ion batteries, as well as long-term stability of Fe3O4@uio66 has been dramatically enhanced compared to pure Fe3O4, due to the preconcentrator feature and thermal stability of the uio66 thin shell. Real-time detection of electrolyte leakage for an actual punctured lithium-ion battery was further demonstrated. The Fe3O4@uio66 sensor, after aging for 3 months, was able to detect the electrolyte leakage in 30 s, while the voltage of the punctured battery was maintained at the same level as that of a pristine battery over 6 h. This practical test results verified ability of the Fe3O4@uio66 sensor with long-term aging stability for hours of early safety warning of lithium-ion batteries.

Is Natural Orifice Specimen Extraction Surgery Really Safe in Radical Surgery for Colorectal Cancer?

Background: The main feature of natural orifice specimen extraction (NOSE) is its avoidance of an auxiliary abdominal incision. The safety of NOSE remains controversial. This study aimed to investigate the early safety of transanal NOSE in the treatment of sigmoid colon and upper rectal cancer from the follow aspects: clinical and pathological characteristics, inflammatory and immune indicators and postoperative complications. Methods: Data from 125 patients diagnosed with sigmoid colon, and upper rectal cancer by gastrointestinal surgery in the First Affiliated Hospital of Wannan Medical College from January 2017 to June 2020 were analyzed. Patients were assigned to two surgical groups: Conventional laparoscopic-assisted radical resection for CRC (CLA, 75cases) and laparoscopic-assisted radical resection for CRC with NOSE (La-NOSE, 50 cases). The following were compared: clinical and pathological characteristics; intraoperative, bacteriological, and oncological results; postoperative inflammation and immune response indexes. Bacteriological results were obtained by aerobic and anaerobic bacterial culture of peritoneal wash fluid and oncology results by cytological analysis of peritoneal wash liquid exudation. Inflammation indicators included postoperative C-reactive protein (CRP) and procalcitonin (PCT) trend reactions. The immune index was the level of postoperative T lymphocytes (CD3, CD4/CD8). All data were analyzed by using SPSS statistical version 18.0 for windows. Measurement data are presented as the means ± standard deviations, and two-group comparisons were performed using the t-test. Comparisons of count data were performed using the chi-square test. p <0.05 indicates that the difference was statistically significant. Results: The bacterial culture positive rate was not significant in the La-NOSE group (15/50 vs 19/75) than in the CLA group. The exfoliative cytology (EC) rate of the peritoneal wash fluid was 0 in both groups.The La-NOSE group had a significantly higher postoperative day 2(POD2) CRP and PCT level than the CLA group. The POD2 CD3 and CD4/CD8 levels were higher in the La-NOSE group than in the CLA group. There was no significant difference in the incidence of postoperative complications between the two groups (La-NOSE group vs CLA group: 3/50 vs 6/75) (p>0.05). Conclusions: Although the incidence of intra-abdominal contamination is high, it does not develop into a severe infectious disease, and does not lead to the implantation of free tumor cells into the abdominal cavity. Therefore, it is safe for the NOSE to treat colorectal cancer.

Prospective randomized study evaluating the effects of PerClot® (Polysaccharide Hemostatic System) application in patients with high bleeding risk undergoing cardiac rhythm device implantation.

BACKGROUND: Thus far, the topic hemostatic agent PerClot® is used for surgical procedures. Data about the use of PerClot® for cardiac-rhythm-devices (CRD) implantation are missing. The aim of this study was to evaluate the safety and efficacy of PerClot® in patients with high bleeding risk. METHODS AND RESULTS: In this prospective randomized study we planned to include 150 patients admitted for CRD-Implantation receiving anticoagulation and/or dual-antiplatelet-therapy. Participants were randomized to receive PerClot® versus standard-of-care. The primary endpoint was the incidence of pocket hematoma. Safety endpoint was pocket infection. After a planned safety-interim-analysis the study was terminated early because of safety concerns. 51 patients were included. The two groups were comparable with regard to age (73±11years vs. 74±10years; p=0.71), CHA2DS2VASc (3.6±1.5 vs. 4.0±1.5; p=0.27) and HASBLED-Score (2.4±1.1 vs. 2.5±1.0; p=0.98), CRD or procedure type, anticoagulant or anti-platelet therapy. The use of PerClot® resulted in a higher incidence of postoperative fever (7 (28%) vs. 0 (0%); p=0.004), higher C-Reactive Protein (66.1±50.5mg/l vs. 25.9±22.5mg/l; p=0.002); and higher postoperative white blood cell count (13.5±4.3/nl vs. 8.8±2.6/nl; p<0.001). Hematoma formation did not differ significantly (p=0.14). Reoperation was not necessary in any patient. CONCLUSION: This first randomized controlled study for the topical use of the hemostatic agent PerClot® in CRD implantation was terminated early by the safety monitoring board because of an augmented rate of fever and inflammatory markers in the PerClot® group. The addition of PerClot® does not suggest a benefit with regard to the frequency of pocket hematoma.

Editor's Highlight: Multiparametric Image Analysis of Rat Dorsal Root Ganglion Cultures to Evaluate Peripheral Neuropathy-Inducing Chemotherapeutics.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major, dose-limiting adverse effect experienced by cancer patients. Advancements in mechanism-based risk mitigation and effective treatments for CIPN can be aided by suitable in vitro assays. To this end, we developed a multiparametric morphology-centered rat dorsal root ganglion (DRG) assay. Morphologic alterations in subcellular structures of neurons and non-neurons were analyzed with an automated microscopy system. Stains for NeuN (a neuron-specific nuclear protein) and Tuj-1 (ß-III tubulin) were used to identify neuronal cell nuclei and neuronal cell bodies/neurites, respectively. Vimentin staining (a component of Schwann cell intermediate filaments) was used to label non-neuronal supporting cells. Nuclei that stained with DAPI, but lacked NeuN represented non-neuronal cells. Images were analyzed following 24 h of continuous exposure to CIPN-inducing agents and 72 h after drug removal to provide a dynamic measure of recovery from initial drug effects. Treatment with bortezomib, cisplatin, eribulin, paclitaxel or vincristine induced a dose-dependent loss of neurite/process areas, mimicking the 'dying back' degeneration of axons, a histopathological hallmark of clinical CIPN in vivo. The IC50 for neurite loss was within 3-fold of the maximal clinical exposure (Cmax) for all five CIPN-inducing drugs, but was >4- or ≥ 28-fold of the Cmax for 2 non-CIPN-inducing agents. Compound-specific effects, eg, neurite fragmentation by cisplatin or bortezomib and enlarged neuronal cell bodies by paclitaxel, were also observed. Collectively, these results support the use of a quantitative, morphologic evaluation and a DRG cell culture model to inform risk and examine mechanisms of CIPN.