The Effects of Salt Concentration on the Rejection of Pharmaceutically Active Compounds by Nanofiltration Membranes

While traces of pharmaceuticals have been found in the environment, the pharmaceutical industry produces waste streams high in pharmaceutically active compounds concentration along with other components such as salts. This work investigated the removal of three common pharmaceuticals, carbamazepine, ibuprofen, and diclofenac, at concentrations found in the pharmaceutical industry, under different monovalent salt concentrations of sodium chloride using a commercially available nanofiltration membrane. The influence of a monovalent salt concentration and temperature on the removal were determined. Pharmaceutical rejection was found to be dependent on the compounds’ molecular weights, charge, and hydrophobicity. Diclofenac and ibuprofen rejections were found to be high (90-99%) and (85-96%) respectively, and the rejection increased with increasing salt concentration. Meanwhile, moderate retention values were found for the neutral carbamazepine (65-77%) and these values decreased with increasing salt concentration, and also decreased with increasing temperatures. A threshold salt concentration was found at which these effects were buffered or even reversed

Efficacy of High Temporal Frequency Photoacoustic Guidance of Laser Ablation Procedures

Inaccurate placement of the ablation catheter and the inability to monitor the real-time temperature within the tissue of interest such as veins curbs the treatment efficacy of laser ablation procedures during thermal therapies. Our previous studies have validated the efficacy of photoacoustic (PA) imaging during endovenous laser ablation (EVLA) procedures. However, the PA-guided therapies suffer from low temporal resolution, due to the low pulse repetition rates of pulsed lasers, which could cause a problem during fast catheter motion and rapid temperature changes. Herein, to enhance the accuracy and sensitivity for tracking the ablation catheter tip and temperature monitoring, we proposed to develop a high frame rate (500 Hz), combined ultrasound (US), and PA-guided ablation system. The proposed PA-guided ablation system was evaluated in a set of ex vivo tissue studies. The developed system provides a 2 ms temporal resolution for tracking and monitoring the ablation catheter tip\u27s location and temperature, which is 50 times higher temporal resolution compared to the previously proposed 10 Hz system. The proposed system also provided more accurate feedback about the temperature variations during rapid temperature increments of 10°C per 250 ms. The co-registered US and PA images have an imaging resolution of about 200 μm and a field of view of 45 × 40 mm(2). Tracking the ablation catheter tip in an excised tissue layer shows higher accuracy during a relatively fast catheter motion (0.5-3 mm/s). The fast US/PA-guided ablation system will potentially enhance the outcome of ablation procedures by providing location and temperature feedback

Photoacoustic-guided endovenous laser ablation: Characterization and in vivo canine study

Endovenous laser ablation (EVLA) is a minimally invasive surgical procedure, often guided by ultrasound (US) imaging, for treating venous insufficiencies. US imaging limitations in accurately visualizing the catheter and the lack of a temperature monitoring system can lead to sub-optimal outcomes. An integrated photoacoustic (PA)-guided EVLA system has been previously developed and reported to overcome the shortcomings of US-guided procedure. In this study, we further characterized the system and tested the in vivo utility. In addition, PA thermometry was further explored by compensating the variation of PA signal with temperature with respect to the temperature-dependent absorption of blood and water. In vivo imaging results indicated that the PA-guided EVLA system can provide high contrast and accurate images of the ablation catheter tip overlaid on US images of the background tissue. Additionally, absorption-compensated PA signal amplitudes over a relevant range of temperature were measured and demonstrated

Single-state Transcarotid Artery Revascularization Experience: Outcomes and Impact on Carotid Procedural and Operative Volumes

Objectives: Transcarotid artery revascularization (TCAR) is an emerging novel approach to carotid intervention, adopted and well-suited for high-risk patients. Our objective was to assess the outcomes of TCAR and determine its impact on the volume of carotid endarterectomy (CEA) and non-TCAR carotid artery stenting (CAS) in a single-state experience. Methods: A large statewide quality consortium registry was queried. The indications and outcomes of TCAR compared with CEA and non-TCAR CAS from January 2018 to October 2019 were reviewed. Non-TCAR CAS included transfemoral, transbrachial stenting and transcarotid stenting without the flow reversal technique. We also assessed the impact of TCAR on the trend of CEA and non-TCAR CAS performed, analyzing data from 2012 to 2019. Outcome comparisons were performed using the χ 2 and Mann-Whitney U tests, depending on the distribution of the outcomes. Results: A total of 438 TCARs were performed by 39 physicians in 16 hospitals; 60% of the patients were asymptomatic and 40% symptomatic. The TCAR indication was physiologic high risk for 369 patients (84%) and restenosis for 69 patients (16%), with most occurring after prior CEA (94%). Of the non-TCAR CAS cases, 94% were performed via transfemoral access. The patients undergoing non-TCAR CAS had the highest 30-day mortality ( P \u3c .001) and the highest incidence of 30-day new neurologic deficits ( P = .008) compared with the patients undergoing CEA and TCAR. CEA had the lowest myocardial infarction rate ( P = .015; Table). The number of TCAR procedures performed and the number of physicians and hospitals performing them increased during the 2-year period. Since the introduction of TCAR, no significant frequency decrease has occurred in the number of non-TCAR CAS or CEA cases by hospitals or physicians (Fig). However, a significant negative trend was found in the number of CEAs performed by physicians since 2012 ( P \u3c .001; Fig). Conclusions: TCAR is a safe method of carotid revascularization and is becoming an increasingly used method. TCAR has not affected the CEA hospital or physician volume since its introduction. CEA volumes and physician usage are declining, which could have future credentialing implications. In the present single-state experience, TCAR compared favorably with CEA and non-TCAR CAS might be less appealing because of its higher neurologic event rate

Incidence and prognosis of vascular complications after percutaneous placement of left ventricular assist device

OBJECTIVE: Mechanical assist devices have found an increasingly important role in high-risk interventional cardiac procedures. The Impella (Abiomed Inc, Danvers, Mass) is a percutaneous left ventricular assist device inserted through the femoral artery under fluoroscopic guidance and positioned in the left ventricular cavity. This study was undertaken to assess the incidence of vascular complications and associated morbidity and mortality that can occur with Impella placement. METHODS: We used a prospective database to review patients who underwent placement of an Impella left ventricular assist device in our tertiary referral center from July 2010 to December 2013. Patient demographics, comorbidities, interventional complications, and 30-day mortality were recorded. RESULTS: The study included 90 patients (60% male). Mean age was 66 years (range, 17-97 years). Hypertension was found in 69% of the patients, 37% were diabetic, 57% had a history of tobacco abuse, and 65% had chronic renal insufficiency. The median preprocedure cardiac ejection fraction was 30%. Most (87%) had undergone coronary artery intervention. Cardiogenic shock was documented in 67 patients (74%). The Impella was placed for an average of 1 day (range, 0-5 days). At least one vascular complication occurred in 15 patients (17%). Acute limb ischemia occurred in 12 patients; of whom four required an amputation and six required open or endovascular surgery. Other complications included groin hematomas and one pseudoaneurysm. All-patient 30-day mortality was 50%, which was not significantly associated with vascular complications. Female sex and cardiogenic shock at the time of insertion were associated with vascular complications (P = .043 and P = .018, respectfully). CONCLUSIONS: Vascular complications are common with placement of the Impella percutaneous left ventricular assist device (17%) and are related to emergency procedures. Vascular complications in this high-risk patient population frequently lead to withdrawal of care. These data provide quality improvement targets for left ventricular assist device programs

Experimental variables that affect human hepatocyte MV transduction in liver chimeric mice

Adeno-associated virus (AAV) vector serotypes vary in their ability to transduce hepatocytes from different species. Chimeric mouse models harboring human hepatocytes have shown translational promise for liver-directed gene therapies. However, many variables that influence human hepatocyte transduction and transgene expression in such models remain poorly defined. Here, we aimed to test whether three experimental conditions influence AAV transgene expression in immunodeficient, fumaryl-acetoactetate-hydrolase-deficient (Fah(-/-)) chimeric mice repopulated with primary human hepatocytes. We examined the effects of the murine liver injury cycle, human donor variability, and vector doses on hepatocyte transduction with various AAV serotypes expressing a green fluorescent protein (GFP). We determined that the timing of AAV vector challenge in the liver injury cycle resulted in up to 7-fold differences in the percentage of GFP expressing human hepatocytes. The GFP+ hepatocyte frequency varied 7-fold between human donors without, however, changing the relative transduction efficiency between serotypes for an individual donor. There was also a clear relationship between AAV vector doses and human hepatocyte transduction and transgene expression. We conclude that several experimental variables substantially affect human hepatocyte transduction in the Fah(-/-) chimera model, attention to which may improve reproducibility between findings from different laboratories

Acute effects of remote ischemic preconditioning on cutaneous microcirculation - a controlled prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Therapeutic strategies aiming to reduce ischemia/reperfusion injury by conditioning tissue tolerance against ischemia appear attractive not only from a scientific perspective, but also in clinics. Although previous studies indicate that remote ischemic intermittent preconditioning (RIPC) is a systemic phenomenon, only a few studies have focused on the elucidation of its mechanisms of action especially in the clinical setting. Therefore, the aim of this study is to evaluate the acute microcirculatory effects of remote ischemic preconditioning on a distinct cutaneous location at the lower extremity which is typically used as a harvesting site for free flap reconstructive surgery in a human in-vivo setting.</p> <p>Methods</p> <p>Microcirculatory data of 27 healthy subjects (25 males, age 24 ± 4 years, BMI 23.3) were evaluated continuously at the anterolateral aspect of the left thigh during RIPC using combined Laser-Doppler and photospectrometry (Oxygen-to-see, Lea Medizintechnik, Germany). After baseline microcirculatory measurement, remote ischemia was induced using a tourniquet on the contralateral upper arm for three cycles of 5 min.</p> <p>Results</p> <p>After RIPC, tissue oxygen saturation and capillary blood flow increased up to 29% and 35% during the third reperfusion phase versus baseline measurement, respectively (both p = 0.001). Postcapillary venous filling pressure decreased statistically significant by 16% during second reperfusion phase (p = 0.028).</p> <p>Conclusion</p> <p>Remote intermittent ischemic preconditioning affects cutaneous tissue oxygen saturation, arterial capillary blood flow and postcapillary venous filling pressure at a remote cutaneous location of the lower extremity. To what extent remote preconditioning might ameliorate reperfusion injury in soft tissue trauma or free flap transplantation further clinical trials have to evaluate.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01235286">NCT01235286</a></p

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701