Salt-tolerant cation exchange HD-Sb hydrogel membrane: mAb purification performance in flowthrough mode

Development of Protein A based purification platforms have simplified the downstream processing of monoclonal antibodies (mAb), the largest component of biopharmaceuticals. The ever increasing titer of the cell culture process is putting more pressure on the downstream process to further increase its productivity. The classical Protein A based mAb purification platform consists of two polishing steps, bind and elute cation-exchanger and flowthrough anion-exchanger. Cation-exchange chromatography is very efficient at the separation of HCP, leached Protein A and product-related impurities such as aggregates and fragments in bind and elute mode. However, anion-exchange chromatography is a proven technology to remove DNA, viruses, endotoxins and HCP in flowthrough mode. This study compares bind and elute mAb purification performance with that in flowthrough mode for the Natrix HD-Sb hydrogel membrane. Natrix HD-Sb is a salt-tolerant strong cation-exchange membrane augmented with hydrophobic butyl groups. This study demonstrates the effectiveness of Natrix HD-Sb chemistry in removing aggregates and HCP from challenging feed at high load with significant improvement in productivity and simplicity. The flowthrough separation performance of Natrix HD-Sb at neutral pH will be highlighted to show the potential of having tandem polishing steps (cation-exchange → anion-exchange) without needing any pH or conductivity adjustment. This tandem membrane approach has the potential for streamlining the downstream process for increased productivity & process efficiency

Hypertrophic cardiomyopathy-septal perforator arteries doppler flow dynamics

Background:Patients with hypertrophic cardiomyopathy (HCM) have been shown to exhibit abnormal diastolic vessel flow; however, flow pattern profiles and their possible association with different grades of diastolic dysfunction have not been studied. Color Doppler 2D echocardiography permits visualization of the septal perforator arteries, and pulsed-wave Doppler allows recording of diastolic septal artery flow (SAF). Through routine visualization of the septal perforator arteries and acquisition of SAF, we noticed three patterns of SAF in patients with HCM. In this study, we aimed to assess the feasibility of the acquisition of SAF and to describe types of SAF in an HCM cohort and their associations with diastolic function. Methods:We reviewed 2D echocardiograms and the electronic records of 108 patients with HCM in whom septal artery color and spectral Doppler had been performed. The peak diastolic and end-diastolic velocities, diastolic slope, diastolic flow time velocity integral, and systolic flow reversal of the septal perforator arteries were recorded with pulsed-wave Doppler. Echocardiographic and clinical characteristics were analyzed. Results:A reproducible pulsed-wave Doppler tracing was recorded in 54% of patients with HCM. Three distinct patterns of SAF were identified: Type 1-smooth, linear holodiastolic velocity decrease, Type 2-with presence of an atrial dip, and Type 3-biphasic velocity decrease with an early, rapid diastolic slope and a mid-to-late gentle slope. These three SAFs correlated with different grades of diastolic dysfunction. Conclusion:SAF could be detected in more than 50% of patients with HCM. Three distinct types of SAF were identified, correlating with different grades of diastolic dysfunction. These three types of SAF can provide additional information about left ventricular end-diastolic pressure and diastolic function in patients with HCM in whom diastolic function may be difficult to determine

Suture closure AFtEr large bore vein access (SAFE-VEIN): A randomized, prospective study of the efficacy and safety of venous closure device

Background: Perclose ProGlide (PPG) Suture-Mediated Closure System™ is safe and can reduce time to hemostasis following procedures requiring arterial access. Aims: We aimed to compare PPG to figure of 8 suture in patients who underwent interventional catheter procedures requiring large bore venous access (LBVA) (≥13 French). Methods: In this physician-initiated, randomized, single-center study [clinicaltrials.gov ID: NCT04632641 ], single-stick venous access was obtained under ultrasound guidance. Eligible patients were randomized 1:1, and 100 subjects received allocated treatment to either PPG (n = 47) or figure of 8 suture (n = 53). No femoral arterial access was used in any patient. Primary outcomes were time to achieve hemostasis (TTH) and time to ambulation (TTA). Secondary outcomes were time to discharge (TTD) and vascular-related complications and mortality. Wilcoxon rank-sum test was used to compare TTH, TTA, and TTD. Results: TTH (minutes) was significantly lower in PPG versus figure of 8 suture [median, (Q1, Q3)] [7 (2,10) vs. 11 (10,15) respectively, p \u3c 0.001]. TTA (minutes) was significantly lower in PPG compared to figure of 8 suture [322 (246,452) vs. 403 (353, 633) respectively, p = 0.005]. TTD (minutes) was not significantly different between the PPG and figure of 8 suture arms [1257 (1081, 1544) vs. 1338 (1171,1435), p = 0.650]. There was no difference in minor bleeding or access site hematomas between both arms. No other vascular complications or mortality were reported. Conclusion: PPG use had lower TTH and TTA than figure of 8 suture in a population of patients receiving LBVA procedures. This may encourage same-day discharge in these patients