Hemostatic efficacy of an advanced bipolar sealer in open gynecologic, thoracic, and colectomy procedures: A prospective cohort study

Background An advanced bipolar (ABP) tissue sealer designed for division of major vessels in open procedures was evaluated in a prospective post-market study. The objective was to provide clinical data for assessment of vessel transection, hemostatic performance and ease of use of the ABP device during open colectomy, gynecologic, and thoracic operations. Materials and methods The ABP test device was used in colectomy (n = 36), gynecologic (n = 44), and thoracic (n = 21) procedure groups. Vessels transected with the ABP device were graded intraoperatively on a hemostasis scale of 1–4, defined as follows: Grade1, no bleeding; Grade 2, minor bleeding with no intervention; Grade 3, minor bleeding requiring touchup with the test device or monopolar cautery; and Grade 4, significant bleeding requiring intervention with any additional hemostatic product. The primary performance measure was the percentage of vessels that achieved hemostasis grades ≤3. The primary safety endpoint was the summarization of all ABP device-related adverse events (AEs). Results For all three procedure groups together, 302 (96.2%) of 314 total vessel transections were scored as hemostasis grades ≤ 3, including 270 (86.0%) that were rated Grade 1. Twelve transections (3.8%) were Grade 4, which included 9 vessels transected in the gynecologic group and 3 in the thoracic group. Three subjects experienced a total of 4 device-related AEs, consisting of hematoma, hypotension, procedural pain, and superficial thermal burn. All 4 device-related AEs were mild in severity. Conclusion The advanced bipolar device exhibited effective hemostasis, an acceptable safety profile, and ease of use during colectomy, thoracic, and gynecologic procedures

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Phospholamban overexpression in rabbit ventricular myocytes does not alter sarcoplasmic reticulum Ca transport

Phospholamban has been suggested to be a key regulator of cardiac sarcoplasmic reticulum (SR) Ca cycling and contractility and a potential therapeutic target in restoring the depressed Ca cycling in failing hearts. Our understanding of the function of phospholamban stems primarily from studies in genetically altered mouse models. To evaluate the significance of this protein in larger mammalian species, which exhibit Ca cycling properties similar to humans, we overexpressed phospholamban in adult rabbit cardiomyocytes. Adenoviral-mediated gene transfer, at high multiplicities of infection, resulted in an insignificant 1.22-fold overexpression of phospholamban. There were no effects on twitch Ca-transient amplitude or decay under basal or isoproterenol-stimulated conditions. Furthermore, the SR Ca load and Na/Ca exchanger function were not altered. These apparent differences between phospholamban overexpression in rabbit compared with previous findings in the mouse may be due to a significantly higher (1.5-fold) endogenous phospholamban-to-sarco(endo)plasmic reticulum Ca-ATPase (SERCA) 2a ratio and potential functional saturation of SERCA2a by phospholamban in rabbit cardiomyocytes. The findings suggest that important species-dependent differences in phospholamban regulation of SERCA2a occur. In larger mammals, a higher fraction of SERCA2a pumps are regulated by phospholamban, and this may influence therapeutic strategies to enhance cardiac contractility and functional cardiac reserve

Laparoscopic Roux-en-Y gastric bypass for excess weight and diabetes: a multicenter retrospective cohort study in China

Aim: The aims of this study were to better understand the outcomes of Roux-en-Y gastric bypass (RYGB) surgery in patients across multiple hospitals in China along with patients with type 2 diabetes mellitus (T2DM) and to explore the potential preoperative predictors of diabetes outcomes after RYGB.Methods: This was a retrospective cohort study in Chinese patients who underwent laparoscopic RYGB at five Chinese hospitals from April 2009 to December 2014 and returned for follow-up approximately one-year post-surgery. The STROCSS guideline checklist was applied.Results: In total, 130 patients underwent RYGB: 85 males and 45 females; age, 43.4 ± 11.3 years; and preoperative body mass index (BMI), 33.1 ± 9.0 kg/m2. Of those, 103 (79.2%) had T2DM duration of 6.6 ± 4.7 years and pre-RYGB HbA1c of 8.1 ± 1.9%. Among the patients with T2DM, glycemic control (HbA1c < 7.0%) increased from 28.7% before surgery to 79.3% at 12 months post-procedure, with a concurrent reduction in the use of anti-hyperglycemic agents, including a reduction in insulin requirement from 55.4% to 27.0%. The percentage of excess weight loss was -42.8 ± 44.2%. Among 71 patients with T2DM and data about remission status, 14 (19.7%) achieved T2DM remission at 12 months post-surgery. Age and duration of T2DM were lower in the remission group, while baseline BMI and weight were higher compared with the non-remission group.Conclusion: RYGB may be effective for weight loss and T2DM control in Chinese patients, and outcomes are consistent with the literature in Western populations. Younger patients with T2DM and with a higher BMI pre-surgery and shorter duration of T2DM were more likely to achieve T2DM remission

Assessment of a circular powered stapler for creation of anastomosis in left-sided colorectal surgery: a prospective cohort study.

BACKGROUND Circular staplers perform a critical function for creation of anastomoses in colorectal surgeries. Powered stapling systems allow for reduced force required by surgeons to fire the device and may provide advantages for creating a secure anastomosis. The objective of this study was to evaluate the clinical performance of a novel circular powered stapler in a post-market setting, during left-sided colectomy procedures. MATERIALS AND METHODS Consecutive subjects underwent left-sided colorectal resections that included anastomosis performed with the ECHELON CIRCULAR™ Powered Stapler (ECP). The primary endpoint was the frequency in which a stapler performance issue was observed. Secondary endpoints included evaluation of ease of use of the device via a surgeon satisfaction questionnaire, and monitoring/recording of procedure-related adverse events (AEs). RESULTS A total of 168 anastomoses were performed with the ECP. Surgical approaches included robotic-assisted (n= 74, 44.0%), laparoscopic (n=71, 42.3%), open (n=20, 11.9%), and hand-assisted minimally invasive (n=3, 1.8%) procedures. There were 22 occurrences of device performance issues in 20 (11.9%) subjects during surgery. No positive intraoperative leak tests were observed, and only 1 issue was related to a procedure-related AE or surgical complication, which was an instance of incomplete surgical donut necessitating re-anastomosis. Postoperative anastomotic leaks were experienced in 4 (2.4%) subjects. Clavien-Dindo classification of all AEs indicated that 92.0% were Grades I or II. Participating surgeons rated the ECP as easier to use compared to previously used manual circular staplers in 85.7% of procedures. CONCLUSION The circular powered stapler exhibited few clinically relevant performance issues, an overall favorable safety profile, and ease of use for creation of left-sided colon anastomoses