Stereochemistry of the Menthyl Grignard Reagent: Generation, Composition, Dynamics, and Reactions with Electrophiles.

Menthyl Grignard reagent 1 from either menthyl chloride (2) or neomenthyl chloride (3) consists of menthylmagnesium chloride (1a), neomenthylmagnesium chloride (1b), trans- p-menthane (4), 2-menthene (8), 3-menthene (9), and Wurtz coupling products including symmetrical bimenthyl 13. The diastereomeric ratio 1a/1b was determined in situ by 13C NMR or after D2O quenching by 2H NMR analysis. Hydrolysis of the C-Mg bond proceeds with retention of configuration at C-1. The kinetic ratio 1a/1b from Grignard reagent generation (dr 59:41 at 50 °C in THF) is close to the thermodynamic ratio (56:44 at 50 °C in THF). Carboxylation of 1 at -78 °C separates diastereomers 1a/b to give the anion of menthanecarboxylic acid (19) from 1a, which combines with unreactive 1b to give neomenthylmagnesium menthanecarboxylate (1bI). The kinetics of epimerization for the menthyl/neomenthylmagnesium system was analyzed (Δ H⧧ = 98.5 kJ/mol, Δ S⧧ = -113 J/mol·K for 1bI → 1aI). Reactions of 1 with phosphorus electrophiles proceed stereoconvergently at C-1 of 1a/b to give predominantly menthyl-configured substitution products: PCl3 and 2 equiv of 1 give Men2PCl (6), which hydrolyzes to dimenthylphosphine P-oxide (7), whereas Ph2PCl with 1 equiv of 1 gave P-menthyldiphenylphosphine oxide (27) after workup in air.

Enhanced Visualization: From Intraoperative Tissue Differentiation to Augmented Reality.

BACKGROUND: Optimal visualization of the operative field and methods that additionally provide supportive optical information form the basis for target-directed and successful surgery. This article strives to give an overview of current enhanced visualization techniques in visceral surgery and to highlight future developments. METHODS: The article was written as a comprehensive review on this topic and is based on a MEDLINE search and ongoing research from our own group and from other working groups. RESULTS: Various techniques for enhanced visualization are described comprising augmented reality, unspecific and targeted staining methods, and optical modalities such as narrow-band imaging. All facilitate our surgical performance; however, due to missing randomized controlled studies for most of the innovations reported on, the available evidence is low. CONCLUSION: Many new visualization technologies are emerging with the aim to improve our perception of the surgical field leading to less invasive, target-oriented, and elegant treatment forms that are of significant benefit to our patients.

Surgical data processing for smart intraoperative assistance systems.

Different components of the newly defined field of surgical data science have been under research at our groups for more than a decade now. In this paper, we describe our sensor-driven approaches to workflow recognition without the need for explicit models, and our current aim is to apply this knowledge to enable context-aware surgical assistance systems, such as a unified surgical display and robotic assistance systems. The methods we evaluated over time include dynamic time warping, hidden Markov models, random forests, and recently deep neural networks, specifically convolutional neural networks.

Implementing an intensified antibiotic stewardship programme targeting daptomycin use in orthopaedic surgery: a cost-benefit analysis from the hospital perspective.

BACKGROUND: Hospital antibiotic stewardship (ABS) programmes offer several evidence-based tools to control prescription rates of antibiotics in different settings, influence the incidence of nosocomial infections and to contain the development of multi-drug-resistant bacteria. In the context of endoprosthetic surgery, however, knowledge of core antibiotic stewardship strategies, comparisons of costs and benefits of hospital ABS programmes are still lacking. MATERIALS AND METHODS: We identified a high daptomycin use for the treatment of methicillin-sensitive staphylococcal infections as a potential target for our ABS intervention. In addition, we endorsed periprosthetic tissue cultures for the diagnosis of PJI. Monthly antibiotic use data were obtained from the hospital pharmacy and were expressed as WHO-ATC defined daily doses (DDD) and dose definitions adapted to local guidelines (recommended daily doses, RDD), normalized per 1000 patient days. The pre-intervention period was defined from February 2012 through January 2014 (24 months). The post-intervention period included monthly time points from February 2014 to April 2015 (15 months). For a basic cost-benefit analysis from the hospital perspective, three cost drivers were taken into account: (1) the cost savings due to changes in antimicrobial prescribing; (2) costs associated with the increase in the number of cultured tissue samples, and (3) the appointment of an infectious disease consultant. Interrupted time-series analysis (ITS) was applied. RESULTS: Descriptive analysis of the usage data showed a decline in overall use of anti-infective substances in the post-intervention period (334.9 vs. 221.4 RDDs/1000 patient days). The drug use density of daptomycin dropped by -75 % (51.7 vs. 12.9 RDD/1000 patient days), whereas the utilization of narrow-spectrum penicillins, in particular flucloxacillin, increased from 13.8 to 33.6 RDDs/1000 patient days. ITS analysis of the consumption dataset showed significant level changes for overall prescriptions, as well as for daptomycin (p < 0.001) and for narrow-spectrum penicillins (p = 0.001). The total costs of antibiotic consumption decreased by an estimated € 4563 per month (p < 0.001), and around 90 % of these savings were linked to a decrease in daptomycin consumption. Overall, the antibiotic stewardship programme was beneficial, as monthly cost savings of € 2575 (p = 0.005) were achieved. INTERPRETATION: In this example of large endoprosthetic surgery department in a community-based hospital, the applied hospital ABS programme targeting daptomycin use has shown to be feasible, effective and beneficial compared to no intervention.

What Do We Really Need? Visions of an Ideal Human-Machine Interface for NOTES Mechatronic Support Systems From the View of Surgeons, Gastroenterologists, and Medical Engineers.

PURPOSE: To investigate why natural orifice translumenal endoscopic surgery (NOTES) has not yet become widely accepted and to prove whether the main reason is still the lack of appropriate platforms due to the deficiency of applicable interfaces. METHODS: To assess expectations of a suitable interface design, we performed a survey on human-machine interfaces for NOTES mechatronic support systems among surgeons, gastroenterologists, and medical engineers. Of 120 distributed questionnaires, each consisting of 14 distinct questions, 100 (83%) were eligible for analysis. RESULTS: A mechatronic platform for NOTES was considered "important" by 71% of surgeons, 83% of gastroenterologist,s and 56% of medical engineers. "Intuitivity" and "simple to use" were the most favored aspects (33% to 51%). Haptic feedback was considered "important" by 70% of participants. In all, 53% of surgeons, 50% of gastroenterologists, and 33% of medical engineers already had experience with NOTES platforms or other surgical robots; however, current interfaces only met expectations in just more than 50%. Whereas surgeons did not favor a certain working posture, gastroenterologists and medical engineers preferred a sitting position. Three-dimensional visualization was generally considered "nice to have" (67% to 72%); however, for 26% of surgeons, 17% of gastroenterologists, and 7% of medical engineers it did not matter (P = 0.018). CONCLUSION: Requests and expectations of human-machine interfaces for NOTES seem to be generally similar for surgeons, gastroenterologist, and medical engineers. Consensus exists on the importance of developing interfaces that should be both intuitive and simple to use, are similar to preexisting familiar instruments, and exceed current available systems.

Reliability of sensor-based real-time workflow recognition in laparoscopic cholecystectomy.

PURPOSE: Laparoscopic cholecystectomy is a very common minimally invasive surgical procedure that may be improved by autonomous or cooperative assistance support systems. Model-based surgery with a precise definition of distinct procedural tasks (PT) of the operation was implemented and tested to depict and analyze the process of this procedure. METHODS: Reliability of real-time workflow recognition in laparoscopic cholecystectomy ([Formula: see text] cases) was evaluated by continuous sensor-based data acquisition. Ten PTs were defined including begin/end preparation calots' triangle, clipping/cutting cystic artery and duct, begin/end gallbladder dissection, begin/end hemostasis, gallbladder removal, and end of operation. Data acquisition was achieved with continuous instrument detection, room/table light status, intra-abdominal pressure, table tilt, irrigation/aspiration volume and coagulation/cutting current application. Two independent observers recorded start and endpoint of each step by analysis of the sensor data. The data were cross-checked with laparoscopic video recordings serving as gold standard for PT identification. RESULTS: Bland-Altman analysis revealed for 95% of cases a difference of annotation results within the limits of agreement ranging from [Formula: see text]309 s (PT 7) to +368 s (PT 5). Laparoscopic video and sensor data matched to a greater or lesser extent within the different procedural tasks. In the majority of cases, the observer results exceeded those obtained from the laparoscopic video. Empirical knowledge was required to detect phase transit. CONCLUSIONS: A set of sensors used to monitor laparoscopic cholecystectomy procedures was sufficient to enable expert observers to reliably identify each PT. In the future, computer systems may automate the task identification process provided a more robust data inflow is available.