Background Neuraxial anesthesia when compared with general anesthesia has shown to improve outcomes following lower extremity total joint arthroplasty. It is unclear whether these benefits are present in outpatient surgery given the selection of healthier patients. Objective To compare the effects of neuraxial versus general anesthesia on outcomes following ambulatory hip and knee arthroplasty. Methods Multicentered retrospective cohort study in ambulatory hip or knee arthroplasty patients between January 2017 and December 2019. Primary endpoint examined 30-day major postoperative complications (mortality, myocardial infarction, deep venous thromboembolism, pulmonary embolism, stroke, and acute renal failure). Results Of 11 523 eligible patients identified, 10 003 received neuraxial anesthesia, while 1520 received general anesthesia. 30-day major complications did not differ between neuraxial anesthesia and general anesthesia groups (1.8% vs 2.3%; aOR=0.85, CI: 0.56 to 1.27, p=0.39). There was no difference in 30-day minor complications (surgical site infection, pneumonia, urinary tract infection; 3.3% vs 4.1%; aOR=0.83, CI: 0.62 to 1.14, p=0.23). The neuraxial group demonstrated reduced pain and analgesia requirements and had less postoperative nausea and vomiting (PONV). Median recovery room length of stay was shorter by 52 min in the general anesthesia group, but these patients were more likely to fail same day discharge (33% vs 23.4%; p<0.01). Conclusion Anesthesia type was not associated with an increased risk for complications. However, neuraxial anesthesia improved outcomes that predict readiness for discharge: patients had less pain, required less opioids, and had a lower incidence of PONV, thus improving the rate of same day discharge. Trial registration number NCT04203732.

THE LOSS OF independence is one of the most devastating events that humans commonly face. In this issue of the Journal of Cardiothoracic and Vascular Anesthesia, Gosling et al.1 described a new instrument for predicting the loss of ability to function independently after cardiac surgery with cardiopulmonary bypass. Numerous risk scores exist for predicting mortality after cardiac surgery, with the Society for Thoracic Surgery (STS) tool2 and the Euroscore3 being the most widely used. However, most patients undergo cardiac surgery hoping for a better quality of life.

The field of abdominal organ transplantation is multifaceted, with the clinician balancing recipient comorbidities, risks of the surgical procedure, and the pathophysiology of immunosuppression to ensure optimal outcomes. An underappreciated element throughout this process is acute pain management related to the surgical procedure. As the opioid epidemic continues to grow with increasing numbers of transplant candidates on opioids as well the increase in the development of enhanced recovery after surgery protocols, there is a need for greater focus on optimal postoperative pain control to minimize opioid use and improve outcomes. This review will summarize the physiology of acute pain in transplant recipients, assess the impact of opioid use on post-transplant outcomes, present evidence supporting nonopioid analgesia in transplant surgery, and briefly address the perioperative approach to the pretransplant recipient on opioids.

INTRODUCTION:Global data sharing is essential. This is the premise of the Academic Research Organization (ARO) Council, which was initiated in Japan in 2013 and has since been expanding throughout Asia and into Europe and the United States. The volume of data is growing exponentially, providing not only challenges but also the clear opportunity to understand and treat diseases in ways not previously considered. Harnessing the knowledge within the data in a successful way can provide researchers and clinicians with new ideas for therapies while avoiding repeats of failed experiments. This knowledge transfer from research into clinical care is at the heart of a learning health system. METHODS:The ARO Council wishes to form a worldwide complementary system for the benefit of all patients and investigators, catalyzing more efficient and innovative medical research processes. Thus, they have organized Global ARO Network Workshops to bring interested parties together, focusing on the aspects necessary to make such a global effort successful. One such workshop was held in Austin, Texas, in November 2017. Representatives from Japan, Taiwan, Singapore, Europe, and the United States reported on their efforts to encourage data sharing and to use research to inform care through learning health systems. RESULTS:This experience report summarizes presentations and discussions at the Global ARO Network Workshop held in November 2017 in Austin, TX, with representatives from Japan, Korea, Singapore, Taiwan, Europe, and the United States. Themes and recommendations to progress their efforts are explored. Standardization and harmonization are at the heart of these discussions to enable data sharing. In addition, the transformation of clinical research processes through disruptive innovation, while ensuring integrity and ethics, will be key to achieving the ARO Council goal to overcome diseases such that people not only live longer but also are healthier and happier as they age. CONCLUSIONS:The achievement of global learning health systems will require further exploration, consensus-building, funding aligned with incentives for data sharing, standardization, harmonization, and actions that support global interests for the benefit of patients.

The 61 CTSA Consortium sites are home to valuable programs and infrastructure supporting translational science and all are charged with ensuring that such investments translate quickly to improved clinical care. Catalog of Assets for Translational and Clinical Health Research (CATCHR) is the Consortium's effort to collect and make available information on programs and resources to maximize efficiency and facilitate collaborations. By capturing information on a broad range of assets supporting the entire clinical and translational research spectrum, CATCHR aims to provide the necessary infrastructure and processes to establish and maintain an open-access, searchable database of consortium resources to support multisite clinical and translational research studies. Data are collected using rigorous, defined methods, with the resulting information made visible through an integrated, searchable Web-based tool. Additional easy-to-use Web tools assist resource owners in validating and updating resource information over time. In this paper, we discuss the design and scope of the project, data collection methods, current results, and future plans for development and sustainability. With increasing pressure on research programs to avoid redundancy, CATCHR aims to make available information on programs and core facilities to maximize efficient use of resources.

e13066 Background: Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface-spreading malignancies in order to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage (PKA) of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) and intravenous fluid (IVF) administration, by affecting intravascular volume, would correlate with PKA. Methods: On an IRB-approved study, we collected blood and peritoneal perfusate from 13 patients undergoing HIPEC with a set dose of 100 mg cisplatin (n=4) or a BSA-based dose of 250 mg/m2 oxaliplatin (n=9), and measured Pt concentrations by Inductively Coupled Plasma Mass Spectrophotometry. Areas under concentration-time curves from 0-60 minutes (AUC0-60) were calculated by Trapezoidal Rule. PKA was calculated by (AUC0-60[peritoneal fluid]/AUC0-60[plasma]). Linear regression and Wilcoxon rank-sum test were performed using SAS. Results: Models with both BSA and IVF as predictors of PKA fit better than BSA alone for cisplatin (p=.022 vs. p=.076) but not for oxaliplatin (p=.119 vs. p=.037). The BSA and IVF model was a better fit for peritoneal cisplatin (p=.003) than for plasma cisplatin (p=.146). The BSA-only model was a better fit for plasma oxaliplatin (p=.013) than for peritoneal oxaliplatin (p=.778). There was no statistically-significant difference between the median PKA of cisplatin vs. oxaliplatin (p=.706). Conclusions: Our results suggest that BSA is a better PKA predictor than the compound’s diffusion properties. When a set drug dose is used, rather than a BSA-based dose, IVF is also an important predictor. This is likely due to HIPEC’s limited duration, thus the drug does not reach equilibrium between the peritoneal and vascular compartments. When monitoring the pharmacokinetic parameters of HIPEC administration, factors influencing intravascular volume, including BSA and IVF, should be considered. Maintaining intravascular volume repletion is a key strategy for maximizing PKA, and thereby minimizing systemic side effects due to HIPEC.

Hemicrania continua (HC) is an uncommon primary headache disorder in which the diagnosis centers on unilaterality and its absolute responsiveness to indomethacin. We describe 3 patients with a long standing history of headache diagnosed as hemicrania continua. There was profound response to indomethacin which was limited by side effects. In one patient the therapy with indomethacin was limited secondary to comorbidities. Initial diagnostic blockade provided significant relief of symptoms based on which radio-frequency ablation of the supraorbital nerve was performed with substantial improvement in symptoms.Traditionally, hemicrania continua has been managed exclusively with oral analgesics and is defined by its singular response to indomethacin. Radio-frequency ablation (RFA) has been reported in the literature for multiple indications. This case series is unique in that it describes 3 patients diagnosed with hemicrania continua with pain referred in the supraorbital nerve distribution, who underwent radiofrequency ablation of the supraorbital nerve with resultant resolution of headaches. Traditionally, hemicrania continua has been managed exclusively with oral analgesics and is defined by its singular response to indomethacin. This report is unique in that it describes three patients diagnosed with hemicrania continua with pain referred in the supraorbital nerve distribution who underwent radiofrequency ablation of the supraorbital nerve with resultant resolution of headaches. After the RFA medical management was minimal to none in both patients. Though the utility and cost efficacy of RFA of peripheral nerves needs to be confirmed in well-designed trials we present these cases as an example of how this minimally invasive technique can safely provide analgesia in a difficult to treat cephalgia. Moreover if precise anatomical localization of the headache is possible then diagnostic blockade of the appropriate peripheral nerve may be performed followed by radiofrequency ablation to provide potentially more sustained analgesia in patients where medical management is ineffective or poorly tolerated.

STR analysis is commonly used in forensic and genetic studies. STRs are currently discriminated based on size, primarily by gel- and column-based approaches. Hybridization-based approaches have the potential to allow high-throughput analysis of STRs; however, development of such approaches has been limited by the difficulty in discriminating between STRs of similar length. We have recently described several innovations to enable STR analysis using an array-based hybridization approach for high- throughput STR analysis. Here we extend that approach by incorporating the array into microspheres and adding a discriminatory branch migration displacement step. This microsphere-based platform uses Luminex xMAP technology and improves the sensitivity, selectivity, and speed of the assay. We demonstrate the feasibility, speed, and reliability of the assay for STR detection by correctly analyzing two STR loci in 20 forensic DNA samples of known STR type. The multiplex, bead-based approach provides a high-throughput and more portable STR analysis.

Ion current rectification with quartz nanopipette electrodes was investigated through the control of the surface charge. The presence and absence of a positively charged poly-L-lysine (PLL) coating resulted in the rectified current with opposite polarity. The results agreed with the theories developed for current-rectifying conical nanopores, suggesting the similar underlying mechanism among asymmetric nanostructure in general. This surface condition dependence can be used as the fundamental principle of multi-purpose real-time in vivo biosensors.

Rapid, sequence-specific DNA detection is essential for applications in medical diagnostics and genetic screening. Electrical biosensors that use immobilized nucleic acids are especially promising in these applications because of their potential for miniaturization and automation. Current DNA detection methods based on sequencing by synthesis rely on optical readouts; however, a direct electrical detection method for this technique is not available. We report here an approach for direct electrical detection of enzymatically catalyzed DNA synthesis by induced surface charge perturbation. We discovered that incorporation of a complementary deoxynucleotide (dNTP) into a self-primed single-stranded DNA attached to the surface of a gold electrode evokes an electrode surface charge perturbation. This event can be detected as a transient current by a voltage-clamp amplifier. Based on current understanding of polarizable interfaces, we propose that the electrode detects proton removal from the 3'-hydroxyl group of the DNA molecule during phosphodiester bond formation.

We describe a novel method for rapidly identifying and distinguishing between different DNA sequences using short tandem repeat (STR) analysis and DNA microarrays. The method can be used to deduce identity, length, and number of STRs of the target molecule. We refer to this technique as the "variable-length probe array" method for STR profiling (VLPA). The method involves hybridization of the unknown STR target sequence to a DNA microarray displaying complementary probes that vary in length to cover the range of possible STRs. A post-hybridization enzymatic digestion of the DNA hybrids is then used to selectively remove labeled single-stranded regions of DNA from the microarray surface. The number of repeats in the unknown target is then deduced based on the pattern of target DNA that remains hybridized to the array. This DNA profiling technique is useful for performing forensic analysis to uniquely identify individual humans or other species.

Single DNA molecules labeled with nanoparticles can be detected by blockades of ionic current as they are translocated through a nanopipette tip formed by a pulled glass capillary. The nanopipette detection technique can provide not only tools for detection and identification of single DNA and protein molecules but also deeper insight and understanding of stochastic interactions of various biomolecules with their environment.

We present proof-of-concept experiments and modeling towards a high-sensitivity magnetic microarray which “tags” a DNA fragment (or other biological samples) with a high-moment magnetic nanoparticle (NanoTag), which is in turn detected by a high-sensitivity spin valve (SV) or magnetic tunnel junction (MTJ) detector array. The detector can count the number of magnetic tags with a resolution of 1–20 magnetic NanoTags, potentially counting individual biomolecules.

We have fabricated a series of highly sensitive spin valve sensors on a micron scale that successfully detected the presence of a single superparamagnetic bead (Dynabeads M-280, 2.8 μm in diameter), and thus showed suitability for identifying biomolecules labeled by such magnetic beads. By polarizing the magnetic microbead on a spin valve sensor with a dc magnetic field and modulating its magnetization with an orthogonal ac magnetic field, we observed a magnetoresistance (MR) signal reduction caused by the magnetic dipole field from the bead that partially cancelled the applied fields to the spin valve. A lock-in technique was used to measure a voltage signal due to the MR reduction. A signal of 1.2 mV rms or 5.2 mΩ of resistance reduction was obtained from a 3 μm wide sensor and a signal of 3.8 mV rms or 11.9 mΩ from a 2.5 μm wide sensor. Micromagnetic simulations were also performed for the spin valve sensors with a single bead and gave results consistent with experiments. Further experiments and simulations suggested that these sensors or their variations can detect 1–10 Co nanoparticles with a diameter of ∼11 nm, and are suitable for DNA fragment detection.