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In 2017, there were ≈47,600 opioid overdose‐related deaths in the United States. US emergency department (ED) visits for suspected opioid overdose increased by 30% between July 2016 and September 2017.2 The current US opioid epidemic makes it critical for emergency physicians to be aware of common and uncommon infectious and non‐infectious complications of injection drug use. Point‐of‐care ultrasound has become a widely available, non‐invasive diagnostic tool in EDs across the United States and worldwide. The increasing population of injection drug use patients is at risk for serious morbidity and mortality from an array of disease states amenable to ultrasound‐based diagnosis. We propose a protocol for clinical ultrasonography in patients who inject drugs (the CUPID protocol), a focused, 3‐system point‐of‐care ultrasound approach emphasizing cardiovascular, thoracic, and musculoskeletal imaging. The protocol is a screening tool, designed to detect high risk infectious and noninfectious complications of injection drug use.

IntroductionIntubation-related complications are less frequent when intubation is successful on the first attempt. The rate of first attempt success in the emergency department (ED) and intensive care unit (ICU) is typically less than 90%. The bougie, a semirigid introducer that can be placed into the trachea to facilitate a Seldinger-like technique of tracheal intubation and is typically reserved for difficult or failed intubations, might improve first attempt success. Evidence supporting its use, however, is from a single academic ED with frequent bougie use. Validation of these findings is needed before widespread implementation.Methods and analysisThe BOugie or stylet in patients Undergoing Intubation Emergently trial is a prospective, multicentre, non-blinded randomised trial being conducted in six EDs and six ICUs in the USA. The trial plans to enrol 1106 critically ill adults undergoing orotracheal intubation. Eligible patients are randomised 1:1 for the use of a bougie or use of an endotracheal tube with stylet for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcome is severe hypoxaemia, defined as an oxygen saturation less than 80% between induction until 2 min after completion of intubation. Enrolment began on 29 April 2019 and is expected to be completed in 2021.Ethics and disseminationThe trial protocol was approved with waiver of informed consent by the Central Institutional Review Board at Vanderbilt University Medical Center or the local institutional review board at an enrolling site. The results will be submitted for publication in a peer-reviewed journal and presented at scientific conferences.Trial registration numberClinicalTrials.gov Registry (NCT03928925).

Background Interest in immunotherapy for breast cancer is rapidly emerging, and applicable animal models that mimic human cancer are urgently needed for preclinical studies. This study aimed to improve a technique for orthotopic inoculation of syngeneic breast cancer cells to be used as a preclinical animal model for immunotherapy. Materials and methods We used our previously reported murine model of orthotopic cancer cell inoculation under direct vision and compared the efficiency of tumorigenesis with tumor cells suspended in either phosphate-buffered saline or Matrigel containing varying numbers of cells. As a model for immune rejection, murine BALB/c–derived 4T1-luc2 breast cancer cells were inoculated orthotopically into both BALB/c and C57BL/6 mice. Results Matrigel-suspended cells formed larger tumors with higher efficiency than phosphate-buffered saline-suspended cells. The maximum volume of Matrigel that could be inoculated without spillage was 20 μL and 30 μL in the #2 and #4 mammary fat pads, respectively. Tumor take rates increased as the injected cell number increased. In this immune rejection model, there were no significant differences in tumor weight between the strains up to day 7, after which tumor weight decreased in C57BL/6 mice. Bioluminescence in C57BL/6 mice was also significantly less than that in BALB/c mice and increased up to day 7, then swiftly decreased thereafter. Conclusions This improved technique of innoculating murine breast cancer cells using bioluminescence technology may be useful in evaluating the efficacy of tumor regression mediated by immune responses, as shown by an allogeneic response in C57BL/6 mice.

Away rotations are common among senior medical students preparing to apply for residency. For competitive specialties, multiple away rotations may be viewed as a de facto requirement for a strong application. Although away rotations are often valuable learning experiences, a variety of noneducational factors motivate students to enroll, including the need for letters of recommendation, students' uncertainty regarding their strength as applicants, perceived competitiveness of residency applications, and conflicting guidance from advisors.Students who enroll in away rotations often benefit from a novel educational environment, opportunities for career exploration, and the chance to assess "fit" with a program. Yet away rotations also come at a significant cost. Students must deal with the time and expenses of rotating at multiple institutions. The application process for away rotations is expensive, disjointed, and inefficient. Students must work hard to make an impression on host institution faculty, and risk hurting their residency applications with a negative letter of recommendation.To reduce the burden of away rotations, future research should assess the impact of multiple away rotations on success in the Match. Allowing students limited access to letters of recommendation content would allow students and advisors to make informed decisions regarding additional rotations. Students would benefit from greater standardization of the application process for away rotations, with uniform dates, timely acceptances and rejections, and a cap for the number of applications per student. Students can maximize their returns by targeting away rotations that provide the most diverse educational experiences and valuable letters of recommendation.

Aims The use of live animals for surgical training is a well-known, deliberated topic. However, medical students who use live animals rate the experience high not only in improving their surgical techniques, but also positively influencing their confidence levels in the operating room later in their careers. Therefore, we hypothesized that the use of live animal models is a unique and influential component of preclinical medical education. Materials and Methods Medical student performed the following surgical procedures using mice; surgical orthotopic implantation of cancer cells into fat pad and subsequently a radical mastectomy. The improvement of skill was then analyzed. Results All cancer cell inoculations were performed successfully. Improvement of surgical skills during the radical mastectomy procedure was documented in all parameters. All wounds healed without breakdown or dehiscence. The appropriate interval between interrupted sutures was ascertained after fifth wound closure. The speed of interrupted sutures was doubled by last wound closure. The time required to complete a radical mastectomy decreased by almost half. A single animal died immediately following the operation due to inappropriate anesthesia, which was attributed to the lack of understanding of the overall operative management. Conclusion Surgical training using live animals for preclinical medical students provides a unique learning experience, not only in improving surgical skills but also and arguably most importantly, to introduce the student to the complexities of the perioperative environment in a way that most closely resembles the stress and responsibility that the operating room demands.

The high affinity of polynuclear platinum compounds (PPCs) for heparan sulfate (HS) is mediated through a “sulfate clamp” and PPC interactions can be conceptualized as “polyarginine” mimics. Strong HS-PPC binding protects the oligosaccharide against sulfate loss through metalloshielding.1 Metalloshielding will in principle affect HS interactions with relevant enzymes and proteins such as heparanase and growth factors, similar in concept to inhibition of DNA-protein binding through modification of DNA structure and conformation.2 PPCs inhibit cleavage of a model pentasaccharide by heparanase and further modulate bFGF binding to HS, and bFGF-induced migration and signaling in colon cancer cells.3 The end-point of functional modulation of HS interactions is inhibition of angiogenesis and metastasis.3 Following proof-of-principle of strong in vivo anti-metastatic activity of PPCs in clinically relevant breast cancer models,4 this contribution examines the underlying mechanism of platinums as anti-metastatic agents. We report on the cellular effects of PPC-HS metalloshielding on multiple growth factor signaling pathways (bFGF, HB-EGF) and specific syndecan (Sdc)-dependent signaling in breast cancer. Coupled with previously demonstrated DNA binding, PPCs represent intrinsically dual- function agents combining platinum cytotoxicity with anti-angiogenic effects derived from first principles through glycan targeting. [1] Mangrum, J.B., Engelmann, B.J., Peterson, E.J., Ryan, J.J., Berners-Price, S.J., Farrell, N.P. Chemical Communications 2014, 50, 4056-4058. [2] Chiodelli, P., Bugatti, A., Urbinati, C., Rusnati, M. Molecules 2015, 20, 6342-6388. [3] Peterson, E.J., Daniel, A.G., Katner, S.J., Bohlmann, L., Chang,C., Bezos, A., Parish, C.R., von Itzstein, M., Berners-Price, S.J., Farrell, N.P. Chem. Sci. 2016, DOI: 10.1039/C6SC02515C. [4] E. Katsuta, S. Demasi, S. Katner, H. Aoki, E. Peterson, E., N.P. Farrell and K. Takabe. (2016). Proc. AACR New Orleans, LA. Abstract #3064. DC 1-5 April 2017 Citation Format: Samantha J. Katner, Erica Peterson J. Peterson, Eriko Katsuta, Stephanie C. DeMasi, Jennifer Koblinski, Kazuaki Takabe, Nicholas P. Farrell. Anti-metastatic platinum through glycan targeting in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 17. doi:10.1158/1538-7445.AM2017-17

Introduction: Since metastatic cancer is the most advanced disease and is associated with the worst outcome, an effective treatment for this Stage is expected to directly improve overall survival. Recent clinical trials demonstrated that Cisplatin is effective in certain metastatic breast cancer, however with severe side effects. Polynuclear platinum analog, Triplatin, was developed to overcome the severe toxicity, however, pharmacokinetics limited its clinical efficacy in Phase II clinical trials. Recent development of Triplatin NC resolved the PK issue, and it is expected to be more clinically useful if it is as effective as Triplatin with less cytotoxic properties. Methods: HUVEC cells were used for tube formation assays. After orthotopic implantation of Murine breast cancer 4T1-luc2 cells, female Balb/C mice were randomized on Day 1 to Day 1, 5, 9 i.p. administration of Triplatin (0.3mg/kg), Triplatin NC (25mg/kg) or Saline and mice were sacrificed on Day 20 when lung metastasis was evaluated by ex vivo imaging. Pancreatic cancer carcinomatosis, generated by ip injection of 1 million Panc02-luc cells into C57/Blk6 mice. Animals were treated every 4 days beginning on day 1 by i.p. injection with either Triplatin (0.3mg/kg), Triplatin NC (25mg/kg) or Vehicle. Results: IC50 of 4T1-luc cells at 72h were 9μM and 8μM for Triplatin and Triplatin NC, respectively. 10μM of Triplatin or Triplatin NC demonstrated significant suppression of tube formation compared from no treatment (p = 0.005 and p = 0.002, respectively). Additionally, 0.1μM of Triplatin NC demonstrated significant suppression of tube formation as well (p = 0.003). In 4T1-luc2 implanted model, bioluminescent imaging on Day 7 demonstrated reduced tumor growth in Triplatin and Triplatin NC to 54% and 57% of the control, respectively. By Day 20, Triplatin and Triplatin NC suppressed the tumor size to 20% and 43% of the control, respectively. Triplatin and Triplatin NC significantly reduced the amount of lung metastasis to 14% and 21% of the control, respectively. In pancreatic cancer peritoneal carcinomatosis model, Triplatin and Triplatin NC reduced total tumor burden to 35% and 39% of the control on Day 9, respectively. Mouse survival was significantly enhanced by Triplatin treatment group in comparison with the control (p < 0.005). All of Triplatin treatment mice survived more than 40 days, whereas all of control group mice died less than 35 days. No mouse developed weight loss more than 25%. Conclusion: Both Triplatin and Triplatin NC effectively suppressed 4T1-luc2 breast cancer cell growth, and angiogenesis in vitro. Both agents demonstrated similar growth suppression not only of the primary tumor, but also in lung metastasis and panc02-luc carcinomatosis. New platinum compounds with less toxicity and favorable pharmacokinetics warrant further investigation for advanced metastatic cancer. Citation Format: Eriko Katsuta, Stephanie C. DeMasi, Samantha J. Katner, Hiroaki Aoki, Erica J. Peterson, Nicholas P. Farrell, Kazuaki Takabe. Newer platinum agent, Triplatin NC, is as effective as Triplatin for metastatic breast cancer and pancreatic cancer carcinomatosis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3064.