Fluorescent Guided Sentinel Lymph Mapping of the Oral Cavity with Fluorescent-Labeled Tilmanocept.

OBJECTIVE: With the shift toward utilization of sentinel lymph node biopsy (SLNB) in oral cavity cancer, improved techniques for intraoperative sentinel node identification are needed. This study investigates the feasibility of fluorescently labeled tilmanoscept in SLNB in an oral cancer rabbit model. METHODS: An animal study was designed using 21 healthy male New Zealand rabbits. Gallium-68-labeled tilmanocept labeled with IRDye800CW was injected submucosally into the buccal mucosa (n = 6) or lateral tongue (n = 7) followed by PET imaging. One hour after injection, SLNB was performed using fluorescence imaging followed by a bilateral neck dissection and sampling of non-nodal surrounding tissue. All tissues were measured for radioactivity and fluorescence. In addition, eight rabbits were injected with delayed SLNB performed 48 h after injection. RESULTS: Buccal injections all had ipsilateral SLN drainage and tongue injections exhibited 18.2% contralateral drainage. An average of 1.9 ± 1.0 SLN (range 1-5) were identified. In addition, an average of 16.9 ± 3.3 non-sentinel lymph nodes were removed per animal. SLNs had an average of 0.69 ± 0.60 percent-of-injected dose (%ID) compared with non-sentinel nodes with 0.012 ± 0.025 %ID and surrounding tissue with 0.0067 ± 0.015 %ID. There was 98.0% agreement between sentinel lymph nodes identified using fluorescence compared to radioactivity with Cohen's kappa coefficient of 0.879. In 48-h delayed SLNB, results were consistent with 97.8% agreement with radioactivity and Cohen's Kappa coefficient of 0.884. Fluorescence identified additional lymph nodes that were not identified by radioactivity, and with one false negative. CONCLUSION: Fluorescent-labeled Tc-99 m-tilmanocept represents a highly accurate adjunct to enhance SLNB for oral cavity cancer. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:1299-1307, 2024.

Macroevolutionary diversity of traits and genomes in the model yeast genus Saccharomyces.

Species is the fundamental unit to quantify biodiversity. In recent years, the model yeast Saccharomyces cerevisiae has seen an increased number of studies related to its geographical distribution, population structure, and phenotypic diversity. However, seven additional species from the same genus have been less thoroughly studied, which has limited our understanding of the macroevolutionary events leading to the diversification of this genus over the last 20 million years. Here, we show the geographies, hosts, substrates, and phylogenetic relationships for approximately 1,800 Saccharomyces strains, covering the complete genus with unprecedented breadth and depth. We generated and analyzed complete genome sequences of 163 strains and phenotyped 128 phylogenetically diverse strains. This dataset provides insights about genetic and phenotypic diversity within and between species and populations, quantifies reticulation and incomplete lineage sorting, and demonstrates how gene flow and selection have affected traits, such as galactose metabolism. These findings elevate the genus Saccharomyces as a model to understand biodiversity and evolution in microbial eukaryotes.

Consequences of anastomotic leaks after minimally invasive esophagectomy: A single-center experience.

Background: Anastomotic leak (AL) after minimally invasive esophagectomy (MIE) is a well-described source of morbidity for patients undergoing surgical treatment of esophageal neoplasm. With improved early recognition and endoscopic management techniques, the long-term impact remains unclear. Methods: A retrospective review was conducted of patients who underwent MIE for esophageal neoplasm between January 2015 and June 2021 at a single institution. Cohorts were stratified by development of AL and subsequent management. Baseline demographics, perioperative data, and post-operative outcomes were examined. Results: During this period, 172 MIEs were performed, with 35 of 172 (20.3%) complicated by an AL. Perioperative factors independently associated with AL were post-operative blood transfusion (leak rate 52.9% versus 16.8%; p = 0.0017), incompleteness of anastomotic rings (75.0% vs 19.1%; p = 0.027), and receiving neoadjuvant therapy (18.5% vs 30.8%; p < 0.0001). Inferior short-term outcomes associated with AL included number of esophageal dilations in the first post-operative year (1.40 vs 0.46, p = 0.0397), discharge disposition to a location other than home (22.9% vs 8.8%, p = 0.012), length of hospital stay (17.7 days vs 9.6 days; p = 0.002), and time until jejunostomy tube removal (134 days vs 79 days; p = 0.0023). There was no significant difference in overall survival between patients with or without an AL at 1 year (79% vs 83%) or 5 years (50% vs 47%) (overall log rank p = 0.758). Conclusions: In this large single-center series of MIEs, AL was associated with inferior short-term outcomes including hospital length of stay, discharge disposition other than to home, and need for additional endoscopic procedures, without an accompanying impact on 1-year or 5-year survival. Key message: In this large, single-center series of minimally invasive esophagectomies, anastomotic leak was associated with worse short-term outcomes including hospital length of stay, discharge disposition other than to home, and need for additional endoscopic procedures, but was not associated with worse long-term survival. The significant association between neoadjuvant therapy and decreased leak rates is difficult to interpret, given the potential for confounding factors, thus careful attention to modifiable pre- and peri-operative patient factors associated with anastomotic leak is warranted.

Extracorporeal Cardiopulmonary Resuscitation: A Narrative Review and Establishment of a Sustainable Program.

The rates of survival with functional recovery for out of hospital cardiac arrest remain unacceptably low. Extracorporeal cardiopulmonary resuscitation (ECPR) quickly resolves the low-flow state of conventional cardiopulmonary resuscitation (CCPR) providing valuable perfusion to end organs. Observational studies have shown an association with the use of ECPR and improved survivability. Two recent randomized controlled studies have demonstrated improved survival with functional neurologic recovery when compared to CCPR. Substantial resources and coordination amongst different specialties and departments are crucial for the successful implementation of ECPR. Standardized protocols, simulation based training, and constant communication are invaluable to the sustainability of a program. Currently there is no standardized protocol for the post-cannulation management of these ECPR patients and, ideally, upcoming studies should aim to evaluate these protocols.

Successful Lung Transplantation for Severe Post-COVID-19 Pulmonary Fibrosis.

Lung transplantation has been well described for patients with coronavirus disease 2019 (COVID-19) in the acute setting, but less so for the resulting pulmonary sequelae. This report describes a case of lung transplantation for post-COVID-19 pulmonary fibrosis. A 52-year-old woman contracted COVID-19 in July 2020 and mounted a partial recovery, but she went on to have declining function over the ensuing 3 months, with development of fibrocystic lung changes. She underwent bilateral lung transplantation and recovered rapidly, was discharged home on postoperative day 14, and has done well in follow-up. This case report demonstrates that lung transplantation is an acceptable therapy for post-COVID-19 pulmonary fibrosis.

A receptor-binding radiopharmaceutical for imaging of traumatic brain injury in a rodent model: [99mTc]Tc-tilmanocept.

INTRODUCTION: Blood-brain barrier (BBB) disruption and subsequent neuro-inflammation occur following traumatic brain injury (TBI), resulting in a spectrum of human nervous system disorders. [99mTc]Tc-tilmanocept is a receptor-binding radiopharmaceutical FDA-approved for sentinel lymph node mapping. We hypothesize that after an intravenous (i.v.) injection, [99mTc]Tc-tilmanocept, will traverse a disrupted BBB and bind to CD206-bearing microglial cells. METHODS: Age-matched mice were divided into three groups: 5-days post TBI (n = 4), and 5-days post sham (n = 4), and naïve controls (n = 4). IRDye800CW-labeled [99mTc]Tc-tilmanocept (0.15 nmol per gram body weight) and FITC-labeled bovine serum albumin (FITC-BSA) were injected (i.v.) into each mouse. Mice were imaged with a high-resolution gamma camera for 45 min. Immediately after imaging, the brains were perfused with fixative, excised, imaged with a fluorescence scanner, assayed for radioactivity, and prepared for histology. RESULTS: In vivo nuclear imaging, ex vivo fluorescence imaging, ex vivo gamma well counting, and histo-microscopy demonstrated enhanced tilmanocept uptake in the TBI region. The normalized [99mTc]Tc-tilmanocept uptake value from nuclear imaging and the maximum pixel intensity from fluorescence imaging of the TBI group (1.12 ±â€¯0.12 and 2288 ±â€¯278 a.u., respectively) were significantly (P < 0.04) higher than the sham group (0.64 ±â€¯0.28 and 1708 ±â€¯101 a.u., respectively) and the naive group (0.76 ±â€¯0.24 and 1643 ±â€¯391 a.u., respectively). The mean [99mTc]Tc-tilmanocept scaled uptake in the TBI brains (0.058 ±â€¯0.013%/g) was significantly (P < 0.010) higher than the scaled brain uptake of the sham group (0.031 ±â€¯0.011%/g) and higher (P = 0.04) than the uptake of the naïve group (0.020 ±â€¯0.002%/g). Fluorescence microscopy demonstrated increased uptake of the IRDye800CW-tilmanocept and FITC-BSA in the TBI brain regions. CONCLUSION: [99mTc]Tc-tilmanocept traverses disrupted blood-brain barrier and localizes within the injured region. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: [99mTc]Tc-tilmanocept could serve as an imaging biomarker for TBI-associated neuroinflammation and any disease process that involves a disruption of the blood-brain barrier.

Performance Improvement With Implementation of a Surgical Skills Curriculum.

OBJECTIVE: To assess the efficacy of an intern surgical skills curriculum involving a boot camp for core open and laparoscopic skills, self-guided practice with positive and negative incentives, and semiannual performance evaluations. DESIGN: Longitudinal cohort study. SETTING: Academic tertiary care center. PARTICIPANTS: Intervention group (n = 15): residents who completed the intern surgical skills curriculum and had performance evaluations in fall of intern year, spring of intern year, and fall of second year. Control group (n = 8): second-year residents who were 1 year ahead of the intervention group in the same residency program, did not participate in the curriculum, and had performance evaluations in fall of second year. RESULTS: In fall of second year of residency, the intervention group had better performance (presented as median values with interquartile ranges) than the control group on one-hand ties (left hand: 9.1 [6.3-10.1] vs 14.6 [13.5-15.4] seconds, p = 0.007; right hand: 8.7 [8.5-9.6] vs 11.5 [9.9-16.8] seconds, p = 0.039). The intervention group also had better performance on all open suturing skills, including mattress suturing (vertical: 33.4 [30.0-40.0] vs 55.8 [50.0-67.6] seconds, p = 0.001; horizontal: 28.7 [27.3-39.9] vs 52.7 [40.7-57.8] seconds, p = 0.003), and a water-filled glove clamp, divide, and ligate task (28.0 [25.0-31.0] vs 59.1 [53.0-93.0] seconds, p < 0.001). Finally, the intervention group had better performance on all laparoscopic skills, including peg transfer (66.0 [59.0-82.0] vs 95.2 [87.5-101.5] seconds, p = 0.018), circle cut (82.0 [69.0-124.0] seconds vs 191.8 [155.5-231.5] seconds, p = 0.002), and intracorporeal suturing (195.0 [117.0-200.0] seconds vs 359.5 [269.0-450.0] seconds, p = 0.002). CONCLUSIONS: Implementation of a comprehensive surgical skills curriculum was associated with improved performance on core open and laparoscopic skills. Further research is needed to understand and optimize motivational factors for deliberate practice and surgical skill acquisition.

Successful Surgical Removal of the Largest Known Spleen.

BACKGROUND: Splenic marginal zone lymphoma (SMZL) is a rare subtype of non-Hodgkin lymphoma that typically presents with symptomatic splenomegaly. The optimal treatment of SMZL not well established. Case Presentation. A 44-year-old man with a history of low-grade B-cell lymphoproliferative disorder previously treated with chemotherapy presented with a three-month history of rapidly enlarging abdominal girth. He was found to have large symptomatic splenomegaly by computed tomography. After workup, he underwent preoperative angioembolization of the splenic artery followed by successful splenectomy. The spleen measured 45 cm in greatest dimension and weighed 12.14 kg, more than 12% of the patient's total body weight, making this both the largest spleen on record as well as the largest spleen ever surgically removed. Pathology was consistent with splenic marginal zone lymphoma. The patient did well and was discharged home on postoperative day 3. CONCLUSIONS: SMZL is an infrequent condition that leads to progressive symptomatic splenomegaly which can be managed surgically providing symptomatic improvement and an overall satisfactory oncologic outcome. A multidisciplinary approach to complex cases of SMZL splenomegaly is imperative to achieving optimal outcomes.

Utilizing the index for mortality prediction after cardiac transplantation risk score to predict hospital resource consumption.

OBJECTIVE: The index for mortality prediction after cardiac transplantation (IMPACT) risk score incorporates 12 preoperative recipient-specific variables, and has been validated as an accurate predictor of short- and long-term mortality after orthotopic heart transplantation (OHTx). We believe it can also be used to predict hospital costs, and we hypothesize that higher preoperative IMPACT risk scores are associated with increased hospital resource consumption. METHODS: All OHTx patients ≥18 years of age at our institution were reviewed from 1 January 2000 to 31 December 2014. Total index hospitalization costs post-transplant were extracted and presented in 2014 consumer price index inflation-adjusted US dollars. Patients were stratified into quartiles (Q) according to IMPACT risk scores. Logarithmic transformation normalized cost data, and linear regression assessed for correlation. A comparison of cost between Q of IMPACT risk score was performed using rank-sum and Kruskal-Wallis tests. Survival was estimated using the Kaplan-Meier method. RESULTS: Three hundred fifty-six (n = 356) OHTx were performed during the study period. The median IMPACT score for the cohort was five (interquartile range [IQR] 3-6). Eight (2.2%) patients died within 30-days and 1-year Kaplan-Meier survival was 88.3%. The median length of stay (LOS) was 16 (IQR 14-24) days. The median hospital cost for index admission was $222 200 (IQR:$169 200-$313 700). Median LOS was longer in Q4 vs Q1 (18 days vs 15 days, P = .01) and index hospital costs in Q4 were significantly higher compared to Q1 patients ($280 400 vs $205 000, P < .01). There was a significant positive correlation between IMPACT risk score and cost (regression coefficient .04, P < .01). CONCLUSION: This is the first study in adult cardiac transplantation to identify a positive correlation between hospital cost and recipient risk using the IMPACT risk score. Cost and resource consumption for the index admission after OHTx were significantly higher in the highest IMPACT risk Q compared with patients in the lowest Q.

Experimental evidence of chemical attraction in the mutualistic zebra mussel-killer shrimp system.

Invasion facilitation, whereby one species has a positive effect on the establishment of another species, could help explain the rapid colonisation shown by some freshwater invasive species, but the underlying mechanisms remain unclear. We employed two-choice test arenas to test whether the presence of zebra mussel (Dreissena polymorpha) could facilitate the establishment of the killer shrimp (Dikerogammarus villosus). Killer shrimp preferred to settle on mats of zebra mussel, but this was unrelated to mat size, and was not different from attraction shown to artificial grass, suggesting that zebra mussel primarily provides substrate and refuge to the killer shrimp. Killer shrimp were strongly attracted to water scented by zebra mussel, but not to water scented by fish. Chemical attraction to the zebra mussel's scent did not differ between sympatric and allopatric populations of killer shrimp, suggesting that chemical attraction is not an acquired or learned trait. Our study shows, for the first time, chemical attraction between two highly invasive freshwater species, thereby providing a plausible mechanism for invasion facilitation. This has implications for managing the spread of killer shrimp, and perhaps other freshwater invasive species, because chemical attraction could significantly increase establishment success in mutualistic systems. Failure to consider invasion facilitation may underestimate the risk of establishment, and likely also the impact of some aquatic invaders.

Postoperative surgical trainee opioid prescribing practices (POST-OPP): A national survey.

BACKGROUND: Increasing opioid-related deaths have heightened focus on combating the opioid epidemic. The impact of surgical trainees on opioid-related deaths is unclear, and there is little data examining the association between trainee pain management education and opioid prescribing practices. METHODS: An anonymous, online survey was distributed to members of the Resident and Associate Society of the American College of Surgeons. The survey covered five themes: education and knowledge, prescribing practices, clinical case scenarios, policy, and beliefs and attitudes. Linear mixed models were used to evaluate the influence of respondent characteristics on reported morphine milligram equivalents (MME) prescribed for common general surgery clinical scenarios. RESULTS: Of 427 respondents, 54 percent indicated receiving training in postoperative pain management during medical school and 66 percent during residency. Only 35 percent agreed that they had received adequate training in prescribing opioids. There was a significant association between undergoing formal pain management training in medical school and prescribing fewer MME for common outpatient general surgery scenarios (94 ± 15.2 vs 108 ± 15.0; p = 0.003). Similarly, formal pain management training in residency was associated with prescribing fewer MME in the survey scenarios (92.6 ± 15.2 vs 109 ± 15.2; p = 0.002). CONCLUSION: In this survey, nearly two-thirds of surgical residents felt that they were inadequately trained in opioid pre-scribing. Our findings additionally suggest that improving education may result in increased resident comfort with man-aging surgical pain, potentially leading to more responsible opioid prescribing. Further work will facilitate residency pro-grams' development of educational curricula for opioid prescribing best practices.

Associations Between National Board Exam Performance and Residency Program Emphasis on Patient Safety and Interprofessional Teamwork.

OBJECTIVE: Several aspects of medical training may contribute to the ultimate goal of producing excellent physicians whose patients will have the best possible outcomes. However, the relative importance of education, evaluation and feedback, duty hours, practice structure, and program culture in achieving this goal is unclear. This study assessed associations among in-training exam performance, Accreditation Council for Graduate Medical Education (ACGME) Resident Survey responses, and American Board of Medical Specialties (ABMS) national board exam performance. METHODS: Residency training programs at a university teaching hospital were classified as having 5-year first-time ABMS pass rates above (n=12) or below (n=3) the national average for their specialty. These groups were compared by ACGME Resident Survey data and in-training exam performance. RESULTS: Surveys were collected from 484/543 eligible residents (89%), including 177 surveys from programs with below-average board pass rates and 307 surveys from programs with aboveaverage board pass rates. In-training exam performance was similar between groups. Aboveaverage programs had stronger agreement with statements that their culture reinforced patient safety (4.72 vs. 4.30, p=0.006) and that information was not lost during transitions of care (4.14 vs. 3.63, p=0.001). Although the occurrence of interprofessional teamwork was similar between groups, above-average programs had stronger agreement with the statement that interprofessional teamwork was effective (4.60 vs. 4.17, p=0.003). CONCLUSION: Residency programs emphasizing patient safety and effective interprofessional teamwork had above-average first-time national board pass rates.

Does nanoscale porous titanium coating increase lumbar spinal stiffness of an interbody fusion cage? An in vivo biomechanical analysis in an ovine model.

BACKGROUND: Quantitative objective measures to determine fusion achievement further enable the comparison of new technologies, such as interbody cage surface enhancement. Our aims were to compare in vivo biomechanical responses of ovine L4/5 lumbar motion segments with two cages: 1) Polyetheretherketone or 2) Polyetheretherketone with a nanosurfaced titanium porous scaffold from Nanovis, Inc. METHODS: Fourteen Merino sheep randomly received either 1) standard Polyetheretherketone cage or 2) Nanocoated Polyetheretherketone cage at L4/L5 with autologous bone graft. At baseline and one-year follow-up, dynamic spinal stiffness was quantified in vivo using a validated mechanical assessment at 2 Hz, 6 Hz, and 12 Hz. The dorsoventral secant stiffness (ky = force/displacement, N/mm) and L4-L5 accelerations were determined at each frequency. A repeated measures analysis of variance with Bonferonni correction was used to evaluate within and between group differences among the biomechanical variables. FINDINGS: Both implants increased spinal stiffness at 2 Hz (21 and 39%, respectively, p < .005), and at 6 Hz (12 and 27%, p < .0001). Significantly greater spinal stiffness was observed with Nanocoated Polyetheretherketone at one-year for both frequencies (p < .05). No significant differences were observed at 12 Hz within or between groups. L4-L5 dorsoventral accelerations were significantly decreased one year following cage placement only with Nanocoated Polyetheretherketone (p < .05) and greater reductions in acceleration were observed with Nanocoated Polyetheretherketone compared to standard Polyetheretherketone (p < .05). INTERPRETATION: Both cages increased spinal stiffness, yet, nanosurfaced cages resulted in greater spinal stiffness changes and decreases in L4-L5 accelerations. These findings may assist in clinical decision making and post-operative recovery strategies.

Molecular Imaging of the Glomerulus via Mesangial Cell Uptake of Radiolabeled Tilmanocept.

An unmet need for the clinical management of chronic kidney disease is a predictive tool of kidney function during the first decade of the disease, when there is silent loss of glomerular function. The objective of this study was to demonstrate receptor-mediated binding of tilmanocept to CD206 within the kidney and provide evidence of kinetic sensitivity of this binding to renal function. Methods: Rats were positioned in a PET scanner with the liver and kidneys within the field of view. After an intravenous injection of 68Ga-IRDye800-tilmanocept, using 1 of 2 scaled molar doses (0.02 nmol/g, n = 5; or 0.10 nmol/g, n = 5), or coinjection (n = 3) of 68Ga-IRDye800-tilmanocept (0.10 nmol/g) and unlabeled tilmanocept (5.0 nmol/g), or a negative control, 68Ga-IRDye800-DTPA-galactosyl-dextran (0.02 nmol/g, n = 5), each animal was imaged for 20 min followed by a whole-body scan. Frozen kidney sections were stained for podocytes and CD206 using immunofluorescence. Molecular imaging of diabetic db/db mice (4.9 wk, n = 6; 7.3 wk, n = 4; 13.3 wk, n = 6) and nondiabetic db/m mice (n = 6) was performed with fluorescence-labeled 99mTc-tilmanocept (18.5 MBq, 2.6 nmol). Thirty minutes after injection, blood, liver, kidneys, and urine were assayed for radioactivity. Renal time-activity curves were generated. Results: Rat PET whole-body images and time-activity curves of 68Ga-IRDye800-tilmanocept demonstrated receptor-mediated renal accumulation with evidence of glomerular uptake. Activity within the renal cortex persisted during the 40-min study. Histologic examination demonstrated colocalization of CD206 and IRDye800-tilmanocept within the glomerulus. The glomerular accumulation of the coinjection and the negative control studies were significantly less than the CD206-targeted agent. The db/db mice displayed a multiphasic renal time-activity curve with high urinary bladder accumulation; the nondiabetic mice exhibited renal uptake curves dominated by a single phase with low bladder accumulation. Conclusion: This study demonstrated receptor-mediated binding to the glomerular mesangial cells and kinetic sensitivity of tilmanocept to chronic renal disease. Given the role of mesangial cells during the progression of diabetic nephropathy, PET or SPECT renal imaging with radiolabeled tilmanocept may provide a noninvasive quantitative assessment of glomerular function.

The Impact of Donor and Recipient Age: Older Lung Transplant Recipients Do Not Require Younger Lungs.

BACKGROUND: Lung transplantation for patients with end-stage lung disease continues to grow worldwide. Increasing demand for this therapy generates significant waitlist mortality, indicating that alternative sources of donor lungs, such as older donors, are needed. The effect of the donor-recipient age relationship on outcomes remains unclear. METHODS: A retrospective review of the United Network for Organ Sharing Standard Transplant Analysis and Research database was performed for adult lung recipients from 2005 to 2015. Variables examined included donor age, recipient age, listing diagnosis, episodes of acute cellular rejection in the first year, and survival. Both donors and recipients were stratified according to age ranges. Survival was compared with the log-rank test. Propensity score matching was done stratifying donors younger than 60 years versus older than 60 years for the recipient population of 60 to 69 years. RESULTS: From May 2005 to February 2015, 15,844 patients underwent lung transplantation. Unadjusted comparisons of donor-to-recipient age showed that older donor age appeared to be more relevant for recipients 60 to 69 years old (p = 0.002). Nevertheless, when propensity matching was done based on relevant covariates for recipients in this age range by donors younger or older than 60 years, there were no differences in survival. CONCLUSIONS: Our results suggest that even though donor and recipient age may be important in lung transplantation, the interplay between donor and recipient age alone is not an independent determinant of survival. Careful selection of lungs from donors older than 60 years old should be exercised, taking into consideration the totality of donor demographics and risk factors rather than dismissing lungs based on advanced age alone.

An inquiry-based exercise in medicinal chemistry: Synthesis of a molecular library and screening for potential antimalarial and anti-inflammatory compounds.

The development of new medicines holds particular fascination for chemistry, biochemistry, and biology students interested in a career in medicine or the life sciences. The identification and refinement of lead compounds to treat diseases requires researchers to be facile in a number of different disciplines including organic synthesis, biochemistry, cell biology, and molecular biology. We have developed an interdisciplinary, inquiry-based laboratory spanning both organic chemistry and biochemistry classes that acquaints students with research in medicinal chemistry. The first part of the exercise takes place in the second semester of organic chemistry, where pairs of students design and execute their own multistep synthesis of a novel compound with anti-inflammatory and/or antimalarial potential. Later, in first semester biochemistry, many of the same students then test these synthesized compounds for cytotoxicity, inhibition of the enzyme nitric oxide synthase, and inhibition of the transcription factor NF-kB. Learning outcomes, measured by the Classroom Undergraduate Research Experience (CURE) survey, suggest that students participating in both classes had higher gains than an average student. © 2018 International Union of Biochemistry and Molecular Biology, 46(5):424-434, 2018.

Molecular Imaging of endometrial sentinel lymph nodes utilizing fluorescent-labeled Tilmanocept during robotic-assisted surgery in a porcine model.

Molecular imaging with a fluorescent version of Tilmanocept may permit an accurate and facile detection of sentinel nodes of endometrial cancer. Tilmanocept accumulates in sentinel lymph nodes (SLN) by binding to a cell surface receptor unique to macrophages and dendritic cells. Four female Yorkshire pigs underwent cervical stromal injection of IRDye800-Tilmanocept, a molecular imaging agent tagged with near-infrared fluorescent dye and radiolabeled with gallium-68 and technetium-99m. PET/CT scans 1.5 hours post-injection provided pre-operative SLN mapping. Robotic-assisted lymphadenectomy was performed two days after injection, using the FireFly imaging system to identify nodes demonstrating fluorescent signal. After removal of fluorescent nodes, pelvic and periaortic node dissections were performed. Nodes were assayed for technetium-99m activity, and SLNs were established using the "10%-rule", requiring that the radioactivity of additional SLNs be greater than 10% of the "hottest" SLN. Thirty-four nodal samples were assayed ex vivo for radioactivity. All the SLNs satisfying the "10%-rule" were detected using the FireFly system. Five fluorescent nodes were detected, corresponding with preoperative PET/CT scan. Three pigs had one SLN and one pig had two SLNs, with 100% concordance between fluorescence and radioactivity. Fluorescent-labeled Tilmanocept permits real-time intraoperative detection of SLNs during robotic-assisted lymphadenectomy for endometrial cancer in a porcine model. When radiolabeled with gallium-68, Tilmanocept allows for preoperative localization of SLNs using PET/CT, and shows specificity to SLNs with persistent fluorescent signal, detectable using the FireFly system, for two days post-injection. In conclusion, these findings suggest that a phase I trial in human subjects is warranted, and that a long-term goal of an intra-operative administration of non-radioactive fluorescent-labeled Tilmanocept is possible.

Postoperative surgical trainee opioid prescribing practices (POST OPP): an institutional study.

BACKGROUND: Increasing mortality from opioid overdoses has prompted increased focus on prescribing practices of physicians. Unfortunately, resident physicians rarely receive formal education in effective opioid prescribing practices or postoperative pain management. Data to inform surgical training programs regarding the utility and feasibility of formal training are lacking. METHODS: Following Institutional Review Board approval, a single institution's resident physicians who had completed at least one surgical rotation were surveyed to assess knowledge of pain management and evaluate opioid prescribing practices. RESULTS: Fifty-three respondents (68% males and 32% females) completed the survey. Most respondents denied receiving formal instruction in opioid pain medication prescribing practices during either medical school (62.3%) or residency (56.6%); however, nearly all respondents stated they were aware of the side effects of opioid pain medications, and a majority felt confident in their knowledge of opioid pharmacokinetics and pharmacodynamics. Of the respondents, 47% either "agreed" or "strongly agreed" that they prescribed more opioid medications than necessary to patients being discharged following a surgical procedure. Individual case scenario responses demonstrated variability in the number of morphine milligram equivalents prescribed across scenarios (P < 0.001). Male and nonsurgical specialty respondents reported prescribing significantly fewer overall morphine milligram equivalents in these scenarios. CONCLUSIONS: This pilot study shows wide variability in opioid prescribing practices and attitudes toward pain management among surgical trainees, illustrating the potential utility of formal education in pain management and effective prescribing of these medications. A broader assessment of surgical trainees' knowledge and perception of opioid prescribing practices is warranted to facilitate the development of such a program.