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Radiation pneumonitis (RP) is a local inflammatory response, and we hypothesize that RP serves as an immune stimulator and is a protective factor against disease progression. Methods: We analyzed patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT) at two institutions. Radiographic RP (RRP) was evaluated and maximal axial dimensions were measured at three-, six-, and twelve-month timepoints with surveillance CT. RRP was measured using radiographic markers such as ground-glass opacities and airspace consolidation. Disease recurrence was evaluated and categorized as local, regional, and distant. Results: Seventy-seven unique patient records were randomly selected from the database, 72 patients (93.5%) had RRP and five patients (6.5%) did not. The median follow-up was 24.3 months (IQR: 12.0 - 41.9). Disease failure occurred in 28.6% of patients with 6.5% local only, 2.6% regional only, 7.8% distant only, and 11.7% with multiple recurrences. Patients with RRP demonstrated a lower rate of disease failure with 25.0% of those with RRP experiencing disease failure and 80% of those without RRP experiencing disease failure (p=0.02). Patients with RRP had a 71% reduced risk of disease recurrence, compared to patients with no RRP, after adjusting for maximum tumor dimension (HR 0.29, p = 0.05). Among patients with RRP, there was no significant difference in recurrence based on extent of RRP (maximal area of RRP on CT). RRP did not correlate with overall survival. Discussion: Most patients who received SBRT had RRP, and this study suggests that it may be protective of cancer recurrence. These results are hypothesis-generating and will need to be validated in larger and independent datasets.

The custom-fabricated total contact cast is commonly used in the treatment of diabetic foot disorders. This resource-consuming treatment option has been associated with iatrogenic morbidity as well as the need for urgent cast removal and inspection of the underlying limb when potential problems arise. Over a 10-year period, 381 diabetic patients had 2265 total contact cast applications by certified orthopaedic technologists, in a university orthopaedic practice, under the supervision of university faculty. Patients were stratified by glycemic control based on hemoglobin A1c levels, and obesity based on body mass index (BMI). Complications were grouped as (1) development of a new ulcer or wound, (2) new or increasing odor or drainage, (3) wound infection, (4) gangrene, (5) newly identified osteomyelitis, and (6) pain or discomfort necessitating cast change or removal. At least 1 complication was observed in 159 of 381 patients. The odds of experiencing a cast-related event for patients with a BMI greater than 30 kg/m2 was 1.55 times greater than patients with a BMI less than 25 kg/m2. As compared to patients with good glycemic control, the odds of experiencing a cast-associated complication was 1.27 times greater in patients with moderate glycemic control and 1.48 times greater in patients with poor glycemic control. The total contact cast is commonly used in the treatment of diabetic foot morbidity. Treatment-associated morbidity may well be greater than previously appreciated. Complications are more likely in patients who have poor glycemic control and are morbidly obese. This information will hopefully stimulate interest in developing commercially available nonrigid alternatives that retain the attributes of the resource-consuming rigid device, with the potential advantage of avoiding the associated morbidity. Levels of Evidence: Level IV, retrospective chart review

Physicians are taught to maintain emotional distance. However, limited research suggests that many have cried in the hospital setting. How physicians understand and manage their emotions is an understudied topic, and public displays of emotion are not adequately addressed in medical education. To better understand physician and trainee views about displaying emotion in front of patients, we conducted a mixed-methods study using vignettes, closed-, and open-ended questions to explore the current attitudes of medical students, residents, and physicians at one academic medical center regarding whether or not it is appropriate for a physician to cry with a patient. Quantitative analyses investigated the effects that vignette constructs, level of training, gender, and history of crying at work within the last six months had on respondents' opinions regarding the appropriateness of physicians crying. An open-ended question, "Describe a situation in the hospital during which you felt like crying," was analyzed for key themes.

We evaluated how race, insurance status, and other sociodemographic, tumor, and treatment variables influenced the response to neoadjuvant chemotherapy (NAC) in breast cancer. We performed an IRB-approved retrospective review of 298 breast cancer patients treated with NAC from 2006-2018 at our institution. Univariable and multivariable binary logistic regression analyses were performed to estimate the effects of race, insurance status, and other variables on outcomes. Outcomes of interest included pathologic complete response (pCR), partial response (pPR), and any response (pCR or pPR). Sixty-nine patients (23%) identified as African American. One hundred sixty-eight (57%) patients had private insurance, 71 (24%) had Medicare, 40 (14%) had Medicaid, and 17 (6%) had no insurance. Insurance status was a predictor for any clinical response to NAC in both univariable and multivariable analyses (p

Purpose To investigate the learning curve associated with performing direct anterior total hip arthroplasty (THA) immediately after fellowship training in this approach. Methods This was a multicenter, retrospective study that collected data on all direct anterior THAs performed by four fellowship-trained arthroplasty surgeons in their first year of practice. Demographic data, surgical time, blood loss, surgical complications, and medical complications were recorded. Regression models were created to evaluate the outcomes of interest. A generalized linear mixed model was used to estimate the effect of the number of THA procedures performed, a proxy for surgical experience with this procedure, on the variables of interest. Results A total of 286 patients undergoing direct anterior THA were included in this study. A decrease in surgical complications after approximately 40 cases and a decrease in medical complications at 25 to 50 cases were observed. Both surgical time and blood loss showed no learning curve. Conclusion Extensive training with a direct anterior approach during fellowship minimizes the learning curve for blood loss and surgical time, but it continues to exist regarding perioperative surgical and medical complications. Recent fellowship graduates should be cautious and expect a learning curve of around 40 cases before complication rates begin to normalize.

High-school sports participation in the United States has increased over the years with a corresponding increase in the number of injuries. Leading medical and sports organizations nationwide advocate for an increase in proper medical supervision of athletes.To analyze athletic medical coverage in Illinois high schools and compare differences between public and private Illinois high school.A survey addressing various components of sports medical coverage was distributed in 2018 to all 810 Illinois High School Association (IHSA) high schools to be completed electronically.The response rate was 50% (407/810 schools). Of the responding schools, 14% were private high schools and 86% public high schools. An orthopedic surgeon, family doctor, pediatrician, or another type of physician were present on sidelines in 9.2% of private high schools and 8.5% of public high schools. Athletic trainers (ATs) were present on sidelines in 91% of private high schools and in 79% of public high schools. There was 68% of private high schools reporting coaches trained in CPR versus 85% in public high schools. Both private and public high schools had high rates of having written emergency action plans (89% vs 91%), AED on site (100% vs 99%), written concussion management protocols (96% vs 97%).Our study found similar rates of high school medical coverage as compared to national studies, with some significant differences found between private and public high schools. Most Illinois high schools had high rates of having written EAPs, concussion management protocols and AEDs on site. Overall, an increase of medical supervision and emergency preparedness is needed, which should come in the form of increasing AT and physician presence alongside community and school engagement for improved implementation of coverage.

Distal radius fractures in the pediatric population are common injuries with a remarkable capability to remodel. The degree of angulation that can reasonably be expected to remodel is controversial though, particularly when it comes to angulation in the coronal plane. The purpose of this study was to quantify the rate of coronal remodeling, via the distal radius physis, present in a retrospective cohort of skeletally immature patients with coronally angulated distal radius fractures.A retrospective chart review was performed to identify skeletally immature patients treated for an angulated distal radius fracture with over 10 degrees of angulation in the coronal plane during the healing process at a single institution by either a pediatric orthopaedic surgeon or an orthopaedic trauma surgeon from 2009 to 2018. Coronal angulation was measured at every visit where radiographs were available from time of injury to the final follow-up visit to determine the rate of remodeling.In total, 36 patients with distal radius fractures with a mean age of 7.93 years (range, 4 to 12 y) at the time of injury were identified. The median peak angulation during the healing process in the coronal plane was 17 degrees (range, 12.4 to 30.4 degrees). The mean follow-up period was 6.4 months from the time of maximum angulation to the final visit. The median time from cast removal to final follow-up was 6.59 months (range, 2.5 to 8.72 mo). At final follow-up, the median coronal angulation was 3.35 degrees (range, 0.24 to 14.0 degrees). At the 95% confidence level, remodeling rates ranged from 2.00 to 2.59 degrees per month. The mean rate of coronal angulation remodeling from maximum angulation to final follow-up was 2.30 degrees per month.Distal radius fractures have a large capacity to remodel in the pediatric population. This remodeling occurs in a predictable and reliable manner, even in the coronal plane. On the basis of this study, coronal angulation was shown to remodel at a rate of at least 2 degrees per month for the first 6 months following the injury, which should likely continue at a similar rate for the first year after the injury. Repeat manipulation is not indicated in skeletally immature patients where the maximum coronal angulation is24 degrees, which provides a conservative estimate of the amount of remodeling that can be expected to occur in the first year after fracture.Level III-retrospective comparative study.

Background The study objective was to compare the reaming congruency of hand, power, and visual feedback axial alignment–guided (Marksman) reamers on glenoid models. We hypothesized that (1) a significant difference in average reaming deviation would be found between reamer types and (2) less ream-to-ream variation would occur with the Marksman reamer. Methods Retroversion correction of 18 identical Sawbones glenoid models was conducted using either a hand, power, or Marksman reamer with a 40-mm curvature radius. Glenoid correction with either 0° or 10° reaming was conducted in triplicate sets for each reamer. Reamed glenoid computed tomography images were 3-dimensionally reconstructed using Mimics Medical software (version 21.0). Congruency between the glenoid surface and a 3-dimensional sphere with a 40-mm curvature radius was analyzed. Average deviation and ream-to-ream variance were compared between the hand, power, and Marksman reamer groups. Results The power reamer demonstrated the smallest median deviation (0.08 mm; interquartile range [IQR], 0.07-0.19 mm), followed by the Marksman (0.09 mm; IQR, 0.08-0.17 mm) and hand (0.11 mm; IQR, 0.10-0.13 mm) reamers. Kruskal-Wallis analysis indicated no significant difference in deviation among the 3 reaming methods (P = .42). The Marksman reamer demonstrated the least variance (0.0034 mm), followed by the power (0.0076 mm) and hand (0.0093 mm) reamers. The results of the Conover squared ranks test indicated no significant difference in variance among the 3 reaming methods (P = .32). Conclusion Our findings showed no statistically significant difference in the accuracy or consistency of reaming between reamer types. Trends showed less variance in the Marksman reamer group compared with the hand and power reamer groups, although differences in variation between groups were not statistically significant.

e16767 Background: Pancreatic Ductal Adenocarcinoma (PDAC) has one of the lowest 5-year survival rates of all cancers. Poor prognosis can be attributed in part to late detection and chemoresistance. Perioperative chemotherapy with or without radiation is the standard treatment for resectable PDAC, however recurrence rates remain high. GRP78 (HSPA5/BiP) is an endoplasmic reticulum (ER) chaperone protein involved in regulation of the ER stress response that leads to pro-survival pathway activation and chemoresistance in tumor cells. Prior studies of suppression of GRP78 expression in PDAC cell lines led to increased pancreatic cell apoptosis in response to gemcitabine. In vivo studies of human PDAC xenografts showed that tumors with higher GRP78 expression were associated with increased chemoresistance. Methods: We conducted a single institution retrospective review of 53 patients who underwent resection of PDAC from 1/1/2009-7/1/2016. Archived tumor tissue expression of GRP78 was assessed by immunohistochemistry (IHC) and scored as 0-3+. GRP78 IHC scores of 0-1+ were categorized as low and scores of 2-3+ as high. Corresponding clinical data were collected. Adjusted effects of GRP78 expression on the hazard of treatment failure or death were estimated using Cox proportional hazards models. Type III Wald Chi-square p-values are reported for the overall effect in each model. Results: GRP78 expression level demonstrated a significant effect on disease free survival (DFS) in unadjusted analyses (HR 2.00, p = 0.05), as well as after adjusting for performance status (p = 0.03), initial overall stage (p = 0.05), pathological tumor stage (p = 0.02), pathological node stage (p < 0.01), resection margins (p = 0.05), and neoadjuvant therapy (p = 0.05) in separate models. In unadjusted analysis, high GRP78 expression showed a trend towards worsened overall survival (OS), but did not reach statistical significance (HR 1.8, p = 0.11). The effect on OS was significant when adjusting for pathological tumor stage (p = 0.04) and pathological node stage (p = 0.01). (575). Conclusions: Consistent with prior animal studies, our retrospective review revealed that high GRP78 expression was associated with worsened DFS in patients with resectable PDAC. When adjusting for pathological staging, high GRP78 expression had a similar impact on OS. These findings warrant further evaluation of the role of GRP78 in prognosis, response to therapy and as a potential treatment target.

The rules by which odor receptors encode odors and allow behavior are still largely unexplored. Although large data sets of electrophysiological responses of receptors to odors have been generated, few hypotheses have been tested with behavioral assays. We use a data set on odor responses of Drosophila larval odor receptors coupled with chemotaxis behavioral assays to examine rules of odor coding. Using mutants of odor receptors, we have found that odor receptors with similar electrophysiological responses to odors across concentrations play non-redundant roles in odor coding at specific odor concentrations. We have also found that high affinity receptors for odors determine behavioral response thresholds, but the rules for determining peak behavioral responses are more complex. While receptor mutants typically show loss of attraction to odors, some receptor mutants result in increased attraction at specific odor concentrations. The odor receptor mutants were rescued using transgenic expression of odor receptors, validating assignment of phenotypes to the alleles. Vapor pressures alone cannot fully explain behavior in our assay. Finally, some odors that did not elicit strong electrophysiological responses are associated with behavioral phenotypes upon examination of odor receptor mutants. This result is consistent with the role of sensory neurons in lateral inhibition via local interneurons in the antennal lobe. Taken together, our results suggest a complexity of odor coding rules even in a simple olfactory sensory system.

e14037 Background: Immune-related adverse events (irAEs) related to immune checkpoint inhibitors (ICIs) may target any organ and originate from autoreactive T cells injuring host tissues. There is a need to develop prognostic and predictive biomarkers to distinguish patients (pts) who will benefit from ICIs avoiding irAEs during treatment. We propose that irAEs are the result of many biological variables. We hypothesize that within each pts complex immunological profile, there may be patterns and associations which exist that represent a state of inflammation that is present prior to ICI therapy and hypothesize this could predict irAEs development. Methods: We created individual immunological profiles of 11 pts diagnosed with MM prior to receiving ICIs. Assays included: PBMC composition, circulating chemokines/cytokines, and IκB degradation status. CD4 and CD8 T cells were studied for their phenotype, activation status, proliferative capacity and cytolytic granules. Clinical data was collected on a larger MM pt cohort (n = 41) and descriptive statistics were utilized to characterize reported irAEs . Results: 110 input markers were utilized for immune signature analysis. 6 of the 11 pts reported grade 2+ irAEs after ICI therapy. The pro-inflammatory CCL13, CCL1, FLT-3, IL12p40, TRAIL, and granzyme b expressing CD4 T cells at steady state and after CD3 activation were significantly higher in pts with irAEs. Known inflammatory suspects (i.e., IL-2, IL-15, TNF-a or % CD8 T cells) were not associated with irAE development . A rank correlation test showed significant associations between the levels of these factors. irAEs were reported in 41% (n = 17) for our larger cohort, most frequently skin rash (7%), colitis (7%), hepatitis (7%) and thyroid dysfunction (4%). Conclusions: The immune signatures of pts with irAEs are highly heterogeneous and possess distinctive immunological patterns. Our results introduce possible molecular mechanisms that may aid understanding of irAE development, perhaps providing the basis for a new model prospectively testing these markers to risk stratify pts receiving ICIs.

Background In the US, dentists prescribe 10% of outpatient antibiotics and are the top specialty prescriber. However, it is difficult to distinguish antibiotic prophylaxis vs. treatment because dentists generally code using procedure codes (CDT), rarely using diagnostic codes (ICD). In VA, dentists use CDT and ICD codes allowing for analyses of prescription (RX) indication. Therefore, the study purpose was to determine prescribing rates and indication for antibiotics prescribed by dentists. Methods Cross-sectional study of 476,451 patients with 1,741,708 visits in 205 VA dental clinics in 2013. Dentist RXs within 7 days of a dental visit were associated for ICD/CDT. The antibiotic indication (treatment vs. prophylaxis) was determined using RX days supply and dental visit ICD. SAS was used for all analyses; P ≤ 0.05 was significant. Results In 2013, there were 119,773 antibiotic RXs for 77,305 patients for a visit-based prescribing rate of 68.8/1000 visits. The most common antibiotic was amoxicillin (64.3%), followed by clindamycin (19.6%). Less than 2% of RX were broad-spectrum agents. The mean duration was 7.81 ± 8.52 days; 35% were > 10 days. The majority (69.9%) of antibiotics were prescribed for prophylaxis, with 30.1% prescribed for treatment of an oral infection. There was geographic variability in prescribing (P < 0.01) with the highest prescribing rate in the West (74.9/1000 visits) and the lowest in the Northeast (57.2/1000 visits). By state, Arkansas (100.7/1000 visits) and North Dakota (33.5/1000 visits) had the highest and lowest rates, respectively (Figure). As compared with other regions, dentists in the Northeast were more likely to prescribe broad-spectrum agents (RR = 1.80; 95% CI: 1.57-2.08), but less likely to prescribe clindamycin as compared with B-lactams (RR = 0.86; 95% CI: 0.82-0.90; P < 0.01 for all). Conclusion This is the first US study to determine indications and prescribing rates of antibiotics prescribed by dentists. Antibiotic dental prescribing varies geographically and differs as compared with prescribing patterns of medical providers. Dentistry may provide a novel opportunity for future stewardship efforts. Disclosures All authors: No reported disclosures. Figure Visit-based antibiotic prescribing rate by state.