Understanding General Surgery Recruitment and Attrition During the COVID-Era: A 1-Year Follow-Up Study.

INTRODUCTION: The COVID-19 pandemic resulted in modifications to resident selection. The success of these new recruitment strategies as well as the impact on trainee attrition and competency is unknown. We previously evaluated how selection of general surgery applicants changed early in the pandemic. Here we supplement that work by reporting further modifications to the recruitment process and the perceived impact on resident attrition and competency. METHODS: An anonymous cross-sectional survey sent via the Association of Program Directors in Surgery listserv in June 2022 to programs directors (PDs) at Accreditation Council for Graduate Medical Education accredited general surgery programs. Surveys contained demographic questions, 5-point Likert scale questions evaluating factors related to recruitment and match process, and postgraduate year 1 performance. RESULTS: 60 PDs responded to the survey. PDs continue to value the same post-COVID factors related to determining a resident's commitment to surgery but began to shift back to nonvirtual based strategies to recruit applicants in this new interview cycle. PD commentary frequently noted desire to return to in-person interviewing. 5.4% of postgraduate year 1s comprising this first class of residents who underwent virtual-only interviews and rotations did not reach Accreditation Council for Graduate Medical Education level 1 milestones, similar to prior years. The attrition rate amongst this class increased from 1.3% to 2.7%. CONCLUSIONS: The attrition rate for postgraduate year 1 categorical general surgery residents has increased since the onset of the pandemic. The recruitment strategies adopted early in the pandemic have not maintained their initial perceived impact.

Smaller Differences in the Comparative Effectiveness of Biologics in Reducing Asthma-Related Hospitalizations Compared With Overall Exacerbations.

BACKGROUND: Evidence on the comparative effectiveness of respiratory biologics remains sparse. OBJECTIVE: We sought to evaluate the comparative effectiveness of omalizumab, mepolizumab, benralizumab, and dupilumab in a matched retrospective cohort of patients with asthma. METHODS: We identified patients with asthma aged ≥18 years who were incident users of these biologics between November 1, 2018, and June 30, 2023, in administrative claims data from the Food and Drug Administration's Sentinel System and Merative MarketScan Commercial Database. We compared asthma-related exacerbations and hospitalizations in the 12 months since biologic prescription in pairwise comparisons of propensity score-matched cohorts. Covariates used in matching included age, sex, allergic comorbidities, baseline asthma medications use, and the Charlson Comorbidity Index. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using negative binomial regression models. RESULTS: A total of 893 patients on mepolizumab, 1300 on benralizumab, 1170 on omalizumab, and 1863 on dupilumab were identified. The average age was 55 years, and two-thirds of the participants were female. At baseline, over 80% of these individuals had an active prescription for an inhaled corticosteroid. Almost half of patients on dupilumab had concomitant nasal polyposis compared with 6% to 13% of patients on the other biologics. Covariates were balanced after matching. In matched analyses, dupilumab was associated with the lowest incidence of exacerbations over the follow-up period (vs dupilumab): mepolizumab (IRR: 1.36; 95% CI: 1.12, 1.64), omalizumab (IRR: 1.33; 95% CI: 1.13, 1.58), benralizumab (IRR: 1.19; 95% CI: 1.00, 1.41). For exacerbations leading to hospitalizations, benralizumab and mepolizumab were associated with the lowest incidence of hospitalizations, and the greatest difference was between mepolizumab versus dupilumab (IRR: 0.76; 95% CI: 0.56, 1.03). CONCLUSIONS: Dupilumab was associated with the lowest incidence of overall exacerbations, and mepolizumab with the lowest incidence of asthma hospitalizations in this administrative claims-based cohort of individuals with asthma. Despite matching propensity scores, residual confounding, such as baseline eosinophil count, may explain some of these findings.

Association of Residency Applicants' Hobbies and Subsequent Technical Proficiency Ratings as General Surgery Chief Residents: A Multi-Institutional Study.

OBJECTIVE: To determine whether participation in certain hobbies (e.g., participation in sports, playing musical instruments, or other hobbies requiring fine motor skills), preresidency, are associated with higher technical skills ratings at the time of residency graduation. DESIGN: Faculty members from 14 general surgery residency programs scored individual graduates from 2017 to 2020 on their technical skills using a 5-point Likert scale. Hobbies for these residents were collected from their Electronic Residency Application Service (ERAS) data. A single reviewer classified each ERAS hobby into predefined categories including musical instruments, sports requiring hand-eye coordination, team sports, and activities necessitating hand-eye coordination. Spearman correlation coefficients were calculated for the relationship between each category of hobby-as well as the total number of hobbies in each category-and the outcome of surgical faculty ratings of residents' technical surgical skills during their last year of residency. A proportional odds model including the above predictive variables was also fit to the data. SETTING: Fourteen general surgery residency programs. PARTICIPANTS: General surgery residency graduates from 14 different programs from 2017 to 2020. RESULTS: There were 296 residents across 14 institutions. The average ranking of residents' technical skills was 3.24 (SD 1.1). A total of 40% of residents played sports involving hand-eye coordination, 31% played team sports, 28% participated in nonsport hobbies that require eye-hand coordination, and 20% played musical instruments. Correlation coefficients were not statistically significant for any of the categories. In the proportional odds model, none of the variables were associated with statistically significant increased odds of a higher technical skills rating. CONCLUSIONS: There was no correlation between general surgery chief residents' technical skills as rated by faculty, and self-reported pre-residency hobbies on the ERAS application. These findings suggest such hobbies prior to residency are unlikely to predict future technical skills prowess.

Gender Differences in Autonomy Granted to Residents and Fellows During Procedural Training: A Systematic Review and Meta-Analysis.

PURPOSE: Supervisors may be prone to implicit (unintentional) bias when granting procedural autonomy to trainees due to the subjectivity of autonomy decisions. The authors aimed to conduct a systematic review and meta-analysis to assess the differences in perceptions of procedural autonomy granted to physician trainees based on gender and/or race. METHOD: MEDLINE, Embase, CENTRAL, Scopus, and Web of Science were searched (search date: January 5, 2022) for studies reporting quantitative gender- or race-based differences in perceptions of procedural autonomy of physician trainees. Reviewers worked in duplicate for article selection and data abstraction. Primary measures of interest were self-reported and observer-rated procedural autonomy. Meta-analysis pooled differences in perceptions of procedural autonomy based on trainee gender. RESULTS: The search returned 2,714 articles, of which 16 were eligible for inclusion. These reported data for 6,109 trainees (median 90 per study) and 2,763 supervisors (median 54 per study). No studies investigated differences in perceptions of autonomy based on race. In meta-analysis of disparities between genders in autonomy ratings (positive number favoring female trainees), pooled standardized mean differences were -0.12 (95% confidence interval [CI] = -0.19, -0.04; P = .003; n = 10 studies) for trainee self-rated autonomy and -0.05 (95% CI = -0.11, 0.01; P = .07; n = 9 studies) for supervisor ratings of autonomy. CONCLUSIONS: Limited evidence suggests that female trainees perceived that they received less procedural autonomy than did males. Further research exploring the degree of gender- and race-based differences in procedural autonomy, and factors that influence these differences, is warranted.

Analysis of COVID-19 Case Demographics and Disease Outcomes in Gary, Indiana.

BACKGROUND: The COVID-19 pandemic further exposed the prevalence of existing health disparities in Black communities in the U.S. The current study evaluates COVID-19 data collected in Gary, Indiana, from June 2020 to June 2021. We hypothesized that the number of COVID-19 cases, hospitalizations, and deaths were influenced by race and income. METHODS: In collaboration with the Gary Health Department (GHD), we analyzed demographic data on COVID-19-positive cases. RESULTS: Compared to Gary's non-Black population, age- and population-adjusted rates of hospitalizations and deaths in the Black population were 3-fold (p < 0.0001) and 2-fold (p < 0.05) higher, respectively. This is despite a higher infection rate (p < 0.0001) in the non-Black population. The median household income of a zip code was negatively correlated with COVID-19 hospitalizations (R2 = 0.6345, p = 0.03), but did not correlate with infections and deaths. CONCLUSIONS: The current study demonstrates clear health disparities of income and race in the context of COVID-19-related infections and outcomes in the city of Gary. Indiana University School of Medicine Northwest and GHD officials can collaborate to utilize these data for the reallocation of resources and health education efforts in Gary's highly populated, low-income, and predominantly Black neighborhoods. It should also prompt further investigation into national health resource allocation.

Investigation of High Molecular Weight Size Variant Formation in Antibody-Drug Conjugates: Microbial Transglutaminase-Mediated Crosslinking.

Microbial transglutaminase (mTG) has become a powerful tool for manufacturing antibody-drug conjugates (ADCs). It enables site-specific conjugation by catalyzing formation of stable isopeptide bond between glutamine (Q) side chain and primary amine. However, the downstream impact of mTG-mediated conjugation on ADC product quality, especially on high molecular weight (HMW) size variant formation has not been studied in a systematic manner. This study investigates the mechanisms underlying the formation of HMW size variants in mTG-mediated ADCs using size exclusion chromatography (SEC) and liquid chromatography-mass spectrometry (LC-MS). Our findings revealed that the mTG-mediated glutamine and lysine (K) crosslinking is the primary source of the increased level of HMW size variants in the ADCs. In the study, two monoclonal antibodies (mAbs) with glutamine engineered for site-specific conjugation were used as model systems. Based on the LC-MS analysis, a single lysine (K56) in the heavy chain (HC) was identified as the major Q-K crosslinking site in one of the two mAbs. The HC C-terminal K was observed to crosslink to the target Q in both mAbs. Quantitative correlation was established between the percentage of HMW size variants determined by SEC and the percentage of crosslinked peptides quantified by MS peptide mapping. Importantly, it was demonstrated that the level of HMW size variants in the second ADC was substantially reduced by the complete removal of HC C-terminal K before conjugation. The current work demonstrates that crosslinking and other side reactions during mTG-mediated conjugation needs to be carefully monitored and controlled to ensure process consistency and high product quality of the final ADC drug product.

Decoupling Transmission and Transduction for Improved Durability of Highly Stretchable, Soft Strain Sensing: Applications in Human Health Monitoring.

This work presents a modular approach to the development of strain sensors for large deformations. The proposed method separates the extension and signal transduction mechanisms using a soft, elastomeric transmission and a high-sensitivity microelectromechanical system (MEMS) transducer. By separating the transmission and transduction, they can be optimized independently for application-specific mechanical and electrical performance. This work investigates the potential of this approach for human health monitoring as an implantable cardiac strain sensor for measuring global longitudinal strain (GLS). The durability of the sensor was evaluated by conducting cyclic loading tests over one million cycles, and the results showed negligible drift. To account for hysteresis and frequency-dependent effects, a lumped-parameter model was developed to represent the viscoelastic behavior of the sensor. Multiple model orders were considered and compared using validation and test data sets that mimic physiologically relevant dynamics. Results support the choice of a second-order model, which reduces error by 73% compared to a linear calibration. In addition, we evaluated the suitability of this sensor for the proposed application by demonstrating its ability to operate on compliant, curved surfaces. The effects of friction and boundary conditions are also empirically assessed and discussed.

Circulatory Support: Artificial Muscles for the Future of Cardiovascular Assist Devices.

Artificial muscles enable the design of soft implantable devices which are poised to transform the way we mechanically support the heart today. Heart failure is a prevalent and deadly disease, which is treated with the implantation of rotary blood pumps as the only alternative to heart transplantation. The clinically used mechanical devices are associated with severe adverse events, which are reflected here in a comprehensive list of critical requirements for soft active devices of the future: low power, no blood contact, pulsatile support, physiological responsiveness, high cycle life, and less-invasive implantation. In this review, prior art in artificial muscles for their applicability in the short and long term is investigated and critically evaluated. The main challenges regarding the effectiveness, controllability, and implantability of recently proposed actuators are highlighted and the future perspectives for attachment, physiological responsiveness, durability, and biodegradability as well as equitable design considerations are explored.

The Patient's Voice in Assessing Resident Communication Skills.

OBJECTIVE: To generate validity evidence for using patient-reported satisfaction ratings of residents' communication skills to determine progress along the Interpersonal and Communication Skills (ICS) Milestones. DESIGN: A single-institution, retrospective study analyzed a CAHPS Clinician and Group Survey (CG-CAHPS) database which collects inpatients' ratings of residents' communication skills using 6 questions on a scale of 1 (very poor) to 5 (very good). CG-CAHPS results for each resident were averaged for each question as well as across the 6 questions. The averaged ratings were compared between low and high performer groups. SETTING: A large, academic, mid-western General Surgery residency program. PARTICIPANTS: General Surgery residents with 3 or more survey responses from July 2020 to June 2021 were included. Residents were dichotomized into low or high performer groups based on their end-of-year ICS1 sub-competency milestone within their post-graduate year (PGY) cohort. RESULTS: 543 CG-CAHPS responses across 44 residents were analyzed with a median of 9 (Interquartile range 6, 17) responses per resident. When residents were compared based on PGY, ratings for the question "resident's knowledge about your medical care of condition" demonstrated statistically significant differences with PGY5s receiving the lowest score (p = 0.05). PGY5s received the lowest averaged ratings across all questions (p = 0.08, η2 = 0.10). When residents were dichotomized into low (n = 21) and high performer groups (n = 23) based on ICS1 milestones, statistically significant differences were noted in ratings for the questions "concern the resident showed for your questions or worries" (4.81 vs. 5, p = 0.047) and "courtesy and respect of the resident" (4.75 vs. 5, p = 0.046). CONCLUSIONS: Analysis of patient ratings of surgery residents' communication skills demonstrated concordant findings between ICS1 milestone and 2 domains of CG-CAHPS responses. When low and high performer groups were compared, CG-CAHPS responses demonstrated a similar pattern. These findings provide validity evidence for CG-CAHPS data as a source of information for ICS1 sub-competency assessment.

Managing Up: Approaching Mentoring From a Mentee's Perspective.

OBJECTIVE: Discuss the evolution of mentorship models in surgical training and how educating the surgical trainees with the concepts from "manage up" theory can empower them to maximize the benefits afforded by mentoring relationships. METHODS: "Manage up" theory is derived from the business world where the subordinate takes ownership of the mentoring relationship with their superior by assessing the strengths and weaknesses of both parties and applying that information in managing a productive relationship. DISCUSSION: Surgery residency programs implement a variety of structured and unstructured mentorship programs to promote mentoring relationships and to encourage professional development. Mentees in successful mentoring relationships demonstrate characteristics and skills that residency programs can promote through formal training. Components of "manage up" theory can be applied by surgical trainees in approaching their mentors and in managing their mentor-mentee relationships. CONCLUSIONS: The benefits gained from a successful mentoring relationship for both the mentor and the mentee depend on active roles played by both parties. Strong evidence supports the need for educating mentees through formal curricula to empower them to assume an active role in their mentoring relationships.

Transcription factor-nucleosome dynamics from plasma cfDNA identifies ER-driven states in breast cancer.

Genome-wide binding profiles of estrogen receptor (ER) and FOXA1 reflect cancer state in ER+ breast cancer. However, routine profiling of tumor transcription factor (TF) binding is impractical in the clinic. Here, we show that plasma cell-free DNA (cfDNA) contains high-resolution ER and FOXA1 tumor binding profiles for breast cancer. Enrichment of TF footprints in plasma reflects the binding strength of the TF in originating tissue. We defined pure in vivo tumor TF signatures in plasma using ER+ breast cancer xenografts, which can distinguish xenografts with distinct ER states. Furthermore, state-specific ER-binding signatures can partition human breast tumors into groups with significantly different ER expression and mortality. Last, TF footprints in human plasma samples can identify the presence of ER+ breast cancer. Thus, plasma TF footprints enable minimally invasive mapping of the regulatory landscape of breast cancer in humans and open vast possibilities for clinical applications across multiple tumor types.

Characteristics Associated With Outstanding General Surgery Residency Graduate Performance, as Rated by Surgical Educators.

Importance: Characteristics of outstanding graduating surgical residents are currently undefined. Identifying these qualities may be important in guiding resident selection and resident education. Objective: To determine characteristics that are most strongly associated with being rated as an outstanding graduating surgical resident. Design, Setting, and Participants: The multi-institutional study had 3 phases. First, an expert panel developed a list of characteristics embodied by top graduating surgical residents. Second, groups of faculty from 14 US general-surgery residency programs ranked 2017 through 2020 graduates into quartiles of overall performance. Third, faculty evaluated their graduates on each characteristic using a 5-point Likert scale. Data were analyzed using Spearman rank-order correlation to identify which individual characteristics were associated with overall graduate performance. A least absolute shrinkage and selection operator (LASSO) ordinal regression was performed to select a parsimonious model to predict the outcome of overall performance rating from individual characteristic scores. Main Outcome and Measures: Surgical educators' rankings of general surgery residency graduates' overall performance. Results: Fifty faculty from 14 US residency programs with a median of 13 (range, 5-30) years of surgical education experience evaluated 297 general surgery residency graduates. Surgical educators identified 21 characteristics that they believed outstanding graduating surgical residents possessed. Two hundred ninety-seven surgical residency graduates were evaluated. Higher scores in every characteristic correlated with better overall performance. Characteristics most strongly associated with higher overall performance scores were surgical judgment (r = 0.728; P < .001), leadership (r = 0.726; P < .001), postoperative clinical skills (r = 0.715; P < .001), and preoperative clinical skills (r = 0.707; P < .001). The remainder of the characteristics were moderately associated with overall performance. The LASSO regression model identified 3 characteristics from which overall resident performance could be accurately predicted without measuring other qualities: surgical judgment (odds ratio [OR] per 1 level of 5-level Likert scale OR, 1.27; 95% CI, 1.03-1.51), leadership (OR, 1.27; 95% CI, 1.06-1.48), and medical knowledge (OR, 1.16; 95% CI, 1.01-1.33). Conclusions and Relevance: All individual characteristics identified by surgical educators as being qualities of outstanding graduating surgical residents were positively associated with overall graduate performance. Surgical judgment and leadership skills had the strongest individual associations. Assessment of only 3 qualities (surgical judgment, leadership, and medical knowledge) were required to predict overall resident performance ratings. These findings highlight the importance of developing specific surgical judgment and leadership skills curricula and assessments during surgical residency.

Operative teaching takes "GUTS": Impact of Educational Time Out on trainee's cognitive load.

BACKGROUND: Educational Time Out (ETO) incorporates intraoperative goal setting, task delineation, and debriefing. ETO has been previously reported to generate positive learning experiences for residents. This study aimed to study the impact of ETO on surgery residents' cognitive load. METHODS: A cross-over study design utilized the ETO arm during the first half of the rotation followed by no ETO for the second half. Surgery residents completed a modified NASA Task Load Index (NASA TLX) questionnaire following each operative case to report their cognitive load. RESULTS: 141 modified NASA TLX questionnaire responses were obtained where ETO occurred in 73 responses and no ETO in 68 responses. Residents reported a higher performance (p = 0.004) and a lower frustration (p = 0.018) component scores when ETO occurred. CONCLUSIONS: This study identified improved cognitive load on the modified NASA TLX instrument with higher performance and lower frustration scores associated with trainees who underwent preoperative goal setting with an ETO using the GUTS method.

Neoadjuvant endocrine therapy expands stromal populations that predict poor prognosis in estrogen receptor-positive breast cancer.

The tumor microenvironment (TME) is an important modulator of response and resistance to endocrine therapy in estrogen receptor alpha (ER) positive breast cancer. Endocrine therapy is highly effective at reducing tumor burden and preventing recurrence in most estrogen receptor alpha (ER) positive breast cancers. Existing drugs work either directly by targeting tumor-cell ER or indirectly by inhibiting estrogen production in stromal cells with aromatase inhibitors (AI). However, many stromal cells also express ER and the direct impact of endocrine therapies on ER + stromal cells remain unclear. In this study, we investigated how neoadjuvant endocrine therapy (NET) directly effects stromal cells by measuring changes in stomal components of the TME that favor tumor progression. We previously defined two major subsets of tumor-associated stromal cells (TASCs): CD146 positive/CDCP1 negative (TASCCD146 ), CD146 negative/CDCP1 positive (TASCCDCP1 ), and generated a differentially expressed genes list associated with each type. Here, we applied the TASC gene list for classification and an algorithm that estimates immune cell abundance (TIMEx) to METABRIC transcriptomic data for ER + breast cancer patients coupled with multiplex imaging and analysis of paired tissue samples pre- and post- NET with the AI exemestane. TASCCDCP1 composition predicted for decreased patient survival in the METABRIC cohort. Exemestane treatment significantly increased expression of TASCCDCP1 and decreased expression of TASCCD146 . The posttreatment shift toward TASCCDCP1 composition correlated with increased macrophage infiltration and increased CD8+ T-cell, B cell, and general stromal components. The effectiveness of NET is currently based solely on the reduction of ER+ breast cancer cells. Here, we show NET displays clear TME effects that promote the expansion of the less favorable TASCCDCP1 population which are correlated with TME remodeling and reshaping immune infiltration supportive of tumor progression. Our findings highlight the need to further understand the role of endocrine therapy on TME remodeling, tumor progression, and patient outcomes.

The Virtual Recruitment Onion: Peeling Back the Layers of the Interview Season During the COVID-era.

OBJECTIVE: We sought to characterize General Surgery residency program directors' (PDs) baseline perspective on how the COVID-19 mandated changes to the recruitment and interview processes impacted how the PDs evaluated and recruited the applicants. DESIGN: An anonymous cross-sectional questionnaire survey. SETTING: A large, mid-western academic general surgery residency program. PARTICIPANTS: 47 PDs of Accreditation Council for Graduate Medical Education (ACGME) accredited General Surgery residency programs. RESULTS: During the virtual-only interviews during the COVID-19 pandemic-era 2020-21 General Surgery residency application cycle, PDs shifted their focus to virtual outreach efforts and bolstered social media presences to recruit strong applicants. Also, our study found statistically significant changes to the increased value of letters of recommendation (LORs) for the PDs when assessing an applicant's commitment to surgery. These findings suggest that the necessity of adapting to the virtual-only interview format significantly altered how the PDs recruited and evaluated applicants for the General Surgery residency match. CONCLUSIONS: A complete replacement of the in-person interviews with virtual-only interviews may be challenging unless buy-in exists from key stakeholders in the surgical community. Our study highlights the PDs' hesitation in assessing candidates' commitment to surgery from virtual interviews alone. Incorporating virtual interviews as a part of the screening process for applicants may serve as an avenue to maximize the benefits of the virtual interview format. Furthermore, COVID-19 pandemic has normalized the growing social media presence of residency programs, adding to the changing landscape of recruiting and interviewing applicants for General Surgery residency match.

The Impact of Simulation Training on Operative Performance in General Surgery: Lessons Learned from a Prospective Randomized Trial.

BACKGROUND: Practice in the simulated environment can improve surgical skills. However, the transfer of open complex surgical skills to the operating room is unclear. This study evaluated the effect of resident operative performance following a simulation experience on a hand-sewn small bowel anastomosis and determined the impact of utilizing proficiency-based training. METHODS: Nine categorical interns performed a hand-sewn small bowel anastomosis in the operating room prior to (pre-test) and following (post-test) a 3-h simulation training session with an assessment at the end. Participants were randomly assigned to 1of 2 simulation training groups: proficiency-based or standard. Operative performance was videotaped. 2 independent, blinded faculty surgeons assessed performances by a global rating scale. Pre- and post-confidence levels were obtained on a 5-point Likert scale. RESULTS: Overall, pre-test and post-test operative performance was similar (3 [IQR, 2.5 -3.5] versus 3 [IQR, 3 -3], P = 0.59). Furthermore, no difference was observed in the post-test performance with proficiency-based or standard training (3 [IQR, 3 -3] versus 3 [IQR, 3 -3], P = 0.73). Self-reported confidence with the skills, however, significantly improved (median 1 versus 4, P = 0.007). CONCLUSIONS: In this prospective, randomized study, we did not observe an improvement in operative performance following simulation instruction and assessment, with both training groups. Overcoming barriers to skills transfer will be paramount in the future to optimize simulation training in general surgery. These findings highlight the importance of continued study for the ideal conditions and timing of technical skills training.

Development of Novel Glucocorticoids for Use in Antibody-Drug Conjugates for the Treatment of Inflammatory Diseases.

Glucocorticoids (GCs) are widely used to treat a variety of autoimmune and inflammatory diseases; however, systemic delivery of GCs is associated with side effects that affect essentially every organ system, reflecting the nearly ubiquitous expression of the glucocorticoid receptor (GR). Targeted delivery of GCs to diseased tissues using antibody-glucocorticoid conjugates (GC-ADCs) offers a therapeutic alternative to overcome these adverse effects. Herein, we describe novel classes of GCs that exhibited greater potency than dexamethasone and budesonide, a 100-fold selectivity toward the GR over other nuclear receptors, and no in vitro safety liability in pharmacology assays (hERG, AMES) and that demonstrated a substantial reduction in tumor necrosis factor-α (TNF-α) release in mice challenged with lipopolysaccharide (LPS). The site-specific conjugated GC-ADCs via cathepsin-cleavable linkers were highly stable in plasma and specifically released GCs in antigen-positive cells, suggesting that these novel GCs can serve as ADC payloads to treat autoimmune and inflammatory diseases.

Value of Standardized Testing in Surgical Training.

Standardized testing remains a cornerstone of assessment in surgical education. Summative standardized tests make up a bulk of the certification requirements that encompasses demonstration of efficient, safe application of clinically relevant surgical knowledge and skills. Formative standardized tests serve similar role to guide teaching endeavors for the programs and comparison of individual trainees on a national level. Ongoing rigorous psychometric evaluations of the standardized tests ensure reliability and validity; however, standardized tests are not without their limitations and biases.

Efficacy and Safety of 1% Progesterone Gel to the Forehead for Ocular Chronic Graft-versus-Host Disease.

There is no Food and Drug Administration-approved treatments for ocular chronic graft-versus-host disease (oGVHD) to date, and current therapeutic options are limited. Forehead application of 1% progesterone gel provides corneal antinociception in preclinical models, suggesting it may be useful in alleviating ocular irritations. This study was conducted to evaluate the efficacy and safety of 1% progesterone gel in treating moderate to severe symptomatic oGVHD. Thirty-three patients with oGVHD following allogeneic stem cell transplantation were enrolled in this single-center, sponsor-initiated, prospective exploratory randomized double-masked placebo-controlled phase II clinical trial. The inclusion criteria included a National Institutes of Health consensus score of ≥2, moderate to severe ocular discomfort level, and receipt of a stable immunosuppression regimen. Twenty-one of the 22 patients in the progesterone arm and all 11 patients in the placebo arm completed the course of twice-daily forehead drug application for 10 weeks. The changes from baseline of self-reported ocular symptom scores and physician-recorded cornea fluorescein staining scores were analyzed using mixed-model repeated-measures regression model in an intention-to-treat population. The 33 patients included 12 women and 21 men, with a median age of 66 years (range, 24 to 75 years). At 10 weeks, there was a significant reduction in ocular symptoms from baseline in the progesterone group compared with the placebo group in symptom frequency (-30.7 versus -2.2; P < .001) and severity (-19.8 versus +1.6; P = .005). At 10 weeks, there was also greater reduction of cornea fluorescein staining centrally (-1.2 versus +.1; P = .001) and inferiorly (-1.4 versus -0.2; P = .005). No difference was noted in superior cornea staining. There were no severe adverse events in the progesterone group. Forehead application of 1% progesterone gel significantly improved ocular signs and symptoms within 10 weeks. It appears to be a safe and effective new therapy for oGVHD, and a novel mechanism for neuroaxis drug delivery. A multicenter phase III clinical trial is planned for further validation.

Don't Judge a Letter by its Title: Linguistic Analysis of Letters of Recommendation by Author's Academic Rank.

OBJECTIVE: This study analyzed the linguistic differences in letters of recommendation (LORs) for general surgery residency applicants written by authors of various academic ranks. Given that many general surgery residency programs require a LOR from the Chair of surgery, this study also examined whether LORs written by the Chair demonstrate linguistic differences to support this practice. DESIGN: A single institution, retrospective review analyzed LORs from two application cycles of general surgery residency applicants who were selected for interview at a large academic institution. Word count (WC) and linguistic characteristics of LORs were analyzed with a previously developed institution-specific dictionary using the Linguistic Inquiry and Word Count software (LIWC2015; Pennebaker Conglomerates, Inc., Austin, Texas). WC and linguistic characteristics of LORs reported as frequencies of terms within twenty-four categories were examined based on the letter authors' academic rank. Further examination compared LORs written by a Chair of surgery with those written by non-Chairs. SETTING: A single large, Midwestern academic general surgery residency program PARTICIPANTS: Four hundred and sixty-five letters of recommendation received during two interview cycles were included for analysis. RESULTS: A total of 465 LORs written by assistant (n = 82), associate (n = 94), and full professors (n = 289) were included in the study. No statistically significant difference was noted in the WC of LORs based on the letter writers' academic ranks (p = 0.95). Assistant professors utilized grindstone, communal, and technical skill terms with higher frequencies compared to associate professors and full professors. LORs written by assistant professors demonstrated the highest authentic variable score followed by associate professors then full professors (4.94, 3.92, 3.28, p < 0.01). LORs written by Chairs (n = 128) had lower authentic variable scores compared to LORs written by non-Chairs (n = 337; 2.71 vs. 3.91, p = 0.001). Only 50 (39%) LORs written by Chairs indicated working directly with the applicant, and sub-group analysis demonstrated a higher authentic variable score in this group compared with LORs written by Chairs who did not indicate having worked directly with the applicant (3.51 vs. 2.5, p = 0.01). CONCLUSIONS: Linguistic analysis of LORs for general surgery residency applicants demonstrated minor yet statistically significant differences based on the author's academic rank. If applicants can obtain linguistically similar LORs from surgeons of any academic rank, but less authentic LORs from writers with higher academic ranks, these LORs may be less valuable for the residency programs when evaluating applicants. Based on the subgroup analysis, less than 40% of Chair LORs indicated that the Chair worked directly with the applicant, calling into question the utility of the Chair LORs as meaningful evaluation of applicants. Further study to compare LORs of applicants selected and not selected for interview may add additional insight into linguistic differences in LORs written by authors of different academic ranks.