Identification of Factors Associated with Orthopaedic Surgery Residency Programs That Preferentially Match Students Who Performed an Elective Rotation Before the Interview Process.

Introduction: The role of elective rotations in the orthopaedic residency selection process varies between programs. Our study aims to identify factors associated with residency programs that interview and match a greater proportion of applicants who have completed an elective rotation with their program. Methods: Data were collected through the American Orthopaedic Association's Orthopaedic Residency Information Network database. Bivariate correlations and multivariate regression models were used to identify independent predictors of programs with a greater proportion of interviewees or residents who completed an elective rotation at the respective program. Results: One hundred seventy-eight of the 218 existing residency programs were included in this study. Programs that offered fewer interviews and more away rotation positions per year were associated with a greater odds of its interviewees (OR = 0.36, p = 0.01; OR = 4.55, p < 0.001, respectively) and residents (OR = 0.44, p = 0.04; OR = 4.23, p < 0.001, respectively) having completed an elective rotation with the program. In addition, programs with fewer attendings (OR = 0.39, p = 0.03) and in-person interviews (OR = 3.04, p = 0.04) matched a greater proportion of their rotators. However, programs that interviewed applicants during the elective rotation were less likely to match their rotators (OR = 0.35, p = 0.04). Conclusion: Certain program characteristics independently predict the likelihood of a program interviewing and matching their rotators. These findings may provide information for applicants and programs regarding the rotation process. Level of Evidence: III.

Analysis of Hip Preservation Questions on the Orthopaedic In-Training Examination Over the Past 20 Years.

Background: The orthopaedic in-training examination (OITE) is a 275-question test for orthopaedic residents administered annually. As the field of orthopaedics changes, the OITE evolves its content. The incidence of hip preservation-related procedures has increased substantially over the past decade; nonetheless, an analysis of the trends of hip preservation questions on the OITE has not yet been performed. Purpose/Hypothesis: The purpose of the study was to evaluate the number and type of questions on the OITE related to hip preservation to determine whether trends over time paralleled the increases in hip-related care in clinical practice. It was hypothesized that the frequency of hip preservation questions on the OITE would increase with time. Study Design: Cross-sectional study. Methods: Each OITE between 2002 and 2021 was reviewed for questions related to hip preservation. The types of questions included under "hip preservation" were those related to femoroacetabular impingement (FAI), athletic soft tissue injuries of the hip, acetabular labral tears, hip arthroscopy, and surgical management of adult hip dysplasia-excluding arthroplasty. Questions were quantified and categorized by topic, taxonomy level, associated imaging, and cited sources. Results: There were 30 hip preservation-related questions between 2002 and 2021. Of these, 77% occurred within the past 10 years. Also, 14 questions (47%) had associated images in the question stem-the most common being radiographs (n = 8 questions). The most commonly tested subcategories were FAI (n = 11 questions [37%]), athletic injuries (n = 7 questions [23%]), and anatomy (n = 7 questions [23%]). Over the last 10 years, 97.9% of citations were from journal articles-the most common being the Journal of the American Academy of Orthopaedic Surgeons, Clinical Orthopedics and Related Research, and the American Journal of Sports Medicine. Conclusion: The frequency of hip preservation-related questions on the OITE has increased with time, reflecting trends in clinical practice.

Racial Disparities in 30-day Readmission After Orthopaedic Surgery: A 5-year National Surgical Quality Improvement Program Database Analysis.

BACKGROUND: Readmission rate after surgery is an important outcome measure in revealing disparities. This study aimed to examine how 30-day readmission rates and causes of readmission differ by race and specific injury areas within orthopaedic surgery. METHODS: The American College of Surgeon-National Surgical Quality Improvement Program database was queried for orthopaedic procedures from 2015 to 2019. Patients were stratified by self-reported race. Procedures were stratified using current procedural terminology codes corresponding to given injury areas. Multiple logistic regression was done to evaluate associations between race and all-cause readmission risk, and risk of readmission due to specific causes. RESULTS: Of 780,043 orthopaedic patients, the overall 30-day readmission rate was 4.18%. Black and Asian patients were at greater (OR = 1.18, P < 0.01) and lesser (OR = 0.76, P < 0.01) risk for readmission than White patients, respectively. Black patients were more likely to be readmitted for deep surgical site infection (OR = 1.25, P = 0.03), PE (OR = 1.64, P < 0.01), or wound disruption (OR = 1.45, P < 0.01). For all races, all-cause readmission was highest after spine procedures and lowest after hand/wrist procedures. CONCLUSIONS: Black patients were at greater risk for overall, spine, shoulder/elbow, hand/wrist, and hip/knee all-cause readmission. Asian patients were at lower risk for overall, spine, hand/wrist, and hip/knee surgery all-cause readmission. Our findings can identify complications that should be more carefully monitored in certain patient populations.

Racial and Ethnic Bias in Medical School Clinical Grading: A Review.

OBJECTIVE: Improving diversity in healthcare is a widely recognized national goal. The diversity of medical student matriculants has increased, yet this trend is not seen in the composition of competitive residency programs. In this review, we examine racial and ethnic disparities in medical student grading during clinical years and explore the consequences of how this may exclude minority students from accessing competitive residency positions. DESIGN: Following PRISMA guidelines, we searched PubMed, Embase, Scopus, and ERIC databases using variations of the terms "race," "ethnicity," "clerkship," "rotation," "grade," "evaluation", or "shelf exam." Of 391 references found using the criteria, 29 were related to clinical grading and race/ethnicity and included in the review. The GRADE criteria were used to determine the quality of evidence. SETTING: Johns Hopkins School of Medicine, Baltimore MD. RESULTS: Five studies examining a total of 107,687 students from up to 113 different schools found racial minority students receive significantly fewer Honors grades in core clerkships compared to White students. Three studies examining 94,814 medical student evaluations from up to 130 different schools found significant disparities in the wording of written clerkship evaluations based on race and/or ethnicity. CONCLUSIONS: A large body of evidence suggests the presence of racial bias in subjective clinical grading and written clerkship evaluations of medical students. Grading disparities can disadvantage minority students when applying to competitive residency programs and may contribute to a lack of diversity in these fields. As low minority representation has a negative impact on patient care and research advancement, strategies to resolve this issue must be further explored.

Amino Acid Availability Determines Plant Immune Homeostasis in the Rhizosphere Microbiome.

Microbes possess conserved microbe-associated molecular patterns (MAMPs) that are recognized by plant receptors to induce pattern-triggered immunity (PTI). Despite containing the same MAMPs as pathogens, commensals thrive in the plant rhizosphere microbiome, indicating they must suppress or evade host immunity. Previous work found that bacterial-secreted gluconic acid is sufficient to suppress PTI. Here, we show that gluconic acid biosynthesis is not necessary for immunity suppression by the beneficial bacterial strain Pseudomonas simiae WCS417. We performed a forward genetic screen with EMS-mutagenized P. simiae WCS417 and a flagellin-inducible CYP71A12pro:GUS reporter as a PTI readout. We identified a loss of function mutant in ornithine carbamoyltransferase argF, which is required for ornithine conversion to arginine, that cannot suppress PTI or acidify the rhizosphere. Fungal pathogens use alkalization through production of ammonia and glutamate, and arginine biosynthetic precursors, to promote their own growth and virulence. While a ΔargF mutant has a growth defect in the rhizosphere, we found that restoring growth with exogenous arginine resulted in rhizosphere alkalization in a mutant that cannot make gluconic acid, indicating that arginine biosynthesis is required for both growth and acidification. Furthermore, blocking bacterial arginine, glutamine, or proline biosynthesis through genetic mutations or feedback inhibition by adding corresponding amino acids, resulted in rhizosphere alkalization. Untargeted metabolomics determined that ornithine, an alkaline molecule, accumulates under conditions associated with rhizosphere alkalization. Our findings show that bacterial amino acid biosynthesis contributes to acidification by preventing accumulation of ornithine and the resulting alkalization. IMPORTANCE Understanding how microbiota evade and suppress host immunity is critical to our knowledge of how beneficial microbes persist in association with a host. Prior work has shown that secretion of organic acids by beneficial microbes is sufficient to suppress plant immunity. This work shows that microbial amino acid metabolism is not only critical for growth in the plant rhizosphere microbiome, but also for regulation of plant rhizosphere pH, and, consequentially, regulation of plant immunity. We found that, in the absence of microbial glutamate and arginine metabolism, rhizosphere alkalization and microbial overgrowth occurs. Collectively, our findings suggest that, by regulating nutrient availability, plants have the potential to regulate their immune homeostasis in the rhizosphere microbiome.

Are There Differences in Postoperative Opioid Prescribing Across Racial and Ethnic Groups? Assessment of an Academic Health System.

BACKGROUND: Previous studies have demonstrated racial disparities in opioid prescribing in emergency departments and after surgical procedures. Orthopaedic surgeons account for a large proportion of dispensed opioid prescriptions, yet there are few data investigating whether racial or ethnic disparities exist in opioid dispensing after orthopaedic procedures. QUESTIONS/PURPOSES: (1) Are Black, Hispanic or Latino, or Asian or Pacific Islander (PI) patients less likely than non-Hispanic White patients to receive an opioid prescription after an orthopaedic procedure in an academic United States health system? (2) Of the patients who do receive a postoperative opioid prescription, do Black, Hispanic or Latino, or Asian or PI patients receive a lower analgesic dose than non-Hispanic White patients when analyzed by type of procedure performed? METHODS: Between January 2017 and March 2021, 60,782 patients underwent an orthopaedic surgical procedure at one of the six Penn Medicine healthcare system hospitals. Of these patients, we considered patients who had not been prescribed an opioid within 1 year eligible for the study, resulting in 61% (36,854) of patients. A total of 40% (24,106) of patients were excluded because they did not undergo one of the top eight most-common orthopaedic procedures studied or their procedure was not performed by a Penn Medicine faculty member. Missing data consisted of 382 patients who had no race or ethnicity listed in their record or declined to provide a race or ethnicity; these patients were excluded. This left 12,366 patients for analysis. Sixty-five percent (8076) of patients identified as non-Hispanic White, 27% (3289) identified as Black, 3% (372) identified as Hispanic or Latino, 3% (318) identified as Asian or PI, and 3% (311) identified as another race ("other"). Prescription dosages were converted to total morphine milligram equivalents for analysis. Statistical differences in receipt of a postoperative opioid prescription were assessed with multivariate logistic regression models within procedure, adjusted for age, gender, and type of healthcare insurance. Kruskal-Wallis tests were used to assess for differences in the total morphine milligram equivalent dosage of the prescription, stratified by procedure. RESULTS: Almost all patients (95% [11,770 of 12,366]) received an opioid prescription. After risk adjustment, we found no differences in the odds of Black (odds ratio 0.94 [95% confidence interval 0.78 to 1.15]; p = 0.68), Hispanic or Latino (OR 0.75 [95% CI 0.47 to 1.20]; p = 0.18), Asian or PI (OR 1.00 [95% CI 0.58 to 1.74]; p = 0.96), or other-race patients (OR 1.33 [95% CI 0.72 to 2.47]; p = 0.26) receiving a postoperative opioid prescription compared with non-Hispanic White patients. There were no race or ethnicity differences in the median morphine milligram equivalent dose of postoperative opioid analgesics prescribed (p > 0.1 for all eight procedures) based on procedure. CONCLUSION: In this academic health system, we did not find any differences in opioid prescribing after common orthopaedic procedures by patient race or ethnicity. A potential explanation is the use of surgical pathways in our orthopaedic department. Formal standardized opioid prescribing guidelines may reduce variability in opioid prescribing. LEVEL OF EVIDENCE: Level III, therapeutic study.

Hamstring Injury Rehabilitation and Prevention in the Female Athlete.

Hamstring injuries (HSIs) are common in female athletes and are associated with a lengthy recovery period and a high rate of reinjury. Currently, the majority of existing literature investigating HSI rehabilitation has been conducted using male participants. However, female athletes display intrinsic anatomical and biomechanical differences compared to males that influences the way this population experiences HSIs and HSI rehabilitation. HSI rehabilitation and injury prevention guidelines for female athletes must take these differences into account. Female athletes display anatomical differences such as increased anterior pelvic tilting, gluteus maximus weakness, an increased pelvic width-to-femoral length ratio, and an increased degree of femoral anteversion, all of which can predispose females to HSIs. Maneuvers designed to strengthen the gluteal musculature and transverse abdominis can overcome these risk factors. Females show increased joint laxity and a greater range of motion of hip flexion and internal rotation compared to males. Females have lower passive hamstring stiffness than males, therefore hamstring flexibility exercises may not be as necessary during rehabilitation for females as in the male athlete population. Female athletes may instead benefit from trunk stabilization exercises and agility training due to neuromuscular control deficits that arise from the maturation and growth of the female pelvis. Existing literature on hamstring injury prevention shows consistent use of the Nordic Hamstring Exercise and balance exercises may reduce the risk of sustaining an HSI in both males and females, though more studies are needed to ascertain the optimal regimen for injury prevention in the female athlete population specifically. The goal of this clinical commentary is to discuss sex-specific anatomic and biomechanical differences of the lumbar, pelvic, and hip regions with the aim of providing guidelines for rehabilitation and injury prevention of HSIs in female athletes. Level of Evidence: 5.

Differential ABC transporter expression during hematopoiesis contributes to neutrophil-biased toxicity of Aurora kinase inhibitors.

Drug-induced cytopenias are a prevalent and significant issue that worsens clinical outcomes and hinders the effective treatment of cancer. While reductions in blood cell numbers are classically associated with traditional cytotoxic chemotherapies, they also occur with newer targeted small molecules and the factors that determine the hematotoxicity profiles of oncologic drugs are not fully understood. Here, we explore why some Aurora kinase inhibitors cause preferential neutropenia. By studying drug responses of healthy human hematopoietic cells in vitro and analyzing existing gene expression datasets, we provide evidence that the enhanced vulnerability of neutrophil-lineage cells to Aurora kinase inhibition is caused by early developmental changes in ATP-binding cassette (ABC) transporter expression. These data show that hematopoietic cell-intrinsic expression of ABC transporters may be an important factor that determines how some Aurora kinase inhibitors affect the bone marrow.

Enteric Coronavirus Infection and Treatment Modeled With an Immunocompetent Human Intestine-On-A-Chip.

Many patients infected with coronaviruses, such as SARS-CoV-2 and NL63 that use ACE2 receptors to infect cells, exhibit gastrointestinal symptoms and viral proteins are found in the human gastrointestinal tract, yet little is known about the inflammatory and pathological effects of coronavirus infection on the human intestine. Here, we used a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by patient organoid-derived intestinal epithelium interfaced with human vascular endothelium to study host cellular and inflammatory responses to infection with NL63 coronavirus. These organoid-derived intestinal epithelial cells dramatically increased their ACE2 protein levels when cultured under flow in the presence of peristalsis-like mechanical deformations in the Intestine Chips compared to when cultured statically as organoids or in Transwell inserts. Infection of the intestinal epithelium with NL63 on-chip led to inflammation of the endothelium as demonstrated by loss of barrier function, increased cytokine production, and recruitment of circulating peripheral blood mononuclear cells (PBMCs). Treatment of NL63 infected chips with the approved protease inhibitor drug, nafamostat, inhibited viral entry and resulted in a reduction in both viral load and cytokine secretion, whereas remdesivir, one of the few drugs approved for COVID19 patients, was not found to be effective and it also was toxic to the endothelium. This model of intestinal infection was also used to test the effects of other drugs that have been proposed for potential repurposing against SARS-CoV-2. Taken together, these data suggest that the human Intestine Chip might be useful as a human preclinical model for studying coronavirus related pathology as well as for testing of potential anti-viral or anti-inflammatory therapeutics.

Author Correction: On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology.

The inaccessibility of living bone marrow (BM) hampers the study of its pathophysiology under myelotoxic stress induced by drugs, radiation or genetic mutations. Here, we show that a vascularized human BM-on-a-chip (BM chip) supports the differentiation and maturation of multiple blood cell lineages over 4 weeks while improving CD34+ cell maintenance, and that it recapitulates aspects of BM injury, including myeloerythroid toxicity after clinically relevant exposures to chemotherapeutic drugs and ionizing radiation, as well as BM recovery after drug-induced myelosuppression. The chip comprises a fluidic channel filled with a fibrin gel in which CD34+ cells and BM-derived stromal cells are co-cultured, a parallel channel lined by human vascular endothelium and perfused with culture medium, and a porous membrane separating the two channels. We also show that BM chips containing cells from patients with the rare genetic disorder Shwachman-Diamond syndrome reproduced key haematopoietic defects and led to the discovery of a neutrophil maturation abnormality. As an in vitro model of haematopoietic dysfunction, the BM chip may serve as a human-specific alternative to animal testing for the study of BM pathophysiology.

A Genome-Wide Screen Identifies Genes in Rhizosphere-Associated Pseudomonas Required to Evade Plant Defenses.

Pseudomonas fluorescens and related plant root ("rhizosphere")-associated species contribute to plant health by modulating defenses and facilitating nutrient uptake. To identify bacterial fitness determinants in the rhizosphere of the model plant Arabidopsis thaliana, we performed a high-throughput transposon sequencing (Tn-Seq) screen using the biocontrol and growth-promoting strain Pseudomonas sp. WCS365. The screen, which was performed in parallel on wild-type and immunocompromised Arabidopsis plants, identified 231 genes that increased fitness in the rhizosphere of wild-type plants. A subset of these genes decreased fitness in the rhizosphere of immunocompromised plants. We hypothesized that these genes might be involved in avoiding plant defenses and verified 7 Pseudomonas sp. WCS365 candidate genes by generating clean deletions. We found that two of these deletion mutants, ΔmorA (encoding a putative diguanylate cyclase/phosphodiesterase) and ΔspuC (encoding a putrescine aminotransferase), formed enhanced biofilms and inhibited plant growth. We found that mutants ΔspuC and ΔmorA induced pattern-triggered immunity (PTI) as measured by induction of an Arabidopsis PTI reporter and FLS2/BAK1-dependent inhibition of plant growth. We show that MorA acts as a phosphodiesterase to inhibit biofilm formation, suggesting a possible role in biofilm dispersal. We found that both putrescine and its precursor arginine promote biofilm formation that is enhanced in the ΔspuC mutant, which cannot break down putrescine, suggesting that putrescine might serve as a signaling molecule in the rhizosphere. Collectively, this work identified novel bacterial factors required to evade plant defenses in the rhizosphere.IMPORTANCE While rhizosphere bacteria hold the potential to improve plant health and fitness, little is known about the bacterial genes required to evade host immunity. Using a model system consisting of Arabidopsis and a beneficial Pseudomonas sp. isolate, we identified bacterial genes required for both rhizosphere fitness and for evading host immune responses. This work advances our understanding of how evasion of host defenses contributes to survival in the rhizosphere.

Rhizosphere-associated Pseudomonas induce systemic resistance to herbivores at the cost of susceptibility to bacterial pathogens.

Plant-associated soil microbes are important mediators of plant defence responses to diverse above-ground pathogen and insect challengers. For example, closely related strains of beneficial rhizosphere Pseudomonas spp. can induce systemic resistance (ISR), systemic susceptibility (ISS) or neither against the bacterial foliar pathogen Pseudomonas syringae pv. tomato DC3000 (Pto DC3000). Using a model system composed of root-associated Pseudomonas spp. strains, the foliar pathogen Pto DC3000 and the herbivore Trichoplusia ni (cabbage looper), we found that rhizosphere-associated Pseudomonas spp. that induce either ISS and ISR against Pto DC3000 all increased resistance to herbivory by T. ni. We found that resistance to T. ni and resistance to Pto DC3000 are quantitative metrics of the jasmonic acid (JA)/salicylic acid (SA) trade-off and distinct strains of rhizosphere-associated Pseudomonas spp. have distinct effects on the JA/SA trade-off. Using genetic analysis and transcriptional profiling, we provide evidence that treatment of Arabidopsis with Pseudomonas sp. CH267, which induces ISS against bacterial pathogens, tips the JA/SA trade-off towards JA-dependent defences against herbivores at the cost of a subset of SA-mediated defences against bacterial pathogens. In contrast, treatment of Arabidopsis with the ISR strain Pseudomonas sp. WCS417 disrupts JA/SA antagonism and simultaneously primes plants for both JA- and SA-mediated defences. Our findings show that ISS against the bacterial foliar pathogens triggered by Pseudomonas sp. CH267, which is a seemingly deleterious phenotype, may in fact be an adaptive consequence of increased resistance to herbivory. Our work shows that pleiotropic effects of microbiome modulation of plant defences are important to consider when using microbes to modify plant traits in agriculture.