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.

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.

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.

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.