Targeting NAD+ regeneration enhances antibiotic susceptibility of Streptococcus pneumoniae during invasive disease.

Anaerobic bacteria are responsible for half of all pulmonary infections. One such pathogen is Streptococcus pneumoniae (Spn), a leading cause of community-acquired pneumonia, bacteremia/sepsis, and meningitis. Using a panel of isogenic mutants deficient in lactate, acetyl-CoA, and ethanol fermentation, as well as pharmacological inhibition, we observed that NAD(H) redox balance during fermentation was vital for Spn energy generation, capsule production, and in vivo fitness. Redox balance disruption in fermentation pathway-specific fashion substantially enhanced susceptibility to killing in antimicrobial class-specific manner. Blocking of alcohol dehydrogenase activity with 4-methylpyrazole (fomepizole), an FDA-approved drug used as an antidote for toxic alcohol ingestion, enhanced susceptibility of multidrug-resistant Spn to erythromycin and reduced bacterial burden in the lungs of mice with pneumonia and prevented the development of invasive disease. Our results indicate fermentation enzymes are de novo targets for antibiotic development and a novel strategy to combat multidrug-resistant pathogens.

Biofilm Growth on Orthopaedic Cerclage Materials: Nonmetallic Polymers Are Less Resistant to Methicillin-Resistant Staphylococcus Aureus Bacterial Adhesion.

BACKGROUND: Data on bacterial adhesion to cerclage cables are sparse. We aimed to compare 5 cerclage products for methicillin-resistant Staphylococcus aureus (MRSA) adhesion to determine the claim: Are nonmetallic polymer cables more resistant to bacterial adhesion than common metallic wires and cables? METHODS: The following 5 cerclage products were compared: (1) monofilament stainless steel (SS) wires; (2) multifilament SS cables; (3) multifilament cobalt chrome cables; (4) multifilament Vitallium alloy (cobalt-chrome-molybdenum [Co-Cr-Mo]) cables; and (5) multifilament nonmetallic polymer cables. Each was cut into 2 cm lengths and placed into 12-well plates. Of the wells, 5 were wire or cables in trypticase soy broth with MRSA, with the remaining wells being appropriate controls incubated for 24 hours at 37° C and 5% CO2 with shaking. Wires and cables were prepared and randomly imaged via scanning electron microscopy, with bacterial counts performed on 3 images of 3 different wires or cables per study group. The scanning electron microscopy technician and counting investigator were blinded. Additionally, SS wire and polymer cables were analyzed by microcalorimetry for metabolic activity and bacterial load. RESULTS: Bacterial attachment differed significantly between study groups in the middle section (P = .0003). Post hoc comparison showed no difference between groups individually (all P > .05) apart from polymer cables (median 551 bacteria) having significantly increased attached bacteria compared to the Vitallium alloy cable (157, P = .0004), SS cable (101, P = .0004), and SS wire (211, P = .0004). There was no difference between polymer and cobalt chrome cables (133, P = .056). Microcalorimetry supported these results, as polymer cables had a shorter time to max heat flow (6.2 versus 7.5 hours, P = .006), increased max heat flow (117 versus 64 uW, P = .045), and increased colony-forming units, indicating an increased bacterial load compared to SS wires. CONCLUSIONS: This in vitro study demonstrated that polymer cables have increased MRSA adhesion compared to common metallic wires and cables. Future studies are necessary to confirm the translation of increased bacterial adherence on polymer cables to increased rates of orthopaedic infections.

Racial Disparities in Treatment and Outcomes of Patients With Hepatitis C Undergoing Elective Total Joint Arthroplasty.

BACKGROUND: African Americans have the highest prevalence of chronic Hepatitis C virus (HCV) infection. Racial disparities in outcome are observed after elective total hip arthroplasty (THA) and total knee arthroplasty (TKA). This study sought to identify if disparities in treatments and outcomes exist between Black and White patients who have HCV prior to elective THA and TKA. METHODS: Patient demographics, comorbidities, HCV characteristics, perioperative variables, in-hospital outcomes, and postoperative complications at 1-year follow-up were collected and compared between the 2 races. Patients who have preoperative positive viral load (PVL) and undetectable viral load were identified. Chi-square and Fisher's exact tests were used to compare categorical variables, while 2-tailed Student's Kruskal-Wallis t-tests were used for continuous variables. A P value of less than .05 was statistically significant. RESULTS: The liver function parameters, including aspartate aminotransferase and model for end-stage liver disease scores, were all higher preoperatively in Black patients undergoing THA (P = .01; P < .001) and TKA (P = .03; P = .003), respectively. Black patients were more likely to undergo THA (65.8% versus 35.6%; P = .002) and TKA (72.1% versus 37.3%; 0.009) without receiving prior treatment for HCV. Consequently, Black patients had higher rates of preoperative PVL compared to White patients in both THA (66% versus 38%, P = .006) and TKA (72% versus 37%, P < .001) groups. Black patients had a longer length of stay for both THA (3.7 versus 3.3; P = .008) and TKA (4.1 versus 3.0; P = .02). CONCLUSIONS: The HCV treatment prior to THA and TKA with undetectable viral load has been shown to be a key factor in mitigating postoperative complications, including joint infection. We noted that Black patients were more likely to undergo joint arthroplasty who did not receive treatment and with a PVL. While PVL rates decreased over time for both races, a significant gap persists for Black patients.

Isothermal microcalorimetry improves accuracy and time to bacterial detection of periprosthetic joint infection after total joint arthroplasty.

Isothermal microcalorimetry (IMC) was evaluated compared to conventional cultures to determine the clinical performance for diagnosing periprosthetic joint infection (PJI) of hip/knee replacements. We prospectively collected three to five deep tissue samples per patient from 152 patients undergoing conversion or revision hip/knee arthroplasty from July 2020 to November 2022. Cultures and IMC for each sample were compared for concordance, median time to detection (TTD), and diagnostic performance based on 2013 Musculoskeletal Infection Society criteria. Secondary analyses involved patients on antibiotics at sampling. The 152 total patients had 592 tissue samples (mean 3.9 ± 0.3) with sample concordance between cultures and IMC of 90%. IMC demonstrated a sensitivity of 83%, specificity of 100%, negative predictive value (NPV) of 89%, and positive predictive value (PPV) of 100% for PJI. Cultures resulted in 69% sensitivity, 100% specificity, 81% NPV, and 100% PPV. The accuracy of IMC was 93% compared to 87% for cultures (P < 0.001). The median TTD of PJI by cultures was 51 (21-410) hours compared to 10 (0.5-148) hours for IMC (P < 0.001). For 39 patients on chronic antibiotics, sensitivity in PJI detection was 93%, specificity 100%, NPV 85%, and PPV 100% by IMC compared to 79% sensitivity, 100% specificity, 65% NPV, and 100% PPV for cultures. The accuracy was 95% for IMC compared to 85% for cultures (P < 0.001) with median TTD of 12 (0.5-127) hours compared to 52 (21-174) hours (P < 0.001). Utilizing IMC for PJI detection improves TTD by nearly 2 days while improving diagnostic accuracy compared to cultures, particularly in patients on chronic antibiotics.

Child-Pugh Class B or C Liver Disease Increases the Risk of Early Mortality in Patients With Hepatitis C Undergoing Elective Total Joint Arthroplasty Regardless of Treatment Status.

BACKGROUND: Patients with hepatitis C virus (HCV) undergoing primary elective total joint arthroplasty (TJA) are at increased risk of postoperative complications. Patients with chronic liver disease and cirrhosis, specifically Child-Pugh Class B and C, who are undergoing general surgery have high 2-year mortality risks, approaching 60% to 80%. However, the role of Child-Pugh and Model for End-Stage Liver Disease classifications of liver status in predicting survivorship among patients with HCV undergoing elective arthroplasty has not been elucidated. QUESTION/PURPOSE: What factors are independently associated with early mortality (< 2 years) in patients with HCV undergoing arthroplasty? METHODS: We performed a retrospective study at three tertiary academic medical centers and identified patients with HCV undergoing primary elective TJA between January 2005 and December 2019. Patients who underwent revision TJA and simultaneous primary TJA were excluded. A total of 226 patients were eligible for inclusion in the study. A further 25% (57) were excluded because they were lost to follow-up before the minimum study requirement of 2 years of follow-up or had incomplete datasets. After the inclusion and exclusion criteria were applied, the final cohort consisted of 75% (169 of 226) of the initial patient population eligible for analysis. The mean follow-up duration was 53 ± 29 months. We compared confounding variables for mortality between patients with early mortality (16 patients) and surviving patients (153 patients), including comorbidities, HCV and liver characteristics, HCV treatment, and postoperative medical and surgical complications. Patients with early postoperative mortality were more likely to have an associated advanced Child-Pugh classification and comorbidities including peripheral vascular disease, end-stage renal disease, heart failure, and chronic obstructive pulmonary disease. However, both groups had similar 90-day and 1-year medical complication risks including myocardial infarction, stroke, pulmonary embolism, and reoperations for periprosthetic joint infection and mechanical failure. A multivariable regression analysis was performed to identify independent factors associated with early mortality, incorporating all significant variables with p < 0.05 present in the univariate analysis. RESULTS: After accounting for significant variables in the univariate analysis such as peripheral vascular disease, end-stage renal disease, heart failure, chronic obstructive pulmonary disease, and liver fibrosis staging, Child-Pugh Class B or C classification was found to be the sole factor independently associated with increased odds of early (within 2 years) mortality in patients with HCV undergoing elective TJA (adjusted odds ratio 29 [95% confidence interval 5 to 174]; p < 0.001). The risk of early mortality in patients with Child-Pugh Class B or C was 64% (seven of 11) compared with 6% (nine of 158) in patients with Child-Pugh Class A (p < 0.001). CONCLUSION: Patients with HCV and a Child-Pugh Class B or C at the time of elective TJA had substantially increased odds of death, regardless of liver function, cirrhosis, age, Model for End-Stage Liver Disease level, HCV treatment, and viral load status. This is similar to the risk of early mortality observed in patients with chronic liver disease undergoing abdominal and cardiac surgery. Surgeons should avoid these major elective procedures in patients with Child-Pugh Class B or C whenever possible. For patients who feel their arthritic symptoms and pain are unbearable, surgeons need to be clear that the risk of death is considerably elevated. LEVEL OF EVIDENCE: Level III, therapeutic study.

Comparison Between Orthopaedic Trauma Versus Arthroplasty Fellowship Training on Outcomes of Total Hip Arthroplasty for Femoral Neck Fracture.

BACKGROUND: This study aimed to identify differences in patient characteristics, perioperative management methods, and outcomes for total hip arthroplasty (THA) for femoral neck fracture (FNF) when performed by orthopaedic surgeons who have arthroplasty versus orthopaedic trauma training. METHODS: This study was a multicenter retrospective review of 636 patients who underwent THA for FNF between 2010 and 2019. There were 373 patients who underwent THA by an arthroplasty surgeon, and 263 who underwent THA by an orthopaedic trauma surgeon. Comorbidities, management methods, and outcomes were compared between patients operated on by orthopaedic surgeons who had arthroplasty versus trauma training. RESULTS: Arthroplasty-trained surgeons had shorter operative times (102 versus 128 minutes, P < .0001) and utilized tranexamic acid more frequently than trauma-trained surgeons (48.8 versus 18.6%, P < .0001). Orthopaedic trauma surgeons more frequently utilized an anterior approach. Patients of arthroplasty-trained surgeons had lower rates of complications including pulmonary embolism (1.6 versus 6.5%, P = .0019) and myocardial infarction (1.6 versus 11.0%, P < .0001). Similarly, patients of arthroplasty-trained surgeons were discharged faster (5.3 versus 7.9 days, P < .0001) with greater ambulation capacity (92.2 versus 57.2 feet, P < .0001). Dislocation, periprosthetic joint infection, and revision were similar between both groups. When adjusted for covariates, there was no difference in 90-day, 1-year, or 2-year mortality. CONCLUSION: A THA performed for FNF by arthroplasty surgeons was associated with lower in-hospital morbidities and improved functional statuses at discharge. However, mortalities and complications after discharge were similar between both specialties when adjusted for confounding variables. Optimization of protocols may further improve outcomes for THA for FNF.

Direct Anterior Approach Total Hip Arthroplasty Is Associated With Reduced 1-Year Mortality and Surgical Complications After Femoral Neck Fracture.

BACKGROUND: In some studies, the direct anterior approach (DAA) for elective total hip arthroplasty (THA) is associated with decreased dislocation and greater functional gains compared to the posterior approach (PA), as well as higher functional outcomes compared to the direct lateral approach (LA) at 2 weeks postoperatively. Given the paucity of literature on femoral neck fracture (FNF), we aspired to determine the association between the surgical approach used in THA and outcomes. METHODS: We conducted a retrospective review of patients undergoing THA for FNF at 9 institutions from 2010 to 2019. Patients who had high-energy injury mechanisms, were nonambulatory prior to injury, had concomitant femoral head or acetabular fractures, or did not reach minimum 1-year follow-up were excluded. The study included 622 THAs, of which 348 (56%) were performed through a DAA, 197 (32%) through a PA, and 77 (12%) through an LA. Postoperative complications and mortalities at 90 days and 1 year were compared between groups. Multivariable logistic regression models were constructed for each outcome of interest. RESULTS: The DAA was associated with a decreased risk of 90-day dislocation (odds ratio [OR] 0.25; 95% confidence interval [CI] 0.10 to 0.62; P = .01), mechanical revision (OR 0.12; 95% CI 0.02 to 0.56; P = .01), and mortality (OR 0.38; 95% CI 0.16 to 0.91; P = .03) compared to the PA. The DAA was also associated with decreased risk of dislocation (OR 0.32; 95% CI 0.14 to 0.74; P = .01), mechanical revision (OR 0.22; 95% CI 0.08 to 0.65; P = .01), and mortality at 1 year compared to PA (OR 0.43; 95% CI 0.21 to 0.85; P = .02). CONCLUSION: The DAA for THA after FNF is associated with higher in-hospital medical complications but lower risks of postoperative reoperation and mortality. Postdischarge care may impact this association and needs to be addressed in future studies. The DAA should be used among surgeons experienced with the approach for FNF to minimize complications. LEVEL OF EVIDENCE: Retrospective cohort, Level III.

Muscle transcriptomic circuits linked to periarticular physiology in end-stage osteoarthritis.

The ability of individuals with end-stage osteoarthritis (OA) to functionally recover from total joint arthroplasty is highly inconsistent. The molecular mechanisms driving this heterogeneity have yet to be elucidated. Furthermore, OA disproportionately impacts females, suggesting a need for identifying female-specific therapeutic targets. We profiled the skeletal muscle transcriptome in females with end-stage OA (n = 20) undergoing total knee or hip arthroplasty using RNA-Seq. Single-gene differential expression (DE) analyses tested for DE genes between skeletal muscle overlaying the surgical (SX) joint and muscle from the contralateral (CTRL) leg. Network analyses were performed using Pathway-Level Information ExtractoR (PLIER) to summarize genes into latent variables (LVs), i.e., gene circuits, and link them to biological pathways. LV differences in SX versus CTRL muscle and across sources of muscle tissue (vastus medialis, vastus lateralis, or tensor fascia latae) were determined with ANOVA. Linear models tested for associations between LVs and muscle phenotype on the SX side (inflammation, function, and integrity). DE analysis revealed 360 DE genes (|Log2 fold-difference| ≥ 1, FDR ≤ 0.05) between the SX and CTRL limbs, many associated with inflammation and lipid metabolism. PLIER analyses revealed circuits associated with protein degradation and fibro-adipogenic cell gene expression. Muscle inflammation and function were linked to an LV associated with endothelial cell gene expression highlighting a potential regulatory role of endothelial cells within skeletal muscle. These findings may provide insight into potential therapeutic targets to improve OA rehabilitation before and/or following total joint replacement.

Anatomical Site-Specific Carbohydrate Availability Impacts Streptococcus pneumoniae Virulence and Fitness during Colonization and Disease.

Streptococcus pneumoniae colonizes the nasopharynx asymptomatically but can also cause severe life-threatening disease. Importantly, stark differences in carbohydrate availability exist between the nasopharynx and invasive disease sites, such as the bloodstream, which most likely impact S. pneumoniae's behavior. Herein, using chemically defined medium (CDM) supplemented with physiological levels of carbohydrates, we examined how anatomical site-specific carbohydrate availability impacted S. pneumoniae physiology and virulence. S. pneumoniae cells grown in CDM modeling the nasopharynx (CDM-N) had reduced metabolic activity and a lower growth rate, demonstrated mixed acid fermentation with marked H2O2 production, and were in a carbon-catabolite repression (CCR)-derepressed state versus S. pneumoniae cells grown in CDM modeling blood (CDM-B). Using transcriptome sequencing (RNA-seq), we determined the transcriptome for the S. pneumoniae wild-type (WT) strain and its isogenic CCR-deficient mutant in CDM-N and CDM-B. Genes with altered expression as a result of changes in carbohydrate availability or catabolite control protein deficiency, respectively, were primarily involved in carbohydrate metabolism, but also encoded established virulence determinants, such as polysaccharide capsule and surface adhesins. We confirmed that anatomical site-specific carbohydrate availability directly influenced established S. pneumoniae virulence traits. S. pneumoniae cells grown in CDM-B formed shorter chains, produced more capsule, were less adhesive, and were more resistant to macrophage killing in an opsonophagocytosis assay. Moreover, growth of S. pneumoniae in CDM-N or CDM-B prior to the challenge of mice impacted relative fitness in a colonization model and invasive disease model, respectively. Thus, anatomical site-specific carbohydrate availability alters S. pneumoniae physiology and virulence, in turn promoting anatomical site-specific fitness.

Isothermal Microcalorimetry Improves the Time to Diagnosis of Fracture-related Infection Compared With Conventional Tissue Cultures.

BACKGROUND: A consensus definition recently was formulated for fracture-related infection, which centered on confirmatory criteria including conventional cultures that take time to finalize and have a 10% to 20% false-negative rate. During this time, patients are often on broad-spectrum antibiotics and may remain hospitalized until cultures are finalized to adjust antibiotic regimens. QUESTIONS/PURPOSES: (1) What is the diagnostic accuracy of isothermal microcalorimetry, and how does its accuracy compare with that of conventional cultures? (2) Does isothermal microcalorimetry decrease time to detection (or diagnosis) of fracture-related infection compared with conventional cultures? (3) Does isothermal microcalorimetry have a diagnostic accuracy or time advantage over conventional cultures in patients on chronic suppressive antibiotics? METHODS: Between July 2020 and August 2021, we treated 310 patients with concerns for infection after prior fracture repair surgery. Of those, we considered all patients older than 18 years of age with fixation hardware in place at the time of presentation as potentially eligible. All included patients returned to the operating room with cultures obtained and assessed by both isothermal microcalorimetry and conventional cultures, and all were diagnosed using the consensus criteria for fracture-related infection. Based on that, 81% (250 of 310) of patients were eligible; a further 51% (157 of 310) were excluded because of the following reasons: the capacity of the isothermal microcalorimetry instrument limited the throughput on that day (34% [106 of 310]), they had only swab cultures obtained in surgery (15% [46 of 310]), or they had less than 3 months follow-up after surgery for infectious concerns (2% [5 of 310]), leaving 30% (93 of 310) of the originally identified patients for analysis. We obtained two to five cultures from each patient during surgery, which were sent to our clinical microbiology laboratory for standard processing (conventional cultures). This included homogenization of each tissue sample individually and culturing for aerobic, anaerobic, acid-fast bacilli, and fungal culturing. The remaining homogenate from each sample was then taken to our orthopaedic research laboratory, resuspended in growth media, and analyzed by isothermal microcalorimetry for a minimum of 24 hours. Aerobic and anaerobic cultures were maintained for 5 days and 14 days, respectively. Overall, there were 93 patients (59 males), with a mean age of 43 ± 14 years and a mean BMI of 28 ± 8 kg/m 2 , and 305 tissue samples (mean 3 ± 1 samples per patient) were obtained and assessed by conventional culturing and isothermal microcalorimetry. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of isothermal microcalorimetry to diagnose fracture-related infection were compared with conventional cultures using a McNemar test based on the consensus definition of fracture-related infection. This consensus criteria is comprised of two levels of certainty for the diagnostic variables. The first is confirmatory criteria, where infection is considered definitely present and includes the presence of fistula/sinus tract/wound breakdown, purulent drainage or the presence of pus, presence of microorganisms in deep tissue specimens on histopathologic examination, presence of more than five neutrophils/high-powered field by histopathologic examination (only for chronic/late onset cases), and identification of phenotypically indistinguishable pathogens by conventional culture from at least two separate deep tissue/implant specimens. The second is suggestive criteria in which further investigation is required to achieve confirmatory status. Fracture-related infection was diagnosed for this study to minimize subjectivity based on the presence of at least one of the confirmatory criteria as documented by the managing surgeon. When suggestive criteria were present without confirmatory criteria, patients were considered negative for fracture-related infection and followed further in clinic after surgical exploration (n = 25 patients). All 25 patients deemed not to have fracture-related infection were considered infection-free at latest follow-up (range 3 to 12 months). The time to detection or diagnosis was recorded and compared via the Mann-Whitney U test. RESULTS: Using the consensus criteria for fracture-related infection, there were no differences with the numbers available between isothermal microcalorimetry and conventional cultures in terms of sensitivity (87% [95% confidence interval 77% to 94%] versus 81% [95% CI 69% to 89%]), specificity (100% [95% CI 87% to 100%] versus 96% [95% CI 79% to 99%]), PPV (100% [95% CI 90% to 100%] versus 98% [95% CI 89% to 99%]), NPV (74% [95% CI 60% to 84%] versus 65% [95% CI 52% to 75%]), or accuracy (90% [95% CI 83% to 96%] versus 85% [95% CI 76% to 91%]; p = 0.13). The concordance by sample between conventional cultures and isothermal microcalorimetry was 85%. Isothermal microcalorimetry had a shorter median (range) time to detection or diagnosis compared with conventional cultures (2 hours [0.5 to 66] versus 51 hours [18 to 147], difference of medians 49 hours; p < 0.001). Additionally, 32 patients used antibiotics for a median (range) duration of 28 days (7 to 1095) before presentation. In these unique patients, there were no differences with the numbers available between isothermal microcalorimetry and conventional cultures in terms of sensitivity (89% [95% CI 71% to 98%] versus 74% [95% CI 53% to 88%]), specificity (100% [95% CI 48% to 100%] versus 83% [95% CI 36% to 99%]), PPV (100% [95% CI 85% to 100%] versus 95% [95% CI 77% to 99%]), NPV (63% [95% CI 37% to 83%] versus 42% [95% CI 26% to 60%]), or accuracy (91% [95% CI 75% to 98%] versus 78% [95% CI 57% to 89%]; p = 0.17). Isothermal microcalorimetry again had a shorter median (range) time to detection or diagnosis compared with conventional cultures (1.5 hours [0.5 to 48] versus 51.5 hours [18 to 125], difference of medians 50 hours; p < 0.001). CONCLUSION: Given that isothermal microcalorimetry considerably decreases the time to the diagnosis of a fracture-related infection without compromising the accuracy of the diagnosis, managing teams may eventually use isothermal microcalorimetry-pending developmental improvements and regulatory approval-to rapidly detect infection and begin antibiotic management while awaiting speciation and susceptibility testing to modify the antibiotic regimen. Given the unique thermograms generated, further studies are already underway focusing on speciation based on heat curves alone. Additionally, increased study sizes are necessary for both overall fracture-related infection diagnostic accuracy and test performance on patients using long-term antibiotics given the promising results with regard to time to detection for this groups as well. LEVEL OF EVIDENCE: Level II, diagnostic study.

Risk Factors for Failure and Optimal Treatment of Total Joint Arthroplasty for Septic Arthritis.

BACKGROUND: Patients with native joint septic arthritis are one of the highest risk groups for developing complications following total joint arthroplasty (TJA), especially periprosthetic joint infection(PJI). There is a paucity of information on the risk factors for developing PJI and the optimal treatment modality of the native septic joint that can mitigate that risk. This multicenter study aimed to determine these risk factors, including prior treatment. METHODS: A retrospective study of 233 TJAs performed, following prior septic arthritis at five institutions, was conducted. Comorbidities, organism profile, prior surgery, etiology of septic arthritis, and other relevant variables were reviewed. The primary outcome was the development of PJI, defined by Musculoskeletal Infection Society criteria. Bivariate and multivariate analyses were performed to identify risk factors for PJI. RESULTS: Overall, the PJI rate was 12.4% in patients who underwent TJA after native septic arthritis. Predisposing risk factors for PJI included antibiotic-resistant organisms, male gender, diabetes, and a postsurgical cause of septic arthritis eg open reduction internal fixation. When controlling for potential confounders, multivariate analysis revealed that male gender, diabetes, and a postoperative etiology were predictors of PJI. The definitive treatment modality for the septic joint did not affect the rate of PJI for both arthroscopy vs irrigation and debridement (I&D), and two-stage exchange vs single-stage procedure. DISCUSSION: This study has identified several risk factors for developing PJI in patients with prior septic joint arthritis, some of which are modifiable. The initial treatment modality of the native septic joint has no bearing on the development of PJI after TJA.

Quality Improvement Tools in Total Joint Arthroplasty: A Systematic Review.

Systems review and quality improvement (QI) is a significant need within orthopaedic surgery. The focus of this paper is to systematically review QI principles utilized in total joint arthroplasty to determine most successful QI tools. A systematic search on MEDLINE/Pubmed, Embase, Cochrane Library and other sources was conducted from September 1991 through October 2018. The three primary improved outcomes from each article were recorded along with the date, author and subspecialty. Thirty-four eligible studies related to joint arthroplasty were identified for inclusion in the systematic review. The most common outcomes that were improved in these publications were: length of stay (LOS), cost, medication management, and patient education. Lean, clinical care pathways (CCP), plan-do-check-act (PDCA), and shared decision-making improved those metrics. Four metrics were found that were consistently improved by certain quality improvement tools: LOS, cost, medication management, and patient education. Further research is warranted to continue to build a framework for quality improvement in orthopaedic surgery. (Journal of Surgical Orthopaedic Advances 30(3):125-130, 2021).

Risk Factors for Surgical Site Infection after Operative Fixation of Acetabular Fractures: Is Psoas Density a Useful Metric?

BACKGROUND: Surgical site infection (SSI) occurs in 5% to 7% of patients undergoing operative fixation of acetabular fractures, with reported risk factors including longer operative duration, increased blood loss, pelvic artery embolization, and concurrent abdominal organ injury, among others. Psoas muscle density is a measure of muscle quality and, as a metric for sarcopenia and/or nutrition status, has been associated with poor outcomes such as mortality across multiple surgical specialties. To date, psoas muscle density has not been explored for its associations with SSI in acetabular fracture patients.Questions/purposes (1) Is decreased psoas muscle density, as measured by Hounsfield units, associated with an increased SSI risk after acetabular fracture fixation? (2) What patient, operative, and hospital variables are associated with an increased SSI risk after acetabular fracture fixation? METHODS: Between 2012 to 2017, surgeons performed 684 acetabular ORIF procedures at one level I trauma center. Of those, 8% (56 of 684) did not meet inclusion criteria, leaving 92% (n = 628) for analysis in this study. The median (range) follow-up duration was 12 months (0.5-77). Patient demographics, comorbidities, operative and in-hospital variables, and psoas muscle density measured using preoperative pelvic CT images-acquired for all operative acetabular fracture patients-were analyzed. SSI was defined by positive culture results obtained during irrigation and débridement. Overall, 7% (42 of 628) of patients had an SSI. A multivariable regression analysis was performed to identify independent risk factors. Sensitivity analysis was performed with minimum follow-up set at 3 months and 6 months. RESULTS: There was no difference in the mean psoas muscle density between patients with SSI (50.9 ± 10.2 Hounsfield units [HUs]) and those who did not have an SSI within 1 year of open reduction and internal fixation (51.4 ± 8.1 HUs) (mean difference: 0.5 [95% confidence interval -2.34 to 3.32]; p = 0.69). Four variables were independently associated with an increased risk of SSI: increased operative time (1.04 [95% CI 1.00 to 1.07]; p = 0.03), estimated blood loss (1.08 [95% CI 1.02 to 1.14]; p = 0.01), female sex (2.34 [95% CI 1.19 to 4.60]; p = 0.01), and intravenous drug use (3.95 [95% CI 1.51 to 10.33]; p = 0.01). Sensitivity analysis showed no change in results using either 3-month or 6-month minimum follow-up. CONCLUSIONS: Risk factors for SSI after acetabular fixation include female sex, intravenous drug use, prolonged operative times, and increased intraoperative blood loss. Although the density of the psoas muscle may be a surrogate for nutritional markers, it was not associated with SSI in our patients with acetabular fractures. Thus, it is not useful for risk assessment of SSI in the general population with acetabular fracture; however, future studies with larger sample sizes of patients older than 60 years may re-investigate this marker for SSI risk. Contrary to the results of previous studies, pelvic artery embolization, intraoperative blood transfusion, and intensive care unit stay did not increase the risk of SSI; however, we may have been underpowered to detect differences in these secondary endpoints. Future large, multisite studies may be needed to address these conflicting results more definitively. LEVEL OF EVIDENCE: Level III, therapeutic study.

The Value of Serological Screening Prior to Conversion Total Hip Arthroplasty.

BACKGROUND: This study sought (1) to assess the value of serological testing prior to conversion total hip arthroplasty (THA) in predicting infection and (2) to identify optimal serological values for routine diagnostic workup prior to conversion THA. METHODS: All patients at our tertiary referral center undergoing conversion THA after hip/acetabular fracture procedure from 2013 to 2018 were retrospectively reviewed. Inclusion criteria were patients previously undergoing hemiarthroplasty or open reduction and internal fixation of acetabular, intertrochanteric, and subtrochanteric fractures that progressed to conversion THA due to post-traumatic arthritis having erythrocyte sedimentation rate/C-reactive protein (CRP) prior to conversion. Infection was defined as positive intraoperative cultures not deemed contaminant in collaboration with infectious disease consult and/or development of PJI within 1 year postoperatively. RESULTS: Twelve of 87 (14%) patients undergoing conversion THA developed infection. The mean erythrocyte sedimentation rate (37.2 vs 24.4 mm/h, P = .2062) and CRP (22.4 vs 9.0 mg/L, P = .0026) in the infected cohort were elevated compared to the noninfected group. An optimal cutoff value for CRP of 12 mg/L (area under the curve = 0.77, 95% confidence interval 0.58-0.97) revealed 75% sensitivity, 84% specificity, 43% positive predictive value, and 95% negative predictive value (P < .0001) in the entire cohort. CONCLUSIONS: Even without clinical signs and symptoms, patients undergoing conversion THA from internal fixation of hip/acetabular fractures are still at high risk for developing periprosthetic joint infection. All patients undergoing conversion THA should have CRP measured preoperatively as a part of the diagnostic workup for underlying infection. Further research should be devoted to creating a preoperative diagnostic algorithm incorporating CRP, similar to Musculoskeletal Infection Society criteria, dedicated to patients undergoing conversion THA. LEVEL OF EVIDENCE: Level III, Diagnostic retrospective cohort study.

Efficacy of Intraoperative Antiseptic Techniques in the Prevention of Periprosthetic Joint Infection: Superiority of Betadine.

BACKGROUND: Povidone-iodine (PI), chlorhexidine gluconate (CHG), and vancomycin (VANC) powder are common intrawound prophylactic agents to prevent periprosthetic joint infection during primary total joint arthroplasty. The aims of this study are (1) to determine the minimal inhibitory concentration (MIC) and time to death for PI, CHG, and VANC against multiple bacteria and (2) to determine time to death against bacteria dried on titanium discs. METHODS: A standard quantitative suspension assay was performed to determine the MIC for PI, CHG, and VANC against methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Haemophilus influenzae, Pseudomonas aeruginosa, Burkholderia cepacia, and Escherichia coli. Time to death assay was performed with time points of 0, 3, 30, and 60 minutes. Concentrations of antiseptic agents for time to death assay were 1% PI, 0.05% CHG, and 5 µg/mL VANC. Dry-phase bacteria on titanium discs were treated in a similar fashion. RESULTS: The MIC of PI was 0.63%, CHG was 0.0031%, and VANC was 1.56 µg/mL. All 7 bacterial isolates were completely killed by PI at all times tested. CHG failed to kill MRSA and B cepacia at 0- and 3-minute exposures. Vancomycin completely killed MRSA and S epidermidis isolates between 18-20 hours of exposure. All bacterial isolates dried on titanium discs were eliminated by PI exposure on contact. E coli and S epidermidis were incompletely eliminated by CHG at 0 minutes, with all isolates eliminated at 3, 10, and 30 minutes. CONCLUSION: Our study suggests that PI kills all bacteria tested immediately on contact and that the exposure time is not the key factor.

Does Surgeon Fellowship Training Influence Outcomes in Hemiarthroplasty for Femoral Neck Fracture?

BACKGROUND: The aim of this study is to compare the outcomes (90 days and 1 year) of patients with femoral neck fracture undergoing hemiarthroplasty by surgeons with different fellowship training: trauma, arthroplasty, and general orthopedics. METHODS: This study is a retrospective review of consecutive patients undergoing hip hemiarthroplasty for femoral neck fracture from 2010 to 2018. Comorbidities, perioperative details, demographics, injury variables, and time-to-surgery were compared between the fellowship training cohorts, in addition to outcomes including dislocation, periprosthetic joint infection, and mortality at 90 days and 1 year. RESULTS: A total of 298 hips with an average age of 77.8 years underwent hemiarthroplasty for femoral neck fracture. Arthroplasty surgeons had a significantly shorter operative duration (82 minutes, P = .0014) and utilized the anterior approach more frequently (P < .0001). The general orthopedists had a significantly increased total surgical complication risk compared to both the arthroplasty and trauma fellowship-trained cohorts at both 90 days (11.8% vs 1.6% vs 3.9%, P = .015) and 1 year (18.2% vs 4.9% vs 7.1%, P = .008). The overall mortality risk was 11.7% at 90 days and 22.8% at 1 year. When adjusted for covariates, including comorbidities, gender, age, and preoperative walking capacity, both the arthroplasty fellowship-trained cohort (odds ratio 0.381, 95% confidence interval 0.159-0.912, P = .030) and the general orthopedist cohort (odds ratio 0.495; 95% confidence interval 0.258-0.952, P = .035) had reduced risk of 1-year mortality compared to the trauma fellowship-trained cohort. CONCLUSION: Hemiarthroplasty performed for femoral neck fractures may result in fewer complications when performed by arthroplasty fellowship-trained surgeons. An arthroplasty weekly on-call schedule and adjusted institutional protocols may be utilized to improve outcomes and reduce complications. LEVEL OF EVIDENCE: Level II, retrospective cohort.

Optimization of Orthopedic Surgical Instrument Trays: Lean Principles to Reduce Fixed Operating Room Expenses.

BACKGROUND: Optimization of surgical instrument trays improves efficiency and reduces cost. The purpose of this study is to assess the economic impact of optimizing orthopedic instrument trays at a tertiary medical center. METHODS: Twenty-three independent orthopedic surgical instrument trays at a single academic hospital were reviewed from 2017 to 2018. Using Lean methodology, surgeons agreed upon the fewest number of instruments needed for each of the procedure trays. Instrument usage counts, cleaning times, room turnover times, tray weight, holes in tray wrapping, wet trays, and time invested to optimize each tray were tracked. Cost savings were calculated. Student's t-test was used to determine statistical significance, with P < .05 considered significant. RESULTS: The mean instrument usage before and after Lean optimization was 23.4% and 54.2% (P < .0001). By Lean methods, 433 of 792 instruments (55%) were removed from 11 unique instrument trays (102 total trays), resulting in a reduction of 3520 instruments. Total weight reduction was 574.3 pounds (22%), ranging from 2.1-16.2 pounds per tray. The number of trays with wrapping holes decreased from 13 to 1 (P < .0001). The process of examining and removing instruments took an average of 7 minutes 35 seconds per tray. The calculated total annual savings was $270,976 (20% overall cost reduction). CONCLUSION: In addition to substantial cost savings, tray optimization decreases tray weights and cleaning times without negatively impacting turnover times. Lean methodology improves efficiency in instrument tray usage, and reduces hospital cost while encouraging surgeon and staff participation through continuous process improvement. LEVEL OF EVIDENCE: Economic Quality Improvement, Level III.

Preoperative Use of Clopidogrel Does Not Affect Outcomes for Femoral Neck Fractures Treated With Hemiarthroplasty.

BACKGROUND: The antiplatelet effect of clopidogrel on blood loss and perioperative complications after surgical intervention remains ambiguous. The purpose of this study was to determine if patients on clopidogrel before hemiarthroplasty for femoral neck fracture are predisposed to greater surgical bleeding and perioperative complications compared with those not taking clopidogrel before surgery. METHODS: We conducted a review of our electronic medical record from 2006-2013 and identified 602 patients who underwent 623 hemiarthroplasty procedures for displaced femoral neck fracture, of which 54 cases (9%) were taking clopidogrel before hospital admission. Patient demographics and comorbidities, operative and surgical variables, and perioperative complications at 90 days were compared between the clopidogrel and nonclopidogrel user groups. RESULTS: The 2 groups of patients had similar baseline characteristics, but patients taking clopidogrel preoperatively were sicker with higher American Society of Anesthesiologists scores (P = .049) and age-adjusted Charlson index (P = .001). They also had a greater incidence of cerebrovascular disease (P = .01), chronic obstructive pulmonary disease (P = .03), diabetes (0.03), and malignancy (P < .001). There was no significant difference between the 2 patient groups with respect to 90-day postoperative medical readmissions (P = .85), surgical readmissions (P = .26), infection (P = .99), and mortality (P = .89). CONCLUSION: Patients taking clopidogrel who present with a displaced femoral neck fracture can safely undergo a hemiarthroplasty while actively on clopidogrel without an increase in medical or surgical complications and mortality. We do not recommend delaying surgical intervention until the antiplatelet effects of clopidogrel subside.

Utility of Synovial White Blood Cell Count and Differential Before Reimplantation Surgery.

BACKGROUND: Determining optimal timing of reimplantation during 2-stage exchange for periprosthetic joint infection (PJI) remains elusive. Joint aspiration for synovial white blood cell (WBC) count and neutrophil percentage (PMN%) before reimplantation is widely performed; yet, the implications are rarely understood. Therefore, this study investigates (1) the diagnostic yield of synovial WBC count and differential analysis and (2) the calculated thresholds for persistent infection. METHODS: Institutional PJI databases identified 129 patients undergoing 2-stage exchange arthroplasty who had joint aspiration before reimplantation between February 2005 and May 2014. Persistent infection was defined as a positive aspirate culture, positive intraoperative cultures, or persistent symptoms of PJI-including subsequent PJI-related surgery. Receiver-operating characteristic curve was used to calculate thresholds maximizing sensitivity and specificity. RESULTS: Thirty-three cases (33 of 129; 25.6%) were classified with persistent PJI. Compared with infection-free patients, these patients had significantly elevated PMN% (62.2% vs 48.9%; P = .03) and WBC count (1804 vs 954 cells/µL; P = .04). The receiver-operating characteristic curve provided thresholds of 62% and 640 cells/µL for synovial PMN% and WBC count, respectively. These thresholds provided sensitivity of 63% and 54.5% and specificity of 62% and 60.0%, respectively. The risk of persistent PJI for patients with PMN% >90% was 46.7% (7 of 15). CONCLUSION: Synovial fluid analysis before reimplantation has unclear utility. Although statistically significant elevations in synovial WBC count and PMN% are observed for patients with persistent PJI, this did not translate into useful thresholds with clinical importance. However, with little other guidance regarding the timing of reimplantation, severely elevated WBC count and differential analysis may be of use.

The ACS NSQIP Risk Calculator Is a Fair Predictor of Acute Periprosthetic Joint Infection.

BACKGROUND: Periprosthetic joint infection (PJI) is a severe complication from the patient's perspective and an expensive one in a value-driven healthcare model. Risk stratification can help identify those patients who may have risk factors for complications that can be mitigated in advance of elective surgery. Although numerous surgical risk calculators have been created, their accuracy in predicting outcomes, specifically PJI, has not been tested. QUESTIONS/PURPOSES: (1) How accurate is the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Surgical Site Infection Calculator in predicting 30-day postoperative infection? (2) How accurate is the calculator in predicting 90-day postoperative infection? METHODS: We isolated 1536 patients who underwent 1620 primary THAs and TKAs at our institution during 2011 to 2013. Minimum followup was 90 days. The ACS NSQIP Surgical Risk Calculator was assessed in its ability to predict acute PJI within 30 and 90 days postoperatively. Patients who underwent a repeat surgical procedure within 90 days of the index arthroplasty and in whom at least one positive intraoperative culture was obtained at time of reoperation were considered to have PJI. A total of 19 cases of PJI were identified, including 11 at 30 days and an additional eight instances by 90 days postoperatively. Patient-specific risk probabilities for PJI based on demographics and comorbidities were recorded from the ACS NSQIP Surgical Risk Calculator website. The area under the curve (AUC) for receiver operating characteristic (ROC) curves was calculated to determine the predictability of the risk probability for PJI. The AUC is an effective method for quantifying the discriminatory capacity of a diagnostic test to correctly classify patients with and without infection in which it is defined as excellent (AUC 0.9-1), good (AUC 0.8-0.89), fair (AUC 0.7-0.79), poor (AUC 0.6-0.69), or fail/no discriminatory capacity (AUC 0.5-0.59). A p value of < 0.05 was considered to be statistically significant. RESULTS: The ACS NSQIP Surgical Risk Calculator showed only fair accuracy in predicting 30-day PJI (AUC: 74.3% [confidence interval {CI}, 59.6%-89.0%]. For 90-day PJI, the risk calculator was also only fair in accuracy (AUC: 71.3% [CI, 59.9%-82.6%]). Conclusions The ACS NSQIP Surgical Risk Calculator is a fair predictor of acute PJI at the 30- and 90-day intervals after primary THA and TKA. Practitioners should exercise caution in using this tool as a predictive aid for PJI, because it demonstrates only fair value in this application. Existing predictive tools for PJI could potentially be made more robust by incorporating preoperative risk factors and including operative and early postoperative variables. LEVEL OF EVIDENCE: Level III, diagnostic study.