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

INTRODUCTION: Data on bacterial adhesion to cerclage cables is sparse. We aimed to compare five cerclage products for methicillin-resistant Staphylococcus aureus (MRSA) adhesion to determine: Are non-metallic polymer cables more resistant to bacterial adhesion than common metallic wires and cables? MATERIALS AND METHODS: The following five cerclage products were compared: 1) monofilament stainless steel (SS) wires; 2) multifilament SS cables; 3) multifilament cobalt chrome (CoCr) cables; 4) multifilament Vitalium alloy (cobalt-chrome-molybdenum [Co-Cr-Mo]) cables; and 5) multifilament non-metallic polymer cables. Each was cut into 2 cm lengths and placed into 12-well plates. Of the wells, five were wire or cables in trypticase soy broth (TSB) with MRSA, with the remaining wells being appropriate controls incubated for 24 hours at 37 degrees C and 5% CO2 with shaking. Wires and cables were prepared, and randomly imaged via scanning electron microscopy (SEM), with bacterial counts performed on 3 images of 3 different wires or cables per study group. The SEM 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 = 0.0003). Post-hoc comparison showed no difference between groups individually (all P > 0.05) apart from polymer cables (median 551 bacteria) having significantly increased attached bacteria compared to the Vitallium alloy cable (157, P = 0.0004), SS cable (101, P = 0.0004), and SS wire (211, P = 0.0004). There was no difference between polymer and CoCr cables (133, P = 0.056). Microcalorimetry supported these results, as polymer cables had a shorter time to max heat flow (6.2 versus 7.5 hours, P = 0.006), increased max heat flow (117 versus 64 uW, P = 0.045), and increased colony-forming units, indicating an increased bacterial load compared to SS wires. ConclusionThis in vitro study demonstrates 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.

Transverse posterior wall acetabular fracture pattern is associated with increased risk of periprosthetic joint infection after conversion total hip arthroplasty.

INTRODUCTION: Acetabular fracture subtypes are associated with varying rates of subsequent conversion total hip arthroplasty (THA) after open reduction internal fixation (ORIF) with transverse posterior wall (TPW) patterns having a higher risk for early conversion. Conversion THA is fraught with complications including increased rates of revision and periprosthetic joint infections (PJI). We aimed to determine if TPW pattern is associated with higher rates of readmissions and complications including PJI after conversion compared to other subtypes. METHODS: We retrospectively reviewed 1,938 acetabular fractures treated with ORIF at our institution from 2005 to 2019, of which 170 underwent conversion that met inclusion criteria, including 80 TPW fracture pattern. Conversion THA outcomes were compared by initial fracture pattern. There was no difference between the TPW and other fracture patterns in age, BMI, comorbidities, surgical variables, length of stay, ICU stay, discharge disposition, or hospital acquired complications related to their initial ORIF procedure. Multivariable analysis was performed to identify independent risk factors for PJI at both 90-days and 1-year after conversion. RESULTS: TPW fracture had higher risk of PJI after conversion THA at 1-year (16.3% vs 5.6%, p = 0.027). Multivariable analysis revealed TPW independently carried increased risk of 90-day (OR 4.89; 95% CI 1.16-20.52; p = 0.03) and 1-year PJI (OR 6.51; 95% CI 1.56-27.16; p = 0.01) compared to the other acetabular fracture patterns. There was no difference between the fracture cohorts in 90-day or 1-year mechanical complications including dislocation, periprosthetic fracture and revision THA for aseptic etiologies, or 90-day all-cause readmission after the conversion procedure. CONCLUSION: Although conversion THA after acetabular ORIF carry high rates of PJI overall, TPW fractures are associated with increased risk for PJI after conversion compared to other fracture patterns at 1-year follow-up. Novel management/treatment of these patients either at the time of ORIF and/or conversion THA procedure are needed to reduce PJI rates. LEVEL OF EVIDENCE: Therapeutic Level III (retrospective study of consecutive patients undergoing an intervention with analyses of outcomes).

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.

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.

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.

Utility of Diagnostic Tests Before Reimplantation in Patients Undergoing 2-Stage Revision Total Joint Arthroplasty: A Systematic Review and Meta-analysis.

INTRODUCTION: Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty (TJA), with treatment failure occurring in 12% to 28% after 2-stage revision. It is vital to identify diagnostic tools indicative of persistent infection or treatment failure after 2-stage revision for PJI. METHODS: The Cochrane Library, PubMed (MEDLINE), and EMBASE were searched for randomized controlled trials and comparative observational studies published before October 3, 2021, which evaluated the utility of serum/plasma biomarkers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], interleukin-6 [IL-6], fibrinogen, D-dimer), synovial biomarkers (white blood cell [WBC] count, neutrophil percentage [PMN %], alpha-defensin [AD], leukocyte esterase [LE]), tissue frozen section, tissue culture, synovial fluid culture, or sonicated spacer fluid culture indicative of persistent infection before the second stage of 2-stage revision for PJI or treatment failure after 2-stage revision for PJI. RESULTS: A total of 47 studies including 6,605 diagnostic tests among 3,781 2-stage revisions for PJI were analyzed. Among those cases, 723 (19.1%) experienced persistent infection or treatment failure. Synovial LE (sensitivity 0.25 [0.10-0.47], specificity 0.99 [0.93-1.00], positive likelihood ratio 14.0 [1.45-135.58]) and serum IL-6 (sensitivity 0.52 [0.33-0.70], specificity 0.92 [0.85-0.96], positive likelihood ratio 7.90 [0.86-72.61]) had the highest diagnostic accuracy. However, no biomarker was associated with a clinically useful negative likelihood ratio. In subgroup analysis, synovial PMN %, synovial fluid culture, serum ESR, and serum CRP had limited utility for detecting persistent infection before reimplantation (positive likelihood ratios ranging 2.33-3.74; negative likelihood ratios ranging 0.31-0.9) and no utility for predicting failure after the second stage of 2-stage revision. CONCLUSIONS: Synovial WBC count, synovial PMN %, synovial fluid culture, serum ESR, and serum CRP have modest sensitivity and specificity for predicting persistent infection during the second stage of 2-stage revision, suggesting some combination of these diagnostic tests might be useful before reimplantation. No biomarker or culture accurately predicted treatment failure after reimplantation. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

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.

Risk Factors for Early Conversion Total Hip Arthroplasty After Pipkin IV Femoral Head Fracture.

OBJECTIVES: To determine risk factors for early conversion total hip arthroplasty (THA) in Pipkin IV femoral head fractures. DESIGN: Retrospective cohort. SETTING: Two level I trauma centers. PATIENTS AND INTERVENTION: One hundred thirty-seven patients with Pipkin IV fractures meeting inclusion criteria with 1 year minimum follow-up managed from 2009 to 2019. MAIN OUTCOME MEASUREMENT: Patients were separated into groups by the Orthopaedic Trauma Association/AO Foundation (OTA/AO) classification of femoral head fracture: 31C1 (split-type fractures) and 31C2 (depression-type fractures). Multivariable regression was performed after univariate analysis comparing patients requiring conversion THA with those who did not. RESULTS: We identified 65 split-type fractures, 19 (29%) underwent conversion THA within 1 year. Surgical site infection ( P = 0.002), postoperative hip dislocation ( P < 0.0001), and older age ( P = 0.049) resulted in increased rates of conversion THA. However, multivariable analysis did not identify independent risk factors for conversion. There were 72 depression-type fractures, 20 (27.8%) underwent conversion THA within 1 year. Independent risk factors were increased age ( P = 0.01) and posterior femoral head fracture location ( P < 0.01), while infrafoveal femoral head fracture location ( P = 0.03) was protective against conversion THA. CONCLUSION: Pipkin IV fractures managed operatively have high overall risk of conversion THA within 1 year (28.5%). Risk factors for conversion THA vary according to fracture subtype. Hip joint survival of fractures subclassified OTA/AO 31C1 likely depends on patient age and postoperative outcomes such as surgical site infection and redislocation. Pipkin IV fractures subclassified to OTA/AO 31C2 type with suprafoveal and posterior head impaction and older age should be counseled of high conversion risk with consideration for alternative management options. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Gravity-Assisted Manipulation (GAM) Technique for the Treatment of Knee Arthrofibrosis.

Arthrofibrosis is a known complication after knee surgery, resulting in stiffness and decreased range of motion for patients. Manipulation under anesthesia is a commonly used technique to address postoperative arthrofibrosis after knee surgery. Often, direct pressure is applied to the knee during the manipulation. This can be difficult and can place undue stress above and below the joint. This Technical Note presents the technique for manipulation under anesthesia using gravity and the native knee motion alone to improve knee range of motion.

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.

Total Joint Arthroplasty Should Not Be Delayed in Hepatitis C Patients After Successful Treatment Achieving a Sustained Viral Load.

Background: Preoperative treatment recommendations and optimal time to perform total joint arthroplasty (TJA) in patients with hepatitis C virus after treatment completion for achieving best outcomes have not been elucidated. We aim to determine (1) if undetectable viral load (UVL) prior to TJA leads to decreased postoperative complication rates, specifically periprosthetic joint infection (PJI), and (2) if delaying TJA after treatment completion has benefit in decreasing PJI. Methods: A retrospective review of all hepatitis C virus patients undergoing TJA at 3 academic tertiary care centers was conducted. A total of 270 TJAs performed from 2005 to 2019 were included, 125 with positive viral load at the time of surgery. The duration from completion of treatment regimen to TJA was recorded for the UVL cohort. The primary study outcome was PJI at 1-year follow-up. Secondary outcomes included in-hospital complications, mechanical revision TJA rates, and optimal time to TJA upon completion of treatment. Results: Patients with positive viral load at the time of TJA had longer length of stay (3.9 vs 2.9 days, P < .0001) and a higher PJI rate at 1 year postoperatively (9% vs 2%, P = .02) than UVL patients. There was no difference of in-hospital complications or revision rates for mechanical etiologies. Delaying TJA after achieving a sustained virologic response did not impact PJI rates. Conclusions: Sustained UVL prior to TJA is critical to minimize PJI irrespective of the treatment regimen utilized. Surgery can be performed with lower complication rates any time after achieving sustained virologic response. Level of Evidence: Level III, prognostic retrospective cohort study.

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.

Perioperative assessment of muscle inflammation susceptibility in patients with end-stage osteoarthritis.

Many individuals with end-stage osteoarthritis (OA) undergo elective total hip/knee arthroplasty (THA/TKA) to relieve pain, improve mobility and quality of life. However, ∼30% suffer long-term mobility impairment following surgery. This may be in part due to muscle inflammation susceptibility (MuIS+), an overt proinflammatory pathology localized to skeletal muscle surrounding the diseased joint, present in some patients with TKA/THA. We interrogated the hypothesis that MuIS+ status results in a perturbed perioperative gene expression profile and decreases skeletal muscle integrity in patients with end-stage OA. Samples were leveraged from the two-site, randomized, controlled trial R01HD084124, NCT02628795. Participants were dichotomized based on surgical (SX) muscle gene expression of TNFRSF1A (TNF-αR). MuIS+/- samples were probed for gene expression and fibrosis. Paired and independent two-tailed t tests were used to determine differences between contralateral (CTRL) and surgical (SX) limbs and between-subject comparisons, respectively. Significance was declared at P < 0.05. Seventy participants (26M/44F; mean age 62.41 ± 8.86 yr; mean body mass index 31.10 ± 4.91 kg/m2) undergoing THA/TKA were clustered as MuIS+ (n = 24) or MuIS- (n = 46). Lower skeletal muscle integrity (greater fibrosis) exists on the SX versus CTRL limb (P < 0.001). Furthermore, MuIS+ versus MuIS- muscle exhibited higher proinflammatory (IL-6R and TNF-α) and catabolic (TRIM63) gene expression (P < 0.001, P = 0.004, and 0.024 respectively), with a trend for greater fibrosis (P = 0.087). Patients with MuIS+ exhibit more inflammation and catabolic gene expression in skeletal muscle of the SX limb, accompanied by decreased skeletal muscle integrity (Trend). This highlights the impact of MuIS+ status emphasizing the potential value of perioperative MuIS assessment to inform optimal postsurgical care.NEW & NOTEWORTHY This study assessed the skeletal muscle molecular characteristics associated with end-stage osteoarthritis and refined an important phenotype, in some patients, termed muscle inflammation susceptibility (MuIS+) that may be an important consideration following surgery. Furthermore, we provide evidence of differential inflammatory and catabolic gene expression between the contralateral and surgical limbs along with differences between the skeletal muscle surrounding the diseased hip versus knee joints.

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.

The fate of positive intraoperative cultures following conversion total hip arthroplasty.

INTRODUCTION: The objectives of this study are to report the rates of positive intraoperative cultures obtained during conversion total hip arthroplasty (THA) according to index surgery, and to describe the natural history of treatment for a consecutive series of patients with unexpected positive intraoperative cultures during conversion THA. METHODS: We reviewed all patients at 2 institutions undergoing conversion THA from prior open reduction and internal fixation (ORIF) of acetabular and hip fractures or hemiarthroplasty for displaced femoral neck fractures from 2011 to 2018. Intraoperative cultures were taken in 105 patients. Positive intraoperative cultures during conversion were recorded and managed with an infectious diseases consult. The outcomes including PJI at 90 days and 1 year follow-up were documented. RESULTS: Overall, 19 of 105 patients (18%) undergoing conversion THA had positive intraoperative cultures, with the highest rates in the hemiarthroplasty 7/16 (44%) and acetabular ORIF 9/48 (19%) groups. All 19 patients were initially treated conservatively: 8 received IV antibiotics, 10 received no additional therapy, and 1 received oral antibiotics. 4/9 acetabular fracture conversions developed PJI at 1 year, with 3 requiring multiple irrigation and debridement/polyethylene exchanges to control the infection while the 4th patient required 2-stage exchange. There were no 1-year PJI from any of the other index procedures after conversion. All 7 hemiarthroplasty patients with positive cultures were treated to resolution with 4-8 weeks IV antibiotics alone. CONCLUSIONS: Patients undergoing conversion THA from prior hip or acetabular fracture have a high rate of positive intraoperative cultures. As such, all patients undergoing conversion THA from prior hip or acetabular fracture fixation should undergo thorough diagnostic workup prior to surgery, and have intraoperative cultures obtained during surgery if infection remains suspicious. Further work should be performed to develop MSIS criteria for preoperative management of patients undergoing conversion THA.

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).

Comparison of Genicular Nerve Block in Combination With Adductor Canal Block in Both Primary and Revision Total Knee Arthroplasty: A Retrospective Case Series.

The management of pain in patients undergoing total knee arthroplasty (TKA) for chronic knee osteoarthritis (OA) has remained a challenge for the anesthesiologist regarding regional anesthesia as no single regional technique is adequate with regard to balancing effective analgesia with minimal muscle weakness. Severe postoperative pain following TKA has been shown to negatively impact patient outcomes and mortality. The genicular nerve block has recently been demonstrated to provide effective analgesia to the anterior and posterior knee capsule in recent studies. In this retrospective case series, we compare the efficacy of combined genicular nerve block (GNB) and adductor canal block (ACB) to only ACB in both primary and revision TKA patients. This combined novel approach for TKA patients can be utilized to improve patient pain scores and early ambulation, limiting the use of opioids and early discharge.

When Total Joint Arthroplasty After Septic Arthritis Can Be Safely Performed.

BACKGROUND: Patients undergoing total joint arthroplasty (TJA) following septic arthritis are at higher risk for developing periprosthetic joint infection (PJI). Minimal literature is available to guide surgeons on the optimal timing of TJA after completing treatment for prior native joint septic arthritis. This multicenter study aimed to determine the optimal timing of TJA after prior septic arthritis and to examine the role of preoperative serology in predicting patients at risk for developing PJI. METHODS: A total of 207 TJAs were performed after prior septic arthritis from 2000 to 2017 at 5 institutions. Laboratory values, prior treatment, time from the initial infection, and other variables were recorded. Bivariate analyses were performed to identify the association between the time from septic arthritis to TJA and the risk of developing subsequent PJI. A subanalysis was performed between patients who underwent TJA in 1 setting (n = 97) compared with those who underwent 2-stage arthroplasties (n = 110). Receiver operating characteristic (ROC) curve analysis was performed for serum markers prior to TJA in predicting the risk of a subsequent PJI. RESULTS: The overall PJI rate was 12.1%. Increasing time from septic arthritis treatment to TJA was not associated with a reduction of PJI, whether considering time as a continuous or categorical variable, for both surgical treatment cohorts (all p > 0.05). Although the ROC curve analysis found that the optimal threshold for timing of TJA from the initial treatment was 5.9 months, there was no difference in the PJI rate when the overall cohort was dichotomized by this threshold and when stratified by 1-stage compared with 2-stage TJA. There was no significant difference in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level prior to conversion TJA between patients who subsequently developed PJI and those who did not. CONCLUSIONS: Serum markers have limited value in predicting subsequent PJI in patients who undergo TJA after prior septic arthritis. There was no optimal interim period between septic arthritis treatment and subsequent TJA; thus, delaying a surgical procedure does not appear to reduce the risk of PJI. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.