Ortho Outcomes Vol 8 by Jefferson

ORTHOPAEDIC OUTCOMES

RESEARCH

Hip & Knee

HOME OF SIDNEY KIMMEL MEDICAL COLLEGE

VOLUME 8

HIP & KNEE

tackling complex multi-faceted issues Dear Colleagues, Jefferson Health is nationally recognized for its hip and knee program. Whether a patient needs total joint replacement or treatment for a fracture or other injury, the team employs the latest techniques and implant materials to ensure that patients return to an active life. In many cases, patients benefit from a minimally invasive procedure or one-day surgery. Arthroplasty (hip or knee replacement) is being done with increasing frequency on younger patients rather than letting people become sidelined for years before getting a new joint. Jefferson Health’s combined team of joint replacement surgeons from Thomas Jefferson University Department of Orthopaedic Surgery and the Rothman Institute is also focused on making surgery as risk-free as possible. As experienced surgeons who also are widely published researchers, they are exploring novel theories that may help prevent periprosthetic joint infections, an uncommon yet much dreaded complication of total joint arthroplasty. One intriguing possibility is that of a gut-joint connection. Jefferson Health’s orthopaedic team is also tackling a complex, multi-faceted issue faced by healthcare providers all across the country: Why are there often disparities in outcomes for patients from disadvantaged communities? Jefferson health researchers are examining societal factors that may impact patients’ ability to recover following joint replacement. Here is a summary of some of the findings made by Jefferson Health researchers. Sincerely,

Alexander R. Vaccaro, MD, PhD, MBA Richard H. Rothman Professor and Chair Department of Orthopaedic Surgery, Jefferson Health

Jefferson Health | Orthopaedic Outcomes & Research

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The loss of mucosal barrier function, particularly in the GI tract, may substantially affect antigen trafficking, ultimately influencing the close bidirectional interaction between the gut microbiome and the immune system. One of the most common organisms causing periprosthetic joint infections (PJI) is Staphylococcus aureus, which has been shown in animal models to be able to translocate from the gut to prosthetic joints or the surgical site. An emerging theory called the “Trojan Horse” hypothesis suggests that the translocation process is not only mediated by blood (bacteremia), but also by blood cells such as neutrophils and macrophages that act as a Trojan Horse to transport pathogens between various sites.

Zonulin ng/mL 300

3 ICM-

1.5 ICM-

ICM+

Infected per 2018 ICM criteria Figure 1. Descriptive plots of gut permeability biomarkers (CD14, zonulin, LPS) are provided. Data were reported as mean and standard deviation. LPS: Lipopolysaccharide. ICM: International Consensus Meeting. **:p < 0.05; ***:p < 0.001. If data were not flagged (*), the comparison was not found significant.

If this association continues to be borne out with a larger cohort and more in-depth analysis, it will have a clinically significant implication in managing patients with PJI.”

“It may be that in addition to the administration of antimicrobials, patients with PJI and other orthopaedic infections may benefit from the administration of gastrointestinal modulators such as pro and prebiotics.”

2 Chronic

To test the theory, a Jefferson Health research team led by Javad Parvizi, MD, and including Emanuele Chisari, MD, tested

ICM+

Infected per 2018 ICM criteria

5.0

A total of 134 patients were included in the study, including 44 patients with PJI and 90 non-PJI patients. Both zonulin and sCD14 levels were significantly elevated in the PJI group compared to the non-infected cases. In addition, higher levels of zonulin were found in acute infections compared to chronic ones. LPS was not found to be correlated with the infections. While recognizing that PJI likely involves multiple complex factors, the researchers concluded that “This prospective study reveals a possible link between gut permeability and the ‘gut-immune-joint’ axis in PJI.

ICM-

ICM+

Infected per 2018 ICM criteria

LPS u/mL

plasma collected as part of a prospective cohort study of patients undergoing primary arthroplasty or revision arthroplasty because of aseptic failure or PJI. All blood samples were collected before antibiotic administration. The blood samples were tested for three markers of gut permeability: Zonulin, soluble CD14 (sCD14) and lipopolysaccharide (LPS). Results were published in Scientific Reports.

Zonulin ng/mL

Prior studies on the etiopathogenesis of surgical site infection (SSI) have suggested three main avenues: Local contamination during surgery; hematogenous translocation of bacteria during concomitant bacteremia and contamination from adjacent infected tissue by the progression of the infective process. While most of the research on SSI has focused on minimizing any source of pathogens at the time of surgery, emerging evidence demonstrates how acute and chronic SSI can emerge more often from endogenous sources of microorganisms such as those found in the gastrointestinal system, especially in the context of unbalanced gut flora, dysbiosis and impaired gut permeability.

***

CD14 ng/mL

Gut Permeability May Be Associated with Periprosthetic Joint Infection after Total Hip and Knee Arthroplasty

650

Acute

Timing of the infection Figure 2. Levels of zonulin based on the timing of the infection. **: p < 0.05. Source: Javad Parvizi, MD

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Zonulin ng/mL

4 3 2 1

12 10

8 6 4

2 0

Arm allocation

800

CPR mg/dL

LPS u/mL

HIP & KNEE

CD14 ng/mL

700 600 500

400 300 0

200 0

Arm allocation Figure 3. Descriptive plots based on arm allocation. Data are reported as mean and standard error. 0: primaries; 1: aseptic revisions; 2: Chronic PJI; 3: acute PJI.

Zonulin ng/mL Figure 4. Correlation plot between Zonulin and C-reactive protein for infected patients. Source: Javad Parvizi, MD

Source: Javad Parvizi, MD

Jefferson Health | Orthopaedic Outcomes & Research

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Periprosthetic Joint Infection and the Trojan Horse Theory: Examining the Role of Gut Dysbiosis and Epithelial Integrity A follow-up study, published in The Journal of Arthroplasty, looked further at a possible gut-joint connection. The study reported on an analysis of a subset of 46 patients undergoing revision arthroplasty who had next-generation sequencing (16S rRNA) of soft tissue and bone samples retrieved during revision surgery. Thirty-eight of the 46 patients had revision for PJI and eight were classified as aseptic failure. An analysis of each of the bacteria retrieved during surgery was performed and those known to be gut commensal were noted. The analysis found that “a significant number of the organisms causing PJI are part of the gut microbiome and frequent commensals.”

found a strong and direct correlation between gut dysbiosis and PJI. This is the first time a clinical study reported empirical evidence of a strong association between gut permeability and the presence of gut commensal bacteria in the surgical site of infected patients. The study was led by Javad Parvizi, MD. If future research on the Trojan Horse theory of PJI pans out, a change in how to manage patients might result. “It is well known that the administration of long-term antibiotics may lead to the emergence of infection with fungal pathogens or antibiotic-resistant organisms,” the study noted. “Manipulation of the gut microbiome may become part of an essential and comprehensive approach for the management of patients with PJI or the prevention of its complication in patients at high risk.”

Using the 16S rRNA sequencing signal retrieved from patients with PJI and measuring the level of gut permeability markers such as zonulin, the researchers

P (Gut commensal? = Yes)

1.00

0.75

0.50

0.25

0.00 0

Zonulin ng/mL Source: Javad Parvizi, MD

Jefferson Health | Orthopaedic Outcomes & Research

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HIP & KNEE

Postacute Care Readmission and Resource Utilization in Patients from Socioeconomically Distressed Communities After Total Joint Arthroplasty There is a well-known association between socioeconomic and racial differences and poor patient outcomes, including with orthopaedics. These disparities may result from upstream factors such as poverty, educational level and neighborhood safety, or downstream factors such as harmful coping behaviors or distress related to a patient’s physical and mental health. Hip and knee arthroplasty (THA and TKA) are among the most common elective orthopaedic procedures. Understanding social factors that may influence outcomes could provide some insight into patients at risk for readmission and shed light on the way in which these patients used postoperative resources. This knowledge can help surgeons better understand which patients are more likely to have complications or preventable readmissions and how to anticipate when additional surveillance or intervention might reduce this risk. Jefferson Health researchers led by Chad A. Krueger, MD, designed a retrospective study to address two key questions: 1) Do patients from communities with a higher distress level experience higher rates of readmission after THA and TKA? 2) Do patients from distressed communities have increased postoperative resource utilization?

same practice. The researchers chose 2016 as the starting date for their analysis because it was when their practice, the Rothman Orthopaedic Institute, began using nurse navigators to better ensure patient followup after surgery. Demographic data, including age, gender, self-reported race, BMI and ZIP code, were recorded for all patients. The race classifications were later combined into Black, White or other for purposes of the study. The Distressed Communities Index (DCI) tool was used to assign a distress score to each patient based on their ZIP code at time of surgery. The scores ranged from 0 (no distress) to 100 (most distress) based on seven metrics of well-being, including percentage of the population with a high school diploma, poverty, race, unemployment rates, housing vacancy rate, median household income, change in employment and change in establishments. For the 5,120 patients who had TKA, the mean age was 66, 59% were women, 69% were White and 14% were Black. For the 5,337 THA patients, the mean age was 63, half were women, 74% were White and 10% were Black. Nearly all patients included in the study had a DCI score assignment.

The study, published in Clinical Orthopaedics and Related Research, included more than 10,000 patients who had THA or TKA between January 1, 2016 and December 31, 2019, with each procedure performed by 21 high-volume arthroplasty surgeons at an urban tertiary care hospital or a suburban orthopaedic specialty hospital within the

The primary outcome was 90-day readmission, though the analysis also examined secondary outcomes, including postoperative medication prescriptions, physical therapy sessions attended, telephone calls between the patient and the surgeon’s office, postoperative office visits and visits to the emergency department after hospital discharge.

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HIP & KNEE

All primary TKAs and THAs performed between 2016–2019 TKA (n = 5,120) THA (n = 5,337) No Distressed Communities Index (DCI) score available TKA (n = 43) THA (n = 38) Cases included in analysis TKA (n = 5,077) THA (n = 5,299) Figure 1: Table outlining patient inclusion and exclusion.

90-DAY READMISSION Distressed

The study found that for TKA, patients from communities classified as distressed according to the DCI score were more likely to be readmitted within 90 days of TKA compared to patients from communities classified as prosperous. There were no differences in readmission rates for TKA when patients from prosperous communities were compared to those from communities characterized as comfortable, mid-tier or at-risk. There were no differences in readmission rates after THA among the various categories of DCI.

At Risk

Mid-Tier

Comfortable

Unlike other studies that have found an association between race and poorer outcomes, the Jefferson Health study found no such association for THA or TKA patients. 0

0.5

1.5

2.53

l = TKA n = THA Figure 2: ORs and 95% CIs for 90-day readmission by DCI category in patients undergoing TKA and THA after adjusting for demographics and CCI. Category 1 (prosperous) was used for reference. Source: Chad A. Krueger, MD

Jefferson Health | Orthopaedic Outcomes & Research

“This indicates that a combination of social factors – much deeper than just race – are associated with readmission in patients from distressed communities,” they reported. On the issue of post-surgery utilization of services, the study found that, for the

most part, patients who lived in distressed communities did not use more postdischarge resources following either THA or TKA. Race was also not associated with different levels of resource utilization. “This finding suggests that patients from distressed communities may have increased needs, but they are not receiving a higher level of surveillance or care until ultimately requiring readmission,” the study said. The researchers suggested that telemedicine might be useful to increase contact with patients who may be at risk for readmission due to their socioeconomic background but have difficulty with transportation to get to an office visit. They gave the example of a patient with concerns about wound healing. More research is needed to identify specific measures that could be useful in reducing barriers and disparities in risk for admission following total joint arthroplasty.

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HIP & KNEE

HIP & KNEE SURGICAL VOLUME April 2022 to March 2023 Thomas Jefferson University Hospital

1,868

Jefferson Abington Hospital

881

Jefferson Bucks Hospital

727

Jefferson Cherry Hill Hospital

493

Jefferson Einstein Hospital – Elkins Park

411

Jefferson Lansdale Hospital

544

Jefferson Torresdale Hospital

148

Jefferson Washington Township Hospital

490

Doylestown Surgical Center

322

Physician Care Surgery Center

163

Physician Care Surgical Hospital

1,467

Rothman Orthopaedic Specialty Hospital

2,716

TOTAL

9,092

Surgical volumes include all procedures performed at Jefferson Health hospitals and ambulatory surgery centers. Source: Jefferson Health internal data

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Funded Clinical Trials 1. P ost-Market Clinical Follow-Up Study of the Zimmer Vivacit-E Highly Crosslinked Polyethylene Liner Used with the Continuum Acetabular Shell. Zimmer Biomet (10/1/2013–ongoing) (Javad Parvizi, MD) 2. Post-Market Study of the Stryker Orthopaedics Triathlon TS Total Knee System. Stryker (04/01/2012—ongoing) (Alvin C. Ong, MD)

16. Multi-Center Clinical Evaluation of the ATTUNE Revision System in Complex Primary Total KneeArthroplasty. DePuy Synthes (05/2019–current). (Zachary Post, MD)

3. Persona Outcomes Knee Study (POLAR). Zimmer Biomet (03/01/2013–ongoing) (Matthew S. Austin, MD)

17. Perioperative Antibiotic Prophylaxis in Patients Undergoing Elective Total Knee Arthroplasty: A prospective, randomized, open-label, controlled multi-center trial (Javad Parvizi, MD)

4. R etrieval of Discarded Surgical Tissue. National Disease Registry Institute (01/12/2004–ongoing) (James J. Purtill, MD)

18. The Effect of Oral Nutrition Optimization on Complications Following Total Joint Arthroplasty (Matthew Austin, MD)

5. Triathlon Tritanium Knee Outcomes Study. Stryker (04/2014–present) (Alvin Ong, MD)

19. Dual Mobility vs Single-bearing Components in THA at High Risk for Prosthetic Dislocation. (4/2019–current) (Paul Maxwell Courtney, MD)

6. Post Market Study of the Stryker Orthopaedics Triathlon PKR Knee System. Stryker (11/2013–present) (Alvin Ong, MD) 7. One Stage Versus Two Stage for Periprosthetic Hip and Knee Infection. Orthopaedic Research and Education Foundation (05/2016–present) (Javad Parvizi, MD) 8. Clinical Outcomes Reporting Study. Stryker Orthopaedics (10/2013–current) (Javad Parvizi, MD; William Hozack, MD) 9. P ost-Market Study of Robotic-Arm Assisted Total Knee Arthroplasty. Stryker, Corp. (07/2016–current) (William J. Hozack, MD) 10. A Retrospective Study of the Navio Robotic-Assisted Surgical System. Smith and Nephew (07/2017–current) (Jess Lonner, MD) 11. Intermediate Clinical and Radiographic Outcomes of Isolated Patellofemoral Arthroplasty and Modular Bicompartmental Knee Arthroplasty. Zimmer Biomet (09/2017–current) (Jess Lonner, MD) 12. A Prospective, Post-Market, Multi-Center Evaluation of the Clinical Outcomes of the Trident II Acetabular Shell. Stryker (09/2017–current) (Alvin C. Ong, MD) 13. Prospective Post-Approval Clinical Follow-Up Study of the Commercially Available U2 Knee System. United Orthopedic Corporation (7/2018–current). (Arjun Saxena, MD) 14. M ulti-Center Clinical Evaluation of the ATTUNE Cementless Rotating Platform Total Knee Arthroplasty. DePuy Synthes (07/2019–current). (Zachary Post, MD)

15. Multi-Center Clinical Evaluation of the ATTUNE Revision System in Revision Total Knee Arthroplasty. DePuy Synthes (05/2019–current). (Zachary Post, MD)

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20. Dual Mobility vs Single bearing components in revision THA. (9/2018–current) (Paul Maxwell Courtney, MD) 21. A Prospective Multicenter Longitudinal Cohort Study of the MyMobility Platform. Zimmer Biomet (7/2019–current) (Jess Lonner, MD) 22. A Prospective Multicenter Longitudinal Cohort Study of the Persona IQ Personalized Knee System with mymobility Platform. Zimmer Biomet (2023) (Yale Fillingham, MD) 23. Medacta M-Vizion™ Macroscopic Radiographic Study, Multicenter, Post-Market Outcomes Study. Medacta (2023) (Yale Fillingham, MD) 24. E lectrochemical test of leukocyte esterase as a marker for periprosthetic joint infection in total hip or total knee arthroplasty. PSI (2023) (Chad Krueger, MD) 25. S afety and Effectiveness of the Hip Innovation Technology Reverse Hip Replacement System in Primary Total Hip Arthroplasty. Hip Innovation Technologies. (2023) (Javad Parvizi, MD) 26. The use of povidone-iodine sterile solution to reduce periprosthetic joint infections: a superiority multicentre randomized trial. PSI (2023) (Javad Parvizi, MD) 27. A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase 3 Study to Determine the Efficacy of TG-C in Subjects with Kellegren and Lawrence Grade 2 or 3 Osteoarthritis of the Knee. TissueGene (2022–ongoing) (Javad Parvizi, MD)

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28. M ulticenter trial of Antibiotic eluting Graft for promoting new bonegrowth in/near Infected bone Cavities (MAGIC). Elute (2023) (Javad Parvizi, MD) 29. A Post-Market Clinical Follow-up Study to Provide Safety, Performance and Clinical Benefits Data Using the Persona Ti-Nidium Total Knee System and Instrumentation. ZimmerBiomet (2023) ( P. Maxwell Courtney, MD) 30. A Second Randomized Controlled Trial of Alternating Irrigation of Vancomycin Hydrochloride and Tobramycin Sulfate in Patients Undergoing Two-Stage Exchange Arthroplasty for Periprosthetic Joint Infection of the Hip or Knee. Osteal Therapeutics (2023) (P. Maxwell Courtney, MD) 31. A follow up Study of Subjects with the REDAPT System Monolithic Sleeveless/ Sleeved Stem and/or Fully Porous Acetabular Shell with XLPE liner and/or Modular Shell Components Previously Implanted. Smith and Nephew (2023) (P. Maxwell Courtney, MD) 32. Comparison of Surgeon Workload, Stress and Ergonomics During Total Knee Arthroplasty using ROSA Knee Robotic System, With and Without OptiVu Mixed Reality. ZimmerBiomet (2022–current) (Jess Lonner, MD) 33. Femoral Rotation Planning in RA TKA. Zimmer Biomet (2022–current) (Jess Lonner, MD) 34. R OSA TKA reduces audible noise following primary knee arthroplasty. Zimmer Biomet (2022–current) (Jess Lonner, MD) 35. R andomized Controlled Trial to Compare Persona OsseoTi Keel Cementless TKA vs Persona Keel Cemented TKA: A prospective, multi-center study to demonstrate safety, performance, and clinical benefits of the Persona Keel CR knee system including instrumentation. ZimmerBiomet. (2023) (Jess Lonner, MD) 36. R andomized Pilot Study Investigating Early Functional Outcomes with the Use of Robotic Assisted Versus Conventional Total Knee Arthroplasty (TKA). CORIN (2022–current) (Matt Austin, MD) 37. W hat factors pre-dispose patients to periprosthetic joint infection following total knee or hip arthroplasty? (2022–current) (Vivek Bilolikar, MD) 38. E ffect of joint preservation surgery on osteoarthritis progression (2022–current) (Seyedalireza Mirghasemi, MD) 39. W hat factors predispose patients to anterior knee pain following total knee arthroplasty? (2022–current) (Seyedalireza Mirghasemi, MD) 40. M anagement of Native Hip Dislocations: Discrepancy and Disparities in the Acute Setting (2021–current) (John Ibrahim, MD)

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Jefferson Health Department of Orthopaedic Surgery Philadelphia, PA 19107 Patient Appointments: 1-800-JEFF-NOW Patient Transfers: 1-800-JEFF-121 Physician Referrals: 215-503-8888 JeffersonHealth.org/Ortho

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