In the absence of reliable evidence, it is the opinion of this work group that in the case that one or more of the following conditions are present, the practitioner should carefully consider the risk before proceeding with surgery:

• Active infection (strongly caution against proceeding with surgery given the risks)
• Anticoagulation status, active thromboprophylaxis (proceed only after careful consideration of the risks)
• Autoimmune disease (proceed only after careful consideration of the risks)
• HIV status (proceed only after careful consideration of the control and risks)
• Institutionalized patients (proceed only after careful consideration of the risks)
• Prior bariatric surgery (proceed only after careful consideration of the risks)

Rationale

Out of 143 studies which met inclusion criteria for this recommendation, there were no high strength studies, and only ten were considered moderate strength. The remaining studies were considered low strength. Many of these studies evaluated multiple variables as it applied to either PJI directly, or to other perioperative complications, necessitating the use of various statistical methods to attempt to control for these variables. These methods were frequently constrained in doing so. Additionally, based on the available literature, whether a risk factor is “modifiable” or if optimization of a listed condition affects the risk of infection remained unclear. No specific threshold value could be endorsed for most listed conditions, but instead the simple binary presence or absence of the condition as defined by the individual study criteria affected the risk of PJI. Furthermore, many of the studies were based on national payor databases or registries, whose data is only as accurate as the data being input. As such, there is often no way to verify that an individual diagnosis or the definition of the diagnosis is accurate, though the sheer numbers in such databases may help correct for errors in    diagnosis. Finally, definitions and clarity of location of infection introduced ambiguity between studies, some clearly indicating PJI, and others with variations of “deep infection,” “deep surgical site infection,” or “involves deep soft tissue,” among other delineations.

Of the listed and reviewed conditions, obesity was the only risk factor for periprosthetic joint infection that met moderate strength criteria for increased risk of periprosthetic joint infection. The rest are based on single moderate strength and/or low strength studies with either conflicted or limited data, with each condition or risk factor individually discussed below.

Potentially increased risk for PJI, but not enough data:


Active infection
Even though only one low strength study (Song 2012) evaluated active infection at other anatomical sites – finding increased risk of deep incisional and/or organ space infection – it is intuitive that a patient with an active infection is more likely to become bacteremic, increasing the risk of PJI.


Anticoagulation/active thromboprophylaxis status at the time of surgery
Three low strength studies met inclusion criteria, all by Bozic and associates.  Of the three, one study (Bozic, 2012) identified a higher risk of PJI in those undergoing hip replacements with coagulopathy (hazard ratio 1.58) based on an administrative database. The other two, including one on knee replacement and the other in 2014 (Bozic, 2014) on hip replacement, identified no increased risk of PJI. However, all three studies were performed using the same database, with limited ability to control for confounding variables, and the accuracy of diagnosis (for or against) in question by the nature of the database.

HIV (diagnosis only)
Five low strength studies assessed the effect of HIV status on risk of PJI.  Only one
 study, by Kildow et al (Kildow, 2017), identified a higher risk of PJI in HIV patients undergoing knee replacement at 2 years (odds ratio 2.51). However, as was true of other included studies, no stratification of the HIV patients in terms of CD4 count or detectable viral load was conducted. Lin and associates (Lin 2013) identified higher risk of need for irrigation and debridement in hip patients with HIV, but no such increased risk for knees, and no increased risk of PJI or wound healing complications in hip or knee patients. Issa and associates (Issa, 2017) did indicate that “all patients with HIV underwent thorough preoperative optimization with their primary care physician and infectious disease specialist,” and noted no difference in risk of PJI for HIV-infected TKA patients. In a study evaluating long-term results of primary TKA in patients with hemophilia, Silva and associates (Silva, 2005) recorded the HIV status and CD4 count in 53 of the 90-patient cohort, identifying no effect on PJI, but given expected incidence and total number of patients in this study, it was likely underpowered.

Prior bariatric surgery
Only three low quality studies on those having undergone bariatric surgery for 
obesity were included. Of these, only one (Nickel BT, 2016) indicated higher risk of PJI in TKA, with significant concern for confounding variables. The other two identified no difference in risk. As such, no reliable evidence is available to support increased risk of PJI in patients with history of bariatric surgery undergoing THA or TKA. However, given significant nutritional shifts associated with bariatric procedures and known effects of malnutrition on tissue healing, caution is still advised.

Institutionalization and autoimmune disease
There was one low strength study involving institutionalized patients that were habitual residents of a healthcare center, which did indicate a higher risk of PJI in such 
patients (Gallardo-Calero et al 2016). But with only one study, it did not meet inclusion criteria for recommendation. Likewise, an isolated low strength study (Jiang et al 2014) evaluated the effect of autoimmune disease on PJI, including rheumatoid arthritis, lupus, or ankylosing spondylitis. They identified n increased risk of PJI in both hip and knee patients, with a hazard ratio of 1.55. We advise caution in these patients.

POSSIBLE RISKS AND HARMS OF IMPLEMENTATION
Candidacy for surgical intervention is at once, one of the most essential and complex decisions in surgical practice, ethically balancing the degree of  pathology and risk of the operation, with the positive benefits to the patient and society at large, in a shared decision-making process between patient and surgeon. The positive effect of indicated lower extremity arthroplasty on quality of life and reduced morbidity is well established. However, its cost to the health care system has been the subject of increased scrutiny. Surgeons are under increasing pressure from payors, health care systems, and peers alike to provide highest value care, balancing the overall cost of care with excellence in patient outcomes. As such, delay or denial of surgical care based on any one or multiple factors in order to avoid one of the most devastating complications of one of the best value surgeries ever practiced should not be taken lightly. Given that all risk factors listed – with the exception of obesity – are supported with only low strength or conflicting evidence, the decision to proceed is individual, and based on myriad other factors, including but not limited to the ability of the system in which the surgeon practices to handle varying degrees of complexity, volume and experience of the surgeon and system, and other confounding factors not herein assessed. Additionally, at this time it is unclear based on the literature if modification of any risk factor, including obesity, actually reduces the risk of PJI. Payors and healthcare systems alike should understand that though tactics to reduce cost may include delaying or avoiding operating on patients with these risk factors, such practice may deny surgery to a much larger proportion of patients who may otherwise significantly benefit and not endure PJI.

FUTURE RESEARCH
Despite the volume of literature addressing risk factors for periprosthetic joint infection, there is a paucity of moderate-quality studies, and complete absence of high-quality studies. Future research must attempt to better control for individual confounding variables prospectively, with better delineation of disease states. For example, though BMI may not be the best measure of obesity overall, its stratification in many studies has helped allow for better comparison between groups, improving the quality of data available. Simply identifying whether or not a disease process is present based off an individual entry of a diagnostic code from the patient’s potentially remote past medical history does not ensure best quality data. Unfortunately, the relatively low incidence of PJI requires large numbers for appropriate statistical power, making registries and large healthcare databases an optimal target for research. Better quality abstraction for such databases is therefore necessary to help de-confound. Additional assessments of markers of disease status and their associated thresholds may also help the clinician further and more accurately stratify risk. Finally, identification of risk associated with a condition or stage of comorbidity does not by itself afford the provider the ability to proselytize for change, as the effect of modification and optimization of the status of a listed condition is still unclear. Future research endeavors should specifically be designed to determine if risk factor modification truly results in a reduction in the risk for PJI after hip or knee arthroplasty surgery. Given frequently conflicting conclusions among studies, the individual system and even provider-specific management of comorbidities – which was typically not delineated – may account for such discrepancies. Prospective, appropriately controlled studies incorporating these considerations will better afford surgeon and patient the ability to predict and potentially minimize risk of periprosthetic joint infection.

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