Karan Goswami

The 2018 Definition of Periprosthetic Hip and Knee Infection: An Evidence-Based and Validated Criteria.

BACKGROUNDnThe introduction of the Musculoskeletal Infection Society (MSIS) criteria for periprosthetic joint infection (PJI) in 2011 resulted in improvements in diagnostic confidence and research collaboration. The emergence of new diagnostic tests and the lessons we have learned from the past 7 years using the MSIS definition, prompted us to develop an evidence-based and validated updated version of the criteria.nnnMETHODSnThis multi-institutional study of patients undergoing revision total joint arthroplasty was conducted at 3 academic centers. For the development of the new diagnostic criteria, PJI and aseptic patient cohorts were stringently defined: PJI cases were defined using only major criteria from the MSIS definition (nxa0= 684) and aseptic cases underwent one-stage revision for a noninfective indication and did not fail within 2 years (nxa0= 820). Serum C-reactive protein (CRP), D-dimer, erythrocyte sedimentation rate were investigated, as well as synovial white blood cell count, polymorphonuclear percentage, leukocyte esterase, alpha-defensin, and synovial CRP. Intraoperative findings included frozen section, presence of purulence, and isolation of a pathogen by culture. A stepwise approach using random forest analysis and multivariate regression was used to generate relative weights for each diagnostic marker. Preoperative and intraoperative definitions were created based on beta coefficients. The new definition was then validated on an external cohort of 222 patients with PJI who subsequently failed with reinfection and 200 aseptic patients. The performance of the new criteria was compared to the established MSIS and the prior International Consensus Meeting definitions.nnnRESULTSnTwo positive cultures or the presence of a sinus tract were considered as major criteria and diagnostic of PJI. The calculated weights of an elevated serum CRP (>1 mg/dL), D-dimer (>860 ng/mL), and erythrocyte sedimentation rate (>30 mm/h) were 2, 2, and 1 points, respectively. Furthermore, elevated synovial fluid white blood cell count (>3000 cells/μL), alpha-defensin (signal-to-cutoff ratio >1), leukocyte esterase (++), polymorphonuclear percentage (>80%), and synovial CRP (>6.9 mg/L) received 3, 3, 3, 2, and 1 points, respectively. Patients with an aggregate score of greater than or equal to 6 were considered infected, while a score between 2 and 5 required the inclusion of intraoperative findings for confirming or refuting the diagnosis. Intraoperative findings of positive histology, purulence, and single positive culture were assigned 3, 3, and 2 points, respectively. Combined with the preoperative score, a total of greater than or equal to 6 was considered infected, a score between 4 and 5 was inconclusive, and a score of 3 or less was not infected. The new criteria demonstrated a higher sensitivity of 97.7% compared to the MSIS (79.3%) and International Consensus Meeting definition (86.9%), with a similar specificity of 99.5%.nnnCONCLUSIONnThis study offers an evidence-based definition for diagnosing hip and knee PJI, which has shown excellent performance on formal external validation.

Can next generation sequencing play a role in detecting pathogens in synovial fluid

Aims The diagnosis of periprosthetic joint infection can be difficult due to the high rate of culturenegative infections. The aim of this study was to assess the use of next‐generation sequencing for detecting organisms in synovial fluid. Materials and Methods In this prospective, single‐blinded study, 86 anonymized samples of synovial fluid were obtained from patients undergoing aspiration of the hip or knee as part of the investigation of a periprosthetic infection. A panel of synovial fluid tests, including levels of C‐reactive protein, human neutrophil elastase, total neutrophil count, alpha‐defensin, and culture were performed prior to next‐generation sequencing. Results Of these 86 samples, 30 were alpha‐defensin‐positive and culture‐positive (Group I), 24 were alpha‐defensin‐positive and culture‐negative (Group II) and 32 were alpha‐defensin‐negative and culture‐negative (Group III). Next‐generation sequencing was concordant with 25 results for Group I. In four of these, it detected antibiotic resistant bacteria whereas culture did not. In another four samples with relatively low levels of inflammatory biomarkers, culture was positive but next‐generation sequencing was negative. A total of ten samples had a positive next‐generation sequencing result and a negative culture. In five of these, alpha‐defensin was positive and the levels of inflammatory markers were high. In the other five, alpha‐defensin was negative and the levels of inflammatory markers were low. While next‐generation sequencing detected several organisms in each sample, in most samples with a higher probability of infection, there was a predominant organism present, while in those presumed not to be infected, many organisms were identified with no predominant organism. Conclusion Pathogens causing periprosthetic infection in both culture‐positive and culture‐negative samples of synovial fluid could be identified by next‐generation sequencing.

Diagnosis of Streptococcus canis periprosthetic joint infection: the utility of next-generation sequencing

A 62-year-old man who had undergone a primary knee arthroplasty 3 years earlier, presented to the emergency department with an infected prosthesis. He underwent prosthesis resection. All cultures failed to identify the infecting organism. Analysis of the intraoperative samples by next-generation sequencing revealed Streptococcus canis (an organism that resides in the oral cavity of dogs). It was later discovered that the patient had sustained a dog scratch injury several days earlier. The patient reports that his dog had licked the scratch. Treatment was delivered based on the sensitivity of S. canis, and the patient has since undergone reimplantation arthroplasty.

Time to Reimplantation: Waiting Longer Confers no Added Benefit

BACKGROUNDnWhile the preferred surgical treatment for chronic periprosthetic joint infection (PJI) in North America is a 2-stage exchange arthroplasty, the optimal time between first-stage and reimplantation surgery remains unknown. This study was conceived to examine the association between time to reimplantation and treatment failure.nnnMETHODSnUsing an institutional database, we identified PJI cases treated with 2-stage exchange arthroplasty between 2000 and 2016. Musculoskeletal Infection Society criteria were used to define PJI, and treatment failure was defined using Delphi criteria. The interstage interval between first-stage and reimplantation surgery for each case was collected, alongside demographics, patient-related and organism-specific data. Multivariate logistic regression analyses were used to examine association with treatment failure.nnnRESULTSnOur final analysis consisted of 282 patients with an average time to reimplantation of 100.2 days (range, 20-648). Sixty-three patients (22.3%) failed at 1 year based on Delphi criteria. Time to reimplantation was not significantly associated with failure in both univariate (Pxa0= .598) and multivariate (Pxa0=xa0.397) models. However, patients reimplanted at >26 weeks were twice as likely to fail in comparison to those reimplanted within <26 weeks (43.8% vs 21.1%), and this finding reached marginal significance (Pxa0= .057). Patients who failed had significantly more comorbidities (Pxa0= .008). Charlson comorbidity index was the only variable significantly associated with treatment failure in regression analysis (odds ratio, 1.40; 95% confidence interval, 1.06-1.86; Pxa0= .019).nnnCONCLUSIONnThe length of the interstage interval was not a statistically significant predictor of failure in patients undergoing 2-stage exchange arthroplasty for PJI.

All Patients Should Be Screened for Diabetes Before Total Joint Arthroplasty

BACKGROUNDnDiabetes is highly prevalent in patients with osteoarthritis before total joint arthroplasty and presents a higher risk of adverse postoperative outcomes. However, the rate of diabetes in this population and optimal screening strategies remain unknown.nnnMETHODSnWe prospectively screened patients undergoing elective total joint arthroplasty for diabetes using glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) levels. Screening was conducted within 2 time periods between 2012 and 2017. The prevalence of diabetes was assessed using a previous diagnosis of diabetes or, in the absence of diagnosis, by measuring if HbA1c ≥ 6.5% or FBG ≥ 126 mg/dL. Prediabetes was defined as 5.7% ≤ HbA1c ≤ 6.4% or 100 mg/dL ≤ FBG ≤ 125 mg/dL. Occurrence of a 90-day periprosthetic joint infection and wound complications was noted.nnnRESULTSnA total of 1461 patients were included in the study. The prevalence of diabetes was 20.6%; 178 patients (59.1%) had diagnosed diabetes, and 123 patients (40.9%) had undiagnosed diabetes. Prediabetes was identified in 559 patients (38.3%), resulting in a combined total of 860 (58.9%) patients with diabetes and prediabetes. Total diabetic rates were significantly higher in patients aged >65 years, of nonwhite ethnicity, and undergoing total knee arthroplasty. No significant differences in periprosthetic joint infection and wound complications were observed while comparing patients with diagnosed and undiagnosed diabetes.nnnCONCLUSIONnA significant proportion of patients with undiagnosed diabetes and prediabetes were identified. Preadmission testing provides an opportunity to identify and address this condition, potentially reducing short-term arthroplasty-related complications and avoiding long-term systemic diabetic complications. We strongly recommend universal glycemic screening to all elective arthroplasty patients.

Increased postoperative glucose variability is associated with adverse outcomes following orthopaedic surgery

Aims The aim of this study was to examine the association between postoperative glycaemic variability and adverse outcomes following orthopaedic surgery. Patients and Methods This retrospective study analyzed data on 12 978 patients (1361 with two operations) who underwent orthopaedic surgery at a single institution between 2001 and 2017. Patients with a minimum of either two postoperative measurements of blood glucose levels per day, or more than three measurements overall, were included in the study. Glycaemic variability was assessed using a coefficient of variation (CV). The length of stay (LOS), in‐hospital complications, and 90‐day readmission and mortality rates were examined. Data were analyzed with linear and generalized linear mixed models for linear and binary outcomes, adjusting for various covariates. Results The cohort included 14 339 admissions, of which 3302 (23.0%) involved diabetic patients. Patients with CV values in the upper tertile were twice as likely to have an in‐hospital complication compared with patients in the lowest tertile (19.4% versus 9.0%, p < 0.001), and almost five times more likely to die compared with those in the lowest tertile (2.8% versus 0.6%, p < 0.001). Results of the adjusted analyses indicated that the mean LOS was 1.28 days longer in the highest versus the lowest CV tertile (p < 0.001), and the odds of an in‐hospital complication and 90‐day mortality in the highest CV tertile were respectively 1.91 (p < 0.001) and 2.10 (p = 0.001) times larger than the odds of these events in the lowest CV tertile. These associations were significant even for non‐diabetic patients. After adjusting for hypoglycaemia, the relationships remained significant, except that the CV tertile no longer predicted mortality in diabetics. Conclusion These results indicate that higher glycaemic variability is associated with longer LOS and inhospital complications. Glycaemic variability also predicted death, although that primarily held for non‐diabetic patients in the highest CV tertile following orthopaedic surgery. Prospective studies should examine whether ensuring low postoperative glycaemic variability may reduce complication rates and mortality. Cite this article: Bone Joint J 2018;100‐B:1125–32.

General Assembly, Diagnosis, Pathogen Isolation: Proceedings of International Consensus on Orthopedic Infections

One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to https://doi.org/10.1016/j.arth.2018.09.072. 1 Question 3. 2 Question 2. 3 Question 4. 4 Question 1.

General Assembly, Prevention, Local Antimicrobials: Proceedings of International Consensus on Orthopedic Infections

General Assembly, Prevention, Local Antimicrobials: Proceedings of International Consensus on Orthopedic Infections Jose Baeza , Marco Bernardo Cury , Andrew Fleischman , Albert Ferrando , Manuel Fuertes , Karan Goswami , Lars Lidgre , Philip Linke , Jorge Manrique , Gabriel Makar , Alex McLaren , T. Fintan Moriarty , Qun Ren , Kelly Vince , Peter Wahl , Jason Webb , Heinz Winkler , Eivind Witsø , Simon W. Young 5

Majority of Total Joint Arthroplasties Are Subtherapeutic on Warfarin at Time of Discharge: Another Reason to Avoid Warfarin as a Venous Thromboembolism Prophylaxis?

BACKGROUNDnWarfarin has been used as prophylaxis against venous thromboembolism (VTE) after total joint arthroplasty (TJA) for over 60 years. With trends of shorter hospital stays for TJA patients, it is important to examine how many patients achieve therapeutic international normalized ratio (INR) at time of discharge. We aimed at elucidating the proportion of patients discharged at therapeutic INR and whether this is affected by inpatient specialty anticoagulation management service (AMS) involvement.nnnMETHODSnWe conducted a retrospective review of 2927 primary TJA patients who received warfarin as postoperative VTE chemoprophylaxis from 2011 to 2016. An electronic chart query determined AMS input, length of stay (LOS), INR at discharge, and in-hospital complications. INR results were categorized as subtherapeutic (INR < 2.0), therapeutic (2.0 ≤ INR < 3.0), and supratherapeutic (INR ≥ 3.0). Descriptive statistics, chi-square, and t-tests were performed for analysis.nnnRESULTSnAt discharge, 93.9% of patients had subtherapeutic INR. Average INR was 1.41 with average LOS of 2.53 days. Factors associated with being subtherapeutic included male gender, shorter LOS, fewer comorbidities, reduced in-hospital complications, and higher body mass index. AMS supervised postoperative warfarin dosing in 64.9% of patients. Patients managed by AMS were less likely to be subtherapeutic at discharge compared to those without AMS input; however, the absolute difference in INR may not be clinically significant. There were 19 VTEs, of which 13 had prolonged hospitalization to achieve therapeutic INR.nnnCONCLUSIONnThe majority of patients are discharged at subtherapeutic INR levels despite management by AMS. Patients may not be adequately anticoagulated with warfarin at time of discharge, raising significant patient safety concerns as well as medicolegal implications.

Defining Treatment Success After 2-Stage Exchange Arthroplasty for Periprosthetic Joint Infection

BACKGROUNDnTwo-stage exchange arthroplasty remains the preferred surgical treatment method for patients with chronic periprosthetic joint infection (PJI). The success of this procedure is not known exactly as various definitions of success have been used. This study aimed at analyzing the difference in outcome following 2-stage exchange arthroplasty using different definitions for success.nnnMETHODSnA retrospective study of 703 patients with PJI who underwent resection arthroplasty and spacer insertion between January 1999 and June 2015 was performed. Chart review identified intraoperative cultures at the time of spacer, reimplantation, and any subsequent reinfections or surgeries following spacer insertion. After applying the exclusion criteria, a total of 570 patients were included in the analysis. Five definitions of treatment success were assessed: (1) Delphi consensus success, (2) modified Delphi consensus success, (3) microbiological success, (4) implant success, and (5) surgical success.nnnRESULTSnOf the 570 patients with PJIs, 458 were reimplanted at a mean of 4.1 months. Mortality was 13.9% with 6.7% occurring before reimplantation. Treatment success was highly variable depending on the definition used (54.2%-88.9%). In 19.6% of PJI cases, the Delphi consensus definition could not be assessed as reimplantation never occurred. Furthermore, 67.0% of these patients underwent reoperations, which may not be accounted for in the Delphi consensus definition.nnnCONCLUSIONnTreatment success rates vary dramatically depending on the definition used at our institution. We hope these definitions can help bring forth awareness for standardized reporting of outcomes, but further validation and agreement of these definitions among surgeons and infectious disease physicians is crucial.