Menopause and endometriosis.

The shift in paradigm from the belief that endometriosis exclusively affects women of reproductive age has brought attention to its manifestation in postmenopausal patients. Despite this emerging awareness, there remains a dearth of information in the literature regarding postmenopausal endometriosis, with uncertainties surrounding its prevalence, clinical significance, optimal management strategies, and prognosis. Clinical manifestations of endometriosis in menopausal patients lack specificity, with pain onset possible at any stage of life. The primary approach for symptomatic postmenopausal endometriosis continues to be surgical excision, serving both diagnostic and therapeutic purposes while mitigating the risk of coexisting malignancies. Managing the disease in postmenopausal women presents challenges due to possible contraindications for menopausal hormone therapy and the elevated risk of recurrence and malignant transformation. However, conclusive data regarding the appropriateness of menopausal hormone therapy in women with endometriosis or a history of the disease are lacking. Current recommendations lean towards prioritizing combined menopausal hormone therapy formulations or tibolone over estrogen-only therapies due to their potentially higher malignancy risk. The possible increased risk of osteoporosis and cardiovascular disease in postmenopausal women with endometriosis is likely linked to a history of surgical menopause at an earlier age, but more research is warranted. This narrative review summarizes the available literature and provides insights into the intricate connection between endometriosis and menopause, shedding light on pathogenesis, symptoms, oncologic risk, diagnosis, and treatment.

Identifying the association between serum urate levels and gout flares in patients taking urate-lowering therapy: a post hoc cohort analysis of the CARES trial with consideration of dropout.

OBJECTIVE: To investigate gout flare rates based on repeated serum urate (SU) measurements in a randomised controlled trial of urate-lowering therapy (ULT), accounting for dropout and death. METHODS: We performed a secondary analysis using data from Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout, which randomised participants to febuxostat or allopurinol, titrated to target SU <6 mg/dL with flare prophylaxis for 6 months. SU was categorised as ≤3.9, 4.0-5.9, 6.0-7.9, 8.0-9.9 or ≥ 10 mg/dL at each 3-6 month follow-up. The primary outcome was gout flare. Poisson regression models, adjusted for covariates and factors related to participant retention versus dropout, estimated gout flare incidence rate ratios by time-varying SU category. RESULTS: Among 6183 participants, the median age was 65 years and 84% were male. Peak gout flare rates for all SU categories were observed in months 0-6, coinciding with the initiation of ULT and months 6-12 after stopping prophylaxis. Flare rates were similar across SU groups in the initial year of ULT. During months 36-72, a dose-response relationship was observed between the SU category and flare rate. Lower flare rates were observed when SU ≤3.9 mg/dL and greater rates when SU ≥10 mg/dL, compared with SU 4.0-5.9 mg/dL (p for trend <0.01). CONCLUSION: Gout flare rates were persistently higher when SU ≥6 mg/dL after the first year of ULT after accounting for censoring. The spike in flares in all categories after stopping prophylaxis suggests a longer duration of prophylaxis may be warranted.

Fractures in Patients With Acute Calcium Pyrophosphate Crystal Arthritis Versus Matched Comparators in a Large Cohort Study.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease was associated with osteopenia in two cross-sectional studies. We compared fracture risks in patients with acute calcium pyrophosphate (CPP) crystal arthritis versus matched comparators. METHODS: We performed a longitudinal cohort study using electronic health record data from a single large academic health system, with data from 1991 to 2023. Patients with one or more episodes of acute CPP crystal arthritis were matched to comparators on the index date (first documentation of "pseudogout" or synovial fluid CPP crystals or matched encounter) and first encounter in the health system. The primary outcome was first fracture at the humerus, wrist, hip, or pelvis. We excluded patients with fracture before the index date. Covariates included demographics, body mass index, smoking, comorbidities, health care use, glucocorticoids, and osteoporosis treatments. We estimated incidence rates and adjusted hazard ratios for fracture. Sensitivity analyses excluded patients prescribed glucocorticoids, patients prescribed osteoporosis treatments, or patients with rheumatoid arthritis and additionally adjusted for chronic kidney disease. RESULTS: We identified 1,148 patients with acute CPP crystal arthritis matched to 3,730 comparators, with a mean age of 73 years. Glucocorticoids and osteoporosis treatments were more frequent in the acute CPP crystal arthritis cohort. Fracture incidence rates were twice as high in the acute CPP crystal arthritis cohort (11.7 per 1,000 person-years) versus comparators (5.5 per 1,000 person-years). After multivariable adjustment, fracture relative risk was twice as high in the acute CPP crystal arthritis cohort (hazard ratio 1.8 [95% confidence interval 1.3-2.3]); results were similar in sensitivity analyses. CONCLUSION: In this first published study of fractures and CPPD, fracture risk was nearly doubled in patients with acute CPP crystal arthritis.

Silver-Coated Distal Femur Megaprosthesis in Chronic Infections with Severe Bone Loss: A Multicentre Case Series.

Periprosthetic joint infections (PJI) and fracture-related infections (FRI) of the distal femur (DF) may result in massive bone defects. Treatment options include articulated silver-coated (SC) megaprosthesis (MP) in the context of a two-stage protocol. However, there is limited evidence in the literature on this topic. A retrospective review of the prospectively maintained databases of three Institutions was performed. Forty-five patients were included. The mean follow-up time was 43 ± 17.1 months. Eight (17.8%) patients had a recurrent infection. The estimated recurrence-free survival rate was 91.1% (93.5% PJI vs. 85.7% FRI) 2 years following MP implantation, and 75.7% (83.2% PJI vs. 64.3% FRI; p = 0.253) after 5 years. No statistically relevant difference was found according to the initial diagnosis (PJI vs. FRI). Among possible risk factors, only resection length was found to significantly worsen the outcomes in terms of infection control (p = 0.031). A total of eight complications not related to infection were found after reimplantation, but only five of them required further surgery. Above-the-knee amputation was performed in two cases (4.4%), both for reinfection. Articulated DF SC MP in a two-stage protocol is a safe and effective treatment for chronic knee infection with severe bone loss.

The 2023 ACR/EULAR Classification Criteria for Calcium Pyrophosphate Deposition Disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score >56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score>56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

Patient-Reported Outcomes in Calcium Pyrophosphate Deposition Disease Compared to Gout and Osteoarthritis.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease prevalence is similar to that of gout and osteoarthritis (OA), yet CPPD outcomes research greatly lags behind research in these other forms of arthritis. We compared validated patient-reported outcome measures in patients with CPPD vs gout and OA. METHODS: Patients with CPPD were recruited from Brigham and Women's Hospital from 2018 to 2022. Presence of CPPD manifestations (acute calcium pyrophosphate [CPP] crystal arthritis, chronic CPP inflammatory arthritis, and/or OA with CPPD) was confirmed by medical record review. Baseline surveys included the Gout Assessment Questionnaire version 2.0, modified to ask about "pseudogout" rather than "gout"; Routine Assessment of Patient Index Data 3 (RAPID-3); and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). We compared responses in patients with CPPD against published gout and OA cohort studies. RESULTS: Among 47 patients with CPPD, the mean age was 71.9 years and 51% were female. Sixty-eight percent had at least 1 episode of acute CPP crystal arthritis, 40% had chronic CPP inflammatory arthritis, and 62% had OA with CPPD. Pain visual analog scale scores during a flare were similar in CPPD (mean 6.8 [SD 1.9]) and gout (mean 6.7 [SD 2.6]; P = 0.78). Patients with CPPD reported significantly greater unmet treatment need than patients with gout (P = 0.04). RAPID-3 scores in CPPD (mean 8.1 [SD 5.6]) were lower than in gout (mean 12.1 [SD 6.2]; P < 0.01) and similar in OA (mean 6.8 [SD 6.1]; P = 0.30). Patients with CPPD had significantly worse WOMAC stiffness scores than patients with mild OA, and significantly better WOMAC function scores than patients with severe OA. CONCLUSION: Patients with CPPD may experience pain comparable to that in gout and OA and reported substantial unmet treatment needs.

Predictors of low spike antibody response in patients with systemic rheumatic disease after an initial course of COVID-19 vaccination.

BACKGROUND: Patients with rheumatic disease may mount a suboptimal serologic response to COVID-19 vaccination. We evaluated predictors of low antibody response in a clinic-based cohort. METHODS: We conducted a cross-sectional study using electronic health record (EHR) data at Brigham and Women's Hospital, Boston, MA. Patients with systemic rheumatic disease that had SARS-CoV-2 spike antibody (Ab) tested using the Roche Elecsys immunoassay, February-August 2021, after 2 doses of mRNA vaccine or 1 dose of adenovirus vector vaccine were identified. Demographics, systemic rheumatic disease, vaccination dates, and disease-modifying antirheumatic drugs (DMARDs) were extracted. The primary outcome was low spike Ab (≤ 200 U/mL). Logistic regression models estimated predictors of low spike Ab. RESULTS: Among 382 patients, the mean age was 57 years, 77% were female, and 37% had low spike Ab. Older age (OR 1.03, 95% CI [1.02, 1.05]), SLE (OR 4.81 [2.08, 8.43], reference: inflammatory arthritis), prednisone (OR 1.67 [1.03, 2.74]), and rituximab (OR 22.91 [9.85, 53.29]) were significantly associated with higher odds of low spike Ab. Use of csDMARD monotherapy (OR 0.12 [0.04, 0.33]) and JAK inhibitors (OR 0.41 [0.18, 0.92]) were associated with significantly lower odds for low spike Ab. After adjusting for systemic rheumatic disease and DMARDs, SLE and rituximab remained significantly associated with low spike Ab. CONCLUSIONS: Over a third of patients with systemic rheumatic disease with spike Ab tested in routine care had low spike Ab after 2 doses of mRNA or 1 dose of adenovirus vector COVID-19 vaccine. SLE and rituximab were significant risk factors for low spike Ab. KEY POINTS: • More than one-third of patients with systemic rheumatic disease that had spike Ab tested in routine care had low spike Ab after 2 doses of mRNA or 1 dose of adenovirus vector COVID-19 vaccine. • Diagnosis of SLE, use of prednisone, and use of rituximab were significantly associated with greater odds of low spike antibodies. • These data underscore the importance of additional doses of COVID-19 vaccine and prophylactic Evusheld in immunosuppressed patients with systemic rheumatic disease as recommended by the US Centers for Disease Control.

Multidisciplinary treatment protocol for ischiatic, sacral, trochanteric or other pressure injuries in people with spinal cord injury: a retrospective cohort study.

STUDY DESIGN: Retrospective cohort study Objectives: to describe the incidence and the associated risk factors of post-surgical complications and recurrence in individuals with spinal cord injury/disorder (SCI/D) presenting deep pressure injuries (PIs), treated with a specific surgical and rehabilitation treatment protocol. SETTING: Tertiary Rehabilitation Hospital for SCI/D in Italy. METHODS: Retrospective analysis of the medical records of adult individuals with SCI/D, who developed a PI after the first discharge from a Spinal Unit, underwent flap surgery for PI between July 2011 and January 2018. The statistical unit of analysis was the surgical intervention. Logistic regression analysis with robust standard errors was performed to assess risk factors of post-surgical complications. RESULTS: 434 surgical intervention records were included, for a total of 378 patients. The treated PIs were ischiatic in 56.2% of the cases, sacral in 32.5%, trochanteric in 15.7%, and 5.8% were in other sites. In 239 cases (55.1%) a histological diagnosis of osteomyelitis was confirmed. Minor complications occurred in 13.6% of interventions, while major complications were 3.9%. Sacral PI (OR = 2.55, 95%CI: 1.50-4.35) and muscular/musculocutaneous flap (OR = 2.12, 95%CI: 1.05-4.28) were significant factors associated with risk of post-surgical complications. After a mean follow-up of 21 months (range 12-36), six people (1.4%) had a recurrence. Patients with a recurrence had at least one comorbidity compared to 57% of people without recurrences (p = 0.036). CONCLUSION: Our results demonstrate that complication and recurrence rates can be minimized when an established interdisciplinary and rehabilitation protocol is integrated in the clinical management.

Cardiovascular Disease Risk in Calcium Pyrophosphate Deposition Disease: A Nationwide Study of Veterans.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease represents a common crystalline arthritis with a range of manifestations. Our goal was to investigate risks for cardiovascular events in patients with CPPD. METHODS: We performed a retrospective matched cohort analysis in the Veterans Health Administration Corporate Data Warehouse, 2010-2014. CPPD was defined by ≥1 International Classification of Diseases, Ninth Revision codes for chondrocalcinosis or calcium metabolism disorder. CPPD patients were age- and sex-matched to approximately 4 patients without codes for CPPD; we excluded patients with a cardiovascular event during the 365 days prior to the index date. Demographic information, traditional cardiovascular risk factors, medications, and health care utilization were assessed at baseline. The primary outcome was a major adverse cardiovascular event (MACE: myocardial infarction, acute coronary syndrome, coronary revascularization, stroke, or death). Secondary outcomes included individual components of MACE. Cox proportional hazards models estimated fully adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: We identified 23,124 CPPD patients matched to 86,629 non-CPPD patients with >250,000 person-years of follow-up. The study population was 96% male, mean age was 78 years, and 75% were White. The frequency of traditional cardiovascular risk factors was similar between the 2 cohorts. CPPD was not significantly associated with risk for MACE (HR 0.98 [95% CI 0.94-1.02]) in fully adjusted models, though risks of myocardial infarction, acute coronary syndrome, and stroke were significantly higher in the CPPD cohort compared to the non-CPPD cohort. CONCLUSION: CPPD did not confer an increased risk for MACE, a composite end point including all-cause mortality. Our results propose CPPD as a novel risk factor for MACE components, including myocardial infarction, acute coronary syndrome, and stroke.

Reliability and Diagnostic Accuracy of Radiography for the Diagnosis of Calcium Pyrophosphate Deposition: Performance of the Novel Definitions Developed by an International Multidisciplinary Working Group.

OBJECTIVE: To assess the reliability and diagnostic accuracy of new radiographic imaging definitions developed by an international multidisciplinary working group for identification of calcium pyrophosphate deposition (CPPD). METHODS: Patients with knee osteoarthritis scheduled for knee replacement were enrolled. Two radiologists and 2 rheumatologists twice assessed radiographic images for presence or absence of CPPD in menisci, hyaline cartilage, tendons, joint capsule, or synovial membrane, using the new definitions. In case of disagreement, a consensus decision was made and considered for the assessment of diagnostic performance. Histologic examination of postsurgical specimens under compensated polarized light microscopy was the reference standard. Prevalence-adjusted bias-adjusted kappa values were used to assess reliability, and diagnostic performance statistics were calculated. RESULTS: Sixty-seven patients were enrolled for the reliability study. The interobserver reliability was substantial in most of the assessed structures when considering all 4 readers (κ range 0.59-0.90), substantial to almost perfect among radiologists (κ range 0.70-0.91), and moderate to almost perfect among rheumatologists (κ range 0.46-0.88). The intraobserver reliability was substantial to almost perfect for all the observers (κ range 0.70-1). Fifty-one patients were included in the accuracy study. Radiography demonstrated an overall specificity of 92% for CPPD, but sensitivity remained low for all sites and for the overall diagnosis (54%). CONCLUSION: The new radiographic definitions of CPPD are highly specific against the gold standard of histologic diagnosis. When the described radiographic findings are present, these definitions allow for a definitive diagnosis of CPPD, rather than other calcium-containing crystal depositions; however, a negative radiographic finding does not exclude the diagnosis.

Association of Ultraviolet B Radiation and Risk of Systemic Lupus Erythematosus Among Women in the Nurses' Health Studies.

OBJECTIVE: Ultraviolet (UV) radiation exposure is associated with photosensitivity, rashes, and flares in systemic lupus erythematosus (SLE). However, it is not known whether UV exposure increases risk of developing SLE. We examined UV exposure and SLE risk in a large prospective cohort. METHODS: The Nurses' Health Study (NHS) enrolled 121,700 US female nurses in 1976; in 1989, 116,429 nurses were enrolled in NHS II. Biennial questionnaires collected lifestyle and medical data. Self-reported incident SLE by American College of Rheumatology classification criteria was confirmed by medical record review. Ambient UV exposure was estimated by linking geocoded residential addresses with a spatiotemporal UV exposure model. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) across tertiles of time-varying cumulative average UV. We examined SLE risk overall and stratified by anti-Ro/La antibodies and by cutaneous manifestations from 1976 through 2014 (NHS)/2015 (NHS II), adjusting for confounders. RESULTS: With 6,054,665 person-years of exposure, we identified 297 incident SLE cases; the mean ± SD age at diagnosis was 49.8 ± 10.6 years. At diagnosis, 16.8% of women had +anti-Ro/La, and 80% had either +anti-Ro/La or ≥1 cutaneous manifestation. Compared with the lowest UV exposure tertile, risk of overall SLE was increased, but not significantly (HR 1.28 [95%CI 0.96-1.70]). Women in the highest tertile had increased risk of malar rash (HR 1.62 [95% CI 1.04-2.52]). CONCLUSION: Cumulative UV exposure was not associated with SLE risk. Higher UV exposure, however, was associated with increased risk of malar rash at presentation. UV exposure may trigger SLE onset with malar rash among susceptible women.

Imaging Features of Calcium Pyrophosphate Deposition Disease: Consensus Definitions From an International Multidisciplinary Working Group.

OBJECTIVE: To develop definitions for imaging features being considered as potential classification criteria for calcium pyrophosphate deposition (CPPD) disease, additional to clinical and laboratory criteria, and to compile example images of CPPD on different imaging modalities. METHODS: The American College of Rheumatology and European Alliance of Associations for Rheumatology CPPD classification criteria Imaging Advisory Group (IAG) and Steering Committee drafted definitions of imaging features that are characteristic of CPPD on conventional radiography (CR), conventional computed tomography (CT), dual-energy CT (DECT), and magnetic resonance imaging (MRI). An anonymous expert survey was undertaken by a 35-member Combined Expert Committee, including all IAG members. The IAG and 5 external musculoskeletal radiologists with expertise in CPPD convened virtually to further refine item definitions and voted on example images illustrating CR, CT, and DECT item definitions, with ≥90% agreement required to deem them acceptable. RESULTS: The Combined Expert Committee survey indicated consensus on all CR definitions. The IAG and external radiologists reached consensus on CT and DECT item definitions, which specify that calcium pyrophosphate deposits appear less dense than cortical bone. The group developed an MRI definition and acknowledged limitations of this modality for CPPD. Ten example images for CPPD were voted acceptable (4 CR, 4 CT, and 2 DECT), and 3 images of basic calcium phosphate deposition were voted acceptable to serve as contrast against imaging features of CPPD. CONCLUSION: An international group of rheumatologists and musculoskeletal radiologists defined imaging features characteristic of CPPD on CR, CT, and DECT and assembled a set of example images as a reference for future clinical research studies.

Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study-The ARTHR-IS Study Group.

INTRODUCTION: Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome. METHODS: A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed. RESULTS: One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin < 10 g/dL, bacteraemia, polymicrobial infection and additional debridement(s). For DAIR, TF was also associated with a body mass index (BMI) > 30 kg/m2 and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin < 10 g/dL, hip fracture and additional joint surgery not related to persistent infection. CONCLUSIONS: TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov, registration no. NCT03826108.

Staphylococcus aureus is one of the most virulent bacteria and frequently causes prosthetic joint infections.Knowledge of the treatment of this type of infection has advanced in recent years, and treatment guidelines have led to improved management. Typically, the successful treatment of these infections has been determined by clinical cure, that is, the symptoms of infection have disappeared, but has not taken into account loss of function (such as significant difficulties walking), which is critical for the patient's quality of life. Our aim in this study was to evaluate the success of current management strategies for S. aureus prosthetic joint infection, including recovery of functionality, and the factors that predict why some of these infections are not cured, to identify areas for improvement.In a multinational cohort of 128 patients with S. aureus prosthetic joint infection, rates of treatment failure were found to be high, with significant rates of loss of function, especially when the prosthesis needed to be removed. Loss of function was less frequent when the infection was initially treated with surgical cleaning without removal of the prosthesis, even when this procedure failed at first. We found that anaemia and obesity were associated with lower treatment success, and that the probability of treatment success increased when surgical cleaning without prosthesis removal was performed early, and when the antibiotic rifampicin was used in combination with another antibiotic.

Synchronous Periprosthetic Joint Infections: A Scoping Review of the Literature.

Prosthetic joint infections (PJIs) occurring in multiple joints at the same time (synchronous PJI) are an extremely rare complication, frequently associated with bacteremia, and are associated with high mortality rates. The presence of three or more prosthetic joints, rheumatoid arthritis, neoplasia, bacteremia and immune-modulating therapy seem to be the recurring risk factors for synchronous PJI. In case of PJIs, all other replaced joints should be considered as potentially infected and investigated if PJI is suspected. Treatments of synchronous multiple PJIs vary and must be decided on a case-by-case basis. However, the advantages of one-stage exchange seem to outweigh the two-stage protocol, as it decreases the number of necessary surgical procedures. Nonetheless, too few studies have been conducted to allow firm conclusions about the best handling of synchronous PJI. Thus, additional studies are needed to understand this devastating complication and to design the most appropriate diagnostic and therapeutic path.

Risk factors for persistent enterococcal bacteraemia: a multicentre retrospective study.

OBJECTIVES: Conditions favouring persistent enterococcal bacteraemia (p-EB) have not been fully investigated yet. The aim of our study is to analyse risk factors for p-EB and its impact on mortality. METHODS: International two-centre retrospective study of all hospitalised adults with enterococcal bacteraemia managed with follow-up blood cultures (BCs) during the period 2011-2019. Exclusion criteria were: (1) death within 72 hours from index BCs and (2) polymicrobial bacteraemia. Primary endpoint was p-EB, defined as further isolation of the same species of Enterococcus spp. from BCs after at least 72 hours of appropriate antibiotic therapy. Multivariable logistic regression model was performed to assess risk factors for p-EB. The impact of p-EB on 30-day mortality was assessed by Kaplan-Meier survival curve and Cox regression multivariable model. RESULTS: During the study period, 244 enterococcal bacteraemia were diagnosed. P-EB were 13.5% (33/244). At multivariable analysis, factors independently associated with p-EB were hematologic malignancy (OR 4.60 [95% CI 1.32-16.00], P = 0.01), infective endocarditis (OR 7.99 [95% CI 2.20-28.9], P = 0.002), and use of daptomycin as initial treatment (OR 4.50 [95% CI 1.29-15.61], P = 0.018). Mortality rate was higher in the p-EB group (32% vs. 18%). Kaplan-Meier survival curve showed that patients with p-EB were less likely to survive at 30 days from index BCs (log-rank P = 0.002). Using a Cox regression model, independent predictors of 30-day mortality were hematologic malignancy (HR 2.30 [95% CI 1.02-4.11], P = 0.043), p-EB (HR 1.93 [95% CI 0.92-4.04], P = 0.08), and septic shock (HR 5.92 [95% CI 2.17-16.30], P = 0.001). CONCLUSION: P-EB was diagnosed mainly in very fragile patients and in those receiving daptomycin as frontline therapy. P-EB may have an impact on mortality.

Preoperative and perioperative risk factors, and risk score development for prosthetic joint infection due to Staphylococcus aureus: a multinational matched case-control study.

OBJECTIVES: We aim to identify the preoperative and perioperative risk factors associated with post-surgical Staphylococcus aureus prosthetic joint infections (PJI) and to develop and validate risk-scoring systems, to allow a better identification of high-risk patients for more efficient targeted interventions. METHODS: We performed a multicenter matched case-control study of patients who underwent a primary hip and knee arthroplasty from 2014 to 2016. Two multivariable models by logistic regression were performed, one for the preoperative and one for perioperative variables; predictive scores also were developed and validated in an external cohort. RESULTS: In total, 130 cases and 386 controls were included. The variables independently associated with S. aureus-PJI in the preoperative period were (adjusted OR; 95% CI): body mass index >30 kg/m2 (3.0; 1.9 to 4.8), resident in a long-term care facility (2.8; 1.05 to 7.5), fracture as reason for arthroplasty (2.7; 1.4 to 5.03), skin disorders (2.5; 0.9 to 7.04), previous surgery in the index joint (2.4; 1.3 to 4.4), male sex (1.9; 1.2 to 2.9) and American Society of Anesthesiologists index score 3 to 4 (1.8; 1.2 to 2.9). The area under the receiver operating characteristic curve was 0.73 (95% CI 0.68 to 0.78). In perioperative model, the risk factors were the previous ones plus surgical antibiotic prophylaxis administered out of the first 60 minutes before incision (5.9; 2.1 to 16.2), wound drainage for >72 hours after arthroplasty (4.5; 1.9 to 19.4) and use of metal bearing material versus ceramic (1.9; 1.1 to 3.3). The area under the receiver operating characteristic curve was 0.78 (95% CI 0.72 to 0.83). The predictive scores developed were validated in the external cohort. DISCUSSION: Predictive scores for S. aureus-PJI were developed and validated; this information would be useful for implementation of specific preventive measures.

Bone and Joint Infections: The Role of Imaging in Tailoring Diagnosis to Improve Patients' Care.

Imaging is needed for the diagnosis of bone and joint infections, determining the severity and extent of disease, planning biopsy, and monitoring the response to treatment. Some radiological features are pathognomonic of bone and joint infections for each modality used. However, imaging diagnosis of these infections is challenging because of several overlaps with non-infectious etiologies. Interventional radiology is generally needed to verify the diagnosis and to identify the microorganism involved in the infectious process through imaging-guided biopsy. This narrative review aims to summarize the radiological features of the commonest orthopedic infections, the indications and the limits of different modalities in the diagnostic strategy as well as to outline recent findings that may facilitate diagnosis.

The efficacy of suppressive antibiotic treatment in patients managed non-operatively for periprosthetic joint infection and a draining sinus.

Objectives: Patients with prosthetic joint infections (PJIs) not suitable for curative surgery may benefit from suppressive antibiotic therapy (SAT). However, the usefulness of SAT in cases with a draining sinus has never been investigated. Methods: A multicentre, retrospective observational cohort study was performed in which patients with a PJI and a sinus tract were eligible for inclusion if managed conservatively and if sufficient follow-up data were available (i.e. at least 2 years). SAT was defined as a period of >  6 months of oral antibiotic therapy. Results: SAT was initiated in 63 of 72 (87.5 %) included patients. Implant retention during follow-up was the same in patients receiving SAT vs. no SAT (79.4 % vs. 88.9 %; p = 0 .68). In total, 27 % of patients using SAT experienced side effects. In addition, the occurrence of prosthetic loosening in initially fixed implants, the need for surgical debridement, or the occurrence of bacteremia during follow-up could not be fully prevented with the use of SAT, which still occurred in 42 %, 6.3 %, and 3.2 % of cases, respectively. However, the sinus tract tended to close more often (42 % vs. 13 %; p = 0 .14), and a higher resolution of pain was observed (35 % vs. 14 %; p = 0 .22) in patients receiving SAT. Conclusions: SAT is not able to fully prevent complications in patients with a draining sinus. However, it may be beneficial in a subset of patients, particularly in those with pain or the hindrance of a draining sinus. A future prospective study, including a higher number of patients not receiving SAT, is needed.

Towards development of core domain sets for short term and long term studies of calcium pyrophosphate crystal deposition (CPPD) disease: A framework paper by the OMERACT CPPD working group.

INTRODUCTION: Although calcium pyrophosphate deposition (CPPD) is common, there are no published outcome domains or validated measurement instruments for CPPD studies. In this paper, we describe the framework for development of the Outcome Measures in Rheumatology (OMERACT) CPPD Core Domain Sets. METHODS: The OMERACT CPPD working group performed a scoping literature review and qualitative interview study. Generated outcomes were presented at the 2020 OMERACT CPPD virtual Special Interest Group (SIG) meeting with discussion focused on whether different core domain sets should be developed for different calcium pyrophosphate deposition (CPPD) clinical presentations and how the future CPPD Core Domain Set may overlap with already established osteoarthritis (OA) domains. These discussions informed development of a future work plan for development of the OMERACT CPPD Core Domain Sets. FINDINGS: Domains identified from a scoping review of 112 studies and a qualitative interview study of 36 people (28 patients with CPPD, 7 health care professionals, one stakeholder) were mapped to core areas of OMERACT Filter 2.1. The majority of SIG participants agreed there was need to develop separate core domain sets for "short term" and "long term" studies of CPPD. Although CPPD + OA is common and core domain sets for OA have been established, participants agreed that existing OA core domain sets should not influence the development of OMERACT core domain sets for CPPD. Prioritization exercises (using Delphi methodology) will consider 40 potential domains for short term studies of CPPD and 47 potential domains for long term studies of CPPD. CONCLUSION: Separate OMERACT CPPD Core Domain Sets will be developed for "short term" studies for an individual flare of acute CPP crystal arthritis and for "long term" studies that may include participants with any clinical presentation of CPPD (acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, and/or CPPD + OA).