Beyond the skin: B cells in pemphigus vulgaris, tolerance and treatment.

Pemphigus vulgaris (PV) is a rare autoimmune bullous disease characterized by blistering of the skin and mucosa owing to the presence of autoantibodies against the desmosome proteins desmoglein 3 and occasionally in conjunction with desmoglein 1. Fundamental research into the pathogenesis of PV has revolutionized its treatment and outcome with rituximab, a B-cell-depleting therapy. The critical contribution of B cells to the pathogenesis of pemphigus is well accepted. However, the exact pathomechanism, mechanisms of onset, disease course and relapse remain unclear. In this narrative review, we provide an overview of the fundamental research progress that has unfolded over the past few centuries to give rise to current and emerging therapies. Furthermore, we summarize the multifaceted roles of B cells in PV, including their development, maturation and antibody activity. Finally, we explored how these various aspects of B-cell function contribute to disease pathogenesis and pave the way for innovative therapeutic interventions.

Pemphigus vulgaris (PV) is a rare autoimmune disease, in which the immune system attacks itself and causes blisters on the skin and inside the mouth. This happens because the body mistakenly attacks specific proteins (called desmosomes) that keep the skin together. Globally, this disease affects anywhere from 0.5 to 16.1 people per million, often older than 50 years. PV is life-threatening when left untreated. From carrying out research as far back as the 1700s, we have made significant strides in understanding PV. For example, research has led to a new treatment with the antibody rituximab, which works by eliminating the cells of the immune system that attack desmosomes (called B cells). However, after therapy is completed, the disease often returns because the same troublesome B cells reappear. There are multiple places that are involved when the body attacks desmosomes. The problems range from the bone marrow where the B cells are made and selected to the ways these cells change as they move around the body. It takes a rare combination of these changes to switch from a normal immune system to one that causes PV. Clinicians and researchers are currently developing new treatment options to better target this skin disease. We want to emphasize that research should continue to uncover how the disease works because a better understanding promotes the development of new therapies, and perhaps even a cure. This is vital, because PV can significantly lower the quality of life of people living with this skin disease.

Genetic Determinants in MRSA Carriage and Their Association with Decolonization Outcome.

Methicillin-resistant Staphylococcus aureus (MRSA) colonization increases the risk of infection. Response to decolonization treatment is highly variable and determinants for successful decolonization or failure of eradication treatment are largely unknown. Insight into genetic predictors of eradication failure is potentially useful in clinical practice. The aim of this study was to explore genetic characteristics that are associated with MRSA decolonization failure. This cohort study was performed in a tertiary care hospital in the Netherlands. Patients with ≥ 1 positive MRSA culture from any site and with available whole -genome sequencing data of the MRSA isolate between 2017 and 2022 were included. Lineages, resistance, and virulence factors were stratified by MRSA decolonization outcome. In total, 56 patients were included: 12/56 (21%) with treatment failure and 44/56 (79%) with successful decolonization (with or without preceding treatment). A significant association was found between ciprofloxacin-resistant lineages and failure of eradication (OR 4.20, 95%CI 1.11-15.96, P = 0.04). Furthermore, livestock-associated MRSA and the major community-associated MRSA lineages ST6-t304 and ST8-t008 were associated with successful eradication treatment or spontaneous clearance. In conclusion, this explorative study showed a higher eradication failure rate in complicated MRSA carriers with ciprofloxacin-resistant MRSA lineages, which are predominantly healthcare-associated. Further studies are warranted to confirm the higher eradication failure risk of ciprofloxacin-resistant lineages, and identify the underlying mechanisms.

Synovial Calprotectin is Superior to Synovial Leukocyte Count in Excluding Chronic Periprosthetic Joint Infections, a Retrospective Cohort Study.

BACKGROUND: Synovial calprotectin is a promising biomarker for diagnosing chronic periprosthetic joint infections (PJIs), but its diagnostic value has not been directly compared to synovial leukocyte count and polymorphonuclear neutrophils. This study aimed to: (1) evaluate and compare the diagnostic accuracy between these markers in patients undergoing revision arthroplasty for chronic PJI or aseptic reasons; and (2) determine the best rule-out and rule-in test for PJI. METHODS: Synovial fluid samples from patients undergoing revision arthroplasty in hip and knee joints were collected and analyzed. Patients diagnosed with an acute PJI, patients treated with antibiotics 2 weeks prior to revision surgery, and/or patients who had active inflammatory joint disease were excluded. Periprosthetic joint infections were diagnosed based on the presence of a sinus tract and/or positive intraoperative cultures according to the European Bone and Joint Infection Society microbiological criteria. RESULTS: A total of 137 patients were included, of whom 19 (14%) were diagnosed with a PJI. Overall, synovial calprotectin had the highest diagnostic accuracy of all studied markers (area under the curve 96%). Synovial calprotectin, with a cutoff of 50 mg/L, had the highest negative predictive value of 100%. However, PMNs (> 80%) combined with a leukocyte count (> 3,000 cells/µL) showed the highest positive likelihood ratio of an infection (PLR 17). CONCLUSIONS: Synovial calprotectin is the most accurate biomarker for ruling out a chronic PJI, while the combination of synovial leukocyte count and PMN is most reliable for ruling in a chronic PJI.

A fluorogenic micrococcal nuclease-based probe for fast detection and optical imaging of Staphylococcus aureus in prosthetic joint and fracture-related infections.

PURPOSE: Staphylococcus aureus is the most common and impactful multi-drug resistant pathogen implicated in (periprosthetic) joint infections (PJI) and fracture-related infections (FRI). Therefore, the present proof-of-principle study was aimed at the rapid detection of S. aureus in synovial fluids and biofilms on extracted osteosynthesis materials through bacteria-targeted fluorescence imaging with the 'smart-activatable' DNA-based AttoPolyT probe. This fluorogenic oligonucleotide probe yields large fluorescence increases upon cleavage by micrococcal nuclease, an enzyme secreted by S. aureus. METHODS: Synovial fluids from patients with suspected PJI and extracted osteosynthesis materials from trauma patients with suspected FRI were inspected for S. aureus nuclease activity with the AttoPolyT probe. Biofilms on osteosynthesis materials were imaged with the AttoPolyT probe and a vancomycin-IRDye800CW conjugate (vanco-800CW) specific for Gram-positive bacteria. RESULTS: 38 synovial fluid samples were collected and analyzed. Significantly higher fluorescence levels were measured for S. aureus-positive samples compared to, respectively, other Gram-positive bacterial pathogens (p < 0.0001), Gram-negative bacterial pathogens (p = 0.0038) and non-infected samples (p = 0.0030), allowing a diagnosis of S. aureus-associated PJI within 2 h. Importantly, S. aureus-associated biofilms on extracted osteosynthesis materials from patients with FRI were accurately imaged with the AttoPolyT probe, allowing their correct distinction from biofilms formed by other Gram-positive bacteria detected with vanco-800CW within 15 min. CONCLUSION: The present study highlights the potential clinical value of the AttoPolyT probe for fast and accurate detection of S. aureus infection in synovial fluids and biofilms on extracted osteosynthesis materials.

Ensuring the quality and specificity of preregistrations.

Researchers face many, often seemingly arbitrary, choices in formulating hypotheses, designing protocols, collecting data, analyzing data, and reporting results. Opportunistic use of "researcher degrees of freedom" aimed at obtaining statistical significance increases the likelihood of obtaining and publishing false-positive results and overestimated effect sizes. Preregistration is a mechanism for reducing such degrees of freedom by specifying designs and analysis plans before observing the research outcomes. The effectiveness of preregistration may depend, in part, on whether the process facilitates sufficiently specific articulation of such plans. In this preregistered study, we compared 2 formats of preregistration available on the OSF: Standard Pre-Data Collection Registration and Prereg Challenge Registration (now called "OSF Preregistration," http://osf.io/prereg/). The Prereg Challenge format was a "structured" workflow with detailed instructions and an independent review to confirm completeness; the "Standard" format was "unstructured" with minimal direct guidance to give researchers flexibility for what to prespecify. Results of comparing random samples of 53 preregistrations from each format indicate that the "structured" format restricted the opportunistic use of researcher degrees of freedom better (Cliff's Delta = 0.49) than the "unstructured" format, but neither eliminated all researcher degrees of freedom. We also observed very low concordance among coders about the number of hypotheses (14%), indicating that they are often not clearly stated. We conclude that effective preregistration is challenging, and registration formats that provide effective guidance may improve the quality of research.

Positive Intraoperative Cultures in Cup Revisions of THA: What Happens to the Stem?

BACKGROUND: Positive intraoperative cultures (PICs) are encountered in some patients undergoing revision of the acetabular cup after a previous THA. It is unknown whether PIC of the cup indicates whether the stem is infected as well and what happens to the stem during follow-up. QUESTIONS/PURPOSES: (1) What proportion of patients undergoing THA who undergo cup revision have PICs? (2) What is the survival of the stem during follow-up in cup revisions with PICs versus that of those with negative cultures? (3) Does antibiotic treatment of PIC of the cup prevent revision THA during follow-up? METHODS: In this retrospective, comparative multicenter study, five surgeons at four centers performed 338 acetabular cup revisions between January 2015 and December 2017. After evaluating the data, we excluded one patient because of an incomplete dataset and 77 patients because fewer than three intraoperative cultures were obtained during surgery, leaving 260 patients for analysis. Follow-up was 2 years. Patients were stratified into three cohorts: no PIC, one PIC, and two or more PICs. RESULTS: The proportion of patients with one or more PIC was 15% (39 of 260). A total of 8% (21 of 260) had one and 7% (18 of 260) had two or more PICs. Stem survival was lower in patients with two or more PICs, but stem revision for periprosthetic joint infection was similar between groups. Two-year survival, which was defined as freedom from revision for any cause or infection, was 97% (95% confidence interval 95% to 99%) in the group without PICs, 100% (95% CI 95% to 100%) in the group with one PIC, and 86% (95% CI 68% to 100%; p = 0.08) in the group with two or more PICs. None of the patients in the no PIC and one PIC groups were treated with antibiotics. In the two or more PICs cohort, 12 of 18 patients were treated. The stem survived in one of 12 patients treated with antibiotics versus two of six patients who were not treated with antibiotics. CONCLUSION: When treated with antibiotics, more than two PICs isolated during cup revision surgery do not have a major impact on survival of the stem during follow-up. A larger cohort of patients with PICs during cup revision might confirm these findings. LEVEL OF EVIDENCE: Level III, therapeutic study.

The European Bone and Joint Infection Society definition of periprosthetic joint infection is meaningful in clinical practice: a multicentric validation study with comparison with previous definitions.

BACKGROUND AND PURPOSE: A new periprosthetic joint infection (PJI) definition has recently been proposed by the European Bone and Joint Infection Society (EBJIS). The goals of this paper are to evaluate its diagnostic accuracy and compare it with previous definitions and to assess its accuracy in preoperative diagnosis. PATIENTS AND METHODS: We retrospectively evaluated a multicenter cohort of consecutive revision total hip and knee arthroplasties. Cases with minimum required diagnostic workup were classified according to EBJIS, 2018 International Consensus Meeting (ICM 2018), Infectious Diseases Society of America (IDSA), and modified 2013 Musculoskeletal Infection Society (MSIS) definitions. 2 years' minimum follow-up was required to assess clinical outcome. RESULTS: Of the 472 cases included, PJI was diagnosed in 195 (41%) cases using EBJIS; 188 (40%) cases using IDSA; 172 (36%) using ICM 2018; and 145 (31%) cases using MSIS. EBJIS defined fewer cases as intermediate (5% vs. 9%; p = 0.01) compared with ICM 2018. Specificity was determined by comparing risk of subsequent PJI after revision surgery. Infected cases were associated with higher risk of subsequent PJI in every definition. Cases classified as likely/confirmed infections using EBJIS among those classified as not infected in other definitions showed a significantly higher risk of subsequent PJI compared with concordant non-infected cases using MSIS (RR = 3, 95% CI 1-6), but not using ICM 2018 (RR = 2, CI 1-6) or IDSA (RR = 2, CI 1-5). EBJIS showed the highest agreement between pre-operative and definitive classification (k = 0.9, CI 0.8-0.9) and was better at ruling out PJI with an infection unlikely result (sensitivity 89% [84-93], negative predictive value 90% [85-93]). CONCLUSION: The newly proposed EBJIS definition emerged as the most sensitive of all major definitions. Cases classified as PJI according to the EBJIS criteria and not by other definitions seem to have increased risk of subsequent PJI compared with concordant non-infected cases. EBJIS classification is accurate in ruling out infection preoperatively.

Preregistration in practice: A comparison of preregistered and non-preregistered studies in psychology.

Preregistration has gained traction as one of the most promising solutions to improve the replicability of scientific effects. In this project, we compared 193 psychology studies that earned a Preregistration Challenge prize or preregistration badge to 193 related studies that were not preregistered. In contrast to our theoretical expectations and prior research, we did not find that preregistered studies had a lower proportion of positive results (Hypothesis 1), smaller effect sizes (Hypothesis 2), or fewer statistical errors (Hypothesis 3) than non-preregistered studies. Supporting our Hypotheses 4 and 5, we found that preregistered studies more often contained power analyses and typically had larger sample sizes than non-preregistered studies. Finally, concerns about the publishability and impact of preregistered studies seem unwarranted, as preregistered studies did not take longer to publish and scored better on several impact measures. Overall, our data indicate that preregistration has beneficial effects in the realm of statistical power and impact, but we did not find robust evidence that preregistration prevents p-hacking and HARKing (Hypothesizing After the Results are Known).

Patient-Tailored Approach for Diagnostics and Treatment of Mycotic Abdominal Aortic Aneurysm.

BACKGROUND: The existing literature on mycotic aortic aneurysm is scarce and focuses on treatment. This study evaluates the clinical characteristics, diagnostics, treatment and outcome of patients with a mycotic abdominal aortic aneurysm treated in a tertiary referral center. METHODS: A retrospective cohort study was conducted including all patients with a proven mycotic abdominal aortic aneurysm admitted between May 2010 and July 2020. Primary outcome was mortality and secondary outcome included complications such as vascular graft/endograft infection. RESULTS: Twenty-four patients with a mycotic abdominal aortic aneurysm were included. Patients had a mean age of 68 ± 9 years and 20 (83%) were male. Thirteen patients (57%) had positive preoperative blood cultures. Streptococcus pneumoniae was most frequently isolated by blood culturing, pus, and vascular, or perivascular tissue cultures (17%). In 19 (83%) patients the mycotic abdominal aortic aneurysm was located infrarenally, in three (13%) patients suprarenally, and in one (4%) patient juxtarenally. Median follow-up was 20 (7-42) months. In 8 patients (33%) vascular graft and or endograft infection was diagnosed after surgical repair. Ten (42%) patients died during the follow-up period. The main causes of death were vascular graft/endograft infection-related (n = 4) and rupture of the mycotic abdominal aortic aneurysm (n = 3). No patient characteristics could be identified as predictive for mortality. CONCLUSIONS: This study shows a large variation in presentation, diagnostic approaches, and surgical and antibiotic treatment of mycotic abdominal aortic aneurysm. The detailed information about the diagnostic approaches to this rare disease and its antibiotic and/or other treatment contributes to existing knowledge of mycotic abdominal aortic aneurysm. Because of the individual variation patients should be discussed in a multidisciplinary team with a vascular surgeon, infectious disease specialist, and clinical microbiologist.

Periprosthetic Joint Infection and the Trojan Horse Theory: Examining the Role of Gut Dysbiosis and Epithelial Integrity.

BACKGROUND: Periprosthetic joint infection (PJI) is an uncommon yet dreadful complication after total joint arthroplasty. Emerging evidence suggested a role for the gut microbiome in the pathogenesis of such infections as a reservoir of opportunistic pathogens. METHODS: A secondary analysis of an ongoing trial looking at gut dysbiosis and PJI was performed on patients that had next-generation sequencing done as part of their workup. Gut permeability and dysbiosis were measured using known biomarkers such as Zonulin. Statistical analysis consisted of descriptive statistics and logistic regression modeling. RESULTS: Among the cohort of 46 (47.8% female) patients, with a mean age of 68.47 years (range, 40 to 91) and a mean BMI 31.15 ± 6.49 kg/m2, 38 patients underwent a revision for PJI (29 chronic and 9 acute infections), and 8 patients were classified as aseptic failures. Then, a review of each of the bacteria retrieved was performed. Those known to be gut commensal based on available literature were noted. When regression modeling was performed, Zonulin levels were found to be associated with an increased probability of a similar finding (Estimate: 0.377, OR: 1.458; P = .001). CONCLUSION: In our study, we report the first clinical evidence of the translocation of bacteria from the gut to the joint in patients with PJI. In particular, when evaluating the microbiological profile of the NGS signal, a great number of known gut commensals were seen in patients with a highly permeable dysbiotic gut. Manipulation of the gut microbiome may become part of an essential and comprehensive approach for management of patients with PJI.

If, When, and How to Use Rifampin in Acute Staphylococcal Periprosthetic Joint Infections, a Multicentre Observational Study.

BACKGROUND: Rifampin is generally advised in the treatment of acute staphylococcal periprosthetic joint infections (PJI). However, if, when, and how to use rifampin remains a matter of debate. We evaluated the outcome of patients treated with and without rifampin, and analyzed the influence of timing, dose and co-antibiotic. METHODS: Acute staphylococcal PJIs treated with surgical debridement between 1999 and 2017, and a minimal follow-up of 1 year were evaluated. Treatment failure was defined as the need for any further surgical procedure related to infection, PJI-related death or the need for suppressive antimicrobial treatment. RESULTS: A total of 669 patients were analyzed. Treatment failure was 32.2% (131/407) in patients treated with rifampin and 54.2% (142/262) in whom rifampin was withheld (P < .001). The most prominent effect of rifampin was observed in knees (treatment failure 28.6% versus 63.9%, respectively, P < .001). The use of rifampin was an independent predictor of treatment success in the multi-variate analysis (OR 0.30, 95% CI 0.20 - 0.45). In the rifampin group, the use of a co-antibiotic other than a fluoroquinolone or clindamycin (OR 10.1, 95% CI 5.65 - 18.2) and the start of rifampin within 5 days after surgical debridement (OR 1.96, 95% CI 1.08 - 3.65) were predictors of treatment failure. The dosing of rifampin had no effect on outcome. CONCLUSIONS: Our data supports the use of rifampin in acute staphylococcal PJIs treated with surgical debridement, particularly in knees. Immediate start of rifampin after surgical debridement should probably be discouraged, but requires further investigation.

How to Handle Concomitant Asymptomatic Prosthetic Joints During an Episode of Hematogenous Periprosthetic Joint Infection, a Multicenter Analysis.

BACKGROUND: Prosthetic joints are at risk of becoming infected during an episode of bacteremia, especially during Staphylocococcus aureus bacteremia. However, it is unclear how often asymptomatic periprosthetic joint infection (PJI) occurs, and whether additional diagnostics should be considered. METHODS: In this multicenter study, we retrospectively analyzed a cohort of patients with a late acute (hematogenous) PJI between 2005-2015 who had concomitant prosthetic joints in situ. Patients without at least 1 year of follow-up were excluded. RESULTS: We included 91 patients with a hematogenous PJI and 108 concomitant prosthetic joints. The incident PJI was most frequently caused by Staphylococcus aureus (43%), followed by streptococci (26%) and Gram-negative rods (18%). Of 108 concomitant prosthetic joints, 13 were symptomatic, of which 10 were subsequently diagnosed as a second PJI. Of the 95 asymptomatic prosthetic joints, 1 PJI developed during the follow-up period and was classified as a "missed" PJI at the time of bacteremia with S. aureus (1.1%). Infected prosthetic joints were younger than the noninfected ones in 67% of cases, and prosthetic knees were affected more often than prosthetic hips (78%). CONCLUSIONS: During an episode of hematogenous PJI, concomitant asymptomatic prosthetic joints have a very low risk of being infected, and additional diagnostic work-up for these joints is not necessary.

The Impact of Surgical Strategy and Rifampin on Treatment Outcome in Cutibacterium Periprosthetic Joint Infections.

BACKGROUND: Cutibacterium species are common pathogens in periprosthetic joint infections (PJI). These infections are often treated with ß-lactams or clindamycin as monotherapy, or in combination with rifampin. Clinical evidence supporting the value of adding rifampin for treatment of Cutibacterium PJI is lacking. METHODS: In this multicenter retrospective study, we evaluated patients with Cutibacterium PJI and a minimal follow-up of 12 months. The primary endpoint was clinical success, defined by the absence of infection relapse or new infection. We used Fisher's exact tests and Cox proportional hazards models to analyze the effect of rifampin and other factors on clinical success after PJI. RESULTS: We included 187 patients (72.2% male, median age 67 years) with a median follow-up of 36 months. The surgical intervention was a 2-stage exchange in 95 (50.8%), 1-stage exchange in 51 (27.3%), debridement and implant retention (DAIR) in 34 (18.2%), and explantation without reimplantation in 7 (3.7%) patients. Rifampin was included in the antibiotic regimen in 81 (43.3%) cases. Infection relapse occurred in 28 (15.0%), and new infection in 13 (7.0%) cases. In the time-to-event analysis, DAIR (adjusted hazard ratio [HR] = 2.15, P = .03) and antibiotic treatment over 6 weeks (adjusted HR = 0.29, P = .0002) significantly influenced treatment failure. We observed a tentative evidence for a beneficial effect of adding rifampin to the antibiotic treatment-though not statistically significant for treatment failure (adjusted HR = 0.5, P = .07) and not for relapses (adjusted HR = 0.5, P = .10). CONCLUSIONS: We conclude that a rifampin combination is not markedly superior in Cutibacterium PJI, but a dedicated prospective multicenter study is needed.

Clinical implications of increased uptake in bone marrow and spleen on FDG-PET in patients with bacteremia.

PURPOSE: To investigate which clinical factors and laboratory values are associated with high FDG uptake in the bone marrow and spleen on 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) in patients with bacteremia. METHODS: One hundred forty-five consecutive retrospective patients with bacteremia who underwent FDG-PET/CT between 2010 and 2017 were included. Mean standard uptake values (SUVmean) of FDG in bone marrow, liver, and spleen were measured. Bone marrow-to-liver SUV ratios (BLR) and spleen-to-liver SUV ratios (SLR) were calculated. Linear regression analyses were performed to examine the association of BLR and SLR with age, gender, hemoglobin, leukocyte count, platelets, glucose level, C-reactive protein (CRP), microorganism, days of antibiotic treatment before FDG-PET/CT, infection focus, use of immunosuppressive drugs, duration of hospital stay (after FDG-PET/CT), ICU admission, and mortality. RESULTS: C-reactive protein (p = 0.006), a cardiovascular or musculoskeletal focus of infection (p = 0.000 for both), and bacteremia caused by Gram-negative bacteria (p = 0.002) were independently and positively associated with BLR, while age (p = 0.000) and glucose level before FDG-PET/CT (p = 0.004) were independently and negatively associated with BLR. For SLR, CRP (p = 0.001) and a cardiovascular focus of infection (p = 0.020) were independently and positively associated with SLR, while age (p = 0.002) and glucose level before FDG-PET/CT (p = 0.016) were independently and negatively associated with SLR. CONCLUSION: High FDG uptake in the bone marrow is associated with a higher inflammatory response and younger age in patients with bacteremia. In patients with high FDG uptake in the bone marrow, a cardiovascular or musculoskeletal focus of infection is more likely than other foci, and the infection is more often caused by Gram-negative species. High splenic FDG uptake is associated with a higher inflammatory response as well, and a cardiovascular focus of infection is also more likely in case of high splenic FDG uptake.

The APOE ε4 allele in relation to pre- and postsurgical cognitive functioning of patients with primary brain tumors.

BACKGROUND: Recent studies suggest a relationship between the APOE ε4 allele and cognitive outcome in patients treated for malignant brain tumors. Still, longitudinal investigations that include a pretreatment cognitive assessment are lacking and APOE's effects in patients with benign tumors are understudied. This study investigated presurgical cognitive performance and postsurgical change in ε4-carrying and non-carrying patients with glioma and meningioma. METHODS: Neuropsychological test scores (CNS Vital Signs battery [seven measures], Digit Span Forward/Backward, Letter Fluency test) were obtained as part of a prospective study in which patients with meningioma and glioma underwent cognitive assessment 1 day before (T0, n = 505) and 3 (T3, n = 418) and 12 months after (T12, n = 167) surgery. APOE isoforms were identified retrospectively. ε4 carriers and non-carriers were compared with regard to pretreatment cognitive performance on the group and individual level. Changes in performances over time were compared with longitudinal mixed model analysis in the total sample and the subgroup receiving adjuvant treatment. RESULTS: Carriers and non-carriers did not differ with regard to pretreatment performance. No significant main effect of ε4 carrier status or interaction between time (T0-T12) and carrier status was found on any of the tests in the whole sample nor in the sample receiving adjuvant treatment. CONCLUSIONS: This study found no evidence of increased vulnerability for pretreatment cognitive dysfunction or cognitive decline within 1 year after surgery in APOE ε4-carrying meningioma and glioma patients. Investigations that include larger samples at longer-term follow-up are recommended to investigate potential late treatment effects.

The importance of appropriate diagnostics in prosthetic joint infection: letter to the editor of BMC musculoskeletal disorders.

Assessment of a new diagnostic test must be performed against an acceptable and validated standard to allow comparison with other studies. We are concerned that the adoption of lower diagnostic criteria in this paper has contributed to an over-diagnosis of prosthetic joint infection and makes interpretation of the results difficult.

Should all hip and knee prosthetic joints be aspirated prior to revision surgery?

AIMS: It is essential to exclude a periprosthetic joint infection (PJI) prior to revision surgery. It is recommended to routinely aspirate the joint before surgery. However, this may not be necessary in a subgroup of patients. The aim of our study was to investigate if specific clinical and implant characteristics could be identified to rule out a PJI prior to revision surgery. METHODS: We retrospectively evaluated clinical and implant characteristics of patients who underwent a hip or knee revision surgery between October 2015 and October 2018. Patients were diagnosed with a PJI according to the MSIS diagnostic criteria. RESULTS: A total of 156 patients were analyzed, including 107 implants that were revised because of prosthetic loosening and 49 because of mechanical failure (i.e. instability, malalignment or malpositioning). No PJI was diagnosed in the group with mechanical failure. In the prosthetic loosening group, 20 of 107 were diagnosed with a PJI (19%). Although there was a significantly lower chance of having a PJI with an implant age of > 5 years combined with a CRP < 5 mg/L, an infection was still present in 3 out of 39 cases (8%). CONCLUSION: Implants with solely mechanical failure without signs of loosening and low inflammatory parameters probably do not require a synovial fluid aspiration. These results need to be confirmed in a larger cohort of patients. In case of prosthetic loosening, all joints need to be aspirated before surgery as no specific characteristic could be identified to rule out an infection.

Debridement, Antibiotics, and Implant Retention Is a Viable Treatment Option for Early Periprosthetic Joint Infection Presenting More Than 4 Weeks After Index Arthroplasty.

BACKGROUND: The success of debridement, antibiotics, and implant retention (DAIR) in early periprosthetic joint infection (PJI) largely depends on the presence of a mature biofilm. At what time point DAIR should be disrecommended is unknown. This multicenter study evaluated the outcome of DAIR in relation to the time after index arthroplasty. METHODS: We retrospectively evaluated PJIs occurring within 90 days after surgery and treated with DAIR. Patients with bacteremia, arthroscopic debridements, and a follow-up <1 year were excluded. Treatment failure was defined as (1) any further surgical procedure related to infection; (2) PJI-related death; or (3) use of long-term suppressive antibiotics. RESULTS: We included 769 patients. Treatment failure occurred in 294 patients (38%) and was similar between time intervals from index arthroplasty to DAIR: the failure rate for Week 1-2 was 42% (95/226), the rate for Week 3-4 was 38% (143/378), the rate for Week 5-6 was 29% (29/100), and the rate for Week 7-12 was 42% (27/65). An exchange of modular components was performed to a lesser extent in the early post-surgical course compared with the late course (41% vs 63%, respectively; P < .001). The causative microorganisms, comorbidities, and durations of symptoms were comparable between time intervals. CONCLUSIONS: DAIR is a viable option in patients with early PJI presenting more than 4 weeks after index surgery, as long as DAIR is performed within at least 1 week after the onset of symptoms and modular components can be exchanged.

Lower Success Rate of Débridement and Implant Retention in Late Acute versus Early Acute Periprosthetic Joint Infection Caused by Staphylococcus spp. Results from a Matched Cohort Study.

BACKGROUND: Surgical débridement, antibiotics and implant retention (DAIR) is currently recommended by international guidelines for both early acute (postsurgical) and late acute (hematogenous) periprosthetic joint infections (PJIs). However, due to a different pathogenesis of infection, a different treatment strategy may be needed. QUESTIONS/PURPOSES: (1) Compared with early acute PJIs, are late acute PJIs associated with a higher risk of DAIR failure? (2) When stratified by microorganism, is the higher risk of failure in late acute PJI associated with Staphylocococcus aureus infection? (3) When analyzing patients with S. aureus infection, what factors are independently associated with DAIR failure? METHODS: In this multicenter observational study, early acute and late acute PJIs treated with DAIR were retrospectively evaluated and matched according to treating center, year of diagnosis, and infection-causing microorganism. If multiple matches were available, the early acute PJI diagnosed closest to the late acute PJI was selected. A total of 132 pairs were included. Treatment success was defined as a retained implant during follow-up without the need for antibiotic suppressive therapy. RESULTS: Late acute PJIs had a lower treatment success (46% [60 of 132]) compared with early acute PJIs (76% [100 of 132]), OR 3.9 [95% CI 2.3 to 6.6]; p < 0.001), but the lower treatment success of late acute PJIs was only observed when caused by Staphylococcus spp (S. aureus: 34% versus 75%; p < 0.001; coagulase-negative staphylococci: 46% versus 88%; p = 0.013, respectively). On multivariable analysis, late acute PJI was the only independent factor associated with an unsuccessful DAIR when caused by S. aureus (OR 4.52 [95% CI 1.79 to 11.41]; p < 0.001). CONCLUSIONS: Although DAIR seems to be a successful therapeutic strategy in the management of early acute PJI, its use in late acute PJI should be reconsidered when caused by Staphylococcus spp. Our results advocate the importance of isolating the causative microorganism before surgery. LEVEL OF EVIDENCE: Level III, therapeutic study.

A Second Surgical Debridement for Acute Periprosthetic Joint Infections Should Not Be Discarded.

BACKGROUND: In acute periprosthetic joint infections (PJIs), a second surgical debridement (debridement, antibiotics, and implant retention [DAIR]) is generally not recommended after a failed first one. We identified the failure rate of a second DAIR and aimed to identify patients in whom an additional debridement might still be beneficial. METHODS: Patients with acute PJI of the hip or knee and treated with DAIR between 2006 and 2016 were retrospectively evaluated. A second DAIR was routinely performed provided that the soft tissue was intact. Failure of a second DAIR was described as (1) the need for additional surgical intervention to achieve infection control, (2) the need for antibiotic suppressive therapy due to persistent clinical and/or biochemical signs of infection, or (3) PJI related death. RESULTS: From the 455 cases treated with DAIR, 144 cases underwent a second debridement (34.6%). Thirty-seven cases failed (37/144, 25.7%). The implant needed to be removed in 23 cases (23/144, 16%). Positive cultures during the second DAIR (odds ratio 3.16, 95% confidence interval 1.29-7.74) and chronic renal insufficiency (odds ratio 13.6, 95% confidence interval 2.03-91.33) were independent predictors for failure in the multivariate analysis. No difference in failure was observed between persistent infection with the same microorganism and reinfection with a new microorganism (failure rate 31.6% vs 34.6%, P = .83). CONCLUSION: A second DAIR had a low failure rate in our cohort of patients and the implant could be retained in the majority of them. Therefore, a second DAIR should not be discarded in acute PJIs.