The cross-sectional and longitudinal interconnectedness of physical, psychological and role functioning following physical trauma: A network analysis.

OBJECTIVE: Surviving physical trauma can have a large impact on one's daily life. Patients are at increased risk for poor physical health, psychological complaints, and problems in role functioning - which is often experienced simultaneously. The present study explores the interconnectedness of physical, psychological, and role functioning during the first two years post-injury, both cross-sectionally and longitudinally from a network perspective. METHODS: 3785 trauma patients (Mage = 64.2 years, SDage = 18.9 years, 50.5% female) completed questionnaires on physical, psychological, and role functioning across six measurement occasions during the first two years post-injury. The Injury Severity Score (ISS) was retrieved from the local trauma registry. Mixed graphical network models and cross-lagged network models were estimated to examine which items of recovery played a central role and were mostly related to other items in cross-sectional and longitudinal networks respectively. RESULTS: The cross-sectional networks showed especially strong interconnections between impairments of physical and role functioning and also within post-traumatic stress symptoms. The longitudinal networks extended these results by showing that pain, impaired mobility, limitations in self-care, anxiety/depressive symptoms, and several post-traumatic stress symptoms were strong predictors for impairments in functioning at later stages of recovery. CONCLUSION: Our findings showed that impairments in physical, psychological, and role functioning experienced by trauma patients are largely intertwined across the two years following injury. Monitoring physical impairments and psychological complaints early in recovery might help to more promptly provide the best fitting aftercare for trauma patients, which can improve recovery on the long-term.

Role of Routine Suppressive Antibiotic Therapy After Debridement, Antibiotics, and Implant Retention for Acute Periprosthetic Joint Infections.

Background: The first-line management strategy for acute periprosthetic joint infections (PJIs) is debridement, antibiotics, and implant retention (DAIR). Suppressive antibiotic therapy (SAT) after DAIR is proposed to improve outcomes, yet its efficacy remains under scrutiny. Methods: We conducted a multicenter retrospective study in patients with acute PJI of the hip or knee who were treated with DAIR in centers from Europe and the United States. We analyzed the effect of SAT using a Cox model landmarked at 12 weeks. The primary covariate of interest was SAT, which was analyzed as a time-varying covariate. Patients who experienced treatment failure or were lost to follow-up within 12 weeks were excluded from the analysis. Results: The study included 510 patients with 66 treatment failures with a median follow-up of 801 days. We did not find a statistically significant association between SAT and treatment failure (hazard ratio, 1.37; 95% CI, .79-2.39; P = .27). Subgroup analyses for joint, country cohort, and type of infection (early or late acute) did not show benefit for SAT. Secondary analysis of country cohorts showed a trend toward benefit for the US cohort (hazard ratio, 0.36; 95% CI, .11-1.15; P = .09), which also had the highest risk of treatment failure. Conclusions: The utility of routine SAT as a strategy for enhancing DAIR's success in acute PJI remains uncertain. Our results suggest that SAT's benefits might be restricted to specific groups of patients, underscoring the need for randomized controlled trials. Identifying patients most likely to benefit from SAT should be a priority in future studies.

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 predictive value of an infection (positive predictive value17). 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.

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.

What Is the Most Effective Treatment for Periprosthetic Joint Infection After Total Joint Arthroplasty in Patients with Rheumatoid Arthritis?: A Systematic Review.

BACKGROUND: Rheumatoid arthritis (RA) is a risk factor for periprosthetic joint infection (PJI) after total joint arthroplasty (TJA). The purpose of this study was to perform a systematic review comparing the failure rates of debridement, antibiotics, and implant retention (DAIR), one-stage exchange arthroplasty/revision (OSR), and 2-stage exchange arthroplasty/revision (TSR) for RA patients with PJI and identify risk factors in the RA population associated with increased treatment failure rate. METHODS: PubMed, Ovid MEDLINE, and Ovid Embase databases were screened with the terms "rheumatoid arthritis," "total joint arthroplasty," "prosthetic joint infection," and "treatment for PJI" on August 29, 2021. Four hundred ninety-one studies were screened, of which 86 were evaluated. The primary outcome evaluated was failure of surgical treatment for PJI. RESULTS: Ten retrospective cohort studies were included after full-text screening, yielding 401 patients with RA. Additional demographic and PJI management data were obtained for 149 patients. Patients with RA who underwent TSR demonstrated a lower failure rate (26.8%) than both DAIR (60.1%) and OSR (39.2%) (χ2 = 37.463, p < 0.00001). Patients with RA who underwent DAIR had a 2.27 (95% CI, 1.66-3.10) times higher risk of experiencing treatment failure than those who underwent TSR. Among risk factors, there was a significant difference in the C-reactive protein of patients who did vs. did not experience treatment failure (p = 0.02). CONCLUSION: TSR has a higher rate of success in the management of PJI patients with RA compared with DAIR and OSR. The complete removal of the infected prosthesis and delayed reimplantation may lower the treatment failure rate. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

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.

The global burden of fracture-related infection: can we do better?

Fracture-related infection is a major complication related to musculoskeletal injuries that not only has important clinical consequences, but also a substantial socioeconomic impact. Although fracture-related infection is one of the oldest disease entities known to mankind, it has only recently been defined and, therefore, its global burden is still largely unknown. In this Personal View, we describe the origin of the term fracture-related infection, present the available data on its global impact, and discuss important aspects regarding its prevention and management that could lead to improved outcomes in both high-resource and low-resource settings. We also highlight the need for health-care systems to be adequately compensated for the high cost of human resources (trained staff) and well-equipped facilities required to adequately care for these complex patients. Our aim is to increase awareness among clinicians and policy makers that fracture-related infection is a disease entity that deserves prioritisation in terms of research, with the goal to standardise treatment and improve patient outcomes on a global scale.

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.

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).

Should We Use Rifampicin in Periprosthetic Joint Infections Caused by Staphylococci When the Implant Has Been Exchanged? A Multicenter Observational Cohort Study.

Background: Previous studies demonstrated the efficacy of a rifampicin-based regimen in the treatment of acute staphylococcal periprosthetic joint infections (PJIs) treated with surgical debridement. However, evidence is lacking to support the use of rifampicin in cases where the implant is exchanged during revision. Methods: We included all consecutive cases of staphylococcal PJIs treated from January 2013 to December 2018 with revision surgery in this international, retrospective, multicenter observational cohort study. PJI was defined according to the European Bone and Joint Infection Society diagnostic criteria. A relapse or reinfection during follow-up, the need for antibiotic suppressive therapy, the need for implant removal, and PJI-related death were defined as clinical failure. Cases without reimplantation or with follow-up <12 months were excluded. Results: A total of 375 cases were included in the final analysis, including 124 1-stage exchanges (33.1%) and 251 2-stage exchanges (66.9%). Of those, 101 cases failed (26.9%). There was no statistically significant difference in failure of patients receiving rifampicin (22.5%, 42/187) and those not receiving rifampicin (31.4%, 59/188; P = .051). A subanalysis of chronic PJIs treated by 2-stage exchange arthroplasty demonstrated a lower failure rate in cases treated with rifampicin (15%) compared with the no-rifampicin group (35.5%; P = .005). In this subgroup, the use of rifampicin and an antibiotic holiday of >2 weeks were independent predictors of clinical success (odds ratio [OR], 0.36; 95% CI, 0.15-0.88; and OR, 0.19; 95% CI, 0.04-0.90; respectively). Conclusions: Combination treatment with rifampicin increases treatment success in patients with chronic staphylococcal PJI treated with 2-stage exchange arthroplasty.

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.

Is an isolated positive sonication fluid culture in revision arthroplasties clinically relevant?

OBJECTIVES: The aim of this study was to investigate the clinical relevance of an isolated positive sonication fluid culture (SFC) in patients who underwent revision surgery of a prosthetic joint. We hypothesized that cases with a positive SFC have a higher rate of infection during follow-up compared with controls with a negative SFC. METHODS: This retrospective multicentre observational study was performed within the European Study Group of Implant-Associated Infections. All patients who underwent revision surgery of a prosthetic joint between 2013 and 2019 and had a minimum follow-up of 1 year were included. Patients with positive tissue cultures or synovial fluid cultures were excluded from the study. RESULTS: A total of 95 cases (positive SFC) and 201 controls (negative SFC) were included. Infection during follow-up occurred in 12 of 95 cases (12.6%) versus 14 of 201 controls (7.0%) (p = 0.125). In all, 79.8% of cases were with treated with antibiotics (76/95). Of the non-treated cases, 89% (17/19) had a positive SFC with a low virulent microorganism. When solely analysing patients who were not treated with antibiotics, 16% of the cases (3/19) had an infection during follow-up versus 5% of the controls (9/173) (p = 0.08). DISCUSSION: Although not statistically significant, infections were almost twice as frequent in patients with an isolated positive SFC. These findings require further exploration in larger trials and to conclude about the potential benefit of antibiotic treatment in these cases.

Efficacy of a digitally supported regional systems intervention for suicide prevention (SUPREMOCOL) in Noord-Brabant, the Netherlands.

OBJECTIVE: We evaluated the effect of a digitally supported systems intervention for suicide prevention (SUPREMOCOL) in Noord-Brabant, the Netherlands. METHOD: Non-randomized stepped wedge trial design (SWTD). Stepwise implementation in the five subregions of the systems intervention. Pre-post analysis for the whole province (Exact Rate Ratio Test, Poisson count). SWTD Hazard Ratios of suicides per person-years for subregional analysis of control versus intervention conditions over five times three months. Sensitivity analysis. RESULTS: Suicide rates dropped 17.8% (p = .013) from 14.4 suicides per 100,000 before the start of implementation of the systems intervention (2017), to 11.9 (2018) and 11.8 (2019) per 100, during implementation; a significant reduction (p = .043) compared to no changes in the rest of the Netherlands. Suicide rates dropped further by 21.5% (p = .002) to 11.3 suicides per 100,000 during sustained implementation in 2021. Sensitivity analysis confirmed the reduction (p = .02). The SWTD analysis over 15 months in 2018-2019 did not show a significant association of this reduction with implementation per subregional level, probably due to insufficient power given the short SWTD timeframe for implementation and low suicide rates per subregion. CONCLUSIONS: During the SUPREMOCOL systems intervention, over four years, there was a sustained and significant reduction of suicides in Noord-Brabant.

Rifampicin in periprosthetic joint infections: where do we stand and where are we headed?

INTRODUCTION: A periprosthetic joint infection (PJI) is a major complication of arthroplasty. Treatment of PJI consists of surgical debridement with or without the exchange of the implant and long-term antimicrobial treatment. Rifampicin is regarded as one of the cornerstones of antimicrobial treatment for staphylococcal PJI, but the exact role of rifampicin for PJI in different clinical scenarios remains to be elucidated. AREAS COVERED: In this perspective article, an overview is provided of in vitro, in vivo and clinical studies that were the basis of the current guidelines and recommendations for rifampicin use in daily practice for PJI. Controversial issues on indication, dosing, timing, duration, and antibiotic drug interactions will be addressed. Finally, the most urgent clinical questions on rifampicin use that need answering in the nearby future will be formulated. EXPERT OPINION: Many inquiries remain concerning the exact indications and clinical use of rifampicin in PJI. Randomized controlled trials are needed to answer these questions.

Meta-analyzing the multiverse: A peek under the hood of selective reporting.

Researcher degrees of freedom refer to arbitrary decisions in the execution and reporting of hypothesis-testing research that allow for many possible outcomes from a single study. Selective reporting of results (p-hacking) from this "multiverse" of outcomes can inflate effect size estimates and false positive rates. We studied the effects of researcher degrees of freedom and selective reporting using empirical data from extensive multistudy projects in psychology (Registered Replication Reports) featuring 211 samples and 14 dependent variables. We used a counterfactual design to examine what biases could have emerged if the studies (and ensuing meta-analyses) had not been preregistered and could have been subjected to selective reporting based on the significance of the outcomes in the primary studies. Our results show the substantial variability in effect sizes that researcher degrees of freedom can create in relatively standard psychological studies, and how selective reporting of outcomes can alter conclusions and introduce bias in meta-analysis. Despite the typically thousands of outcomes appearing in the multiverses of the 294 included studies, only in about 30% of studies did significant effect sizes in the hypothesized direction emerge. We also observed that the effect of a particular researcher degree of freedom was inconsistent across replication studies using the same protocol, meaning multiverse analyses often fail to replicate across samples. We recommend hypothesis-testing researchers to preregister their preferred analysis and openly report multiverse analysis. We propose a descriptive index (underlying multiverse variability) that quantifies the robustness of results across alternative ways to analyze the data. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cultures in periprosthetic joint infections, the imperfect gold standard?

Culture-negative periprosthetic joint infections (PJI) are commonly described in the literature. By implementing a routine diagnostic workup and by optimizing tissue sampling and processing, the culture-negative rate can easily be reduced. When faced with a culture-negative PJI, several serological and molecular techniques are available that may aid in finding the causative microorganism. Clinical clues may guide the treating physician towards more atypical and rare microorganisms. A multidisciplinary team consisting of orthopaedic surgeons, microbiologists and infectious disease specialist are warranted in tailoring diagnostic testing and deciding on the surgical and antibiotic treatment approach.