Rifampin-resistant periprosthetic joint infections are associated with worse functional outcome in both acute and chronic infection types.

Periprosthetic joint infections (PJI) pose a significant challenge in orthopaedic surgery, often requiring extensive surgical debridement and prolonged antibiotic treatment to eliminate the causative pathogens. Rifampin, known for its potent activity against biofilms, has been crucial in managing PJI by penetrating and disrupting these formations, thereby improving treatment efficacy. In this sense, antibiotic protocols lacking rifampin have shown increased failure rates. Consequently, the development of rifampin resistance could severely influence the prognosis of PJI. The aim of this clinical study was to assess how rifampin resistance affects the functional outcome in patients with PJI. In this single-centre comparative cohort study, we systematically documented all patients who presented with a PJI during the period spanning from 2018 to 2020. Two distinct groups were established for the study: Group 1 comprised 35 patients with a PJI caused by rifampin-susceptible pathogens and group 2 consisted of 28 patients with PJI caused by rifampin-resistant pathogens. A total of 63 patients (34 females) with a mean age of 68 years and a mean follow up of 37 months were included. The examination of patient-specific parameters did not reveal any identified risk factors as influential. Patients with a rifampin-resistant pathogen underwent a greater number of surgical revisions (6.9 ± 5.1 compared to 3.59 ± 3.39, p = 0.0011) and had extended durations of antibiotic treatment (p = 0.0052). The results of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score revealed significant differences in clinical outcome between both groups in every domain, even when stratified by acute and chronic entities. In total the WOMAC increased significantly from 21.57 ± 14.9 points in group 1 to 71.47 ± 62.7 points in group 2 (p < 0.001). The higher failure rates observed in group 2 were not statistically significant (p = 0.44). The current study demonstrates that PJI caused by rifampin-resistant bacteria are associated with a significantly worse functional outcome in both acute and chronic infection types without significantly affecting total failure rates.

Persistent cytopenias after anti-BCMA CAR T-cell therapy are associated with reduced hematopoietic activity in posttreatment bone marrows.

OBJECTIVES: We attempt to analyze bone marrow findings and correlation with cytopenia(s) after anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell infusion in this study. METHODS: Relevant clinicopathologic data, including complete blood counts, neutrophil counts, relevant therapy history, and pre- and posttherapy bone marrow evaluations, were studied in 12 patients who received anti-BCMA CAR T-cell therapy. RESULTS: Bone marrow findings after CAR T-cell therapy were available in 6 of 12 cases, 3 of which showed markedly hypocellular marrow with either markedly reduced or essentially absent hematopoiesis. One case showed a hypocellular marrow with trilineage hematopoiesis, while the remaining 2 cases showed persistent involvement by plasma cell myeloma. Reticulin stains did not reveal significant fibrosis. Ten patients had anemia, and 8 patients had leukopenia and thrombocytopenia at day 90 posttherapy. Long-term follow-up showed persistent disease in 10 of 12 cases. CONCLUSIONS: Prolonged cytopenias occur in most patients after BCMA CAR T-cell therapy with bone marrow evaluations demonstrating associated marked hypocellularity with minimal or no hematopoiesis without an increase in fibrosis.

Sepsis and delayed cerebral ischemia are associated and have a cumulative effect on poor functional outcome in aneurysmal subarachnoid hemorrhage.

Objective: Although sepsis and delayed cerebral ischemia (DCI) are severe complications in patients with aneurysmal subarachnoid hemorrhage (aSAH) and share pathophysiological features, their interrelation and additive effect on functional outcome is uncertain. We investigated the association between sepsis and DCI and their cumulative effect on functional outcome in patients with aSAH using current sepsis-3 definition. Methods: Patients admitted to our hospital between 11/2014 and 11/2018 for aSAH were retrospectively analyzed. The main explanatory variable was sepsis, diagnosed using sepsis-3 criteria. Endpoints were DCI and functional outcome at hospital discharge (modified Rankin Scale (mRS) 0-3 vs. 4-6). Propensity score matching (PSM) and multivariable logistic regressions were performed. Results: Of 238 patients with aSAH, 55 (23.1%) developed sepsis and 74 (31.1%) DCI. After PSM, aSAH patients with sepsis displayed significantly worse functional outcome (p < 0.01) and longer ICU stay (p = 0.046). Sepsis was independently associated with DCI (OR = 2.46, 95%CI: 1.28-4.72, p < 0.01). However, after exclusion of patients who developed sepsis before (OR = 1.59, 95%CI: 0.78-3.24, p = 0.21) or after DCI (OR = 0.85, 95%CI: 0.37-1.95, p = 0.70) this statistical association did not remain. Good functional outcome gradually decreased from 56.3% (76/135) in patients with neither sepsis nor DCI, to 43.8% (21/48) in those with no sepsis but DCI, to 34.5% (10/29) with sepsis but no DCI and to 7.7% (2/26) in patients with both sepsis and DCI. Conclusion: Our study demonstrates a strong association between sepsis, DCI and functional outcome in patients with aSAH and suggests a complex interplay resulting in a cumulative effect towards poor functional outcome, which warrants further studies.

Cohort profile: BioMD-Y (biopsychosocial factors of major depression in youth) - a biobank study on the molecular genetics and environmental factors of depression in children and adolescents in Munich.

PURPOSE: BioMD-Y is a comprehensive biobank study of children and adolescents with major depression (MD) and their healthy peers in Germany, collecting a host of both biological and psychosocial information from the participants and their parents with the aim of exploring genetic and environmental risk and protective factors for MD in children and adolescents. PARTICIPANTS: Children and adolescents aged 8-18 years are recruited to either the clinical case group (MD, diagnosis of MD disorder) or the typically developing control group (absence of any psychiatric condition). FINDINGS TO DATE: To date, four publications on both genetic and environmental risk and resilience factors (including FKBP5, glucocorticoid receptor activation, polygenic risk scores, psychosocial and sociodemographic risk and resilience factors) have been published based on the BioMD-Y sample. FUTURE PLANS: Data collection is currently scheduled to continue into 2026. Research questions will be further addressed using available measures.

Nudix hydrolase 23 post-translationally regulates carotenoid biosynthesis in plants.

Carotenoids are essential for photosynthesis and photoprotection. Plants must evolve multifaceted regulatory mechanisms to control carotenoid biosynthesis. However, the regulatory mechanisms and the regulators conserved among plant species remain elusive. Phytoene synthase (PSY) catalyzes the highly regulated step of carotenogenesis and geranylgeranyl diphosphate synthase (GGPPS) acts as a hub to interact with GGPP-utilizing enzymes for the synthesis of specific downstream isoprenoids. Here, we report a function of Nudix hydrolase 23 (NUDX23), a Nudix domain-containing protein, in post-translational regulation of PSY and GGPPS for carotenoid biosynthesis. NUDX23 expresses highly in Arabidopsis (Arabidopsis thaliana) leaves. Overexpression of NUDX23 significantly increases PSY and GGPPS protein levels and carotenoid production, whereas knockout of NUDX23 dramatically reduces their abundances and carotenoid accumulation in Arabidopsis. NUDX23 regulates carotenoid biosynthesis via direct interactions with PSY and GGPPS in chloroplasts, which enhances PSY and GGPPS protein stability in a large PSY-GGPPS enzyme complex. NUDX23 was found to co-migrate with PSY and GGPPS proteins and to be required for the enzyme complex assembly. Our findings uncover a regulatory mechanism underlying carotenoid biosynthesis in plants and offer promising genetic tools for developing carotenoid-enriched food crops.

Validity and value of metabolic connectivity in mouse models of ß-amyloid and tauopathy.

Among functional imaging methods, metabolic connectivity (MC) is increasingly used for investigation of regional network changes to examine the pathophysiology of neurodegenerative diseases such as Alzheimer's disease (AD) or movement disorders. Hitherto, MC was mostly used in clinical studies, but only a few studies demonstrated the usefulness of MC in the rodent brain. The goal of the current work was to analyze and validate metabolic regional network alterations in three different mouse models of neurodegenerative diseases (ß-amyloid and tau) by use of 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET) imaging. We compared the results of FDG-µPET MC with conventional VOI-based analysis and behavioral assessment in the Morris water maze (MWM). The impact of awake versus anesthesia conditions on MC read-outs was studied and the robustness of MC data deriving from different scanners was tested. MC proved to be an accurate and robust indicator of functional connectivity loss when sample sizes ≥12 were considered. MC readouts were robust across scanners and in awake/ anesthesia conditions. MC loss was observed throughout all brain regions in tauopathy mice, whereas ß-amyloid indicated MC loss mainly in spatial learning areas and subcortical networks. This study established a methodological basis for the utilization of MC in different ß-amyloid and tau mouse models. MC has the potential to serve as a read-out of pathological changes within neuronal networks in these models.

Cemented versus Cementless Stem Fixation in Revision Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.

The number of revision knee arthroplasties (rTKA) is growing significantly as is the use of intramedullary stems for optimized stability. The choice of the most appropriate stem fixation method is still controversial. The purpose of this meta-analysis is to compare cemented versus cementless stem fixation in rTKA. Publications with patients undergoing rTKA with a follow-up > 24 months were systemically reviewed. Extracted parameters included total revision and failure rates for any reason, incidence of aseptic loosening, periprosthetic infection, and radiolucent lines, as well as the clinical outcome. A statistical regression analysis was then performed on all extracted clinical and radiological outcome data. A total of 35 publications met the inclusion criteria and were included and analyzed. Overall, 14/35 publications compared cementless versus cemented stem fixation, whereas 21/35 publications investigated only one stem fixation method. There were no significant differences in revision (p = 0.2613) or failure rates (p = 0.3559) and no differences in the incidence of aseptic loosening (p = 0.3999) or periprosthetic infection (p = 0.1010). The incidence of radiolucent lines was significantly higher in patients with cemented stems (26.2% versus 18.6%, p < 0.0001). However, no differences in clinical outcomes were observed. No superiority of a specific stem fixation method in rTKA was found. Rates of revision or failure for any reason as well as incidence of aseptic loosening and periprosthetic infection in cemented versus cementless stem fixation showed no significant difference. A higher incidence of radiolucent lines was observed in cemented stem fixation; however, no effect was observed on the clinical outcome.

Failure of CAR-T cell therapy in relapsed and refractory large cell lymphoma and multiple myeloma: An urgent unmet need.

Since its FDA approval, chimeric antigen receptor (CAR)-T cell therapy is changing the landscape of the treatment algorithm for relapsed and refractory large cell lymphoma and multiple myeloma. While initially hailed as a game changer and received widely with great enthusiasm, the reality of treatment failure soon became a major disappointment. This situation left patients and clinicians alike wondering about the next treatment options. CAR-T cell therapy failure for aggressive lymphoma or multiple myeloma creates a very poor prognosis and the treatment options are very limited. New emerging data, however, show promise for the use of approaches that include bispecific antibodies and other strategies to rescue affected patients. In this review, we summarize the current emerging data on the treatment options for patients whose disease has relapsed or remains refractory after CAR-T cell therapy failure, an area of great unmet need.

Cervical vertebral body replacement using a modern in situ expandable and angulable corpectomy cage system: early clinical and radiological outcome.

PURPOSE: Vertebral body replacement (VBR) cages are commonly implanted to reconstruct the cervical vertebrae in cases of tumour, trauma, spondylodiscitis, and degeneration. Expandable cages have been widely used for this purpose; however, the lacking congruence at the implant-bone interface and consequent implant displacement were considered as a serious drawback of such systems. Aim of this study is to evaluate the early clinical and radiological outcome of a modern in situ not only expandable but also angulable cervical corpectomy cage system. METHODS: A total of 42 patients who underwent a single or multilevel cervical VBR procedure were included and retrospectively evaluated in this single-centre case series. The neurological status was assessed using American Spinal Injury Association (ASIA) score. Complications were categorized into surgical (including implant-associated) and general medical. Radiographic parameters included regional angulation, segmental height, and coronal alignment. RESULTS: Mean age was 59.5 ± 20.6 years. The recorded ASIA score improved postoperatively by 10 points (p  0.0001). Surgical including implant-associated complication rates were 19.05%. Radiographic evaluation showed a height gain of 11.2 mm (p < 0.0001), lordotic correction of 7° (p < 0.0001), and coronal alignment of 3° (p < 0.0001). At the last follow-up, loss of angulation correction of 1.9° (p  0.0002), subsidence of 1.92 mm (p  0.0006), and fusion rates of 68.42% were observed. CONCLUSIONS: The use of an in situ angulable and expandable cage system in cervical VBR seems to offer better results compared to conventional static or expandable cages regarding segmental height gain, lordotic correction, and clinical improvement as well as low complication and revision rates. Significant height gain in multilevel surgeries is associated with higher rates of implant-associated complications.

No needles needed: All-oral therapy options for relapsed and refractory multiple myeloma.

Immense progress has been made for the treatment of multiple myeloma over the past two decades, with patient outcomes improving dramatically as a result. Patient quality of life, however, is constantly challenged by complications of the disease, side effects of therapy and the overall burden receiving continuous treatment. Compared to parenteral agents, all-oral regimens can provide logistically favorable alternatives and are associated with improved quality of life. Here, we review the currently available and investigational oral therapies for relapsed and refractory multiple myeloma and provide a practical clinical reference tool. We explore the factors that dictate the selection of therapy, such as prior drug refractoriness, disease biology and patient-specific considerations. Regimens with their respective supporting clinical data are organized by the degree of prior treatment, from lenalidomide-sensitive to heavily pretreated patients. We explore common challenges such as renal insufficiency and cytopenias. Lastly, we review investigational oral agents.

Novel fabrication tools for dynamic compression targets with engineered voids using photolithography methods.

Mesoscale imperfections, such as pores and voids, can strongly modify the properties and the mechanical response of materials under extreme conditions. Tracking the material response and microstructure evolution during void collapse is crucial for understanding its performance. In particular, imperfections in the ablator materials, such as voids, can limit the efficiency of the fusion reaction and ultimately hinder ignition. To characterize how voids influence the response of materials during dynamic loading and seed hydrodynamic instabilities, we have developed a tailored fabrication procedure for designer targets with voids at specific locations. Our procedure uses SU-8 as a proxy for the ablator materials and hollow silica microspheres as a proxy for voids and pores. By using photolithography to design the targets' geometry, we demonstrate precise and highly reproducible placement of a single void within the sample, which is key for a detailed understanding of its behavior under shock compression. This fabrication technique will benefit high-repetition rate experiments at x-ray and laser facilities. Insight from shock compression experiments will provide benchmarks for the next generation of microphysics modeling.

Second primary malignancies in patients with haematological cancers treated with lenalidomide: a systematic review and meta-analysis.

BACKGROUND: Lenalidomide has been standard therapy for multiple myeloma and other haematological malignancies for more than a decade. Previous meta-analyses identified an association between lenalidomide and second primary malignancies (SPM) in patients with multiple myeloma. However, newer randomised controlled trials using lenalidomide for other indications have not reported an increased incidence of SPM. The aim of this study was to investigate the risk of developing SPM with lenalidomide use in all disease settings. METHODS: We did a systematic review of randomised controlled trials that reported SPM in patients treated with lenalidomide. PubMed, Embase, CENTRAL, Europe PubMed Central, and ClinicalTrials.gov were searched from Jan 1, 2004, to March 18, 2022. Randomised controlled trials with at least one lenalidomide group and one non-lenalidomide group were selected, regardless of the disease setting. Studies with a median follow-up of less than 12 months were excluded. Summary data were extracted by two reviewers (KS and KL) independently and verified by a third reviewer (JF). We then conducted a meta-analysis to assess the risk ratio (RR) of SPM with lenalidomide use across various disease subtypes using a random-effects model. We chose random effects for the primary analysis because of anticipated heterogeneity between different diseases, but we used fixed effects for stratified meta-analysis of multiple myeloma studies. Risk of bias was assessed with the PROTECT tool. The study was registered with PROSPERO, CRD42021257508. FINDINGS: Our search yielded 9078 studies, and 38 trials that included 14 058 patients were eligible for meta-analysis after screening, 18 of which were in multiple myeloma. The RR across all malignancies was 1·16 (95% CI 0·96-1·39). However, there was heterogeneity across indications (p=0·020). The RR when lenalidomide was used for multiple myeloma was 1·42 (1·09-1·84). There was no increase in SPM in lymphoma or chronic lymphocytic leukaemia (0·90 [0·76-1·08]) and myelodysplastic syndrome (0·96 [0·23-3·97]) trials. In the setting of multiple myeloma, lenalidomide increased both solid and haematological SPM, both in the no-transplantation and post-transplantation settings. From the 38 trials, 21 (55%) had low risk of bias, 12 (32%) had unclear risk of bias, and five (13%) had high risk of bias. INTERPRETATION: Based on the current data, lenalidomide-induced SPM seem to occur exclusively in patients with multiple myeloma. Thus, lenalidomide can be used for other indications without the major concern of a therapy-related neoplasm. In the multiple myeloma setting, lenalidomide is an effective drug, but patients should be monitored both for haematological and solid tumour SPM. This monitoring includes patients that have not received autologous haematopoietic stem-cell transplantation. Further investigations are needed to improve understanding on why lenalidomide only promotes SPM in patients with multiple myeloma. FUNDING: None.

Multi-frame, ultrafast, x-ray microscope for imaging shockwave dynamics.

Inertial confinement fusion (ICF) holds increasing promise as a potential source of abundant, clean energy, but has been impeded by defects such as micro-voids in the ablator layer of the fuel capsules. It is critical to understand how these micro-voids interact with the laser-driven shock waves that compress the fuel pellet. At the Matter in Extreme Conditions (MEC) instrument at the Linac Coherent Light Source (LCLS), we utilized an x-ray pulse train with ns separation, an x-ray microscope, and an ultrafast x-ray imaging (UXI) detector to image shock wave interactions with micro-voids. To minimize the high- and low-frequency variations of the captured images, we incorporated principal component analysis (PCA) and image alignment for flat-field correction. After applying these techniques we generated phase and attenuation maps from a 2D hydrodynamic radiation code (xRAGE), which were used to simulate XPCI images that we qualitatively compare with experimental images, providing a one-to-one comparison for benchmarking material performance. Moreover, we implement a transport-of-intensity (TIE) based method to obtain the average projected mass density (areal density) of our experimental images, yielding insight into how defect-bearing ablator materials alter microstructural feature evolution, material compression, and shock wave propagation on ICF-relevant time scales.

Boosting regulatory T cell function for the treatment of autoimmune diseases - That's only half the battle!

Regulatory T cells (Treg) represent a subset of specialized T cells that are essential for the regulation of immune responses and maintenance of peripheral tolerance. Once activated, Treg exert powerful immunosuppressive properties, for example by inhibiting T cell-mediated immune responses against self-antigens, thereby protecting our body from autoimmunity. Autoimmune diseases such as multiple sclerosis, rheumatoid arthritis or systemic lupus erythematosus, exhibit an immunological imbalance mainly characterized by a reduced frequency and impaired function of Treg. In addition, there has been increasing evidence that - besides Treg dysfunction - immunoregulatory mechanisms fail to control autoreactive T cells due to a reduced responsiveness of T effector cells (Teff) for the suppressive properties of Treg, a process termed Treg resistance. In order to efficiently treat autoimmune diseases and thus fully induce immunological tolerance, a combined therapy aimed at both enhancing Treg function and restoring Teff responsiveness could most likely be beneficial. This review provides an overview of immunomodulating drugs that are currently used to treat various autoimmune diseases in the clinic and have been shown to increase Treg frequency as well as Teff sensitivity to Treg-mediated suppression. Furthermore, we discuss strategies on how to boost Treg activity and function, and their potential use in the treatment of autoimmunity. Finally, we present a humanized mouse model for the preclinical testing of Treg-activating substances in vivo.

Comparative Analyses of the Impact of Different Criteria for Sepsis Diagnosis on Outcome in Patients with Spontaneous Subarachnoid Hemorrhage.

Data on sepsis in patients with a subarachnoid hemorrhage (SAH) are scarce. We assessed the impact of different sepsis criteria on the outcome in an SAH cohort. Adult patients admitted to our ICU with a spontaneous SAH between 11/2014 and 11/2018 were retrospectively included. In patients developing an infection, different criteria for sepsis diagnosis (Sepsis-1, Sepsis-3_original, Sepsis-3_modified accounting for SAH-specific therapy, alternative sepsis criteria compiled of consensus conferences) were applied and their impact on functional outcome using the modified Rankin Scale (mRS) on hospital discharge and in-hospital mortality was evaluated. Of 270 SAH patients, 129 (48%) developed an infection. Depending on the underlying criteria, the incidence of sepsis and septic shock ranged between 21-46% and 9-39%. In multivariate logistic regression, the Sepsis-1 criteria were not associated with the outcome. The Sepsis-3 criteria were not associated with the functional outcome, but in shock with mortality. Alternative sepsis criteria were associated with mortality for sepsis and in shock with mortality and the functional outcome. While Sepsis-1 criteria were irrelevant for the outcome in SAH patients, septic shock, according to the Sepsis-3 criteria, adversely impacted survival. This impact was higher for the modified Sepsis-3 criteria, accounting for SAH-specific treatment. Modified Sepsis-3 and alternative sepsis criteria diagnosed septic conditions of a higher relevance for outcomes in patients with an SAH.

Sex differences in the genetic regulation of the blood transcriptome response to glucocorticoid receptor activation.

Substantial sex differences have been reported in the physiological response to stress at multiple levels, including the release of the stress hormone, cortisol. Here, we explore the genomic variants in 93 females and 196 males regulating the initial transcriptional response to cortisol via glucocorticoid receptor (GR) activation. Gene expression levels in peripheral blood were obtained before and after GR-stimulation with the selective GR agonist dexamethasone to identify differential expression following GR-activation. Sex stratified analyses revealed that while the transcripts responsive to GR-stimulation were mostly overlapping between males and females, the quantitative trait loci (eQTLs) regulation differential transcription to GR-stimulation was distinct. Sex-stratified eQTL SNPs (eSNPs) were located in different functional genomic elements and sex-stratified transcripts were enriched within postmortem brain transcriptional profiles associated with Major Depressive Disorder (MDD) specifically in males and females in the cingulate cortex. Female eSNPs were enriched among SNPs linked to MDD in genome-wide association studies. Finally, transcriptional sensitive genetic profile scores derived from sex-stratified eSNPS regulating differential transcription to GR-stimulation were predictive of depression status and depressive symptoms in a sex-concordant manner in a child and adolescent cohort (n = 584). These results suggest the potential of eQTLs regulating differential transcription to GR-stimulation as biomarkers of sex-specific biological risk for stress-related psychiatric disorders.

Superinfection with Difficult-to-Treat Pathogens Significantly Reduces the Outcome of Periprosthetic Joint Infections.

Periprosthetic joint infection (PJI) is a serious complication after total joint arthroplasty. In the course of a PJI, superinfections with pathogens that do not match the primary infecting micro-organism may occur. To our knowledge, there are no published data on the outcome of such infections in the literature. The aim of this study was to assess the outcome of PJI with superinfections with a difficult-to-treat (DTT) pathogen. Data of 169 consecutive patients with PJI were retrospectively analyzed in this single-center study. Cases were categorized into: Group 1 including non-DTT-PJI without superinfection, Group 2 DTT-PJI without superinfection, Group 3 non-DTT-PJI with DTT superinfection, and Group 4 non-DTT-PJI with non-DTT superinfection. Group 3 comprised 24 patients and showed, after a mean follow-up of 13.5 ± 10.8 months, the worst outcome with infection resolution in 17.4% of cases (p = 0.0001), PJI-related mortality of 8.7% (p = 0.0001), mean revision rate of 6 ± 3.6 (p < 0.0001), and duration of antibiotic treatment of 71.2 ± 45.2 days (p = 0.0023). PJI caused initially by a non-DTT pathogen with a superinfection with a DTT pathogen is significantly associated with the worst outcome in comparison to non-DTT-PJI, PJI caused initially by a DTT pathogen, and to non-DTT-PJI with a non-DTT superinfection.

Periprosthetic Infections of the Shoulder Joint: Characteristics and 5-Year Outcome of a Single-Center Series of 19 Cases.

Periprosthetic shoulder infection (PSI) remains a devastating complication after total shoulder arthroplasty (TSA). Furthermore, there is a paucity in the literature regarding its diagnostic and therapeutic management, especially the absence of therapy concepts devised exclusively for PSI. The aim of the presenting study is to examine the characteristics and outcome of patients with PSI who were treated according to well-established algorithms developed originally for periprosthetic joint infection (PJI) of the hip and knee and determine if these algorithms can be applied to PSI. This single-center case series included all patients with a PSI presenting between 2010 and 2020. Recorded parameters included age, sex, affected side, BMI, ASA score, Charlson comorbidity index, preoperative anticoagulation, indication for TSA (fracture, osteoarthritis or cuff-arthropathy), and type of infection (acute or chronic PSI). The outcome was divided into treatment failure or infect resolution. Staphylococcus epidermidis and aureus were the commonest infecting pathogens. Acute PSI was mainly treated with debridement, irrigation, and retention of the prosthesis (DAIR) and chronic cases with two/multiple-stage exchange. The treatment failure rate was 10.5%. C-reactive protein was preoperatively elevated in 68.4% of cases. The mean number of operative revisions was 3.6 ± 2.6, and the mean total duration of antibiotic treatment was 72.4 ± 41.4 days. The most administered antibiotic was a combination of clindamycin and fluoroquinolone. In summary, the data of the current study suggest that therapeutical algorithms and recommendations developed for the treatment of PJI of the hip and knee are also applicable to PSI.

Delayed Rifampin Administration in the Antibiotic Treatment of Periprosthetic Joint Infections Significantly Reduces the Emergence of Rifampin Resistance.

Rifampin is one of the most important biofilm-active antibiotics in the treatment of periprosthetic joint infection (PJI), and antibiotic regimens not involving rifampin were shown to have higher failure rates. Therefore, an emerging rifampin resistance can have a devastating effect on the outcome of PJI. The aim of this study was to compare the incidence of rifampin resistance between two groups of patients with a PJI treated with antibiotic regimens involving either immediate or delayed additional rifampin administration and to evaluate the effect of this resistance on the outcome. In this retrospective analysis of routinely collected data, all patients who presented with an acute/chronic PJI between 2018 and 2020 were recorded in the context of a single-center comparative cohort study. Two groups were formed: Group 1 included 25 patients with a PJI presenting in 2018-2019. These patients received additional rifampin only after pathogen detection in the intraoperative specimens. Group 2 included 37 patients presenting in 2019-2020. These patients were treated directly postoperatively with an empiric antibiotic therapy including rifampin. In all, 62 patients (32 females) with a mean age of 68 years and 322 operations were included. We found a rifampin-resistant organism in 16% of cases. Rifampin resistance increased significantly from 12% in Group 1 to 19% in Group 2 (p < 0.05). The treatment failure rate was 16% in Group 1 and 16.2% in Group 2 (p = 0.83). The most commonly isolated rifampin-resistant pathogen was Staphylococcus epidermidis (86%) (p < 0.05). The present study shows a significant association between the immediate start of rifampin after surgical revision in the treatment of PJI and the emergence of rifampin resistance, however with no significant effect on outcome.