Influence of sports on cortical excitability in patients with spinal cord injury: a TMS study.

Background: Patients with spinal cord injury (SCI) show abnormal cortical excitability that might be caused by deafferentation. We hypothesize a reduced short-interval intracortical inhibition preceding movement in patients with SCI compared with healthy participants. In addition, we expect that neuroplasticity induced by different types of sports can modulate intracortical inhibition during movement preparation in patients with SCI. Methods: We used a reaction test and paired-pulse transcranial magnetic stimulation to record cortical excitability, assessed by measuring amplitudes of motor-evoked potentials in preparation of movement. The participants were grouped as patients with SCI practicing wheelchair dancing (n = 7), other sports (n = 6), no sports (n = 9), and healthy controls (n = 24). Results: There were neither significant differences between healthy participants and the patients nor between the different patient groups. A non-significant trend (p = .238), showed that patients engaged in sports have a stronger increase in cortical excitability compared with patients of the non-sportive group, while the patients in the other sports group expressed the highest increase in cortical excitability. Conclusion: The small sample sizes limit the statistical power of the study, but the trending effect warrants further investigation of different sports on the neuroplasticity in patients with SCI. It is not clear how neuroplastic changes impact the sensorimotor output of the affected extremities in a patient. This needs to be followed up in further studies with a greater sample size.

[Acute postoperative infections after dual head arthroplasty in geriatric patients]. / Akute postoperative Infektion nach Duokopfprothesenimplantation beim geriatrischen Patienten.

Acute periprosthetic joint infections (PJI) after dual head arthroplasty represent a major challenge with a 1-year mortality rate up to 50% in the mostly multimorbid geriatric patient collective. Due to the limited possibilities of preoperative patient optimization, infection rates of up to 9% have been reported, which is significantly higher than in elective arthroplasty. A therapeutic gold standard has not yet been established due to the heterogeneous study situation and the lack of prospective randomized studies. The most promising therapeutic option currently appears to be a single-stage stem replacement in combination with implantation of a cup component (conversion to total hip arthroplasty, infection eradication in up to 100%). An approach of débridement, antibiotics, implant retention (DAIR) alone shows significantly poorer success rates (16-82%). Surgical treatment should always be followed by antibiotic treatment with a total duration of 12 weeks. In addition to the established perioperative antibiotic prophylaxis, the use of antibiotic-loaded bone cement seems to be superior to cementless stem fixation in preventing PJI in dual head arthroplasty.

Adverse Events Associated with Prolonged Antibiotic Therapy for Periprosthetic Joint Infections-A Prospective Study with a Special Focus on Rifampin.

Periprosthetic Joint Infection (PJI) is a significant contributor to patient morbidity and mortality, and it can be addressed through a range of surgical interventions coupled with antibiotic therapies. Following surgical intervention(s), prolonged administration of oral antibiotics is recommended to cure PJI. There is a lack of reports on the adverse events (AEs) associated with oral antibiotics, particularly rifampin. This investigation sought to elucidate the occurrence of antibiotic-related AEs after an initial regimen of intravenous antibiotic administration, supplemented by an extended course of oral antibiotics. A prospective study of patients diagnosed with PJI of the hip, knee, or shoulder who underwent single-stage exchange arthroplasty (SSE) (10%), two-stage exchange arthroplasty (TSE) (81%), or debridement, antibiotics, and implant retention (DAIR) (6%) was performed. The primary outcome of interest was the detection of AEs, the secondary outcome the detection of a correlation between rifampin use and the incidence of AEs, and the tertiary outcome was whether oral antibiotic treatment needed to be adjusted or discontinued due to AEs. In addition, subjective tolerability was monitored throughout the study. A total of 336 events were identified for 73 out of 80 patients. The most frequently used antibiotics were rifampin and co-trimoxazole. Most AEs occurred in the gastrointestinal tract (46%). The most frequent AEs were nausea, inappetence, diarrhea, and skin rash. In 6% of cases, the AEs led to antibiotic discontinuation, and in 29% of cases, a dose adjustment of the oral therapy occurred, mainly with amoxicillin or co-trimoxazole. The majority of patients (55%) rated the subjective tolerability as good. In conclusion, AEs during antibiotic treatment for PJI are common. They mainly affect the gastrointestinal tract. Rifampin use might be a reason for the higher incidence of AEs compared to non-rifampin antibiotic treatment.

High treatment failure rate in haematogenous compared to non-haematogenous periprosthetic joint infection.

Aims: A higher failure rate has been reported in haematogenous periprosthetic joint infection (PJI) compared to non-haematogenous PJI. The reason for this difference is unknown. We investigated the outcome of haematogenous and non-haematogenous PJI to analyze the risk factors for failure in both groups of patients. Methods: Episodes of knee or hip PJI (defined by the European Bone and Joint Infection Society criteria) treated at our institution between January 2015 and October 2020 were included in a retrospective PJI cohort. Episodes with a follow-up of > one year were stratified by route of infection into haematogenous and non-haematogenous PJI. Probability of failure-free survival was estimated using the Kaplan-Meier method, and compared between groups using log-rank test. Univariate and multivariate analysis was applied to assess risk factors for failure. Results: A total of 305 PJI episodes (174 hips, 131 knees) were allocated to the haematogenous (n = 146) or the non-haematogenous group (n = 159). Among monomicrobial infections, Staphylococcus aureus was the dominant pathogen in haematogenous PJI (76/140, 54%) and coagulase-negative staphylococci in non-haematogenous PJI (57/133, 43%). In both groups, multi-stage exchange (n = 55 (38%) in haematogenous and n = 73 (46%) in non-haematogenous PJI) and prosthesis retention (n = 70 (48%) in haematogenous and n = 48 (30%) in non-haematogenous PJI) were the most common surgical strategies. Median duration of antimicrobial treatment was 13.5 weeks (range, 0.5 to 218 weeks) and similar in both groups. After six years of follow-up, the probability of failure-free survival was significantly lower in haematogenous compared to non-haematogenous PJI (55% vs 74%; p = 0.021). Infection-related mortality was significantly higher in haematogenous than non-haematogenous PJI (7% vs 0% episodes; p = 0.001). Pathogenesis of failure was similar in both groups. Retention of the prosthesis was the only independent risk factor for failure in multivariate analysis in both groups. Conclusion: Treatment failure was significantly higher in haematogenous compared to non-haematogenous PJI. Retention of the prosthesis was the only independent risk factor for failure in both groups.

ESSKA and EBJIS recommendations for the management of infections after anterior cruciate ligament reconstruction (ACL-R): prevention, surgical treatment and rehabilitation.

PURPOSE: Infection after anterior cruciate ligament reconstruction (ACL-R) is a rare but severe complication. Despite an increase in articles published on this topic over the last decade, solid data to optimized diagnostic and therapeutic measures are scarce. For this reason, the European Bone and Joint Infection Society (EBJIS) and the European Society for Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) collaborated in order to develop recommendations for the diagnosis and management of infections after ACL-R. The aim of the workgroup was to perform a review of the literature and provide practical guidance to healthcare professionals involved in the management of infections after ACL-R. METHODS: An international workgroup was recruited to provide recommendations for predefined clinical dilemmas regarding the management of infections after ACL-R. MEDLINE, EMBASE, Cochrane Library and Scopus databases were searched for evidence to support the recommended answers to each dilemma. RESULTS: The recommendations were divided into two articles. The first covers etiology, prevention, diagnosis and antimicrobial treatment of septic arthritis following ACL-R and is primarily aimed at infectious disease specialists. This article includes the second part of the recommendations and covers prevention of infections after ACL-R, surgical treatment of septic arthritis following ACL-R and subsequent postoperative rehabilitation. It is aimed not only at orthopedic surgeons, but at all healthcare professionals dealing with patients suffering from infections after ACL-R. CONCLUSION: These recommendations guide clinicians in achieving timely and accurate diagnosis as well as providing optimal management, both of which are paramount to prevent loss of function and other devastating sequelae of infection in the knee joint. LEVEL OF EVIDENCE: V.

Recommendations on diagnosis and antimicrobial treatment of infections after anterior cruciate ligament reconstruction (ACL-R) endorsed by ESSKA and EBJIS.

Infection after anterior cruciate ligament reconstruction (ACL-R) is a rare but devastating complication affecting predominantly young and sportive individuals. A timely and correct diagnosis as well as optimized management is paramount to circumvent serious sequelae and compromise in life quality. These recommendations are primarily intended for use by infectious disease specialists and microbiologists, but also orthopedic surgeons and other healthcare professionals who care for patients with infections after ACL-R. They are based on evidence mainly originating from observational studies and opinions of experts in the field, and cover the management of infections after ACL-R with a special focus on etiology, diagnosis, antimicrobial treatment and prevention. Comprehensive recommendations on surgical treatment and rehabilitation are presented separately in a document primarily addressing orthopedic professionals.

Guideline for management of septic arthritis in native joints (SANJO).

This clinical guideline is intended for use by orthopedic surgeons and physicians who care for patients with possible or documented septic arthritis of a native joint (SANJO). It includes evidence and opinion-based recommendations for the diagnosis and management of patients with SANJO.

Outcome and Failure Analysis of 132 Episodes of Hematogenous Periprosthetic Joint Infections-A Cohort Study.

Background: The outcomes of hematogenous periprosthetic joint infection (PJI) and reasons for failure are largely unknown. Methods: The outcomes of consecutive patients with hematogenous PJI treated at our institution between 2010 and 2019 were evaluated. Failure was classified as persistence or relapse of infection or new infection. Failure-free survival was assessed using Kaplan-Meier analysis. Proportions between groups were compared with the Fisher exact test. Results: One hundred thirty-two hematogenous PJI episodes involving knee (n = 76), hip (n = 54), shoulder (n = 1), or elbow (n = 1) prostheses experienced by 110 patients were included. The median follow-up (range) was 20.7 (0.2-89.9) months. Hematogenous PJIs were caused by Staphylococcus aureus (n = 49), Streptococcus spp. (n = 36), Enterococcus faecalis (n = 17), Enterobacterales (n = 16), coagulase-negative staphylococci (n = 9), and other (n = 6). Debridement and implant retention were performed in 50 (38%), prosthesis exchange or removal in 79 (60%), and no surgery in 3 episodes (2%). Treatment failed in 42 episodes (32%), including 6 infection-related deaths. Among 36 nonfatal failures, 21 were caused by a new pathogen and 8 by the same pathogen, in 7 episodes no pathogen was isolated. Of all nonfatal failures, 19 (53%) PJIs were of hematogenous origin. Identification of the primary focus, causative pathogen, and CRIME80 Score did not influence treatment outcome, but the failure rate was higher following prosthesis retention compared with multistage exchange. Conclusions: Persistence-/relapse-free survival after treatment of hematogenous PJI was high (84%). New hematogenous PJI due to the same or a new pathogen occurred frequently, reducing treatment success to 62% after 4 years of follow-up, suggesting an individual predisposition to hematogenous PJI. The outcome was similar for different pathogens but worse in episodes treated with prosthesis retention compared with multistage exchange.

The value of conventional radiographs for diagnosing internal fixation-associated infection.

BACKGROUND: The aim of the study is to  assess the diagnostic value of preoperative conventional radiographs for diagnosing infection associated with internal fixation devices. METHODS: We prospectively collected data of patients undergoing removal of internal fixation devices for any reason. Infection was diagnosed in case of purulence, sinus tract, positive histopathology and/or positive peri-implant tissue or sonication fluid culture. In radiographs radiolucent lines, implant breakage or displacement, or periosteal reaction were assessed. White blood cell count (WBC) and serum C-reactive protein (CRP) were determined at admission. RESULTS: We included 421 surgeries in 380 patients (median age 53.6 years, range 11-98 years), mainly indicated for infection (24.9%), nonunion (20.0%) and symptomatic implants (13.5%). Radiologic signs of infection included radiolucent lines (11.4%); implant breakage (12.4%) or displacement (10.7%); and periosteal reaction (7.1%). Infection was confirmed in 116 cases (27.6%). Only radiolucent lines (OR = 1.86 [95%CI: 1.00-3.38]) and periosteal reaction (OR = 2.48 [95%CI: 1.17-5.26]) were associated with infection, with a low sensitivity (16.4 and 12.1%, respectively), and high specificity (90.5 and 94.8%, respectively). Preoperative WBC and CRP had a sensitivity of 23.0 and 35.3%, and specificity of 91.7 and 89.5%, respectively. CONCLUSIONS: Radiological signs suggestive of infection were uncommon. Radiolucency and periosteal reaction were associated with infection, though with low sensitivity.

Cognitive Effects of Montelukast: A Pharmaco-EEG Study.

Montelukast is a well-established antiasthmatic drug with little side effects. It is a leukotriene receptor antagonist and recent research suggests cognitive benefits from its anti-inflammatory actions on the central nervous system. However, changes in brain activity were not directly shown so far in humans. This study aims to document changes in brain activity that are associated with cognitive improvement during treatment with Montelukast. We recorded EEG and conducted neuropsychological tests in 12 asthma-patients aged 38-73 years before and after 8 weeks of treatment with Montelukast. We found no significant changes on neuropsychological scales for memory, attention, and mood. In the EEG, we found decreased entropy at follow up during rest (p < 0.005). During episodic memory acquisition we found decreased entropy (p < 0.01) and acceleration of the background rhythm (p < 0.05). During visual attention performance, we detected an increase in gamma power (p < 0.005) and slowing of the background rhythm (p < 0.05). The study is limited by its small sample size, young age and absence of baseline cognitive impairment of the participants. Unspecific changes in brain activity were not accompanied by cognitive improvement. Future studies should examine elderly patients with cognitive impairment in a double-blind study with longer-term treatment by Montelukast.

Controversy about the Role of Rifampin in Biofilm Infections: Is It Justified?

Rifampin is a potent antibiotic against staphylococcal implant-associated infections. In the absence of implants, current data suggest against the use of rifampin combinations. In the past decades, abundant preclinical and clinical evidence has accumulated supporting its role in biofilm-related infections.In the present article, experimental data from animal models of foreign-body infections and clinical trials are reviewed. The risk for emergence of rifampin resistance and multiple drug interactions are emphasized. A recent randomized controlled trial (RCT) showing no beneficial effect of rifampin in patients with acute staphylococcal periprosthetic joint infection treated with prosthesis retention is critically reviewed and data interpreted. Given the existing strong evidence demonstrating the benefit of rifampin, the conduction of an adequately powered RCT with appropriate definitions and interventions would probably not comply with ethical standards.

Preoperative synovial fluid culture poorly predicts the pathogen causing periprosthetic joint infection.

PURPOSE: We investigated the value of preoperative pathogen detection and evaluated its concordance with intraoperative cultures in patients with culture-positive periprosthetic joint infection (PJI). METHODS: Culture-positive PJI episodes with available preoperative (synovial fluid) and intraoperative cultures (periprosthetic tissue, synovial or sonication fluid) were analyzed. The pathogen detection rate in preoperative and intraoperative cultures was compared using Fisher's exact test and their concordance was calculated. RESULTS: Among 167 included PJI episodes, 150 were monomicrobial with coagulase-negative staphylococci (n = 55, 37%), S. aureus (n = 34, 23%), and streptococci (n = 21, 14%) being the most common pathogens. Seventeen episodes (10%) were polymicrobial infections. The pathogen(s) grew in preoperative culture in 110 and in intraoperative cultures in 153 episodes (66% vs. 92%, p < 0.001). The pathogen detection rate was lower in preoperative compared to intraoperative cultures for low-virulent pathogens (40% vs. 94%, p < 0.001), polymicrobial infections (59% vs. 100%, p = 0.007), and in delayed and late PJI (63% vs. 94%, and 66% vs. 91%, respectively, p < 0.001). Full concordance of preoperative and intraoperative cultures was found in 87 episodes (52%). The pathogen was detected solely preoperatively in 14 episodes (8%) and solely intraoperatively in 57 cases (34%); an additional pathogen was found in 3 episodes (2%) preoperatively and in 6 episodes (4%) intraoperatively. CONCLUSION: The concordance of preoperative and intraoperative cultures was poor (52%). The sole or an additional pathogen was found exclusively in intraoperative cultures in 38% of PJI episodes, hence preoperative synovial fluid cultures are considered unreliable for pathogen detection in PJI.

Spinal implant-associated infections: a prospective multicentre cohort study.

This study evaluated the clinical, laboratory, microbiological, radiological and treatment characteristics of patients with early-onset and late-onset spinal implant-associated infections. Patients diagnosed with spinal implant-associated infection between 2015-2019 were prospectively included and treated according to a standardised algorithm. Infections were classified as early-onset (≤6 weeks) and late-onset (>6 weeks). Among 250 patients, 152 (61%) had early-onset and 98 (39%) had late-onset infection. Local inflammatory signs was the most common manifestation in early-onset infections (84%), whereas late-onset infections presented mainly with persisting or increasing local pain (71%). Sonication fluid was more often positive than peri-implant tissue samples (90% vs. 79%; P = 0.016), particularly in late-onset infections (92% vs. 75%; P = 0.005). Predominant pathogens were coagulase-negative staphylococci, Staphylococcus aureus and Cutibacterium spp. Debridement and implant retention was the most common surgical approach in early-onset infections (85%), whereas partial or complete implant exchange was mainly performed in late-onset infections (62%). Of the 250 patients, 220 (88%) received biofilm-active antibiotics, and median treatment duration was 11.7 weeks. Moreover, 49 patients (20%) needed more than one revision for infection and six patients (2.4%) died during hospital stay. Concluding, most spinal implant-associated infections were acquired during surgery and presented within 6 weeks of surgery. Infections presented mainly with local inflammatory signs in early-onset and with persisting or increasing pain in late-onset infections. Sonication was the most sensitive microbiological method, particularly in late-onset infections. Debridement and implant retention was used in well-integrated implants without loosening, independent of the time of infection onset.

Thermogenic diagnosis of periprosthetic joint infection by microcalorimetry of synovial fluid.

BACKGROUND: Synovial fluid culture is the standard investigation for the preoperative diagnosis of periprosthetic joint infection (PJI). However, the culture has limited sensitivity and requires several days until result. We evaluated the value of isothermal microcalorimetry for real-time diagnosis of PJI based on heat produced by microbial growth in synovial fluid. METHODS: Patients undergoing aspiration of prosthetic hip or knee joint before revision surgery were prospectively included between 2014 and 2015. The performance of microcalorimetry was compared to synovial fluid culture using McNemar's chi-squared test. Pearson's correlation coefficient was calculated for synovial fluid leukocyte count and microcalorimetric heat. RESULTS: Of 107 included patients (58 knee and 49 hip prosthesis), PJI was diagnosed in 46 patients (43%) and aseptic failure in 61 patients (57%) according to institutional criteria. In 26 PJI cases (56%) the pathogen grew in synovial fluid and intra-operative cultures. The sensitivity of synovial fluid culture and microcalorimetry was both 39% and the results were concordant in 98 patients (92%). In patients with PJI, microcalorimetry missed 4 pathogens which grew in synovial fluid culture, whereas culture missed 4 pathogens detected by microcalorimetry. A linear correlation (r = 0.366) was found between leukocyte count and microcalorimetric heat in synovial fluid (p < 0.001). The median time to positivity of microcalorimetry was 9 h (range, 1-64 h) vs. 3 days for cultures (range, 1-14 days). CONCLUSION: Microcalorimetry of synovial fluid allows thermogenic diagnosis of periprosthetic joint infection in synovial fluid. The diagnostic performance of synovial fluid microcalorimetry is comparable to culture and delivers results considerably faster. TRIAL REGISTRATION: This prospective study was registered on August 21, 2015 with the public clinical trial identification NCT02530229.

The global state of clinical research and trends in periprosthetic joint infection: A bibliometric analysis.

OBJECTIVES: The purpose of this study was to estimate the trends and state of research in periprosthetic joint infection (PJI). METHODS: Publications on PJI published between 1998 and 2018 were searched in the Web of Science database and analyzed using bibliometrics. The Altmetric score and Research Interest score were combined to provide a weighted count. The scope of the Altmetric score includes >16 weighted composite scores from websites such as Twitter, Facebook, and YouTube, whereas the Research Interest score is calculated from information derived from ResearchGate. RESULTS: Total of 3245 published documents were identified. The largest contribution was made by the United States, with the institution contributing most being the Rothman Institute. The most relative articles were published by the Journal of Arthroplasty, whereas the highest citation frequency journal was Clinical Orthopaedics and Related Research. There was a positive correlation between citation counts and Research Interest scores, while the Altmetric Attention score showed a negative value for highly cited articles. CONCLUSIONS: Based on the current trends of globalization, there is a rising trend in publications on PJI, with the largest annual contributions made by the United States. The most influential contributors are researchers from the United States and Europe. Twitter is used as a platform to communicate knowledge by most PJI researchers. The most recent research has focused on the diagnosis and risk factors of PJI.

Outcome of spinal implant-associated infections treated with or without biofilm-active antibiotics: results from a 10-year cohort study.

PURPOSE: Biofilm-active antibiotics are suggested to improve the outcome of implant-associated infections; however, their role in infections after spinal instrumentation is unclear. Therefore, we evaluated the outcome of patients with spinal implant-associated infections treated with and without biofilm-active antibiotics. METHODS: The probability of infection-free survival was estimated for treatment of spinal implant-associated infections with and without biofilm-active antibiotics using the Kaplan-Meier method; Cox proportional-hazards regression model was used to identify factors associated with treatment failure. RESULTS: Among 93 included patients, early-onset infection was diagnosed in 61 (66%) and late-onset in 32 infections (34%). Thirty patients (32%) were treated with biofilm-active antibiotic therapy and 63 (68%) without it. The infection-free survival after a median follow-up of 53.7 months (range, 8 days-9.4 years) was 67% (95% confidence interval [CI], 55-82%) after 1 year and 58% (95% CI 43-71%) after 2 years. The infection-free survival after 1 and 2 years was 94% (95% CI 85-99%) and 84% (95% CI 71-93%) for patients treated with biofilm-active antibiotics, respectively, and 57% (95% CI 39-80%) and 49% (95% CI 28-61%) for those treated without biofilm-active antibiotics, respectively (p = 0.009). Treatment with biofilm-active antibiotics (hazard ratio [HR], 0.23, 95% CI 0.07-0.77), infection with Staphylococcus auras (HR, 2.19, 95% CI 1.04-4.62) and polymicrobial infection (HR, 2.44, 95% CI 1.09-6.04) were significantly associated with treatment outcome. Severe pain was observed more often in patients without biofilm-active antibiotic therapy (49% vs. 18%, p = 0.027). CONCLUSION: Treatment with biofilm-active antibiotics was associated with better treatment outcome and less postoperative pain intensity.

Value of multiplex PCR for detection of antimicrobial resistance in samples retrieved from patients with orthopaedic infections.

BACKGROUND: The performance of multiplex PCR (mPCR) for detection of antimicrobial resistance from clinical isolates is unknown. We assessed the ability of mPCR to analyse resistance genes directly from clinical samples. Patients with orthopedic infections were prospectively included. Phenotypical and genotypical resistance was evaluated in clinical samples (synovial and sonication fluid) where identical pathogens were identified by culture and mPCR. RESULT: A total of 94 samples were analysed, including 60 sonication fluid and 34 synovial fluid samples. For coagulase-negative staphylococcus strains, mPCR detected resistance to oxacillin in 10 of 23 isolates (44%) and to rifampin in none of 6 isolates. For S. aureus isolates, detection rate of oxacillin and rifampin-resistance was 100% (2/2 and 1/1, respectively). Fluoroquinolone-resistance was confirmed by mPCR in all 3 isolates of Enterobacteriaceae, in enterococci resistance to aminoglycoside-high level was detected in 1 of 3 isolates (33%) and in streptococci resistance to macrolides/lincosamides in none of 2 isolates. The overall sensitivity for different pathogens and antimicrobials was 46% and specificity 95%, the median concordance was 80% (range, 57-100%). Full agreement was observed for oxacillin in S. aureus, vancomycin in enterococci, carbapenems/cephalosporins in Enterobacteriaceae and rifampin in Cutibacterium species. CONCLUSION: The overall sensitivity for detection of antimicrobial resistance by mPCR directly from clinical samples was low. False-negative mPCR results occurred mainly in coagulase-negative staphylococci, especially for oxacillin and rifampin. However, the specificity of mPCR was high and a positive result reliably predicted antimicrobial resistance. Including universal primers in the PCR test assay may improve the detection rate but requires additional sequencing step. TRIAL REGISTRATION: www.clinicaltrials.gov No. NCT02530229, registered at 21 August 2015 (retrospectively registered).