What are the age-related factors linked to aseptic revisions in constrained and unconstrained TKA as well as UKA? A register-based study from the German arthroplasty registry (EPRD).

PURPOSE: The implantation rate of total knee arthroplasties (TKA) is continuously growing. Aseptic problems are a major cause of revision. The aim of the following study was to determinate the incidence of aseptic revisions in primary knee arthroplasty as well as aseptic revision rates and influencing factors according to the patients' age and type of procedure. METHODS: Data collection was performed using the German Arthroplasty Registry. Influencing factors were analyzed according to the patients' age and type of procedure. Risk factors were calculated using multiple Log-rank test with the Holm's method. Incidence and comparison of aseptic revisions according to the patients' age and type of procedure were analyzed using Kaplan-Meier-estimates. Cox regression was applied to calculate the hazard ratio. RESULTS: Overall, 300,998 knee arthroplasties with 254,144 (84.4%) unconstrained TKA, 9,993 (3.3%) constrained TKA and 36,861 (12.3%) unicondylar knee arthroplasties (UKA) were analyzed. Patients younger than 65 years suffered a significantly higher aseptic revision rate than older patients (p < 0.0001). After one year, a revision rate of 1.1% was recorded for patients 65-74 years, 1.6% for patients under 65 years, and 1.3% for patients beyond 74 years. After seven years, patients younger than 65 years sustained in 5.0%, patients 65-74 years in 2.9% and patients beyond 74 years in 2.4% revision. In unconstrained TKA, an increased Elixhauser-score (HR = 1,75; HR = 1,54; HR = 1,7; p < 0,001) was a risk factor regardless the age. A TKA volume of 101-250 regardless the age (HR = 0,66; HR = 0,69; HR = 0,79) and > 250 under 75 years (< 65: HR = 0,72; 65-74: HR = 0,78; p = 0,001) were protective for aseptic revision. In UKA, male gender (HR = 0,81; HR = 0,72; HR = 0,57; p < 0,001), a UKA volume ≥ 51 for patients under 75 years (< 65: HR = 0,62; 65-74: HR = 0,59; p = 0,003) as well as cemented UKA for patients younger than 75 years (< 65: HR = 0,37; 65-74: HR = 0,37; p < 0,001) were detected as preventive factors. CONCLUSION: A significant increased rate of aseptic revisions was reported for patients younger than 65 years compared to older patients. An increased Elixhauser score was a risk factor, whereas male and a high volume of performed UKA or TKA could be identified as preventive factors. LEVEL OF EVIDENCE: III, cohort study.

[Low UKA implantation volume, comorbidities, male sex, and implantation of constrained TKA are risk factors for septic revision after knee arthroplasty implantation : A register-based study from the German Arthroplasty Register]. / Geringes UKA-Implantationsvolumen, Komorbiditäten, männliches Geschlecht und die Implantation einer gekoppelten TKA sind Risikofaktoren für septische Revisionen nach Knieprothesenimplantation : Eine registerbasierte Studie aus dem Deutschen Endoprothesenregister (EPRD).

AIM: Periprosthetic joint infection (PJI) is one of the main causes of revision surgeries after total knee arthroplasty (TKA) and unicondylar knee replacement. Patient- and hospital-related risk factors must be evaluated to prevent PJI. This study identifies influencing factors and differences in infection rates between various types of implant. METHODS: The basis for the data is the German Arthroplasty Register (EPRD). Septic revisions were calculated with the aid of Kaplan-Meier estimates, with septic revision surgery defined as the primary endpoint. Patients with constrained and unconstrained TKA or UKA were analysed using the Holm multiple log-rank test and the Cox proportional hazard model. The 300,998 cases of knee arthroplasty analysed included 254,144 (84.4%) unconstrained TKA, 9993 (3.3%) constrained TKA and 36,861 (12.3%) UKA, with a maximum follow-up of 7 years. RESULTS: After 1 year, the PJI rate was 0.5% for UKA and 2.8% for TKA, whereas after 7 years it was 4.5% for UKA and 0.9% for TKA (p < 0.0001). In constrained TKA, the PJI rate was significantly increased compared with unconstrained TKA (p < 0.0001). After 1 year, the PJI rate was 2.0% for constrained TKA and 0.8% for unconstrained TKA, as well as 3.1% and 1.4% respectively after 7 years. Implantation of a constrained TKA (HR = 2.55), male sex (HR = 1.84), an increased Elixhauser Comorbidity Index score (HR = 1.18-1.56) and an implantation volume of less than 25 UKA per year (HR = 2.15) were identified as risk factors for revision surgeries; an Elixhauser Comorbidity Index score of 0 (HR = 0.80) was identified as a preventive factor. CONCLUSIONS: A reduced implantation volume and constrained knee arthroplasty are linked to a higher risk of PJI. Comorbidities (increased Elixhauser Comorbidity Index score), male sex and a low UKA-implantation volume were identified as risk factors for PJI. Patients who fulfil these criteria need specific infection prevention measures. Further analyses are required to investigate the potential influence of prevention and risk factor modification. LEVEL OF EVIDENCE: III.

[Unicondylar knee arthroplasties demonstrate a significantly increased risk of aseptic revisions compared with unconstrained and constrained TKA : Analysis of aseptic revisions after unicondylar and primary total knee arthroplasty of the German Arthroplasty Register]. / Unikondyläre Knieendoprothesen zeigen ein signifikant erhöhtes Risiko für aseptische Revisionen im Vergleich zu ungekoppelten und gekoppelten TKA : Eine Analyse von aseptischen Revisionen nach unikondylärer und primärer totaler Knieendoprothetik des Endoprothesenregisters Deutschland (EPRD).

OBJECTIVE: Owing to the ageing population the implantation rate of total knee arthroplasty (TKA) continues to rise. Aseptic revisions in primary TKA are one of the main causes of revision. The aim of the following study was to determine the incidence of and reasons for aseptic revision in constrained and unconstrained TKA and in unicondylar knee arthroplasty (UKA). METHODS: The data collection was carried out with the help of the German Arthroplasty Register (EPRD). The reasons for aseptic revision surgery were worked out using this. The incidence and the comparison of aseptic revisions were analysed with the aid of Kaplan-Meier estimates. A multiple Chi-squared test with the Holm method was used to identify group differences in collateral ligament deficiencies. RESULTS: In total, 300,998 cases of knee arthroplasties were analysed, of which 254,144 (84.4%) were unconstrained TKA, 9993 (3.3%) were constrained TKA and 36,861 (12.3%) were UKA. The rate of aseptic revisions was significantly increased compared with unconstrained and constrained TKA (p < 0.0001). In constrained TKA, a revision rate of 2.0% for aseptic reasons was reported, whereas in unconstrained TKA 1.1% and in UKA 2.7% revision surgeries were identified. After 7 years the rates of aseptic revisions amounted to 3.3% for constrained TKA, 2.8% for unconstrained TKA and 7.8% for UKA. Ligament instability was the most common cause of aseptic revisions and accounted for 13.7% of unconstrained TKA. In constrained TKA ligament instability led to a revision in 2.8% of cases. In UKA, tibial loosening was identified to be the most common cause of revisions at 14.6%, whereas the progression of osteoarthritis was responsible for 7.9% of revisions. Ligament instability was observed in 14.1% of men compared with 15.9% of women in unconstrained TKA and in UKA in 4.6% of cases for both sexes. CONCLUSION: In patients with UKA the rates of aseptic revision are significantly higher than in unconstrained and constrained TKA. Ligament instability was the most common cause of aseptic revision in unconstrained TKA. In UKA, tibial loosening was the most common cause of revision surgery, whereas the progression of osteoarthritis was the second most common cause. Comparable levels of ligament instability were observed in both sexes. LEVEL OF EVIDENCE:  III, cohort study.

[18F]FDG PET/CT Imaging Is Associated with Lower In-Hospital Mortality in Patients with Pyogenic Spondylodiscitis-A Registry-Based Analysis of 29,362 Cases.

BACKGROUND: While MRI is the primary diagnostic tool for the diagnosis of spondylodiscitis, the role of [18F]-fluorodeoxyglucose ([18F]FDG) PET/CT is gaining prominence. This study aimed to determine the frequency of [18F]FDG PET/CT usage and its impact on the in-hospital mortality rate in patients with spondylodiscitis, particularly in the geriatric population. METHODS: We conducted a Germany-wide cross-sectional study from 2019 to 2021 using an open-access, Germany-wide database, analyzing cases with ICD-10 codes M46.2-, M46.3-, and M46.4- ('Osteomyelitis of vertebrae', 'Infection of intervertebral disc (pyogenic)', and 'Discitis unspecified'). Diagnostic modalities were compared for their association with in-hospital mortality, with a focus on [18F]FDG PET/CT. RESULTS: In total, 29,362 hospital admissions from 2019 to 2021 were analyzed. Of these, 60.1% were male and 39.9% were female, and 71.8% of the patients were aged 65 years and above. The overall in-hospital mortality rate was 6.5% for the entire cohort and 8.2% for the geriatric subgroup (p < 0.001). Contrast-enhanced (ce) MRI (48.1%) and native CT (39.4%) of the spine were the most frequently conducted diagnostic modalities. [18F]FDG PET/CT was performed in 2.7% of cases. CeCT was associated with increased in-hospital mortality (OR = 2.03, 95% CI: 1.90-2.17, p < 0.001). Cases with documented [18F]FDG PET/CT showed a lower frequency of in-hospital deaths (OR = 0.58, 95% CI: 0.18-0.50; p = 0.002). This finding was more pronounced in patients aged 65 and above (OR = 0.42, 95% CI: 0.27-0.65, p = 0.001). CONCLUSIONS: Despite its infrequent use, [18F]FDG PET/CT was associated with a lower in-hospital mortality rate in patients with spondylodiscitis, particularly in the geriatric cohort. This study is limited by only considering data on hospitalized patients and relying on the assumption of error-free coding. Further research is needed to optimize diagnostic approaches for spondylodiscitis.

Multidisciplinary Teams in Musculoskeletal Infection - From a Pathologist's Perspective.

Multidisciplinary team (MDT) meetings have emerged as a promising approach for the treatment of cancer patients. These meetings involve a team of healthcare professionals from different disciplines working together to develop a holistic, patient-centered treatment. Although MDT meetings are well established in oncology, they play a minor role in other diseases. Recent evidence suggests that the implementation of MDT meetings can improve patient outcomes in musculoskeletal infections. The aim of this retrospective, observational study was to present the agenda of our multidisciplinary limb board including live microscopy with a special focus on the pathologist's role. The descriptive analysis of the limb board included 66 cases receiving live microscopy at the meeting and a total of 124 histopathological findings and 181 stainings. We could elucidate that pathologists seem to play an important role especially in clarifying the correct diagnosis. In 80.3 % of the findings, the pathologist specified the clinical diagnosis of the requesting physician leading to a consensus-based treatment plan for each patient. The implementation of MDT meetings including live microscopy in patients with musculoskeletal infections holds potential benefits, such as improved communication, scientific collaboration, and raising clinicians' awareness and understanding of histopathology findings. However, potential challenges, such as organizational effort and technical prerequisites should be considered.

Repetitive combined doses of bacteriophages and gentamicin protect against Staphylococcus aureus implant-related infections in Galleria mellonella.

Aims: Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the Staphylococcus aureus phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in Galleria mellonella. Methods: For the haematogenous infection, G. mellonella larvae were implanted with a Kirschner wire (K-wire), infected with S. aureus, and subsequently phages and/or gentamicin were administered. For the early-stage biofilm implant infection, the K-wires were pre-incubated with S. aureus suspension before implantation. After 24 hours, the larvae received phages and/or gentamicin. In both models, the larvae also received daily doses of phages and/or gentamicin for up to five days. The effect was determined by survival analysis for five days and quantitative culture of bacteria after two days of repetitive doses. Results: In the haematogenous infection, a single combined dose of phages and gentamicin, and repetitive injections with gentamicin or in combination with phages, resulted in significantly improved survival rates. In the early-stage biofilm infection, only repetitive combined administration of phages and gentamicin led to a significantly increased survival. Additionally, a significant reduction in number of bacteria was observed in the larvae after receiving repetitive doses of phages and/or gentamicin in both infection models. Conclusion: Based on our results, a single dose of the combination of phages and gentamicin is sufficient to prevent a haematogenous S. aureus implant-related infection, whereas gentamicin needs to be administered daily for the same effect. To treat early-stage S. aureus implant-related infection, repetitive doses of the combination of phages and gentamicin are required.

Case report: Local bacteriophage therapy for fracture-related infection with polymicrobial multi-resistant bacteria: hydrogel application and postoperative phage analysis through metagenomic sequencing.

Fracture-related infections can be challenging, particularly with concomitant severe bone defects and multi-resistant microorganisms. We present a case of a 42-year-old patient with a fracture-related infection following a war injury from a gunshot, resulting in a 12-cm subtrochanteric segmental bone defect and the detection of four different multi-resistant Gram-negative bacteria. Due to antibiotic drug resistance, treatment with bacteriophages was considered. Phage susceptibility testing revealed the activity of a commercially available bacteriophage cocktail (Intesti bacteriophage, Eliava Institute, Tbilisi, Georgia). This phage cocktail was included in a modified two-stage Masquelet technique. During the first intervention, the bone was debrided and samples for microbiological and phage testing were harvested. The indwelling intramedullary rod was removed, and the bone defect was filled with a PMMA spacer loaded with colistin and the bone stabilized with a plate. During the second procedure, the PMMA spacer was removed and a silver-coated angular stable plate was implanted. The bone defect was filled with a fibular autograft and allograft cancellous bone chips. At the end of the procedure, the Intesti bacteriophage cocktail was injected into a DAC hydrogel and this bacteriophage hydrogel composite was then put onto the angular stable plate. Postoperatively the wound fluid was collected over 72 h, and high-throughput metagenomic sequencing was performed. This showed a time-dependent release of the bacteriophages in the wound fluid, with a relatively high concentration after 12 h, decreasing to DNA copies of 0 after 72 h. Furthermore, we have assessed the release of phages from DAC gel and the effect of DAC gel on the phages in vitro. The results showed a stable and rapid release of phages from the DAC gel (~1×103 PFU/mL). The clinical course of the patient showed no relapse of the infection with good bone consolidation of the bone defect after 1 year without the need for any surgical revision. To the best of our knowledge, this is the first case that shows the detection of bacteriophage DNA copies by high-throughput metagenomics sequencing in a patient with a complex fracture-related infection. Successful treatment of this case encourages further investigation of bacteriophage therapy in patients with complex bone and joint infections.

Managing more than bones: the psychological impact of a recurrent fracture-related infection.

Aims: Fracture-related infections (FRIs) are a devastating complication of fracture management. However, the impact of FRIs on mental health remains understudied. The aim of this study was a longitudinal evaluation of patients' psychological state, and expectations for recovery comparing patients with recurrent FRI to those with primary FRI. Methods: A prospective longitudinal study was conducted at a level 1 trauma centre from January 2020 to December 2022. In total, 56 patients treated for FRI were enrolled. The ICD-10 symptom rating (ISR) and an expectation questionnaire were assessed at five timepoints: preoperatively, one month postoperatively, and at three, six, and 12 months. Results: Recurrent FRI cases consistently exceeded the symptom burden threshold (0.60) in ISR scores at all assessment points. The difference between preoperative-assessed total ISR scores and the 12-month follow-up was not significant in either group, with 0.04 for primary FRI (p = 0.807) and 0.01 for recurrent FRI (p = 0.768). While primary FRI patients showed decreased depression scores post surgery, recurrent FRI cases experienced an increase, reaching a peak at 12 months (1.92 vs 0.94; p < 0.001). Anxiety scores rose for both groups after surgery, notably higher in recurrent FRI cases (1.39 vs 1.02; p < 0.001). Moreover, patients with primary FRI reported lower expectations of returning to normal health at three (1.99 vs 1.11; p < 0.001) and 12 months (2.01 vs 1.33; p = 0.006). Conclusion: The findings demonstrate the significant psychological burden experienced by individuals undergoing treatment for FRI, which is more severe in recurrent FRI. Understanding the psychological dimensions of recurrent FRIs is crucial for comprehensive patient care, and underscores the importance of integrating psychological support into the treatment paradigm for such cases.

Midterm survival and risk factor analysis in patients with pyogenic vertebral osteomyelitis: a retrospective study of 155 cases.

Background: Pyogenic vertebral osteomyelitis (VO) represents a clinical challenge and is linked to substantial morbidity and mortality. This study aimed to examine mortality as well as potential risk factors contributing to in-hospital mortality among patients with VO. Methods: This retrospective analysis involved patients receiving treatment for VO at University Regensburg in Germany from January 1, 2000, to December 3, 2020. It included in-hospital mortality rate, comorbidities and pathogens. Patients were identified using ICD-10 diagnosis codes: M46.2, M46.3, M46.4, and M46.5. Kaplan-Meier probability plots and odds ratios (OR) for mortality were calculated. Results: Out of the total cohort of 155 patients with VO, 53 patients (34.1%) died during a mean follow-up time of 87.8 ± 70.8 months. The overall mortality was 17.2% at one year, 19.9% at two years and 28.3% at five years. Patients with congestive heart failure (p = 0.005), renal disease (p < 0.001), symptoms of paraplegia (p = 0.029), and sepsis (p = 0.006) demonstrated significantly higher overall mortality rates. In 56.1% of cases, pathogens were identified, with Staphylococcus aureus (S. aureus) and other unidentified pathogens being the most common. Renal disease (OR 1.85) and congestive heart failure (OR 1.52) were identified as significant risk factors. Conclusion: Early assessment of the specific risk factors for each patient may prove beneficial in the management and treatment of VO to reduce the risk of mortality. These findings demonstrate the importance of close monitoring of VO patients with underlying chronic organ disease and early identification and treatment of sepsis. Prioritizing identification of the exact pathogens and antibiotic sensitivity testing can improve outcomes for patients in this high-risk group.

Low implantation volume, comorbidities, male sex and implantation of constrained TKA identified as risk factors for septic revision in knee arthroplasty: A register-based study from the German Arthroplasty Registry.

PURPOSE: Periprosthetic joint infection (PJI) is a major cause of revision surgery after total knee arthroplasty (TKA) and unicondylar knee arthroplasty (UKA). Patient- and hospital-related risk factors need to be assessed to prevent PJI. This study identifies influential factors and differences in infection rates between different implant types. METHODS: Data were obtained from the German Arthroplasty Registry. Septic revisions were calculated using Kaplan-Meier estimates with septic revision surgery as the primary endpoint. Patients with constrained and unconstrained TKA or UKA were analysed using Holm's multiple log-rank test and Cox's proportional hazards ratio. The 300,998 cases of knee arthroplasty analysed included 254,144 (84.4%) unconstrained TKA, 9993 (3.3%) constrained TKA and 36,861 (12.3%) UKA with a maximum follow-up of 7 years. RESULTS: At 1 year, the PJI rate was 0.5% for UKA and 2.8% for TKA, whereas at 7 years, the PJI rate was 4.5% for UKA and 0.9% for TKA (p < 0.0001). The PJI rate significantly increased for constrained TKA compared to unconstrained TKA (p < 0.0001). The PJI rate was 2.0% for constrained TKA and 0.8% for unconstrained TKA at 1 year and 3.1% and 1.4% at 7 years. Implantation of a constrained TKA (hazard ratio [HR] = 2.55), male sex (HR = 1.84), increased Elixhauser score (HR = 1.18-1.56) and implant volume of less than 25 UKA per year (HR = 2.15) were identified as risk factors for revision surgery; an Elixhauser score of 0 (HR = 0.80) was found to be a preventive factor. CONCLUSIONS: Reduced implant volume and constrained knee arthroplasty are associated with a higher risk of PJI. Comorbidities (elevated Elixhauser score), male sex and low UKA implant volume have been identified as risk factors for PJI. Patients who meet these criteria require specific measures to prevent infection. Further research is required on the potential impact of prevention and risk factor modification. LEVEL OF EVIDENCE: Level III.

Unicondylar knee arthroplasty demonstrating a significant increased risk for aseptic revisions compared to unconstrained and constrained total knee arthroplasty: An analysis of aseptic revisions after unicondylar and primary total knee arthroplasty of the German Arthroplasty Registry.

PURPOSE: Due to ageing population, the implantation rate of total knee arthroplasties (TKAs) is continuously growing. Aseptic revisions in primary knee arthroplasty are a major cause of revision. The aim of the following study was to determinate the incidence and reasons of aseptic revisions in constrained and unconstrained TKA, as well as in unicondylar knee arthroplasties (UKAs). METHODS: Data collection was performed using the German Arthroplasty Registry. Reasons for aseptic revisions were calculated. Incidence and comparison of aseptic revisions were analysed using Kaplan-Meier estimates. A multiple χ2 test with Holm's method was used to detect group differences in ligament ruptures. RESULTS: Overall, 300,998 cases of knee arthroplasty with 254,144 (84.4%) unconstrained TKA, 9993 (3.3%) constrained TKA and 36,861 (12.3%) UKA were analysed. Aseptic revision rate in UKA was significantly increased compared to unconstrained and constrained TKA (p < 0.0001). In constrained TKA, a 2.0% revision rate for aseptic reasons were reported after 1 year, while in unconstrained TKA 1.1% and in UKA, 2.7% of revisions were identified. After 7 years in constrained TKA 3.3%, in unconstrained TKA 2.8%, and in UKA 7.8% sustained aseptic revision. Ligament instability was the leading cause of aseptic revision accounting for 13.7% in unconstrained TKA. In constrained TKA, 2.8% resulted in a revision due to ligament instability. In the UKA, the most frequent cause of revisions was tibial loosening, accounting for 14.6% of cases, while progression of osteoarthritis accounted for 7.9% of revisions. Ligament instability was observed in 14.1% of males compared to 15.9% of females in unconstrained TKA and in 4.6% in both genders in UKA. CONCLUSION: In patients with UKA, aseptic revision rates are significantly higher compared to unconstrained and constrained TKA. Ligament instability was the leading cause of aseptic revision in unconstrained TKA. In UKA, the most frequent cause of revisions was tibial loosening, while progression of osteoarthritis was the second most frequent cause of revisions. Comparable levels of ligament instability were observed in both sexes. LEVEL OF EVIDENCE: Level III, cohort study.

Waning waves of mood: The declining trend of hospitalized patients with affective disorders in Germany.

INTRODUCTION: Affective disorders profoundly affect individuals' emotional well-being and quality of life. This study investigates the epidemiology of affective disorders in Germany from 2011 to 2021, focusing on incidence rates, age- and sex-standardized rates, and developmental trends. METHODS: Using nationwide data of ICD-10 diagnosis codes from 2011 to 2021, this cross-sectional study analyzed inpatient cases of affective disorders in individuals aged 20 years or older. Age- and sex-standardized incidence rates were calculated based on the population size of each birth cohort in the 16 German federal states. Incidence rate ratios (IRRs) for 2011 to 2021 and 2019 to 2021 were compared with a two-sample z-test. RESULTS: Between 2011 and 2021, F30 (manic episode) showed a decline of 42.8 % to an incidence of 4.9 per 100,000 inhabitants, even though not statistically significant (p = 0.322). F31 (bipolar affective disorder) remained relatively stable with a reduction of 15.3 % to an incidence of 13.6 per 100,000 inhabitants in 2021 (p = 0.653). F32 (depressive episode) decreased statistically significant by 25.7 % to an incidence of 64.1 per 100,000 inhabitants (p = 0.072). F33 (recurrent depressive disorder) slightly increased by 18.3 % to an incidence of 94.6 per 100,000 inhabitants (p = 0.267). No statistically significant differences were found when comparing the COVID-19 pandemic year 2021 to 2019 incidences (p ≥ 0.529). CONCLUSION: The study provides valuable insights into the changing landscape of affective disorders in Germany over the past decade. The observed decline in incidence rates underscores the importance of continued efforts to promote mental health awareness and access to care.

In-hospital mortality of patients with periprosthetic joint infection.

Aims: Periprosthetic joint infection (PJI) demonstrates the most feared complication after total joint replacement (TJR). The current work analyzes the demographic, comorbidity, and complication profiles of all patients who had in-hospital treatment due to PJI. Furthermore, it aims to evaluate the in-hospital mortality of patients with PJI and analyze possible risk factors in terms of secondary diagnosis, diagnostic procedures, and complications. Methods: In a retrospective, cross-sectional study design, we gathered all patients with PJI (International Classification of Diseases (ICD)-10 code: T84.5) and resulting in-hospital treatment in Germany between 1 January 2019 and 31 December 2022. Data were provided by the Institute for the Hospital Remuneration System in Germany. Demographic data, in-hospital deaths, need for intensive care therapy, secondary diagnosis, complications, and use of diagnostic instruments were assessed. Odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality were calculated. Results: A total of 52,286 patients were included, of whom 1,804 (3.5%) died. Hypertension, diabetes mellitus, and obesity, the most frequent comorbidities, were not associated with higher in-hospital mortality. Cardiac diseases as atrial fibrillation, cardiac pacemaker, or three-vessel coronary heart disease showed the highest risk for in-hospital mortality. Postoperative anaemia occurred in two-thirds of patients and showed an increased in-hospital mortality (OR 1.72; p < 0.001). Severe complications, such as organ failure, systemic inflammatory response syndrome (SIRS), or septic shock syndrome showed by far the highest association with in-hospital mortality (OR 39.20; 95% CI 33.07 to 46.46; p < 0.001). Conclusion: These findings highlight the menace coming from PJI. It can culminate in multi-organ failure, SIRS, or septic shock syndrome, along with very high rates of in-hospital mortality, thereby highlighting the vulnerability of these patients. Particular attention should be paid to patients with cardiac comorbidities such as atrial fibrillation or three-vessel coronary heart disease. Risk factors should be optimized preoperatively, anticoagulant therapy stopped and restarted on time, and sufficient patient blood management should be emphasized.

Direct Hospital Costs per Case of Periprosthetic Hip and Knee Joint Infections in Europe - A Systematic Review.

BACKGROUND: The rise of periprosthetic joint infections (PJIs) due to aging populations is steadily increasing the number of arthroplasties and treatment costs. This study analyzed the direct health care costs of PJI for total hip arthroplasty and total knee arthroplasty (TKA) in Europe. METHODS: The databases PubMed, Scopus, Embase, Cochrane, and Google Scholar were systematically screened for direct costs of PJI in Europe. Publications that defined the joint site and the procedure performed were further analyzed. Mean direct health care costs were calculated for debridement, antibiotics, and implant retention (DAIR), one-stage, and 2-stage revisions for hip and knee PJI, respectively. Costs were adjusted for inflation rates and reported in US-Dollar (USD). RESULTS: Of 1,374 eligible publications, 12 manuscripts were included in the final analysis after an abstract and full-text review. Mean direct costs of $32,933 were identified for all types of revision procedures for knee PJI. The mean direct treatment cost including DAIR for TKA after PJI was $19,476. For 2-stage revisions of TKA, the mean total cost was $37,980. For all types of hip PJI procedures, mean direct hospital costs were $28,904. For hip DAIR, one-stage and 2-stage treatment average costs of $7,120, $44,594, and $42,166 were identified, respectively. CONCLUSIONS: Periprosthetic joint infections are associated with substantial direct health care costs. As detailed reports on the cost of PJI are scarce and of limited quality, more detailed financial data on the cost of PJI treatment are urgently required.

What Are the Mortality, Infection, and Nonunion Rates After Periprosthetic Femoral Fractures in the United States?

BACKGROUND: Periprosthetic femoral fractures are a serious complication that put a high burden on patients. However, comprehensive analyses of their incidence, mortality, and complication rates based on large-registry data are scarce. QUESTIONS/PURPOSES: In this large-database study, we asked: (1) What is the incidence of periprosthetic femoral fractures in patients 65 years and older in the United States? (2) What are the rates of mortality, infection, and nonunion, and what factors are associated with these outcomes? METHODS: In this retrospective, comparative, large-database study, periprosthetic femoral fractures occurring between January 1, 2010, and December 31, 2019, were identified from Medicare physician service records encompassing services rendered in medical offices, clinics, hospitals, emergency departments, skilled nursing facilities, and other healthcare institutions from approximately 2.5 million enrollees. These were grouped into proximal, distal, and shaft fractures after TKA and THA. We calculated the incidence of periprosthetic femur fractures by year. Incidence rate ratios (IRR) were calculated by dividing the incidence in 2019 by the incidence in 2010. The Kaplan-Meier method with Fine and Gray subdistribution adaptation was used to calculate the cumulative incidence rates of mortality, infection, and nonunion. Semiparametric Cox regression was applied with 23 measures as covariates to determine factors associated with these outcomes. RESULTS: From 2010 to 2019, the incidence of periprosthetic femoral fractures increased steeply (TKA for distal fractures: IRR 3.3 [95% CI 1 to 9]; p = 0.02; THA for proximal fractures: IRR 2.3 [95% CI 1 to 4]; p = 0.01). One-year mortality rates were 23% (95% CI 18% to 28%) for distal fractures treated with THA, 21% (95% CI 19% to 24%) for proximal fractures treated with THA, 22% (95% CI 19% to 26%) for shaft fractures treated with THA, 21% (95% CI 18% to 25%) for distal fractures treated with TKA , 22% (95% CI 17% to 28%) for proximal fractures treated with TKA, and 24% (95% CI 19% to 29%) for shaft fractures treated with TKA. The 5-year mortality rate was 63% (95% CI 54% to 70%) for distal fractures treated with THA, 57% (95% CI 54% to 62%) for proximal fractures treated with THA, 58% (95% CI 52% to 63%) for shaft fractures treated with THA, 57% (95% CI 52% to 62%) for distal fractures treated with TKA , 57% (95% CI 49% to 65%) for proximal fractures treated with TKA, and 57% (95% CI 49% to 64%) for shaft fractures treated with TKA. Age older than 75 years, male sex, chronic obstructive pulmonary disease (HR 1.48 [95% CI 1.32 to 1.67] after THA and HR 1.45 [95% CI 1.20 to 1.74] after TKA), cerebrovascular disease after THA, chronic kidney disease (HR 1.28 [95% CI 1.12 to 1.46] after THA and HR 1.50 [95% CI 1.24 to 1.82] after TKA), diabetes mellitus, morbid obesity, osteoporosis, and rheumatoid arthritis were clinical risk factors for an increased risk of mortality. Within the first 2 years, fracture-related infections occurred in 5% (95% CI 4% to 7%) of patients who had distal fractures treated with THA, 5% [95% CI 5% to 6%]) of patients who had proximal fractures treated with THA, 6% (95% CI 5% to 7%) of patients who had shaft fractures treated with THA, 6% (95% CI 5% to 7%) of patients who had distal fractures treated with TKA , 7% (95% CI 5% to 9%) of patients who had proximal fractures treated with TKA, and 6% (95% CI 4% to 8%) of patients who had shaft fractures treated with TKA. Nonunion or malunion occurred in 3% (95% CI 2% to 4%) of patients with distal fractures treated with THA, 1% (95% CI 1% to 2%) of patients who had proximal fractures treated with THA, 2% (95% CI 1% to 3%) of patients who had shaft fractures treated with THA, 4% (95% CI 3% to 5%) of those who had distal fractures treated with TKA, , 2% (95% CI 1% to 4%) of those who had proximal fractures treated with TKA, and 3% (95% CI 2% to 4%) of those who had shaft fractures treated with TKA. CONCLUSION: An increasing number of periprosthetic fractures were observed during the investigated period. At 1 and 5 years after periprosthetic femur fracture, there was a substantial death rate in patients with Medicare. Conditions including cerebrovascular illness, chronic kidney disease, diabetes mellitus, morbid obesity, osteoporosis, and rheumatoid arthritis are among the risk factors for increased mortality. After the surgical care of periprosthetic femur fractures, the rates of fracture-related infection and nonunion were high, resulting in a serious risk to affected patients. Patient well-being can be enhanced by an interdisciplinary team in geriatric traumatology and should be improved to lower the risk of postoperative death. Additionally, it is important to ensure that surgical measures to prevent fracture-related infections are followed diligently. Furthermore, there is a need to continue improving implants and surgical techniques to avoid often-fatal complications such as fracture-associated infections and nonunion, which should be addressed in further studies. LEVEL OF EVIDENCE: Level III, therapeutic study.

The Potential of Bacteriophage Therapy as an Alternative Treatment Approach for Antibiotic-Resistant Infections.

OBJECTIVE: This study aimed to provide a comprehensive overview of the current state of the literature on the therapeutical application of bacteriophages. METHODS: First, a bibliometric analysis was performed using the database Web of Science to determine annual number of publications and citations. Second, a systematic literature review was conducted on randomized-controlled trials (RCTs) of phage therapy in PubMed. RESULTS: Over the past decade, the number of publications on bacteriophage therapy increased more than fourfold with 212 articles in 2011 and 739 in 2022. The systematic search in PubMed yielded 7 RCTs eligible for inclusion, reporting on a total of 418 participants. Identified indications in this study included bacterial diarrhea, urinary tract infections, infected burn wounds, chronic otitis, chronic venous leg ulcers, and chronic rhinosinusitis. In three studies, mild to moderate adverse events were reported in 10/195 participants (5.1%). Three of the studies reported a statistically significant difference in outcomes comparing phage therapy with standard of care or placebo. CONCLUSION: Phage therapy has gained increasing interest over the years. RCTs on different indications suggest the safety of phage therapy; however, reasons why phage therapy is not yet well accepted are limitations in the study designs. For a successful translation into clinical practice researchers and clinicians should learn from the earlier experiences and consider issues such as the quality of phage preparation, sensitivity testing, titer and dosages, as well as access to the infection site and stability for standardized protocols and future trials.

Fracture-Related Infection-Epidemiology, Etiology, Diagnosis, Prevention, and Treatment.

BACKGROUND: Fracture-related infection (FRI) is a challenge to physicians and other workers in health care. In 2018, there were 7253 listed cases of FRI in Germany, corresponding to an incidence of 10.7 cases per 100 000 persons per year. METHODS: This review is based on pertinent publications retrieved from a search in PubMed with the search terms "fracture," "infection," "guideline," and "consensus." Aside from the primary literature, international guidelines and consensus recommendations were evaluated as well. RESULTS: FRI arise mainly from bacterial contamination of the fracture site. Staphylococcus aureus is the most commonly detected pathogen. The treatment is based on surgery and antibiotics and should be agreed upon by an interdisciplinary team; it is often difficult because of biofilm formation. Treatment options include implant-preserving procedures and single-stage, two-stage, or multi-stage implant replacement. Treatment failure occurs in 10.3% to 21.4% of cases. The available evidence on the efficacy of various treatment approaches is derived mainly from retrospective cohort studies (level III evidence). Therefore, periprosthetic joint infections and FRI are often discussed together. CONCLUSION: FRI presents an increasing challenge. Preventive measures should be optimized, and the treatment should always be decided upon by an interdisciplinary team. Only low-level evidence is available to date to guide diagnostic and treatment decisions. High-quality studies are therefore needed to help us meet this challenge more effectively.

Healing beyond the joint: Addressing mental health in periprosthetic joint infection in a prospective longitudinal study.

OBJECTIVE: Periprosthetic joint infection (PJI) is a devastating complication following joint replacement surgeries. While the somatic impacts of PJI have been extensively explored, the influence on mental health remains understudied. This study aimed to longitudinally assess the psychological burden, quality of life, and expectations in individuals undergoing treatment for PJI. METHODS: A prospective study was conducted at a German trauma center between January 2020 and December 2022. Patients diagnosed with PJI (n = 29, mean age 71.4 ± 8.8 years) were assessed at five timepoints, within one week before revision surgery, one month, three, six, and twelve months postoperatively. Outcomes included the ICD-10 symptom-rating (ISR), German Short-Form 36 (SF-36), European Quality of Life 5 Dimensions (EQ-5D), and an expectation questionnaire. RESULTS: Psychological scores exhibited significant upward trends over time. The ISR score increased from 0.55 preoperatively to 0.87 at the 12-month follow-up (p = 0.002), surpassing the clinically relevant threshold. Depression and anxiety scores peaked at 6 months (1.6, p = 0.005) and 12 months (1.12, p = 0.001), respectively. Quality of life, measured by SF-36, showed stable physical component summary scores but declining mental component summary scores. Patients' expectations of returning to normal health consistently decreased (p = 0.009). CONCLUSION: Patients undergoing treatment for PJI experience significant psychological burden, with implications for quality of life and expectations of recovery. The findings underscore the importance of addressing psychological well-being in the management of PJI and emphasize the need for comprehensive care strategies that encompass both somatic and psychological dimensions.

Fracture related Infection - Challenges in definition and diagnosis.

In the field of orthopedics and trauma surgery, the rise of periprosthetic joint infections following joint replacement and fracture-related infections (FRI) has become a growing concern. The recent establishment of a definitive definition for FRI aimed to standardize diagnosis and treatment approaches while considering unique aspects of implant-associated infections in the presence of concomitant bone fractures. Diagnosing FRI can be challenging due to the varied clinical symptoms, and confirmatory criteria may not always be evident, necessitating additional diagnostic measures. Blood markers like leukocyte count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) have limited specificity. Although novel biomarkers such as D-dimer and interleukin-6 (IL-6) show potential, they require further investigation. The use of microbiological diagnostics with tissue samples and sonication has improved pathogen detection. Cross-sectional imaging techniques like CT scans and MRI scans help evaluate bone status, soft tissue infiltration, and abscesses. Nuclear medicine techniques are accurate but may not always be practical in routine clinical practice. Histopathological interpretation for FRI remains less standardized compared to periprosthetic joint infections (PJI). FRI diagnosis requires the identification of visible microorganisms in deep tissue specimens and the quantification of polymorphonuclear neutrophils (PMNs). The defined concept of FRI has opened doors for better diagnostic and treatment approaches. However, challenges persist, especially in preoperative diagnosis, particularly for cases with unclear clinical presentations. Future endeavors aimed at optimizing diagnostic procedures and establishing a histopathological classification for FRI could lead to improved treatment recommendations and outcomes.