Risk factors for in-hospital mortality in geriatric patients aged 80 and older with axis fractures: a nationwide, cross-sectional analysis of concomitant injuries, comorbidities, and treatment strategies in 10,077 cases.

PURPOSE: To investigate the association between treatment, comorbidities, concomitant injuries, and procedures with in-hospital mortality in patients aged 80 years or older with axis fractures. METHODS: Data were extracted from the German InEK (Institut für das Entgeltsystem im Krankenhaus) GmbH database (2019-2021) for patients aged 80 years or older with axis fractures and the in-hospital mortality rate was calculated. Differences in comorbidities and concomitant diseases and injuries were analyzed using the Chi-square test. In surgically treated patients, odds ratios (OR) with 95% confidence intervals (95% CI) were used to analyze potential risk factors for in-hospital mortality. RESULTS: Among 10,077 patients, the in-hospital mortality rate was 8.4%, with no significant difference between surgically (9.4%) and non-surgically treated patients (7.9%; p = 0.103). The most common comorbidities were essential hypertension (67.3%), atrial fibrillation (28.2%), and chronic kidney disease (23.3%), while the most common concomitant injuries were head and face wounds (25.9%), concussions (12.8%), and atlas fractures (11.6%). In surgically treated patients, spinal cord injury (OR = 4.62, 95% CI: 2.23-9.58), acute renal failure (OR = 3.20, 95% CI: 2.26-4.53), and acute bleeding anemia (OR = 2.06, 95% CI: 1.64-2.59) were associated with increased in-hospital mortality (all p < 0.01). Screw-rod-system fixation of one segment (OR = 0.74, 95% CI: 0.56-0.97) and intraoperative navigation (OR = 0.45, 95% CI: 0.16-0.71) were identified as potential protective factors (both p < 0.05). CONCLUSION: Comprehensive geriatric assessment and optimization of comorbidities during treatment are crucial. The indication for surgical treatment must be carefully individualized. Future studies should focus on the choice of surgical technique, perioperative blood management, and intraoperative navigation as potential protective factors.

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.

No effect of dislocation status at arrival in emergency department on outcome of knee joint dislocations.

PURPOSE: Knee dislocation is a rare but severe injury of the lower extremities. The aim of this study was to report on the epidemiology, diagnostics and treatment of such injuries and to identify negative predictors of clinical outcomes. METHODS: This retrospective analysis included all knee dislocations treated at a Level I Trauma Centre in Germany between 2009 and 2021. Medical records were categorised, collected and analysed in a standardised manner. A follow-up visit 1 year after the injury focused on limitations in knee mobility. RESULTS: A total of 120 knee dislocations were included in the study. 29.3% of patients presented to the emergency department with a dislocated joint, and 17.5% (n = 21) had a neurovascular lesion. At follow-up 12 months after the injury, 65.8% of the patients reported limitations in the range of motion, and 11.7% (n = 14) reported severe limitations in daily activities. Site infections due to surgery occurred in 3.3% of patients. Increased body weight (r = 0.294; p < 0.001 and r = 0.259; p = 0.004), an increased body mass index above 25 kg/m2 (body mass index, r = 0.296; p < 0.001 and r = 0.264; p = 0.004) and deficits in peripheral perfusion as well as sensory and motor function (r = 0.231; p = 0.040 and r = -0.192; p = 0.036) were found to be negative predictive factors for clinical outcome. For posttraumatic neurovascular injury, lack of peripheral perfusion, insufficient sensory and motor function (r = -0.683; p < 0.0001), as well as a higher Schenck grade (r = 0.320; p = 0.037), were identified as independent risk factors. The status of dislocation at the site of the accident and on arrival at the emergency department had no impact on the outcome or neurovascular injury. CONCLUSION: Knee dislocation is a rare injury with a high rate of severe complications such as neurovascular lesions. In particular, the initial status of neurovascular structures and injury classification showed a relevant negative correlation with the posttraumatic status of nerves and vessels. In particular, patients with these characteristics need close monitoring to prevent negative long-term consequences. 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.

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.

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.

Risk of surgical site infection after hip hemiarthroplasty of femoral neck fractures: a systematic review and meta-analysis.

INTRODUCTION: Surgical site infection (SSI) is a major complication following hemiarthroplasty surgery for displaced neck of femur fractures. Our aim is to systematically analyse relevant peer-reviewed studies for recent clinical information on the quantitative risk of surgical site infection (SSI) after hemiarthroplasty (HA) of hip fracture patients and on the factors which influence the SSI rates. METHODS: A comprehensive search of electronic databases (PubMed, Cochrane) was performed for clinical articles published between 2005 and 2023 and systematically reviewed with a defined list of inclusion and exclusion criteria. The methodology was undertaken and reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement checklist, while the detailed search strings and study protocol were published in PROSPERO (CRD42023458150). The pooled risks of SSIs were calculated in both primary and subgroup analyses. RESULTS: The primary analysis showed a pooled superficial SSI rate after hemiarthroplasty of 1.3% (95% confidence interval (CI) 0.71; 2.04) from 17 studies with 29,288 patients and a deep SSI rate of 2.14% (1.87; 2.42) from 29 studies with 192,392 patients. Higher infection rates were observed with longer follow-up periods for deep SSI: pooled rates increased from 1.24% (0.73; 1.87) at 1 month to 2.64% (2.03; 3.31) at 12 months. Additionally, studies using defined criteria for infection diagnosis reported higher rates compared to undefined criteria: pooled deep SSI rates were 2.91% (1.40; 4.92) vs. 0.62% (0.34; 0.96) for defined vs. undefined criteria respectively, and 3.18% (2.23; 4.29) vs. 1.7% (1.44; 1.99) for superficial SSI. CONCLUSIONS: The results of this study demonstrate a substantial SSI risk and a high variability of the infection rates following hemiarthroplasty for hip fracture patients. A standardization of infection criteria and an extended follow-up period are advisable and should be considered in guidelines aimed at improving the standard of care for these patients.

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.

Long-term patient-related quality of life outcomes and ICD-10 symptom rating (ISR) of patients with pyogenic vertebral osteomyelitis: What is the psychological impact of this life-threatening disease?

PURPOSE: We aimed to evaluate the long-term impact of the treatment of pyogenic vertebral osteomyelitis (VO) on functional outcomes and patients' quality of life (QoL) with a special focus on psychological well-being. METHODS: A total of 156 patients with VO with a minimum clinical follow-up of 12 months were retrospectively identified and asked to participate. Patient-reported outcome measures were evaluated with the EuroQol five-dimension questionnaire (EQ-5D) and German Short-Form 36 (SF-36) outcome instruments as well as with an ICD-10 based symptom rating (ISR) and compared to normative data. Spine-specific outcomes were assessed with the Core Outcome Measure Index and the Oswestry disability index (ODI) or the Neck disability index (NDI), respectively. RESULTS: From n = 156 eligible patients, n = 129 patients could be contacted and n = 40 returned questionnaires, yielding a response rate of 31.0%. The mean time from hospital discharge to follow-up was 83.0 ± 3.8 (13-193) months. Spine-specific outcomes showed mild to moderate disability. The mean physical health component score of the SF-36 (37.1 ± 16.7), the mean mental health component score (38.2 ± 14.0) and the mean EQ-5D VAS rating (57.1 ± 21.5) were significantly lower in comparison with the scores of an age-matched reference population (all p < 0.05). The mean total score of the ISR was 0.53 ± 0.23. On average, the cohort did not cross the threshold of clinically relevant symptom burden on any subscale. CONCLUSION: Even almost seven years on average after completed treatment of VO, patients report impaired QoL. Assessment of psychological disorders should be implemented in clinical practice and future prospective studies.

Staphylococcus aureus From an Acute Fracture-related Infection Displays Important Bacteriological and Histopathologic Differences From a Chronic Equivalent in a Murine Bone Infection Model.

BACKGROUND: Staphylococcus aureus is the leading pathogen in fracture-related infection. Previous in vitro experiments, in vivo testing in wax moth larvae, and genomic analysis of clinical S. aureu s isolates from fracture-related infection identified low-virulence (Lo-SA5464) and high-virulence (Hi-SA5458) strains. These findings correlated with acute fracture-related infection induced by Hi-SA5458, whereas Lo-SA5464 caused a chronic fracture-related infection in its human host. However, it remains unclear whether and to what extent the causative pathogen is attributable to these disparities in fracture-related infections. QUESTION/PURPOSE: Are there differences in the course of infection when comparing these two different clinical isolates in a murine fracture-related infection model, as measured by (1) clinical observations of weight loss, (2) quantitative bacteriology, (3) immune response, and (4) radiographic and histopathologic morphology? METHODS: Twenty-five (including one replacement animal) female (no sex-specific influences expected), skeletally mature C57Bl/6N inbred mice between 20 and 28 weeks old underwent femoral osteotomy stabilized by titanium locking plates. Fracture-related infection was established by inoculation of high-virulence S. aureus EDCC 5458 (Hi-SA5458) or low-virulence S. aureus EDCC 5464 (Lo-SA5464) in the fracture gap. Each of these groups consisted of 12 randomly assigned animals. Mice were euthanized 4 and 14 days postsurgery, resulting in six animals per group and timepoint. The severity and progression of infection were assessed in terms of clinical observation of weight loss, quantitative bacteriology, quantitative serum cytokine levels, qualitative analysis of postmortem radiographs, and semiquantitative histopathologic evaluation. RESULTS: For clinical observations of weight change, no differences were seen at Day 4 between Hi-SA5458- and Lo-SA5464-infected animals (mean -0.6 ± 0.1 grams versus -0.8 ± 0.2 grams, mean difference -0.2 grams [95% CI -0.8 to 0.5 grams]; p =0.43), while at 14 days, the Hi-SA5458 group lost more weight than the Lo-SA5464 group (mean -1.55 ± 0.2 grams versus -0.8 ± 0.3 grams; mean difference 0.7 grams [95% CI 0.2 to 1.3 grams]; p = 0.02). Quantitative bacteriological results 4 days postoperatively revealed a higher bacterial load in soft tissue samples in Hi-SA5458-infected animals than in the Lo-SA5464-infected cohort (median 6.8 x 10 7 colony-forming units [CFU]/g, range 2.2 x 10 7 to 2.1 x 10 9 CFU/g versus median 6.0 x 10 6 CFU/g, range 1.8 x 10 5 to 1.3 x 10 8 CFU/g; difference of medians 6.2 x 10 7 CFU/g; p = 0.03). At both timepoints, mice infected with the Hi-SA5458 strain also displayed higher proportions of bacterial dissemination into organs than Lo-SA5464-infected animals (67% [24 of 36 organs] versus 14% [five of 36 organs]; OR 12.0 [95% CI 3.7 to 36]; p < 0.001). This was accompanied by a pronounced proinflammatory response on Day 14, indicated by increased serum cytokine levels of interleukin-1ß (mean 9.0 ± 2.2 pg/mL versus 5.3 ± 1.5 pg/mL; mean difference 3.6 pg/mL [95% CI 2.0 to 5.2 pg/mL]; p < 0.001), IL-6 (mean 458.6 ± 370.7 pg/mL versus 201.0 ±89.6 pg/mL; mean difference 257.6 pg/mL [95% CI 68.7 to 446.5 pg/mL]; p = 0.006), IL-10 (mean 15.9 ± 3.5 pg/mL versus 9.9 ± 1.0 pg/mL; mean difference 6.0 pg/mL [95% CI 3.2 to 8.7 pg/mL]; p < 0.001), and interferon-γ (mean 2.7 ± 1.9 pg/mL versus 0.8 ± 0.3 pg/mL; mean difference 1.8 pg/mL [95% CI 0.5 to 3.1 pg/mL]; p = 0.002) in Hi-SA5458-infected compared with Lo-SA5464-infected animals. The semiquantitative histopathologic assessment on Day 4 revealed higher grades of granulocyte infiltration in Hi-SA5458-infected animals (mean grade 2.5 ± 1.0) than in Lo-SA5464-infected animals (mean grade 1.8 ± 1.4; mean difference 0.7 [95% CI 0.001 to 1.4]; p = 0.0498). On Day 14, bone healing at the fracture site was present to a higher extent in Lo-SA5464-infected animals than in Hi-SA5458-infected animals (mean grade 0.2 ± 0.4 versus 1.8 ± 1.2; mean difference -1.6 [95% CI -2.8 to -0.5]; p = 0.008). CONCLUSION: Similar to septic infection in a human host, infection with Hi-SA5458 in this murine model was characterized by a higher bacterial load, more-pronounced systemic dissemination, and stronger systemic and local inflammation. Thus, there is strong support for the idea that pathogenic virulence plays a crucial role in fracture-related infections. To confirm our observations, future studies should focus on characterizing S. aureus virulence at the genomic and transcriptomic levels in more clinical isolates and patients. Comparing knockout and wildtype strains in vitro and in vivo, including the S. aureus strains studied, could confirm our findings and identify the genomic features responsible for S. aureus virulence in fracture-related infections. CLINICAL RELEVANCE: For translational use, virulence profiles of S. aureus may be useful in guiding treatment decisions in the future. Once specific virulence targets are identified, one approach to fracture-related infections with high-virulence strains might be the development of antivirulence agents, particularly to treat or prevent septic dissemination. For fracture-related infections with low virulence, prolonged antimicrobial therapy or exchange of an indwelling implant might be beneficial owing to slower growth and persistence capacity.

Ultrastructural Evidence of Mitochondrial Dysfunction in Osteomyelitis Patients.

Osteomyelitis is a difficult-to-treat disease with high chronification rates. First studies suggest increases in mitochondrial fission and mitochondrial dysfunction as possible contributors to the accumulation of intracellular reactive oxygen species and thereby to the cell death of infected bone cells. The aim of the present study is to analyze the ultrastructural impact of bacterial infection on osteocytic and osteoblastic mitochondria. Human infected bone tissue samples were visualized via light microscopy and transmission electron microscopy. Osteoblasts, osteocytes and their mitochondria were analyzed histomorphometrically and compared with the control group of noninfectious human bone tissue samples. The results depicted swollen hydropic mitochondria including depleted cristae and a decrease in matrix density in the infected samples. Furthermore, perinuclear clustering of mitochondria could also be observed regularly. Additionally, increases in relative mitochondrial area and number were found as a correlate for increased mitochondrial fission. In conclusion, mitochondrial morphology is altered during osteomyelitis in a comparable way to mitochondria from hypoxic tissues. This gives new perspectives on the treatment strategies since the manipulation of mitochondrial dynamics may improve bone cell survival as a potential new target for the therapy of osteomyelitis.

3D Visualization, Skeletonization and Branching Analysis of Blood Vessels in Angiogenesis.

Angiogenesis is the process of new blood vessels growing from existing vasculature. Visualizing them as a three-dimensional (3D) model is a challenging, yet relevant, task as it would be of great help to researchers, pathologists, and medical doctors. A branching analysis on the 3D model would further facilitate research and diagnostic purposes. In this paper, a pipeline of vision algorithms is elaborated to visualize and analyze blood vessels in 3D from formalin-fixed paraffin-embedded (FFPE) granulation tissue sections with two different staining methods. First, a U-net neural network is used to segment blood vessels from the tissues. Second, image registration is used to align the consecutive images. Coarse registration using an image-intensity optimization technique, followed by finetuning using a neural network based on Spatial Transformers, results in an excellent alignment of images. Lastly, the corresponding segmented masks depicting the blood vessels are aligned and interpolated using the results of the image registration, resulting in a visualized 3D model. Additionally, a skeletonization algorithm is used to analyze the branching characteristics of the 3D vascular model. In summary, computer vision and deep learning is used to reconstruct, visualize and analyze a 3D vascular model from a set of parallel tissue samples. Our technique opens innovative perspectives in the pathophysiological understanding of vascular morphogenesis under different pathophysiological conditions and its potential diagnostic role.

Incidence and treatment of intracapsular femoral neck fractures in Germany.

INTRODUCTION: Intracapsular femoral neck fractures are one of the most common fractures in Germany. Nevertheless, the epidemiology and treatment modalities are not described comprehensively. For this reason, this study highlights the epidemiology of femoral neck fractures in different age groups and summarizes treatment strategies within the period from 2009 to 2019 based on nationwide data. MATERIALS AND METHODS: In this retrospective cohort study all cases of intracapsular femoral neck fractures (ICD-10: S72.0) between 2009 and 2019 in Germany were analyzed with regard to epidemiology, incidence and treatment. Operation and procedure classification system (OPS)- codes in combination with intracapsular femoral neck fracture as main diagnosis were taken to investigation. Data was provided by the Federal Statistical Office of Germany (Destatis). RESULTS: A total of 807,834 intracapsular femoral neck fractures with a mean incidence of 110.0 per 100,000 inhabitants annually was detected within eleven years. In 68.8% of all fractures patients were female. Most patients were older than 70 years (82.4%), and 56.7% were older than 80 years. The overall increase of fracture numbers between 2009 and 2019 was 23.2%. Joint replacement has been most often performed (80.4%). Hemiarthroplasty (56.8%) and total hip arthroplasty (22.8%) were the most common procedures with an increase of 27.1 and 38.6%, respectively. The proportion of cemented hemiarthroplasties was 86.2% while 51.3% of all total hip arthroplasties were totally or partially cemented. Osteosyntheses were mainly conducted using dynamic compression screws (34.0%), conventional screws (31.3%) and nails (22.2%). CONCLUSION: The incidence of intracapsular femoral neck fractures in Germany has been increasing continuously within the last decade. In particular, patients over 80 years suffered predominantly from this type of fracture. The majority was treated with a joint replacement procedure, mainly cemented hemiarthroplasty.

Retrospective analysis of mortality and quality of life after hip disarticulation or hemipelvectomy: a report on 15 patients.

BACKGROUND: Hip disarticulation and hemipelvectomy are defined as major ablative amputations of the lower limb. Due to the small number of patients, little is known about the outcome and follow-up. AIMS: We aimed to assess (1) reasons for performed major ablative surgeries such as hip disarticulation and hemipelvectomy in a German center for trauma and orthopedic surgery. (2) In addition, mortality and quality of life after hip disarticulation and hemipelvectomy as well as (3) patient and treatment characteristics should be investigated. METHODS: During a period of twelve years, 15 patients underwent hip disarticulation or hemipelvectomy. Mortality, EQ-5D-3L quality of life by EQ-5D-3L and time-trade-off (TTO), VAS, cause of disarticulation, length of hospital stays, revisions, comorbidities, Charlson comorbidity index (CCI), and ASA score were evaluated retrospective for all patients. RESULTS: The overall mortality rates were 26.7% at 30 days, 60.0% after one year and 66.7% after three years. The five surviving patients reported about moderate problems in the EQ-5D-3L. The average VAS score reached 45 (range 15-65). The mean TTO was 9.8 (range 6-12). Indications for amputation were infection (n = 7), tumor (n = 6), trauma (n = 1) and ischemia (n = 1). CONCLUSION: Hip disarticulation and hemipelvectomy are followed by a high postoperative mortality. Quality of life of the affected patients is impaired in long-term follow-up. Especially amputations performed due to infections show high mortality within one month after surgery despite average young age and low CCI. Surgeons should be aware of this devastating outcome and extraordinary vigilant for these vulnerable patient cohorts.

Aseptic revisions and pulmonary embolism after surgical treatment of femoral neck fractures with cemented and cementless hemiarthroplasty in Germany: an analysis from the German Arthroplasty Registry (EPRD).

BACKGROUND: Femoral neck fractures (FNF) are among the most common fractures in Germany and are often treated by hemiarthroplasty (HA). The aim of this study was to compare the occurrence of aseptic revisions after cemented and uncemented HA for the treatment of FNF. Secondly, the rate of pulmonary embolism was investigated. METHODS: Data collection for this study was performed using the German Arthroplasty Registry (EPRD). HAs after FNF were divided into subgroups stratified by stem fixation (cemented vs uncemented) and paired according to age, sex, BMI, and the Elixhauser score using Mahalanobis distance matching. RESULTS: Examination of 18,180 matched cases showed a significantly increased rate of aseptic revisions in uncemented HA (p < 0.0001). After 1 month 2.5% of HAs with uncemented stems required an aseptic revision, while 1.5% were reported in cemented HA. After 1 and 3 years' follow-up 3.9% and 4.5% of uncemented HA and 2.2% and 2.5% of cemented HA needed aseptic revision surgery. In particular, the proportion of periprosthetic fractures was increased in cementless implanted HA (p < 0.0001). During in-patient stays, pulmonary emboli occurred more frequently after cemented HA [0.81% vs 0.53% in cementless HA (OR: 1.53; p = 0.057)]. CONCLUSION: For uncemented hemiarthroplasties a statistically significantly increased rate of aseptic revisions and periprosthetic fractures was evident within a time period of 5 years after implantation. During the in-hospital stay, patients with cemented HA experienced an increased rate of pulmonary embolism, but without statistically significant results. Based on the present results, with knowledge of prevention measurements and correct cementation technique, cemented HA should be preferred when using HA in the treatment of femoral neck fractures. TRAIL REGISTRATION: The study design of the German Arthroplasty Registry was approved by the University of Kiel (ID: D 473/11). LEVEL OF EVIDENCE: Level III, Prognostic.

Factors associated with mortality after proximal femoral fracture.

Proximal femoral fractures are a serious complication, especially for elderly patients. Therefore, we have aimed to answer the following research question: What is the postfracture mortality rate in the elderly population and what are associated risk factors? For this, proximal femoral fractures that occurred between 1 January 2009 and 31 December 2019 were identified from the Medicare Physician Service Records database. The Kaplan-Meier (KM) method with the Fine and Gray subdistribution adaptation was used to determine rates of mortality. A semiparametric Cox regression model was applied, incorporating 23 measures as covariates to identify risk factors. The estimated 1 year mortality rate was 26.8% after head/neck fracture, 28.2% after intertrochanteric fracture, and 24.2% after subtrochanteric fracture. Male sex, age over 70 years, chronic obstructive pulmonary disease (COPD), cerebrovascular disease, chronic kidney disease, a concomitant fracture, congestive heart failure, diabetes mellitus, hypertension, insulin use, ischemic heart disease, morbid obesity, osteoporosis, tobacco dependence, and median household income were determined as risk factors for increased mortality. An early assessment of individual risk factors accessible for therapeutic treatment is crucial in the management of proximal femur fractures to aid in attempts at reducing the high mortality apparent in the elderly US population.

Comparison of mortality rate and septic and aseptic revisions in total hip arthroplasties for osteoarthritis and femoral neck fracture: an analysis of the German Arthroplasty Registry.

BACKGROUND: Indications for total hip arthroplasties (THA) differ from primary osteoarthritis (OA), which allows elective surgery through femoral neck fractures (FNF), which require timely surgical care. The aim of this investigation was to compare mortality and revisions in THA for primary OA and FNF. METHODS: Data collection for this study was performed using the German Arthroplasty Registry (EPRD) with analysis THA for the treatment of FNF and OA. Cases were matched 1:1 according to age, sex, body mass index (BMI), cementation, and the Elixhauser score using Mahalanobis distance matching. RESULTS: Overall 43,436 cases of THA for the treatment of OA and FNF were analyzed in this study. Mortality was significantly increased in FNF, with 12.6% after 1 year and 36.5% after 5 years compared with 3.0% and 18.7% in OA, respectively (p < 0.0001). The proportion for septic and aseptic revisions was significantly increased in FNF (p < 0.0001). Main causes for an aseptic failure were mechanical complications (OA: 1.1%; FNF: 2.4%; p < 0.0001) and periprosthetic fractures (OA: 0.2%; FNF: 0.4%; p = 0.021). As influencing factors for male patients with septic failure (p < 0.002), increased BMI and Elixhauser comorbidity score and diagnosis of fracture (all p < 0.0001) were identified. For aseptic revision surgeries, BMI, Elixhauser score, and FNF were influencing factors (p < 0.0001), while all cemented and hybrid cemented THA were associated with a risk reduction for aseptic failure within 90 days after surgery (p < 0.0001). CONCLUSION: In femoral neck fractures treated with THA, a significant higher mortality, as well as septic and aseptic failure rate, was demonstrated compared with prosthesis for the therapy of osteoarthritis. Increased Elixhauser comorbidity score and BMI are the main influencing factors for development of septic or aseptic failure and can represent a potential approach for prevention measures. LEVEL OF EVIDENCE: Level III, Prognostic.

High injury rates and weak injury prevention strategies in football referees at all levels of play.

Football referees need other physiological requirements on field than football players and are affected by different types of injury. The absence of referees may result in canceled matches, so special focus should be placed on injury prevention through specific training programs for referees. This study retrospectively analyzed injury occurrence and prevention strategies for German football referees at the different levels of play over one season. Data were collected by means of seasonal injury reports based on the consensus statement of injury definition and data collection. Of the 923 participating referees, 91 (9.9%) played at the professional level, 151 (16.3%) at the semi-professional, and 681 (73.8%) at the amateur level. 86.2% (n = 796) were men and 13.8% (n = 127) women. Referees at the amateur level showed the highest injury incidence (3.14/1000 h football) compared to referees at the semi-professional (1.92/1000 h; p < 0.001) and professional level (1.01/1000 h; p < 0.001). Most referees at the amateur (n = 372; 56.4%) and semi-professional level (n = 46; 31.3%) conducted warm-up programs of <10 min, whereas the mean warm-up duration of professional referees was >11 min (n = 75; 82.4%). Although running and stretching exercises were common among referees during warm-up, preventive exercises focusing on coordination and trunk muscles were less frequent, especially among amateur referees (jumping: 15.9%; strengthening: 9.7%; balance exercises: 7.9%). Injury incidence was highest at lower amateur levels, which thus has specific need for injury prevention. Appropriate training exercises to prevent injuries of referees were weak at all levels of play, especially the lack of strength, plyometric, and balance exercises in training and warm-up programs.

Structural Analysis of Mitochondrial Dynamics-From Cardiomyocytes to Osteoblasts: A Critical Review.

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.

Managing periprosthetic joint infection-a qualitative analysis of nursing staffs' experiences.

BACKGROUND: Periprosthetic joint infection represents a major complication in orthopaedics and trauma surgery. For an ideal management approach, it is important to understand the distinct challenges for all persons involved in the treatment. Therefore, it was aimed at investigating (1) the impact of periprosthetic joint infection (PJI) on the well-being of nursing staff to (2) identify challenges, which could be improved facilitating the management of PJI. METHODS: This is a qualitative interview study. In total, 20 nurses of a German university orthopedic trauma center specialized on infectious complications were recruited using a purposive sampling strategy. Content analysis was performed on transcripts of individual in-person interviews conducted between March 2021 and June 2021. RESULTS: Three major themes could be extracted including (i) feelings associated with the management of PJI and the need for emotional support, illustrating the negative emotional impact on nurses, whereby receiving collegial support was perceived as an important coping strategy, (ii) patients' psychological burden, highlighting the nurses' lack of time to address mental issues adequately and, (iii) realization of the severity of PJI and compliance problems. CONCLUSION: Identified facilitating factors for PJI management include strengthening of mental care in the treatment of PJI, providing opportunities for exchange among multidisciplinary team members and implementing compliance-enhancing strategies. The findings of this study can be beneficial for improving professionals' satisfaction, optimising the work environment, creating organizational structures which enhance opportunities for exchange and preventing mental health issues among the nursing team.