Gentamicin and clindamycin antibiotic-eluting depot technology eradicates S. aureus in an implant-associated osteomyelitis pig model without systemic antibiotics.

The therapeutic challenges of orthopedic device-related infections and emerging antimicrobial resistance have attracted attention to drug delivery technologies. This study evaluates the preclinical efficacy of local single- and dual-antibiotic therapy against implant-associated osteomyelitis (IAO) using a drug-eluting depot technology, CarboCell, that provides sustained release of high-dose antibiotics and allows for strategic in situ placement in relation to infectious lesions. Clindamycin and gentamicin were formulated in CarboCell compositions. One-stage-revision of tibial Staphylococcus aureus IAO was conducted in 19 pigs. Pigs were treated locally with CarboCell containing either gentamicin alone for 1 week or a co-formulation of gentamicin and clindamycin for 1 or 3 weeks. Bone, soft tissue, and antibiotic depots were collected for microbiology, histology, and HPLC analyses. Supporting in vivo release studies of CarboCell formulations were performed on mice. Both single- and dual-antibiotic CarboCell formulations were developed and capable of eradicating the infectious bacteria in bone and preventing colonization of implants inserted at revision. Eradication in soft tissue was observed in all pigs after 3 weeks and in 6/9 pigs after 1 week of treatment. Neutrophil counts in bone tissue were below the infection cut-off in all pigs receiving the dual-antibiotic therapies, but above in all pigs receiving the single-antibiotic therapy. Histological signs of active bone reorganization and healing were observed at 3 weeks. In conclusion, all CarboCell formulations demonstrated strong therapeutic activity against IAO, eradicating S. aureus in bone tissue and preventing colonization of implants even without the addition of systemic antibiotic therapy.

New approach to testing treatments for osteoarthritis: FastOA.

Animal models of post traumatic osteoarthritis have shown many promising treatments for disease, but human trials have mostly failed to identify effective treatments. This viewpoint suggests that the frequent failure of drug and treatment development in osteoarthritis is due, in part, to the advanced stage of disease of patients in trials and suggests that mirroring the animal model approach might be more successful. It suggests a path forward by enriching trial enrollees with those likely to develop post traumatic OA quickly.

3D Specimen Scanning and Mapping in Musculoskeletal Oncology: A Feasibility Study.

BACKGROUND: Surgical resection is the primary treatment for bone and soft tissue tumors. Negative margin status is a key factor in prognosis. Given the three-dimensional (3D) anatomic complexity of musculoskeletal tumor specimens, communication of margin results between surgeons and pathologists is challenging. We sought to perform ex vivo 3D scanning of musculoskeletal oncology specimens to enhance communication between surgeons and pathologists. METHODS: Immediately after surgical resection, 3D scanning of the fresh specimen is performed prior to frozen section analysis. During pathologic grossing, whether frozen or permanent, margin sampling sites are annotated on the virtual 3D model using computer-aided design (CAD) software. RESULTS: 3D scanning was performed in seven cases (six soft tissue, one bone), with specimen mapping on six cases. Intraoperative 3D scanning and mapping was performed in one case in which the location of margin sampling was shown virtually in real-time to the operating surgeon to help achieve a negative margin. In six cases, the 3D model was used to communicate final permanent section analysis. Soft tissue, cartilage, and bone (including lytic lesions within bone) showed acceptable resolution. CONCLUSIONS: Virtual 3D scanning and specimen mapping is feasible and may allow for enhanced documentation and communication. This protocol provides useful information for anatomically complex musculoskeletal tumor specimens. Future studies will evaluate the effect of the protocol on positive margin rates, likelihood that a re-resection contains additional malignancy, and exploration of targeted adjuvant radiation protocols using a patient-specific 3D specimen map.

Assessment of the antimicrobial and antibiofilm activity of the combination of N-acetyl cysteine and carvacrol against Staphylococcus aureus, the most common orthopedic infectious agent.

BACKGROUND: The increasing prevalence of antibiotic-resistant bacterial infections has led to the search for new approaches. OBJECTIVE: This study aimed to evaluate the effects of carvacrol and N-acetyl cysteine, both individually and in combination, on the planktonic cells and biofilm formations of Staphylococcus aureus, including methicillin-resistant and methicillin-sensitive strains. Additionally, the study sought to perform cytotoxicity tests and chemical characterization to further understand the properties and potential applications of these substances. METHODS: A total of 19 S. aureus strains were included in the study. Minimum inhibitory concentration and minimum bactericidal concentration were determined by assays. Synergy analysis tests were carried out. Cytotoxicity tests were conducted on the fibroblast cell line. Characterization test was performed. RESULTS: While Minimum inhibitory concentration and minimum bactericidal concentration values for carvacrol varied between 250 and 500 µg/ml, these values were in the range of 32-64 mg/ml for N-acetyl cysteine. Biofilm formation activities were identified. A total of eight strains, including six clinical and two standard strains with the highest biofilm-forming ability, were selected for combination studies. The combination of Carvacrol and N-acetyl cysteine exhibited synergistic and partially synergistic effects on the tested planktonic and biofilm strains, and these effects were dose-dependent. Carvacrol was found to be the most active drug at the end of 24, 48, and 72 h. Regarding the synergistic effect of N-acetyl cysteine + carvacrol, it was revealed to exhibit higher activity than N-acetyl cysteine and lower activity than carvacrol. CONCLUSION: The combination of carvacrol and N-acetyl cysteine demonstrated synergistic and partially synergistic effects against both planktonic and biofilm forms of Staphylococcus aureus. These results suggest potential for novel approaches in managing orthopedic infections, warranting further research to explore their therapeutic applications.

Distinct trajectories of neuropsychiatric symptoms in the 12 months following traumatic brain injury (TBI): a TRACK-TBI study.

BACKGROUND: Neuropsychiatric symptoms are common after traumatic brain injury (TBI) and often resolve within 3 months post-injury. However, the degree to which individual patients follow this course is unknown. We characterized trajectories of neuropsychiatric symptoms over 12 months post-TBI. We hypothesized that a substantial proportion of individuals would display trajectories distinct from the group-average course, with some exhibiting less favorable courses. METHODS: Participants were level 1 trauma center patients with TBI (n = 1943), orthopedic trauma controls (n = 257), and non-injured friend controls (n = 300). Trajectories of six symptom dimensions (Depression, Anxiety, Fear, Sleep, Physical, and Pain) were identified using growth mixture modeling from 2 weeks to 12 months post-injury. RESULTS: Depression, Anxiety, Fear, and Physical symptoms displayed three trajectories: Stable-Low (86.2-88.6%), Worsening (5.6-10.9%), and Improving (2.6-6.4%). Among symptomatic trajectories (Worsening, Improving), lower-severity TBI was associated with higher prevalence of elevated symptoms at 2 weeks that steadily resolved over 12 months compared to all other groups, whereas higher-severity TBI was associated with higher prevalence of symptoms that gradually worsened from 3-12 months. Sleep and Pain displayed more variable recovery courses, and the most common trajectory entailed an average level of problems that remained stable over time (Stable-Average; 46.7-82.6%). Symptomatic Sleep and Pain trajectories (Stable-Average, Improving) were more common in traumatically injured groups. CONCLUSIONS: Findings illustrate the nature and rates of distinct neuropsychiatric symptom trajectories and their relationship to traumatic injuries. Providers may use these results as a referent for gauging typical v. atypical recovery in the first 12 months post-injury.

Therapeutic applications and challenges in myostatin inhibition for enhanced skeletal muscle mass and functions.

Myostatin, a potent negative regulator of skeletal muscle mass, has garnered significant attention as a therapeutic target for muscle dystrophies. Despite extensive research and promising preclinical results, clinical trials targeting myostatin inhibition in muscle dystrophies have failed to yield substantial improvements in muscle function or fitness in patients. This review details the mechanisms behind myostatin's function and the various inhibitors that have been tested preclinically and clinically. It also examines the challenges encountered in clinical translation, including issues with drug specificity, differences in serum myostatin concentrations between animal models and humans, and the necessity of neural input for functional improvements. Additionally, we explore promising avenues of research beyond muscle dystrophies, particularly in the treatment of metabolic syndromes and orthopedic disorders. Insights from these alternative applications suggest that myostatin inhibition may hold the potential for addressing a broader range of pathologies, providing new directions for therapeutic development.

Internal hemipelvectomy: A single institution's learning curve and longitudinal experience.

BACKGROUND AND OBJECTIVES: Wide margin resection for pelvic tumors via internal hemipelvectomy is among the most technically challenging procedures in orthopedic oncology. As such, surgeon experience and technique invariably affect patient outcomes. The aim of this clinical study was to assess how an individual surgeon's experiences and advancements in technology and techniques in the treatment of internal hemipelvectomy have impacted patient outcomes at our institution. METHODS: This study retrospectively examined a single tertiary academic institution's consecutive longitudinal experience with internal hemipelvectomy for primary sarcoma or pelvic metastases over a 26-year period between the years 1994 and 2020. Outcomes were assessed using two separate techniques. The first stratified patients into cohorts based on the date of surgery with three distinct "eras" ("early," "middle," and "modern"), which reflect the implementation of new techniques, including three-dimensional (3D) computer navigation and cutting guide technology into our clinical practice. The second method of cohort selection grouped patients based on each surgeon's case experience with internal hemipelvectomy ("inexperienced," "developing," and "experienced"). Primary endpoints included margin status, complication profiles, and long-term oncologic outcomes. Whole group multivariate analysis was used to evaluate variables predicting blood loss, operative time, tumor-free survival, and mortality. RESULTS: A total of 72 patients who underwent internal hemipelvectomy were identified. Of these patients, 24 had surgery between 1994 and 2007 (early), 28 between 2007 and 2015 (middle), and 20 between 2016 and 2020 (modern). Twenty-eight patients had surgery while the surgeon was still inexperienced, 24 while developing, and 20 when experienced. Evaluation by era demonstrated that a greater proportion of patients were indicated for surgery for oligometastatic disease in the modern era (0% vs. 14.3% vs. 35%, p = 0.022). Fewer modern cases utilized freehand resection (100% vs. 75% vs. 55%, p = 0.012), while instead opting for more frequent utilization of computer navigation (0% vs. 25% vs. 20%, p = 0.012), and customized 3D-printed cutting guides (0% vs. 0% vs. 25%, p = 0.002). Similarly, there was a decline in the rate of massive blood loss observed (72.2% vs. 30.8% vs. 35%, p = 0.016), and interdisciplinary collaboration with a general surgeon for pelvic dissection became more common (4.2% vs. 32.1% vs. 85%, p < 0.001). Local recurrence was less prevalent in patients treated in middle and modern eras (50% vs. 15.4% vs. 25%, p = 0.045). When stratifying by case experience, surgeries performed by experienced surgeons were less frequently complicated by massive blood loss (66.7% vs. 40% vs. 20%, p = 0.007) and more often involved a general surgeon for pelvic dissection (17.9% vs. 37.5% vs. 65%, p = 0.004). Whole group multivariate analysis demonstrated that the use of patient-specific instrumentation (PSI) predicted lower intraoperative blood loss (p = 0.040). However, surgeon experience had no significant effect on operative time (p = 0.125), tumor-free survival (p = 0.501), or overall patient survival (p = 0.735). CONCLUSION: While our institution continues to utilize neoadjuvant and adjuvant therapies following current guideline-based care, we have noticed changing trends from early to modern periods. With the advent of new technologies, we have seen a decline in freehand resections for hemipelvectomy procedures, and a transition to utilizing more 3D navigation and customized 3D cutting guides. Furthermore, we have employed the use of an interdisciplinary team approach more regularly for these complicated cases. Although our results do not demonstrate a significant change in perioperative outcomes over the years, our institution's willingness to treat more complex cases likely obscures the benefits of surgeon experience and recent technological advances for patient outcomes.

Antibiotic utilization at an orthopedic inpatient department in a large governmental hospital in the north of the West Bank, Palestine; a retrospective observational study.

BACKGROUND: Studies evaluating the patterns of antibiotic consumption are becoming increasingly necessary as a result of the increased use of antibiotics and development of antibiotic resistance globally. This study aimed to evaluate the use of antibiotics in in terms of both quantity and quality at the largest surgical hospital in the north of the West Bank, Palestine. METHODS: An observational retrospective study with a total population sampling method was conducted to collect data from the inpatients of the orthopedic departments of a large governmental hospital in the northern West Bank, Palestine. The data were collected from patients' files and evaluated using the anatomical therapeutic chemical and defined daily dose (ATC/DDD) methodology, and the drug utilization 90% (DU90%) index. The ATC/DDD methodology, designed by the World Health Organization (WHO), as a well-trusted and standardized tool that allows measuring and comparing antibiotic utilization across different contexts. Antibiotic prescriptions were classified using the World Health Organization Access, Watch and Reserve classification (WHO AWaRe). RESULTS: Of the 896 patients who were admitted to the hospital in the year 2020 and included in the study, 61.9% were males, and 38.1% were females. The percentage of patients who received antibiotics was 97.0%, and the overall antibiotic usage was 107.91 DDD/100 bed days. The most commonly prescribed antibiotic was cefazolin (50.30 DDD/100 bed days), followed by gentamicin (24.15 DDD/100 bed days) and ceftriaxone (17.35 DDD/100 bed days). The DU90% segment comprised four different agents. Classification of antibiotics according to the WHO AWaRe policy revealed that 75.9% of antibiotics were prescribed from the access list. CONCLUSION: This study comes as part of the efforts exerted to combat the growing problem of antibiotic resistance in Palestine. Our results showed that the consumption of antibacterial agents in the orthopedic unit at a large governmental hospital in Palestine was relatively high. The results of this study provide valuable insights for the decision-makers to create policies aimed at regulating antibiotic prescriptions. This study also aims to provide a look into the antibiotic prescription patterns, offering a clearer understanding of the current situation of antibiotic consumption in Palestine. It also emphasizes the need for antibiotic stewardship and surveillance programs.

Adherence to clinical care standards and mortality after hip fracture surgery in New South Wales, 2015-2018: a retrospective population-based study.

OBJECTIVES: To determine whether adherence to hip fracture clinical care quality indicators influences mortality among people who undergo surgery after hip fracture in New South Wales, both overall and by individual indicator. STUDY DESIGN: Retrospective population-based study; analysis of linked Australian and New Zealand Hip Fracture Registry (ANZHFR), hospital admissions, residential aged care, and deaths data. SETTING, PARTICIPANTS: People aged 50 years or older with hip fractures who underwent surgery in 21 New South Wales hospitals participating in the ANZHFR, 1 January 2015 - 31 December 2018. MAIN OUTCOME MEASURES: Thirty-day (primary outcome), 120-day, and 365-day mortality (secondary outcomes) by clinical care indicator adherence level (low: none to three of six indicators achieved; moderate: four indicators achieved; high: five or six indicators achieved) and by individual indicator. RESULTS: Registry data were available for 9236 hip fractures in 9058 people aged 50 years or older during 2015-2018; the mean age of patients was 82.8 years (standard deviation, 9.3 years), 5510 patients were women (69.4%). Complete data regarding adherence to clinical care indicators were available for 7951 fractures (86.1%); adherence to these indicators was high for 5135 (64.6%), moderate for 2249 (28.3%), and low for 567 fractures (7.1%). After adjustment for age, sex, comorbidity, admission year, pre-admission walking ability, and residential status, 30-day mortality risk was lower for high (adjusted relative risk [aRR], 0.40; 95% confidence interval [CI], 0.30-0.52) and moderate indicator adherence hip fractures (aRR, 0.61; 95% CI, 0.46-0.82) than for low indicator adherence hip fractures, as was 365-day mortality (high adherence: aRR, 0.59 [95% CI, 0.51-0.68]; moderate adherence: aRR, 0.74 [95% CI, 0.63-0.86]). Orthogeriatric care (365 days: aRR, 0.78; 95% CI, 0.61-0.98) and offering mobilisation by the day after surgery (365 days: aRR, 0.74; 95% CI, 0.67-0.83) were associated with lower mortality risk at each time point. CONCLUSIONS: Clinical care for two-thirds of hip fractures attained a high level of adherence to the six quality care indicators, and short and longer term mortality was lower among people who received such care than among those who received low adherence care.

Pregnancy and infertility in orthopedics: A review of the current state.

BACKGROUND: Orthopedic surgery continues to have one of the lowest rates of female trainees among all medical specialties in the United States. Barriers to pursuing a surgical residency include the challenges of family planning and work-life balance during training. METHODS: A systematic literature search of articles published between June 2012 and December 2022 in the MEDLINE, EMBASE, and Cochrane databases was performed in January 2023 according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). Studies were included if they evaluated pregnancy and peripartum experience and/or outcomes amongst orthopedic surgeons or trainees. RESULTS: Eighteen studies were included. Up to 67.3% of female orthopedic surgeons and trainees and 38.7% of their male counterparts delayed childbearing during residency. The most reported reasons for this delay included career choice as an orthopedic surgeon, residency training, and reputational concerns among faculty or co-residents. Infertility ranged from 17.0% to 30.4% in female orthopedic surgeons and up to 31.2% suffered obstetric complications. Assisted Reproductive Technology (ART) resulted in 12.4%-56.3% of successful pregnancies. Maternity and paternity leaves ranged from 1 to 11 weeks for trainees with more negative attitudes associated with maternal leave. CONCLUSIONS: Female orthopedic trainees and attending delay childbearing, experience higher rates of obstetric complications, and more stigma associated with pregnancy compared to their male colleagues. Program and institutional policies regarding maternity and paternity leave are variable across programs, and therefore, attention should be directed toward standardizing policies.

Orthopedic surgery in Palau-Current capacity, needs, and future directions.

BACKGROUND: Palau, an island nation in Micronesia, is a medically underserved area with a shortage of specialty care services. Orthopedic diagnoses in Palau remain among the three most common reasons for costly off-island medical referral. The purpose of this study was to assess Palau's current orthopedic surgery capacity and needs to inform interventions to build capacity to improve care access and quality. METHODS: Orthopedic needs and capacity assessment tools developed by global surgical outreach experts were utilized to gather information and prompt discussions with a broad range of Palau's most knowledgeable stakeholders (n = 6). Results were reported descriptively. RESULTS: Finance, community impact, governance, and professional development were the lowest-scored domains from the Capacity Assessment Tool for orthopedic surgery (CAT-os), indicating substantial opportunity to build within these domains. According to administrators (n = 3), governance and finance were the greatest capacity-building priorities, followed by professional development and partnership. Belau National Hospital (BNH) had adequate surgical infrastructure. Skin grafting, soft tissue excision/resection, infection management, and amputation were the most commonly selected procedures by stakeholders reporting orthopedic needs. CONCLUSIONS: This study utilizes a framework for orthopedic capacity-building in Palau which may inform partnership between Palau's healthcare system and orthopedic global outreach organizations with the goal of improving the quality, safety, and value of the care delivered. This demonstration of benchmarking, implementation planning, and subsequent re-evaluation lays the foundation for the understanding of capacity-building and may be applied to other medically underserved areas globally to improve access to high-quality orthopedic care.

Agreement between patient- and proxy-reported outcome measures in adult musculoskeletal trauma and injury: a scoping review.

PURPOSE: Patient-reported outcome measures (PROMs) are widely used in medicine. As older adults, who may rely on a proxy caregiver for answers due to cognitive impairment, are representing an increasing share of the traumatically injured patient population, proxy-reported outcome measures (proxROMs) offer a valuable alternative source of patient-centered information although its association with PROMs is unclear. The objective of this scoping review is to discuss all available literature comparing PROM and proxROMs in adult patients with musculoskeletal trauma to guide future research in this field. METHODS: The PRISMA extension for Scoping Reviews was used to guide this review. MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched without date limit for articles comparing PROM and proxROMs in setting of musculoskeletal trauma. Abstract and full-text screening were performed by two independent reviewers. Variables included study details, patient and proxy characteristics, and reported findings on agreement between PROMs and proxROMs. RESULTS: Of 574 unique records screened, 13 were included. Patient and proxy characteristics varied greatly, while patients' cognitive status and type of proxy perspective were poorly addressed. 18 different PROMs were evaluated, mostly reporting on physical functioning and disability (nine, 50%) or quality of life (six, 33%). Injury- and proxy-specific tools were rare, and psychometric properties of PROMs were often not described. Studies reported moderate to good agreement between PROMs and proxROMs. There is less agreement on subjective outcome measures (e.g., depression score) compared to observable items, and proxy bias results in in worse outcomes compared to patient self-reports. CONCLUSION: Current literature, though limited, demonstrates moderate to good agreement between injured patients' self- and proxy-reports. Future studies should be mindful of current guidelines on proxy reporting when developing their studies and consider including neglected populations such as cognitively impaired patients to improve clinical validity.

Mindful attention is inversely associated with pain via mediation by psychological distress in orthopedic patients.

BACKGROUND: Orthopedic patients report pain as their main symptom complaint. Subjective pain experience is correlated with self-reported psychological state, such as distress. PURPOSE: This study tests whether scores from a measure of mindful attention are associated with subjective pain levels and whether psychological distress scores function as a mediation path. METHODS: During routine visits to a single orthopedic clinic in East Los Angeles, California, 525 patients were recruited to participate in the study. Participants reported on measures of pain (Universal Pain Assessment Tool [UPAT]), mindful attention (Five-Facet Mindfulness Questionnaire [FFMQ]), and psychological distress (Depression, Anxiety, Stress Scale [DASS]). We used Pearson correlations to examine relationships between FFMQ and UPAT scores and mediation analyses to test indirect effects of DASS scores as a mediation path. RESULTS: The average age of the sample was 54 years (range 18-98 years), 61% were male, and 64% were non-Hispanic White individuals. The locations of injury were the shoulder (72%), elbow (21%), and clavicle or wrist (7%). Ninety-one percent reported mild or greater pain in the prior 2 weeks (mean = 4.2 ± 2.5, range 0-10), and 49% reported mild or more severe distress symptoms (DASS: 13.0 ± 11.5). FFMQ scores inversely predicted UPAT scores (ß = -0.22, P < .01), mediated through DASS scores. DASS subscale scores for depression (ß = -0.10, P = .02) and stress (ß = -0.08, P = .04) but not anxiety (ß = -0.03, P = .33) produced significant indirect effects. FFMQ acting-with-awareness and non-judging subscales had the largest effect on depression and stress DASS subscale scores. CONCLUSIONS: We find statistical support to suggest that distress-particularly depressed mood and stress-mediates the association between mindful attention and pain intensity among orthopedic patients. A disposition of mindful attention might counter distress ailments that exacerbate subjective pain, and this has possible implications for mindfulness training interventions offered to orthopedic patients.

Incidence and factors associated with deep vein thrombosis among hospitalized adult patients at Hawassa university comprehensive specialized hospital Hawassa city, Sidama, Ethiopia: retrospective cohort study.

PURPOSE: Deep vein thrombosis is a public health problem with substantial morbidity and mortality globally. In Ethiopia, death due to complications of DVT is very significant however its incidence, risk factors, and preventive methods are not well studied. To assess the incidence and factors associated with deep vein thrombosis among hospitalized adult patients at Hawassa University Comprehensive Specialized Hospital, Hawassa, Ethiopia. METHOD: Intuitional-based retrospective study design was employed in July1-August 30, 2022 in 660 randomly selected patients' record cards. The patients' record cards were reviewed from 2012 to 2014 at Hawassa University Compressive Specialized Hospital. The data entry and analysis were done by using Epi Info and SPSS version 24. After adjusting covariates at a 95% confidence interval, an independent variable with a P value < 0.05 was declared significantly associated with deep vein thrombosis. An odds ratio was calculated to measure the strength of the relationship independent variable and deep vein thrombosis. RESULTS: The overall incidence of DVT was 10.6% [95% CI: 8.5%, 13.1%]. After adjusting for covariates, orthopedic trauma; AOR = 2.6 (95% CI (1.2-5.4), corona virus; AOR = 2.5 (95%CI (1.07-5.1), and hospital stay > 15 days; AOR = 2.2 (95% CI (1.25-3.94) were significantly associated with deep vein thrombosis. CONCLUSION: DVT incidence is high among hospitalized patients. An orthopedic trauma, a recent infection of the coronavirus, and a hospital stay above 15 days were a risk to acquire deep vein thrombosis. Early identification and detection of patients at high risk of developing DVT and provision of prophylaxis are recommended.

Titanium nanoparticles released from orthopedic implants induce muscle fibrosis via activation of SNAI2.

Titanium alloys represent the prevailing material employed in orthopedic implants, which are present in millions of patients worldwide. The prolonged presence of these implants in the human body has raised concerns about possible health effects. This study presents a comprehensive analysis of titanium implants and surrounding tissue samples obtained from patients who underwent revision surgery for therapeutic reasons. The surface of the implants exhibited nano-scale corrosion defects, and nanoparticles were deposited in adjacent samples. In addition, muscle in close proximity to the implant showed clear evidence of fibrotic proliferation, with titanium content in the muscle tissue increasing the closer it was to the implant. Transcriptomics analysis revealed SNAI2 upregulation and activation of PI3K/AKT signaling. In vivo rodent and zebrafish models validated that titanium implant or nanoparticles exposure provoked collagen deposition and disorganized muscle structure. Snai2 knockdown significantly reduced implant-associated fibrosis in both rodent and zebrafish models. Cellular experiments demonstrated that titanium dioxide nanoparticles (TiO2 NPs) induced fibrotic gene expression at sub-cytotoxic doses, whereas Snai2 knockdown significantly reduced TiO2 NPs-induced fibrotic gene expression. The in vivo and in vitro experiments collectively demonstrated that Snai2 plays a pivotal role in mediating titanium-induced fibrosis. Overall, these findings indicate a significant release of titanium nanoparticles from the implants into the surrounding tissues, resulting in muscular fibrosis, partially through Snai2-dependent signaling.

Optimal ultrasonic treatment frequency and duration parameters were used to detect the pathogenic bacteria of orthopedic implant-associated infection by ultrasonic oscillation.

INTRUDUCTON: The most accurate method for detecting the pathogen of orthopedic implant-associated infections (OIAIs) is sonication fluid (SF). However, the frequency and duration of ultrasound significantly influence the number and activity of microorganisms. Currently, there is no consensus on the selection of these two parameters. Through this study, the choice of these two parameters is clarified. METHODS: We established five ultrasonic groups (40kHz/10min, 40kHz/5min, 40 kHz/1min, 20kHz/5min, and 10kHz/5min) based on previous literature. OIAIs models were then developed and applied to ultrasound group treatment. Subsequently, we evaluated the efficiency of bacteria removal by conducting SEM and crystal violet staining. The number of live bacteria in the SF was determined using plate colony count and live/dead bacteria staining. RESULTS: The results of crystal violet staining revealed that both the 40kHz/5min group and the 40kHz/10min group exhibited a significantly higher bacterial clearance rate compared to the other groups. However, there was no significant difference between the two groups. Additionally, the results of plate colony count and fluorescence staining of live and dead bacteria indicated that the number of live bacteria in the 40kHz/5min SF group was significantly higher than in the other groups. CONCLUSION: 40kHz/5min ultrasound is the most beneficial for the detection of pathogenic bacteria on the surface of orthopedic implants.

Effectiveness of Virtual Reality-Based Rehabilitation Interventions in Improving Postoperative Outcomes for Orthopedic Surgery Patients.

PURPOSE OF REVIEW: The surge in orthopedic surgeries strains the US healthcare system, necessitating innovative rehabilitation solutions. This review examines the potential of virtual reality (VR)-based interventions for orthopedic rehabilitation. RECENT FINDINGS: The effectiveness of VR-based interventions in orthopedic surgery patients is scrutinized. While some studies suggest better patient-reported outcomes and satisfaction, mixed results emerge from others, demonstrating comparable or varied results compared to traditional rehabilitation. The underlying mechanisms of VR-based rehabilitation are elucidated, showing its positive impact on proprioception, pain management, agency, and balance. Challenges of unfamiliarity, patient engagement, and drop-out rates are identified, emphasizing the need for tailored approaches. VR technology's immersive environments and multisensory experiences offer a novel approach to addressing functional deficits and pain post-surgery. The conclusion drawn is that VR-based rehabilitation complements rather than replaces conventional methods, potentially aiding in pain reduction and functional improvement. VR-based rehabilitation holds promise for enhancing orthopedic surgery outcomes, presenting a dynamic approach to recovery. Its potential to reshape healthcare delivery and reimbursement structures underscores its significance in modern healthcare. Overall, VR-based rehabilitation offers a promising avenue for optimizing postoperative recovery in orthopedic surgery patients.

Incorporating preoperative frailty to assist in early prediction of postoperative pneumonia in elderly patients with hip fractures: an externally validated online interpretable machine learning model.

BACKGROUND: This study aims to implement a validated prediction model and application medium for postoperative pneumonia (POP) in elderly patients with hip fractures in order to facilitate individualized intervention by clinicians. METHODS: Employing clinical data from elderly patients with hip fractures, we derived and externally validated machine learning models for predicting POP. Model derivation utilized a registry from Nanjing First Hospital, and external validation was performed using data from patients at the Fourth Affiliated Hospital of Nanjing Medical University. The derivation cohort was divided into the training set and the testing set. The least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression were used for feature screening. We compared the performance of models to select the optimized model and introduced SHapley Additive exPlanations (SHAP) to interpret the model. RESULTS: The derivation and validation cohorts comprised 498 and 124 patients, with 14.3% and 10.5% POP rates, respectively. Among these models, Categorical boosting (Catboost) demonstrated superior discrimination ability. AUROC was 0.895 (95%CI: 0.841-0.949) and 0.835 (95%CI: 0.740-0.930) on the training and testing sets, respectively. At external validation, the AUROC amounted to 0.894 (95% CI: 0.821-0.966). The SHAP method showed that CRP, the modified five-item frailty index (mFI-5), and ASA body status were among the top three important predicators of POP. CONCLUSION: Our model's good early prediction ability, combined with the implementation of a network risk calculator based on the Catboost model, was anticipated to effectively distinguish high-risk POP groups, facilitating timely intervention.

Medication-based profiling of older orthopedic patients: a multicenter cross-sectional study.

BACKGROUND: Managing medication use in older orthopedic patients is imperative to extend their healthy life expectancy in an aging society. However, the actual situation regarding polypharmacy, the intake of potentially inappropriate medications (PIMs), and fall risk-increasing drugs (FRIDs) among older orthopedic patients is not well characterized. This study aimed to investigate the medication-based profiles of older orthopedic patients to highlight the critical points of concern. METHODS: We retrospectively reviewed the clinical data of consecutive patients aged ≥ 65 years who underwent orthopedic surgery at two acute care hospitals between April 2020 and March 2021. The cutoff number of prescribed drugs for polypharmacy was set at 6. According to the specified guidelines, 19 categories of drugs were identified as PIMs, and 10 categories were classified as FRIDs. RESULTS: A total of 995 older patients with orthopedic surgery were assessed, of which 57.4% were diagnosed with polypharmacy, 66.0% were receiving PIMs, and 41.7% were receiving FRIDs. The prevalence of FRID intake did not significantly differ among patients with degenerative spinal disease (n = 316), degenerative disease of extremities (n = 331), and fractures (n = 272). Compared with patients with degenerative disease of the extremities, the multivariable-adjusted prevalence ratios (PRs) of polypharmacy and PIM intake were significantly higher in patients with degenerative spinal disease (1.26 [confidence intervals (CI): 1.11-1.44] and 1.12 [CI: 1.00-1.25]), respectively. Use of antiemetic drugs (adjusted PR, 13.36; 95% CI: 3.14-56.81) and nonsteroidal anti-inflammatory drugs (adjusted PR, 1.37; 95% CI: 1.05-1.78) was significantly higher in patients with degenerative spinal disease. Among patients with degenerative spinal disease, the prevalence of antiemetic drug intake was 8.7% in lumbar spinal patients and 0% in cervical spinal patients. CONCLUSIONS: More than half of the orthopedic patients in this study were affected by polypharmacy, and approximately two-thirds were prescribed some form of PIMs. Patients with degenerative spinal disease showed a significantly higher prevalence of polypharmacy and PIM use compared with other orthopedic diseases. Particular attention should be paid to the high frequency of antiemetic drugs and nonsteroidal anti-inflammatory drugs intake among patients with degenerative lumbar spine conditions.

Postoperative delirium among elderly elective orthopedic patients in Addis Ababa Ethiopia: a multicentere longitudinal study.

BACKGROUND: Delirium is a neurocognitive disorder characterized by an acute and relatively rapid decline in cognition, disturbance of consciousness, reduced ability to focus, and shift of attention. It mainly affects elderly patients with an incidence of about 8-23% after an operation. It frequently occurs between 24-hrs and 5 days after surgery. It results in serious medical management problems. Hence, identifying the incidence and associated factors may help prevent and manage its sequel in the elderly. OBJECTIVE: Assessment of the incidence and associated factors of postoperative delirium(POD) among elderly elective orthopedic surgical patients in Addis Ababa public hospitals, Ethiopia, 2024. METHODS: A multi-centered longitudinal study was conducted on 220 elderly (age ≥ 65 years) patients in four selected public hospitals of the study area from February 2024 to May 2024, and a systematic sampling technique was used to select the study units. Data was collected through chart review and interviews of patients, and postoperative delirium was assessed using the confusion assessment method (CAM). Both bivariable and multivariable logistic regression models were used for statistical analysis. The strength of association was determined with an adjusted odds ratio (AOR) with a 95% confidence interval(CI) at a p-value of < 0.05. RESULTS: A total of 220 patients were studied, and the incidence of POD among elderly elective orthopedic surgical patients was 33.7%. Age 65-75(AOR = 0.47, 95%CI (0.226-0.97)), Induction using ketamine (AOR = 1.32, 95%CI(1.109-3.87), p = 0.003)), perioperative opioid use (AOR = 2.20, 95%CI(1.073 4.5313)), intraoperative anticholinergic use(AOR = 2.24,95%CI(1.831-4.235)), recent hospitalization history (AOR = 2.24,95%CI(1.202-4.206)), and transfusion (AOR = 2.83,95%CI(1.295-6.193)) were significantly associated with POD (p < 0.05). CONCLUSION AND RECOMMENDATIONS: The incidence of POD in the study area was high (33.7%); advanced age, hospitalization history, Anesthesia induction by Ketamine, perioperative anticholinergic uses, opioid use, and blood transfusion use were associated factors for postoperative delirium. We recommend giving due attention to elderly patients with advanced age, history of hospitalization, perioperative Ketamie use, perioperative anticholinergic uses, opioid use, and blood transfusion use undergoing elderly elective orthopedic surgery.