Benchmarking seeks to evaluate implant survivorship at certain follow-up time points against predetermined standards. The International Society of Arthroplasty Registries (ISAR) International Prosthesis Benchmarking Working Group (IPBWG) developed a predefined set of standards in which receiving a benchmark indicates that an implant has acceptable revision-free survivorship, whereas not receiving a benchmark suggests that the revision rate exceeded these established standards. Although benchmarking of TKA implant systems has been performed in select international countries, applications of benchmarks to TKA systems used in a US-based cohort are lacking. We sought to apply the ISAR IPBWG benchmarking standards to our US-based healthcare system's total joint replacement registry and identify TKA implant systems meeting (1) early 2- and 5-year benchmarks, (2) midpoint 10-year benchmarks, and (3) late 15-year benchmarks. As a secondary aim, we sought to evaluate the consistency of these benchmarks when stratified by patient gender and age. Data from our US-based healthcare system's Total Joint Replacement Registry were used to conduct a retrospective cohort study. The registry is well suited for benchmarking analyses because it captures all primary and revision TKAs performed within a closed, longitudinal healthcare system, enabling near-complete outcome tracking and comprehensive implant tracking through barcode-based documentation, with routinely audited administrative and clinical coding. Patient follow-up was 96%, 91%, 85%, and 80% at 2, 5, 10, and 15 years, respectively. Surgeons complete intraoperative registry forms via the electronic health record (EHR) for all TKAs, which are crosschecked against implant information-including manufacturer, implant name, and catalog number-recorded in the EHR via barcode scan and extracted into the registry. Patients are longitudinally followed for revision surgery until healthcare plan termination or death, and all identified revisions are manually validated through chart review. We identified all primary TKAs for osteoarthritis performed from January 1, 2001, through December 31, 2024. The final sample included 288,584 primary TKAs performed by 605 surgeons at 68 facilities. The cohort had a mean ± SD age of 68 ± 9 years, mean ± SD BMI of 31.2 ± 5.5 kg/m2, was predominantly women (61% [176,641 of 288,584]), and largely comprised patients with ASA class I to II (59% [171,306 of 288,584]). Each unique implant system, defined as the femoral and tibial component brand, fixation for each component, insert stability, and tibial insert mobility, was evaluated separately; systems with < 250 TKAs recorded into the registry were excluded. All-cause revision incidence during follow-up was evaluated using 1 - the Kaplan-Meier estimate and reported as cumulative percent revision (CPR) and 95% confidence interval (CI). Benchmark standards proposed by the IPBWG were used to evaluate the 2-, 5-, 10-, and 15-year time points; at each time point, at least 250 TKAs had to remain at risk to receive a benchmark. Implant systems received an early benchmark at 2 and 5 years after the primary TKA when the lower bound of the CPR 95% CI was less than or equal to the revision rate benchmark standards of 2% and 3%, respectively. Superiority and noninferiority relative to the benchmark standard were determined for 10-year midpoint and 15-year late benchmarks; the noninferiority margin was set at a 20% higher relative revision rate than the benchmark standard. For the 10-year time point, the system was considered superior when the upper bound of the 95% CI was less than or equal to 5%; when the upper bound of the 95% CI was less than or equal to 6% (20% above the 5% benchmark standard, or a 1% noninferiority margin), the system was considered noninferior; when it was above 6%, the system did not receive a 10-year benchmark. For the 15-year time point, systems with the upper bound of the 95% CI less than or equal to 6.5% were considered superior, and those in which the upper bound was less than or equal to 7.8% were considered noninferior; systems in which the 95% CI was above the noninferiority margin did not receive a benchmark. Of the 45 TKA implant systems evaluated, 93% (42) received a benchmark at 2 years, representing 99% (284,929 of 288,584) of the TKAs included. The three implant systems not receiving a 2-year benchmark included the Smith & Nephew cemented, bicruciate-stabilized, fixed-bearing Journey™ (n = 889; CPR 3.1 [95% CI 2.1 to 4.5]); the Smith & Nephew cemented, bicruciate-stabilized, fixed-bearing Journey II/Journey (n = 2200; CPR 2.8 [95% CI 2.1 to 3.6]); and the Zimmer Biomet cemented, ultracongruent or anterior-stabilized, fixed-bearing Natural Knee®/Natural Knee II (n = 566; CPR 3.9 [95% CI 2.6 to 5.9]). Of the 42 implant systems evaluated for 5-year benchmarks, 88% (37) received a benchmark, representing 96% (274,056 of 286,020) of the cohort evaluated for this time point. Five implants did not receive a 5-year benchmark: the DePuy cemented, posterior-stabilized, rotating PFC Sigma®/MBT (n = 7899; CPR 3.6 [95% CI 3.2 to 4.0]); the Smith & Nephew cemented, bicruciate-stabilized, fixed-bearing Journey (n = 889; CPR 5.4 [95% CI 4.1 to 7.1]); the Smith & Nephew cemented, bicruciate-stabilized, fixed-bearing Journey II/Journey (n = 2200; CPR 5.1 [95% CI 4.1 to 6.4]); the Zimmer Biomet cemented, cruciate-retaining, fixed-bearing Natural Knee II (n = 410; CPR 4.9 [95% CI 3.2 to 7.7]); and the Zimmer Biomet cemented, ultracongruent or anterior-stabilized, fixed-bearing Natural Knee/Natural Knee II (n = 566; CPR 5.9 [95% CI 4.2 to 8.2]). Of 25 implant systems considered for the 10-year benchmark, 52% (13) of systems received a superior benchmark, and 16% (4) of systems received a noninferior benchmark. Eight implant systems did not receive any 10-year benchmark. Implant systems receiving a superior benchmark were used in 91% (204,633 of 224,619) of the eligible TKAs, whereas implants that did not receive any 10-year benchmark were used in only 3% (6385 of 224,619) of the eligible TKAs. At the 15-year time point, 50% (6 of 12) of the implant systems evaluated received a superior benchmark, representing 89% (119,871 of 135,060) of the cohort evaluated at this time point. Forty-two percent (5) of the implant systems received a noninferior benchmark, and 8% (1) of the systems did not receive a benchmark at the 15-year time point. The same implant systems consistently failed to receive benchmarks at various time points in gender- and age-stratified analyses. Applying IPBWG benchmarking to a large US-based arthroplasty registry identified TKA implant systems with consistently inferior, adequate, or superior revision performance at mid- and long-term follow-up. These findings support prioritizing implant systems that meet benchmark standards for primary TKA and reevaluating routine use of implants that fail to achieve benchmarks when alternatives with reliable mid- and long-term performance are available. Future studies integrating benchmarking with risk-adjusted analyses are needed to clarify factors driving implant performance and to strengthen postmarket surveillance. Level III, therapeutic study.
Bibliometric analysis. To analyze the global application of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and identify status and emerging trends in SCI research. Not applicable. Articles published between 2020 and 2023 were retrieved from the Web of Science Core Collection. Data on disciplines, ISNCSCI versions, research aims, journals, keywords, countries, authors, and collaboration patterns were manually extracted. Visualization and mapping analyses were performed using VOSviewer and CiteSpace. A total of 595 articles involving 3498 authors from 46 countries were included. Among them, 569 were ISNCSCI application studies and 26 were development or version-related studies. Within the application studies, the leading disciplines were neurology (507 articles), orthopedics (180), and rehabilitation (179). The 2011 ISNCSCI edition was the most frequently reported version (30.8%), although 56.2% of studies did not specify the version. The journals publishing the most articles were Spinal Cord, Journal of Neurotrauma, and Archives of Physical Medicine and Rehabilitation. The main research topics were SCI prognosis (15.8%), rehabilitation efficacy (15.4%), and SCI-related complications (15.4%). The United States, China, and Canada were the top publishing countries. Frequently emerging keywords in 2023 included "predictors," "cardiovascular disease," "features," and "disability." ISNCSCI is a widely accepted standardized tool in SCI research and clinical practice. The field is characterized by expanding international participation, stronger interdisciplinary collaboration, and increasingly diverse applications. Better reporting of ISNCSCI versions may improve consistency and comparability across future studies. None.
To examine the frequency of use and establish routine clinical practice of patient-reported outcome measures (PROMs), performance-based OMs and clinician-reported OMs in the assessment of a suspected case of lateral elbow tendinopathy (LET). Physiotherapists from eight countries completed an anonymous online survey, rating their frequency of use (never, rarely, sometimes, often and always) for unidimensional PROMs, multidimensional PROMs, performance-based OMs and clinician-reported OMs. To establish clinical practices, responses were dichotomised into routine (≥70% often/always) and not-routine (≥70% sometimes/rarely/never); items below both thresholds were classified as neither. Two hundred ninety-nine respondents completed the survey. No outcome measure met the criteria for routine practice. Eight of 17 multidimensional PROMs, and six of eight clinician-reported OMs met the criteria for not-routine practice. All unidimensional PROMs and performance-based OMs, and a select number of multidimensional PROMs and clinician-reported OMs did not meet the threshold for routine or not-routine practice. Our results suggest no single outcome measure is routinely used by physiotherapists assessing a suspected case of LET. It is plausible that physiotherapists select OMs based on patient presentation, rather than the clinical diagnosis, or that outcome measures are perhaps seen more as a research tool than common place in clinical practice.
Influx of large numbers of neutrophils is characteristic of pleural infection; however, neutrophil behaviour is understudied. We designed an observational multicohort study with the aims to discover and validate the association between neutrophil extracellular traps (NETs), disease severity, one-year survival, and the extent of sonographic septations. We analysed five independent datasets across three countries. The PILOT cohort (UK, n=215) was used as a discovery cohort for the association of NETs with disease severity with validation in four independent cohorts across three countries (UK, Greece, Italy, n=100). The PILOT cohort was further analysed to assess the association of NETs with one-year survival and the development and extent of sonographic septations. A separate cohort (the Oxford-Osler cohort, UK, n=30) was used to assess the relationship between NETs and the need for intrapleural enzyme therapy (IET) as rescue treatment. A ten-unit increase in NETs was associated with 13% higher odds of being into a higher RAPID Score group (OR=1.13, 95% CI: 1.02-1.27, p=0.02), and this association remained robust in the independent validation cohort (OR=1.29, 95% CI: 1.11-1.40, p=0.0005). A ten-unit increase in NETs was also associated with a 15% higher risk of one-year mortality (HR=1.15, 95% CI: 1.01-1.32, p=0.04) independent of the RAPID Score, and a 17% higher likelihood of sonographic septations (OR=1.17, 95% CI: 1.01-1.37, p=0.04). Citrullinated fibrin was associated with septation severity (OR=1.10, 95% CI: 1.04-1.16, p=0.00005). Pleural fluid NETs are a biomarker of disease severity and one-year mortality, in pleural infection. Future studies are required to assess the combination of NET-targeting strategies in combination with existing treatments.
We performed a single-center observational cohort study on patients with COVID-19. We retrospectively analyzed 54 patients with confirmed SARS-CoV-2 infection, diagnosed as critically ill. Severely ill patients have a poor prognosis and it is a matter of great interest to identify these cases for an adequate management. Current findings revealed that altered levels of some blood markers might be linked with the degree of severity and mortality of patients with COVID-19. Our study aimed to assess the relationship between inflammation and coagulation in SARS-CoV-2 infection and to find out if pro-inflammatory markers are correlated with coagulation parameters in COVID-19. Pro-inflammatory markers included leptin and classical biomarkers. This paper highlights the results obtained. We found statistically significant associations between blood levels of various biomarkers including leptin, IL-6, ferritin, neutrophil-lymphocyte ratio, C-reactive protein, fibrinogen, erythrocyte sedimentation rate and lactate dehydrogenase and the presence of coagulopathy, as indicated by the Pearson Chi-Square and Likelihood Ratio tests. The relationships are not linear, as indicated by the nonsignificant Linear-by-Linear Association test. The correlations between some biomarkers such as leptin, IL-6, ferritin, neutrophil-lymphocyte ratio, C-reactive protein, fibrinogen, erythrocyte sedimentation rate and lactate dehydrogenase and coagulopathy are weak and not statistically significant and the correlation between IL-6 levels and coagulopathy is very weak and negative and not statistically significant. Different crosstabulations between serum leptin levels and D-dimers, Prothrombin time, Prothrombin activity, International-normalized-ratio and activated partial thromboplastin time have been performed including the analysis of a potentional correlation. There are statistically significant associations between serum leptin levels and coagulation parameters, including D-dimers, prothrombin time, prothrombin activity and activated partial thromboplastin time, as indicated by the Pearson Chi-Square test. There is also a statistically significant association between serum leptin levels and international-normalized ratio (INR) as indicated by the Pearson Chi-Square test. The Linear-by-Linear Association test indicates a significant linear relationship between Leptin levels and international-normalized ratio. Pearson R shows a moderate positive correlation, which is statistically significant.
The World Health Organization (WHO), together with the International Academy of Cytology and the International Agency for Research on Cancer, has introduced a standardized framework for reporting lung cytopathology. This approach clarifies diagnostic tiers, provides malignancy risk estimates, and integrates with the latest WHO Tumour Classification. Derived partly from the Papanicolaou Society of Cytopathology model, it strengthens diagnostic reproducibility and clinical risk categorization. The aim of this study is to evaluate the diagnostic accuracy of fine-needle aspiration biopsy (FNAB) in lung lesions reported under the WHO system. A comprehensive search of Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov and conference abstracts was carried out using predefined terms ("lung," "diagnostic accuracy," "FNAB"). Studies applying the WHO reporting scheme to lung FNAB were eligible, with histopathology or clinical follow-up as reference standards. Meta-analysis examined sensitivity and specificity at 3 thresholds: (1) malignant only, (2) suspicious or higher, and (3) atypical or higher. Pooled diagnostic odds ratios and summary receiver operating characteristic analyses were undertaken. Four studies met inclusion criteria. Risk of malignancy increased across WHO categories, from 27% in benign to 92% in malignant. Sensitivity and specificity differed by cut-off: malignant only (33%, 100%), suspicious or higher (73%, 96%), atypical or higher (83%, 84%). Aggregate diagnostic odds ratios and summary receiver operating characteristic curves supported the diagnostic robustness of the system. The WHO reporting system provides effective stratification of lung FNABs. Defining positivity at "suspicious" or higher offers the best diagnostic balance, while including "atypical" increases sensitivity with minimal loss of specificity, supporting its clinical utility.
Little is known about the causes of serum aquaporin 4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (AQP4-positive NMOSD) or how its pathophysiology differs from other demyelinating autoimmune diseases, which limits therapeutic and preventative opportunities despite available diagnostic biomarkers. By performing a pan-ancestry genome-wide association study (GWAS), we aimed to deepen our understanding of the genetic architecture of AQP4-positive NMOSD and to explore shared heritability with other autoimmune diseases. We performed a pan-ancestry GWAS in 2833 individuals, including 1573 AQP4-positive NMOSD cases and 1260 controls (comprising non-affected relatives, healthy non-relatives, and those with other autoimmune diseases). Samples were collected from the International NMOSD Genetics Consortium, comprising 36 hospitals and research facilities across the world. All individuals with AQP4-positive NMOSD fulfilled the 2015 international consensus diagnostic criteria for NMOSD, including positive AQP4-IgG status. We also performed a second GWAS with only the 1857 samples of European ancestry (803 cases and 1054 controls). We then compared our GWAS findings to those from other autoimmune diseases. We found three independent associations with AQP4-positive NMOSD that reached genome-wide significance: two within the MHC and a third within an intron of the STAT4 gene. In the pan-ancestry study, we identified a complement C4A-associatied variant, rs1150753 (chr6:32092090:A>G, p=1·61 × 10-29, odds ratio [OR] 2·95, 95% CI 2·44-3·56), rs607929 (chr6:32619221:C>G, p=2·87 × 10-24, OR 1·93, 95% CI 1·70-2·20), and a STAT4-associated variant, rs35593987 (chr2:191051800:AC>A, p=8·49 × 10-14, OR 1·75, 95% CI 1·51-2·03). In Europeans, we identified variants that were either in linkage disequilibrium with or the same as those from the pan-ancestry study: rs1270942 (chr6:31951083:A>G, p=2·52 × 10-28, OR 3·01, 95% CI 2·47-3·66), rs607929 (p=1·12 × 10-20, OR 1·99, 95% CI 1·72-2·30), and rs3821236 (chr2:191038032:G>A, p=1·20 × 10-10, OR 1·74, 95% CI 1·47-2·06). rs1270942 is in linkage disequilibrium with rs1150753 (r2=0·96) as well as two AQP4-positive NMOSD-associated HLA alleles, HLA-DRB1*03:01 (p=2·80 × 10-26, OR 2·79, 95% CI 2·30-3·37) and HLA-B*08:01 (p=1·02 × 10-24, OR 2·68, 95% CI 2·22-3·24). A priori testing of the P1104A variant (rs34536443, chr19:10352442:G>C) within the TYK2 gene, which acts upstream in the STAT4 pathway, found it to be protective (p=0·0008, OR 0·52, 95% CI 0·35-0·76 in the pan-ancestry study). Genetic sharing was observed with several comorbid autoimmune diseases for both the complement C4A-associated and STAT4-associated variants, including Sjögren's syndrome and systemic lupus erythematosus. AQP4-positive NMOSD is more genetically similar to systemic autoimmune diseases than to multiple sclerosis, despite sharing overlapping clinical phenotypes. Specifically, a polymorphism associated with reduced complement C4 was identified as the biggest disease genetic risk factor, which has been shown to facilitate the development of autoantibody-producing B cells. Our findings also support a pathogenic role of HLA-restricted CD4+ T cells, owing to both a genome-wide significant association of HLA-DRB1*03:01 as well as heritable risk within the TYK2-STAT4 signalling pathway. Having already been shown to be a successful target for treating psoriatic arthritis and, potentially, systemic lupus erythematosus, we propose the TYK2-STAT4 pathway as a possible therapeutic target in AQP4-positive NMOSD. The OAK Foundation, The Guthy Jackson Charitable Trust Foundation, and the UK Medical Research Council.
Globally, 537 million persons live with diabetes, and a lifetime risk of up to 34% of developing diabetic foot ulcers (DFUs) necessitates strengthened preventive initiatives. The study aimed to develop and evaluate a clinical decision support system (CDSS) to be used by health care professionals in foot assessment and risk stratification as a base for prevention. Based on principles of human-computer interaction, the CDSS was developed for DFU risk assessment. Users, health care professionals from Region Västra Götaland in Sweden, evaluated the functions regarding effectiveness, efficiency, and satisfaction using a mixed methods usability testing approach. Expectations and experiences of using the CDSS were evaluated with the System Usability Scale (SUS). A total of 9 participants participated. User expectations of the CDSS, measured by SUS, averaged 77.2 (SD 14.6). Posttest SUS scores were 68.9 (SD 14.3), with a mean difference of 8.3 (P=.07), a nonsignificant reduction of usability after testing. The effectiveness of the CDSS in supporting users to complete 9 clinical tasks showed that for 7 (78%) tasks, at least 5 (56%) testers successfully achieved the intended goals. Tasks involving the identification of ingrown toenails and the confirmation of foot status, including risk stratification for the patient, were completed by fewer testers. Efficiency, measured as mean task completion time, ranged from 7 seconds to 9 minutes 20 seconds, and qualitative feedback informed recommendations for further system refinement. Users reported that a structured CDSS has the potential to support more equitable, consistent, and person-centered DFU prevention within a digital health service. A digital health service for DFU risk stratification was developed based on national and international guidelines. Although the users' expectations of the usability were higher compared to how they experienced the CDSS, the SUS test was near a threshold of 70, indicating that the system being tested was above average in usability. Further development and validation, both nationally and internationally, with continued attention to users' needs and contextual factors, are recommended.
Return to sport (RTS) success rates remain suboptimal for high sports demand individuals (HSDs) following anterior cruciate ligament reconstruction (ACLR). Traditional rehabilitation model (TRM) primarily focuses on strength recovery and range of motion but demonstrates deficiencies in neuromuscular control and sport-specific conditioning. This study aimed to compare the effects of functional rehabilitation model (FRM) versus Traditional rehabilitation model (TRM) on post-operative functional recovery and RTS outcomes in HSDs. A prospective single-blind randomised controlled trial was conducted including 64 HSDs who underwent ACLR (exercise ≥3 times per week, Tegner score >5), randomly allocated to the FRM group ( n = 32) and TRM group ( n = 32). The FRM group received a performance-based progressive 24-week rehabilitation protocol incorporating multimodal sensory training, closed-chain exercises, unstable surface proprioceptive training and sport-specific skill integration. The TRM group received a standard time-oriented 24-week rehabilitation protocol. The primary outcomes included 48-week RTS rate and functional recovery trajectory. The secondary outcomes included isokinetic strength, single-leg hop tests, modified star excursion balance test, proprioception and patient-reported outcomes (International Knee Documentation Committee [IKDC], Lysholm and Anterior Cruciate Ligament-Return to Sport after Injury [ACL-RSI]). Assessment time points included pre-operative baseline, 24 weeks and 48 weeks postoperatively. Repeated measures analysis of variance was used to evaluate longitudinal changes. Fifty-seven patients completed follow-up (retention rate: 89.1%). The FRM group demonstrated significantly higher 48-week successful RTS rate compared to the TRM group (89.3% vs. 62.1%, P = 0.038), with relative risk 1.44 (95% confidence interval: 1.05-1.97) and number needed to treat 3.7. Repeated measures analysis revealed that the FRM group significantly outperformed the TRM group in quadriceps peak torque (48 weeks: 124.17 ± 7.25 vs. 98.42 ± 8.73 Nm, P < 0.001) and limb symmetry index (89.15% ± 3.85% vs. 69.45% ± 5.15%, P < 0.001). In single-leg hop tests, the FRM group demonstrated superior performance in lateral hop time (5.54 ± 2.25 vs. 7.84 ± 3.37 s, P = 0.004) and box hop symmetry index (97.50% ± 29.60% vs. 76.20% ± 31.40%, P = 0.011). Proprioceptive testing showed that the FRM group had smaller position sense errors at 30° (2.83° ± 1.63° vs. 4.25° ± 1.85°, P = 0.002) and 45° knee flexion angles (6.37° ± 1.69° vs. 7.57° ± 1.73°, P = 0.008). Patient-reported outcomes demonstrated the FRM group superiority in IKDC (89.45 ± 9.72 vs. 83.45 ± 12.73, P = 0.028), Lysholm (88.71 ± 5.78 vs. 76.12 ± 12.38, P < 0.001) and ACL-RSI scores (79.52 ± 8.17 vs. 70.35 ± 10.24, P < 0.001). The FRM group exhibited sustained linear improvement patterns, while the TRM group showed a recovery plateau after 24 weeks. Compared to TRM, FRM significantly improved functional recovery trajectories and RTS outcomes in HSDs through enhanced neuromuscular control, improved dynamic performance and increased psychological readiness.
Anterior cruciate ligament (ACL) ruptures are prevalent, particularly among young athletes. Although ligament reconstruction is the gold standard treatment, the rehabilitation process is extensive and has high reinjury rates. Recovery is often hindered by muscle inhibition and psychological factors like kinesiophobia and associated fear of reinjury. Emerging evidence suggests that motor imagery and action observation could enhance rehabilitation outcomes. Immersive virtual reality (VR) offers a novel way to integrate these techniques, potentially accelerating recovery. In this parallel randomized controlled trial, patients undergoing ACL reconstruction were randomly assigned to receive either conventional rehabilitation alone or conventional rehabilitation plus VR training. Our VR content incorporated several novel elements, including embodiment in a virtual body, first-person perspective, and the performance of virtual exercises guided by a virtual physiotherapist. Another innovative feature was that patients conducted the daily VR training independently at home using a standalone head-mounted display. The VR group performed a 20-min daily VR rehabilitation program for 4 weeks post-surgery, visualizing, planning, and executing movements using an embodied virtual avatar. Self-reported disability (International Knee Documentation Committee score, IKDC), quadriceps strength limb symmetry, active knee extension range of motion (ROM) limb symmetry, and kinesiophobia (Tampa Scale of Kinesiophobia-short form, TSK-11) were measured at baseline, 4, 12, and 36 weeks. Forty-seven participants were randomized, with 44 completing treatment. IKDC scores were not statistically significantly different between groups, despite moderate effect sizes at 4 and 36 weeks (Cohen's d = 0.559, and d = 0.722, respectively). The VR intervention group showed significantly lower kinesiophobia at 4 weeks post-surgery compared to controls (27.00 ± 6.58 vs. 33.35 ± 5.07, Cohen's d = - 0.971, p = 0.045). Both groups demonstrated significant improvements in all outcomes over time (p < 0.001). No significant differences were found for range of motion or quadriceps strength limb symmetry. No adverse events were reported related to the intervention. Reducing kinesiophobia is crucial for timely and effective rehabilitation and return to sport, and for reducing reinjury risk. To our knowledge, this is the first clinical study to investigate the independent use of therapeutic VR at home during post-orthopedic surgery rehabilitation. Future research should explore different VR interventions, including more active exercises and personalized programs, to enhance adherence and optimize recovery. The study was pre-registered with the National Library of Medicine (NCT05080894; first registered 09/20/2021).
Purpose: To critically evaluate the role or effect of platelet-rich plasma (PRP) in anterior cruciate ligament (ACL) reconstruction in terms of clinical and radiological outcomes. Method: We conducted a systematic search of PubMed, Embase, the Cochrane Library, and Web of Science to identify relevant studies. Clinical outcomes included the Visual Analogue Scale (VAS), International Knee Documentation Committee (IKDC) subjective and objective evaluations, Lysholm score, Tegner score, anterior knee laxity, Knee Injury and Osteoarthritis Outcome Score (KOOS), Kujala score, Victorian Institute of Sport Assessment (VISA) scale, proprioception, isokinetic strength, and physical examination tests (anterior drawer, Lachman, and pivot-shift tests). Radiological outcomes encompassed measures obtained via magnetic resonance imaging (MRI), computed tomography (CT), X-ray, and ultrasound. Statistical significance was defined as a p value < 0.05, and all analyses were performed using R software (version 4.1.3). Results: A total of 23 studies, including 19 randomized controlled trials, met the inclusion criteria, encompassing 1072 patients overall. The meta-analysis showed significant differences between PRP group and non-PRP group with regard to VAS score at 6- and 12-month follow-up, Lysholm score at 6-month follow-up, and Tegner score at 6-month follow-up. Meta-regression showed that the two group differences in VAS score changed significantly with follow-up time (p < 0.01). In terms of radiological findings, about half of the assessments favored PRP to facilitate the graft maturation and integration at 6-month follow-up. Conclusions: PRP application in ACL reconstruction compared with non-PRP, may produce short-term but not long-term clinical outcomes such as VAS score, Lysholm score and Tegner score. While some short-term statistical differences exist, their magnitude and durability do not yet justify routine clinical adoption of PRP in ACL reconstruction. Larger samples and higher-quality studies are needed to support our results and further explore the advantages of PRP in other aspects. Level of evidence: Level II.
Early open fracture management aims to minimise the risk of complications. For the most severe open fracture wounds, multiple irrigation and debridement surgeries are required to overcome severe wound contamination, to reassess the evolving tissue injury or to temporise and plan further surgery. When multiple irrigation and debridement surgeries are needed, uncertainty remains about how the open fracture wound should be managed to best minimise complications. The primary aim of this trial is to compare the antibiotic cement bead pouch vs negative pressure wound therapy in the management of patients with severe open tibia fracture wounds. BvV is a multicentre, pragmatic, parallel arm randomised controlled trial that aims to enrol 312 adult patients admitted to a participating centre with a severe open tibia fracture requiring multiple irrigation and debridement surgeries. Participants will be randomly allocated on a 1:1 basis to either antibiotic cement bead pouch or negative pressure wound therapy. The primary outcome will be a composite outcome to evaluate clinical status 6 months after randomisation. Using the win ratio approach, we will hierarchically assess the composite outcome in the following order: (i) all-cause mortality, (ii) injury-related amputation of the lower extremity, (iii) unplanned reoperation to manage wound complications, an infection or promote fracture healing and (iv) clinical fracture healing assessed using the Functional IndeX for Trauma (FIX-IT) instrument. The BvV trial has been approved by a central institutional review board (IRB) (Advarra) for clinical sites in the USA, the ethics board at the coordinating centre at McMaster University (Hamilton Integrated Research Ethics Board), and participating sites not using the central institutional IRB (Fraser Health Research Ethics Board, The University of British Columbia Clinical Research Ethics Board, Newfoundland and Labrador Health Research Ethics Board, University of Manitoba Biomedical Research Ethics Board). Additional clinical sites who are in the start-up phase, as well as any new selected clinical sites, will obtain local approvals prior to initiating trial activities. This will include a clinical site in the UK who is in the process of obtaining the necessary approvals. Recruitment began in November 2023. Both interventions are frequently used to manage severe open fracture wounds, ensuring that the trial results can be easily transitioned into clinical practice. The results of this trial will be disseminated to national and international partners through peer-reviewed publications, academic conferences and stakeholder engagement activities. NCT05615844.
Anterior cruciate ligament (ACL) reconstruction remains one of the most commonly performed orthopedic procedures worldwide, with graft selection representing a key determinant of postoperative outcomes. In recent years, the peroneus longus tendon has emerged as a promising alternative to the traditionally used hamstring tendon autograft. Previous meta-analyses have suggested comparable or favorable outcomes; however, several new randomized controlled trials and observational studies have since been published, necessitating an updated synthesis of the evidence. This systematic review and meta-analysis, therefore, aims to comprehensively evaluate and compare the clinical, functional, and stability outcomes of peroneus longus tendon versus hamstring tendon autografts in primary ACL reconstruction. A systematic literature search was conducted across PubMed, Cochrane Library, Web of Science, and Embase from inception until January 2026. Studies comparing the peroneus longus tendon with hamstring tendon autografts reporting at least one predefined outcome were eligible for inclusion. A total of 32 studies comprising 10 randomized controlled trials and 22 observational studies were included. Pooled analyses were performed using random-effects models, with outcomes reported as mean differences (MDs) or odds ratios with 95% confidence intervals. No statistically significant differences were observed between the two groups in terms of International Knee Documentation Committee (IKDC) score (MD: -0.74, 95% CI: -1.58 to 0.09) or Lysholm score (MD: -0.50, 95% CI: -1.17 to 0.18). Additionally, objective knee stability measures, including the anterior drawer, Lachman, and pivot shift tests, were also not significantly different between the two groups. Subgroup analysis of randomized controlled trials demonstrated significantly higher IKDC and Lysholm scores in the peroneus longus tendon group. Patients in the hamstring tendon group exhibited significantly greater thigh circumference reduction compared to the peroneus longus tendon group (MD: 0.92 cm, 95% CI: 0.72 to 1.11), indicating more pronounced donor site muscle atrophy. Ankle function, assessed by American Orthopaedic Foot and Ankle Society (AOFAS) scores, remained comparable between groups. Peroneus longus tendon autograft demonstrates comparable functional and stability outcomes to hamstring tendon autograft while offering superior preservation of thigh muscle mass. These findings support its consideration as a viable alternative graft option in primary ACL reconstruction, particularly in patients where minimizing knee donor site morbidity is a priority.
To determine the association between surgical delay, anterior cruciate ligament (ACL) tissue quality, failure rates, and clinical outcomes at a minimum 2-year follow-up after arthroscopic ACL primary repair (ACLPR). Consecutive patients with complete, proximal (type I/II) ACL tears who underwent arthroscopic ACLPR and had a minimum 2-year follow-up were included. Surgical delay was stratified into 3 categories: acute (≤21 days), subacute (22-90 days), and chronic (>90 days). Intraoperative tissue quality was assessed according to synovial sheath integrity (grade 1, completely intact; grade 2, >50% intact; grade 3, <50% intact) and rupture pattern (1-bundle, 2-bundle, and complex tear). Failure was defined as instrumented laxity >3 mm anterior tibial translation side-to-side difference, pivot shift grade ≥2, and/or subjective instability. Clinical and patient-reported outcomes were compared and Patient Acceptable Symptom State thresholds established. Between 2008 and 2021, 276 of 298 (loss to follow-up, 7.4%) patients (mean age, 39.7 ± 10.7 years; females, 50.3%) who underwent ACLPR with a follow-up of 2.9 ± 1.0 years (2.0-6.5 years) met the inclusion criteria. Sixty-eight (24.6%) ACLPR were acute, 152 (50.1%) subacute, and 56 (20.3%) chronic. Surgical delay was not significantly correlated with worse tissue quality (grade 2, P = .79; grade 3, P = .06) or increased failure risk (P = .57). ACLPR failure occurred in 28 patients (10.1%), with no significant differences among groups (acute, 10.2%; subacute, 11.2%; chronic, 7.1%; P = .76). Reoperation rates (P = .62) and anterior tibial translation side-to-side difference (P = .90), as well as patient-reported outcomes (all P > .28) and Patient Acceptable Symptom State threshold achievements (overall: International Knee Documentation Committee, 84.7%; Lysholm, 83.3%; Forgotten Joint Score-12, 87.3%; and ACL-Return to Sport after Injury, 88.5%) were comparable across groups (all P > .05). Injury chronicity did not adversely affect failure rates or clinical outcomes at minimum 2-year follow-up after ACLPR. Therefore, in the case of a proximal tear location and sufficient tissue quality, surgical delay alone should not be considered a contraindication for ACLPR. Level III, retrospective comparative case series.
Cutibacterium acnes (C. acnes) is the most common pathogen in shoulder periprosthetic joint infection (PJI) but remains difficult to distinguish from contamination due to its low virulence and presence as a skin commensal. Diagnostic ambiguity and variable antibiotic resistance further complicate management. We analyzed 87 C. acnes isolates from patients undergoing evaluation for shoulder PJI across two institutions. Isolates were obtained from intraoperative cultures and stored for subsequent analysis. Hemolysis, aerotolerance, and growth rate were assessed in vitro. Antimicrobial susceptibility to five antibiotics was determined using minimum inhibitory concentration (MIC) testing, with interpretive breakpoints defined by both the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Infection status was classified per the 2018 International Consensus Meeting (ICM) criteria into definite, probable, possible, or unlikely categories. Associations between phenotypic traits and infection classification were assessed using univariate and multivariable statistical models. Only 12.6% (n = 11) of cases met criteria for definite infection, while the majority (48.3%) were classified as probable. Hemolysis and aerotolerance were observed in 51.7% and 54.0% of isolates, respectively, and were strongly associated with one another (P < .001); however, neither phenotype was associated with infection classification in univariate or multivariable analysis. Clindamycin resistance was observed in a minority of isolates but varied by standard, with 12.6% classified as resistant by EUCAST and 6.9% as non-susceptible by CLSI. No isolates were resistant to vancomycin; doxycycline and rifampin MICs were uniformly low. Neither hemolysis nor aerotolerance reliably distinguished definite PJI from non-definite cases, limiting their diagnostic utility in this cohort. Clindamycin resistance was uncommon, yet classification differed based on the interpretive criteria used (CLSI vs. EUCAST), highlighting potential inconsistencies in clinical reporting. Moreover, the predominance of "probable" infections illustrates a critical limitation of current consensus criteria, which may both underestimate true infection burden in indolent presentations and overestimate infection due to reliance on positive cultures in the absence of clear clinical findings. More precise diagnostic frameworks may help address current classification challenges and better support clinical decision-making in shoulder arthroplasty.
Anterior cruciate ligament (ACL) rupture is a common injury in young, active individuals, and arthroscopic ACL reconstruction (ACLR) is the standard of care. Internal brace augmentation has been proposed to enhance graft protection and potentially facilitate earlier return to sport, but comparative clinical data remain limited. This study aimed to compare early functional outcomes, knee stability, return to sports, and complications between internal brace augmentation ACLR and standard ACLR in patients with ACL rupture. This prospective comparative study was conducted at Medical College Kolkata, a tertiary care teaching hospital in Kolkata, India. Seventy patients with unilateral ACL rupture were analyzed: Group A (internal brace augmentation ACLR, n = 40) and Group B (standard ACLR, n = 30). Baseline demographics and injury characteristics were recorded. Functional outcomes (International Knee Documentation Committee (IKDC) and Lysholm scores) were assessed preoperatively and at six months. Knee range of motion (ROM), clinical stability tests (anterior drawer, Lachman, and pivot shift), time to return to sports, and postoperative complications were also evaluated. Between-group comparisons used Mann-Whitney U and chi-square or Fisher's exact tests, with p < 0.05 considered significant. Baseline characteristics, including age (27.00 ± 5.60 vs. 26.53 ± 3.07 years; p = 0.638), sex, side, and mechanism of injury, were comparable between groups. Preoperative IKDC scores were similar (49.48 ± 3.19 vs. 49.83 ± 3.19; p = 0.659), improving at six months to 78.98 ± 4.54 in Group A and 77.83 ± 6.72 in Group B (p = 0.858). Preoperative Lysholm scores (54.28 ± 3.29 vs. 54.57 ± 3.07; p = 0.672) improved to 88.88 ± 4.31 and 87.60 ± 6.58, respectively (p = 0.761). At six months, most patients achieved ROM 0-130° or 0-140° (39 (97.5%) Group A, 27 (90.0%) Group B; p = 0.288), and all had negative anterior drawer and Lachman tests; pivot shift was Grade 0 in 30 (75.0%) vs. 20 (66.7%) and Grade 1 in 10 (25.0%) vs. 10 (33.3%) (p = 0.445). Internal brace patients returned to sports significantly earlier (6.38 ± 0.98 vs. 8.20 ± 0.61 months; p < 0.001). Complications were low and comparable: knee stiffness 1 (2.5%) vs. 3 (10.0%) and effusion 3 (7.5%) vs. 2 (6.7%). Internal brace augmentation ACLR provides early functional outcomes, knee stability, and complication rates comparable to standard ACLR, with the added benefit of a significantly earlier return to sports. These findings support internal brace augmentation as a safe and effective option for young, active ACL rupture patients, while longer-term studies are warranted.
Nanoplastics (NPs), as emerging environmental pollutants, are increasingly detected in human musculoskeletal tissues, but their impact on osteoarthritis (OA) pathogenesis remains unclear. This study aimed to investigate whether NPs exposure accelerates osteoarthritis progression in osteoarthritic mice, to elucidate the underlying molecular mechanisms, and to evaluate the therapeutic potential of quercetin. OA was induced in C57BL/6 mice via destabilization of the medial meniscus (DMM), with or without exposure to 20-nm polystyrene NPs (0.5 mg/mL in drinking water). For therapeutic intervention, quercetin (25 or 50 mg/kg) or indomethacin (3 mg/kg) was administered daily. Cartilage destruction was assessed by histology using the Osteoarthritis Research Society International (OARSI) scoring system, immunohistochemistry, and X-ray. In vitro, primary murine chondrocytes were treated with NPs and/or quercetin. Mechanisms were investigated using transmission electron microscopy, immunofluorescence, Western blot, organelle staining, and siRNA knockdown. NPs exposure significantly accelerated cartilage degradation and OA progression in DMM mice. Internalized NPs accumulated in chondrocyte lysosomes, inducing lysosomal membrane permeabilization (LMP), cathepsin B release, and subsequent NLRP3 inflammasome activation, leading to pyroptosis (evidenced by cleavage of gasdermin D N-terminal, GSDMD-N) and extracellular matrix loss. Quercetin restored lysosomal integrity, inhibited the LMP-NLRP3-pyroptosis axis in chondrocytes, and markedly attenuated NPs-aggravated cartilage destruction in vivo. This study identifies nanoplastics as novel environmental risk factors that act as pathological amplifiers in the context of osteoarthritis by inducing lysosomal destabilization-mediated pyroptosis in chondrocytes. Quercetin alleviates this pathological cascade by stabilizing lysosomes, highlighting its potential as a therapeutic agent against nanoplastics-exacerbated OA.
As the incidence of ATR is increasing the risk of ruptures being missed escalates and more injuries are suspected to become chronic. This study aimed to assess the incidence and causes of delayed diagnosis in chronic ATR. Additionally, the patient-reported outcome of surgical versus non-surgical treatment following delayed presentation was evaluated. The study is of patients with chronic ATR treated at the Sahlgrenska University Hospital between 2015 and 2020. Patients were identified using specific International Classification of Diseases (ICD) codes for ATR and included all patients in whom the treatment had been delayed for more than 14 days. The patients who accepted to participate in the study completed the Achilles tendon Total Rupture Score (ATRS) and a questionnaire regarding recovery rate in percentage. Out of the 958 patients with ATR, 102 were identified as chronic, comprising 11% of the overall dataset. A total of 75 patients were included. Patients with chronic injury exhibited higher age, BMI, and comorbidity rates compared with patients with acute ruptures. Fifty-two (84%) patients delayed seeking medical attention. The rates of patients initially receiving an incorrect diagnosis was low, with 10 (1%) directly associated with trauma and 28 (3%) during later medical visits. Patients that were surgically treated (n = 57) for their chronic Achilles tendon rupture yielded significantly higher median (IQR) ATRS scores; 77 (50 ; 92) vs. 34 (23 ; 82) and recovery rates; 85% (70 ; 95) vs. 40% (20 ; 78) compared with patients treated with a non-surgical approach (n = 18). This study reveals that chronic ATRs constitute a significant portion of all ATR. These were primarily due to "patient's delay" rather than the relatively rare misdiagnosis. Patient-reported outcomes, such as ATRS scores and self-reported recovery, exhibit considerable variability. Surgical intervention gave superior patient reported outcome compared with non-surgical treatment for patients affected by a chronic Achilles tendon rupture.
BackgroundArticular cartilage injuries often heal with fibrocartilage rather than native hyaline cartilage, resulting in inferior biomechanical properties and increased osteoarthritis risk. Curcumin has anti-inflammatory and antioxidant properties that may support cartilage repair; however, clinical use is limited by poor bioavailability. Micellar formulations enhance systemic absorption.PurposeTo evaluate the effects of orally administered micellar curcumin on structural and molecular markers of osteochondral repair in a rat distal femoral defect model.MethodsThirty-two female Wistar rats were randomly allocated to 4 groups (n = 8 per group). Standardized 2-mm osteochondral defects were created in the distal femur. Animals received 250 mg/kg/day micellar curcumin or distilled water for 30 or 90 days. Macroscopic repair was assessed using the International Cartilage Repair Society (ICRS) scoring system. Histological evaluation followed ICRS guidelines and was performed in a blinded manner by 2 independent observers (intraclass correlation coefficient ICC = 0.89). Immunohistochemical analyses included SRY-box transcription factor 9 (SOX9), collagen type I (COL I), collagen type II (COL II), aggrecan, and matrix metalloproteinase-13 (MMP-13).ResultsCurcumin-treated groups demonstrated significantly higher macroscopic and histological scores than controls, particularly at 90 days. Increased expression of hyaline cartilage markers (SOX9, collagen II, aggrecan) and reduced collagen I expression were observed in treated groups. MMP-13 expression did not differ significantly between groups.ConclusionOral micellar curcumin enhanced structural and molecular parameters of osteochondral repair in this preclinical model. Further translational and clinical studies are required before therapeutic application.