Influence of female sex and double-quadruple semitendinosus-gracilis graft on the incidence of postoperative symptomatic cyclops lesions after ACL reconstruction.

PURPOSE: Risk factors for the development of symptomatic cyclops lesion after anterior cruciate ligament reconstruction (ACLR) surgery are not entirely identified yet. This study aimed to investigate whether the choice of hamstring graft (semitendinosus-gracilis; STG vs. semitendinosus; ST) affects the risk of developing a symptomatic cyclops lesion after ACLR. METHODS: This retrospective cohort study included 1416 patients receiving either an ST graft (n = 1209) or an STG graft (n = 207) ACLR with a follow-up of at least 2 years. A persisting extension limitation was clinically determined, and cyclops lesions were confirmed by magnetic resonance imaging (MRI) and second-look arthroscopy. Graft-specific incidence of cyclops lesions was examined with χ2 test and combined with the factors number of graft bundles, graft diameter and sex evaluated with a binominal logistic regression model. RESULTS: In total, 46 patients developed symptomatic cyclops lesions (3.2%), with 36 having ACLR with an ST graft (3.0%) and 10 with an STG graft (4.8%) (n.s). The mean time from ACLR to the second-look arthroscopy for cyclops removal was 1.1 ± 0.6 years. Female patients were 2.5 times more likely to develop a cyclops lesion than male patients. Patients with an STG graft and larger graft diameters did not have a higher risk of developing cyclops lesions. Patients who received an STG graft with both tendons folded four times (double-quadruple) had significantly higher risk of developing a cyclops compared with all other numbers of graft bundles combined (8.3%, respectively 3.0%; p = 0.014). CONCLUSION: This study could not prove an increased risk of developing a symptomatic cyclops lesion for patients with an STG graft compared with an ST graft used for ACLR. However, patients with a double-quadruple ACLR had a higher percentage of cyclops lesions compared with all other numbers of graft bundles. Female sex was associated with an increased risk of developing cyclops lesions. LEVEL OF EVIDENCE: Level III.

Height is a predictor of hamstring tendon length and ACL graft characteristics in adolescents.

BACKGROUND: Knowing the potential hamstring tendon length is relevant for planning ligament reconstructions in children and adolescents, as it is not uncommon to encounter small hamstring tendons intraoperatively. The aim of this study is to predict semitendinosus and gracilis tendon length based on anthropometric values in children and adolescents. The secondary aim is to analyse hamstring tendon autograft characteristics in a closed socket anterior cruciate ligament reconstructions and to evaluate the relationship with anthropometric variables. The hypothesis of this study was that height is predictor of hamstring tendon length and thereby graft characteristics. METHODS: This observational study included two cohorts of adolescents undergoing ligament reconstructions between 2007-2014 and 2017-2020. Age, sex, height and weight were recorded preoperatively. Semitendinosus and gracilis tendon length and graft characteristics were measured intraoperatively. Regression analysis was performed on tendon length and anthropometric values. Subgroup analyses of the closed socket ACL reconstruction were performed and the relation between anthropometric values and graft characteristics were analysed. RESULTS: The population consisted of 171 adolescents from 13 to 17 years of age, with a median age of 16 years [IQR 16-17]. The median semitendinosus tendon length was 29 cm [IQR 26-30] and gracilis tendon length was 27 cm [IQR 25-29]. Height was a significant predictor of semitendinosus and gracilis tendon length. Subgroup analysis of the closed socket ACL reconstructions showed that in 75% of the procedure, the semitendinosus tendon alone was sufficient to create a graft with a minimum diameter of 8.0 mm. CONCLUSIONS: Height is a significant predictor of semitendinosus and gracilis tendon length in adolescents between 13 and 17 years of age and outcomes are similar to data in adults. In 75% of the closed socket ACL reconstructions, the semitendinosus tendon alone is sufficient to create an adequate graft with a minimum diameter of 8 mm. Additional use of the gracilis tendon is more often necessary in females and shorter patients.

Digital Health Applications to Establish a Remote Diagnosis of Orthopedic Knee Disorders: Scoping Review.

BACKGROUND: Knee pain is highly prevalent worldwide, and this number is expected to rise in the future. The COVID-19 outbreak, in combination with the aging population, rising health care costs, and the need to make health care more accessible worldwide, has led to an increasing demand for digital health care applications to deliver care for patients with musculoskeletal conditions. Digital health and other forms of telemedicine can add value in optimizing health care for patients and health care providers. This might reduce health care costs and make health care more accessible while maintaining a high level of quality. Although expectations are high, there is currently no overview comparing digital health applications with face-to-face contact in clinical trials to establish a primary knee diagnosis in orthopedic surgery. OBJECTIVE: This study aimed to investigate the currently available digital health and telemedicine applications to establish a primary knee diagnosis in orthopedic surgery in the general population in comparison with imaging or face-to-face contact between patients and physicians. METHODS: A scoping review was conducted using the PubMed and Embase databases according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) statement. The inclusion criteria were studies reporting methods to determine a primary knee diagnosis in orthopedic surgery using digital health or telemedicine. On April 28 and 29, 2021, searches were conducted in PubMed (MEDLINE) and Embase. Data charting was conducted using a predefined form and included details on general study information, study population, type of application, comparator, analyses, and key findings. A risk-of-bias analysis was not deemed relevant considering the scoping review design of the study. RESULTS: After screening 5639 articles, 7 (0.12%) were included. In total, 2 categories to determine a primary diagnosis were identified: screening studies (4/7, 57%) and decision support studies (3/7, 43%). There was great heterogeneity in the included studies in algorithms used, disorders, input parameters, and outcome measurements. No more than 25 knee disorders were included in the studies. The included studies showed a relatively high sensitivity (67%-91%). The accuracy of the different studies was generally lower, with a specificity of 27% to 48% for decision support studies and 73% to 96% for screening studies. CONCLUSIONS: This scoping review shows that there are a limited number of available applications to establish a remote diagnosis of knee disorders in orthopedic surgery. To date, there is limited evidence that digital health applications can assist patients or orthopedic surgeons in establishing the primary diagnosis of knee disorders. Future research should aim to integrate multiple sources of information and a standardized study design with close collaboration among clinicians, data scientists, data managers, lawyers, and service users to create reliable and secure databases.

Diagnostic values of history taking, physical examination and KT-1000 arthrometer for suspect anterior cruciate ligament injuries in children and adolescents: a prospective diagnostic study.

BACKGROUND: Diagnosing anterior cruciate ligament (ACL) injuries in children and adolescents are more challenging compared to adults. Delayed diagnosis may result in meniscal or chondral injuries. The aim of this study was to determine the diagnostic values of history taking, physical examination and KT-1000 arthrometer for suspect ACL injuries in children and adolescents. METHODS: In this prospective diagnostic study, all children and adolescents (< 18 years) with post-traumatic knee complaints presenting at the out-patient department of the Máxima MC were eligible for inclusion. One experienced knee specialised orthopaedic surgeon was blinded and performed history taking, physical examination and KT-1000 arthrometer measurement. All patients had a magnetic resonance imaging (MRI) for the final diagnosis. Diagnostic values of interest were sensitivity, specificity, positive and negative predictive values (PPV and NPV). The outcomes of the KT-1000 arthrometer were drafted in a relative operating characteristics (ROC) curve to determine the optimal cut-off points. RESULTS: Sixty-six patients were included, of which 50 had an ACL rupture and 16 had no ACL rupture on MRI. Report of a popping sensation during trauma had a specificity and PPV of 100% for diagnosing ACL injuries. The PPV and NPV of the Lachman test (in case of describing end-feel) were 95 and 82%, of the anterior drawer test 87 and 90% and of the pivot shift test 95 and 81% respectively. The optimal cut-off point of the KT-1000 arthrometer at 133 N force was an absolute translation of ≥7 mm with a PPV and NPV of 97 and 88% respectively. CONCLUSIONS: Report of a popping sensation during trauma has a specificity and PPV of 100% for diagnosing ACL injuries in children and adolescents. Although potentially difficult in children, the Lachman test, anterior drawer test and pivot shift test have a high PPV and NPV when performed by an experienced orthopaedic surgeon. An absolute anterior translation of ≥7 mm of the injured knee in the KT-1000 arthrometer at 133 N has the highest diagnostic values of all tests for diagnosing ACL injuries.

Arthroscopic partial meniscectomy versus physical therapy for traumatic meniscal tears in a young study population: a randomised controlled trial.

OBJECTIVE: To compare outcomes from arthroscopic partial meniscectomy versus physical therapy in young patients with traumatic meniscal tears. METHODS: We conducted a multicentre, open-labelled, randomised controlled trial in patients aged 18-45 years, with a recent onset, traumatic, MRI-verified, isolated meniscal tear without knee osteoarthritis. Patients were randomised to arthroscopic partial meniscectomy or standardised physical therapy with an optional delayed arthroscopic partial meniscectomy after 3-month follow-up. The primary outcome was the International Knee Documentation Committee (IKDC) score (best 100, worst 0) at 24 months, which measures patients' perception of symptoms, knee function and ability to participate in sports activities. RESULTS: Between 2014 and 2018, 100 patients were included (mean age 35.1 (SD 8.1), 76% male, 34 competitive or elite athletes). Forty-nine were randomised to arthroscopic partial meniscectomy and 51 to physical therapy. In the physical therapy group, 21 patients (41%) received delayed arthroscopic partial meniscectomy during the follow-up period. In both groups, improvement in IKDC scores was clinically relevant during follow-up compared with baseline scores. At 24 months mean (95% CI) IKDC scores were 78 (71 to 84) out of 100 points in the arthroscopic partial meniscectomy group and 78 (71 to 84) in the physical therapy group with a between group difference of 0.1 (95% CI -7.6 to 7.7) points out of 100. CONCLUSIONS: In this trial involving young patients with isolated traumatic meniscal tears, early arthroscopic partial meniscectomy was not superior to a strategy of physical therapy with optional delayed arthroscopic partial meniscectomy at 24-month follow-up. TRIAL REGISTRATION: https://www.trialregister.nl/trials.

Reduced Vitamin K Status as a Potentially Modifiable Risk Factor of Severe Coronavirus Disease 2019.

BACKGROUND: Respiratory failure and thromboembolism are frequent in severe acute respiratory syndrome coronavirus 2-infected patients. Vitamin K activates both hepatic coagulation factors and extrahepatic endothelial anticoagulant protein S, required for thrombosis prevention. In times of vitamin K insufficiency, hepatic procoagulant factors are preferentially activated over extrahepatic proteins. Vitamin K also activates matrix Gla protein (MGP), which protects against pulmonary and vascular elastic fiber damage. We hypothesized that vitamin K may be implicated in coronavirus disease 2019 (COVID-19), linking pulmonary and thromboembolic disease. METHODS: A total of 135 hospitalized COVID-19 patients were compared with 184 historic controls. Inactive vitamin K-dependent MGP (desphospho-uncarboxylated [dp-uc] MGP) and prothrombin (PIVKA-II) were measured inversely related to extrahepatic and hepatic vitamin K status, respectively. Desmosine was measured to quantify the rate of elastic fiber degradation. Arterial calcification severity was assessed using computed tomography. RESULTS: dp-ucMGP was elevated in COVID-19 patients compared with controls (P < .001), with even higher dp-ucMGP in patients with poor outcomes (P < .001). PIVKA-II was normal in 82.1% of patients. dp-ucMGP was correlated with desmosine (P < .001) and with coronary artery (P = .002) and thoracic aortic (P < .001) calcification scores. CONCLUSIONS: dp-ucMGP was severely increased in COVID-19 patients, indicating extrahepatic vitamin K insufficiency, which was related to poor outcome; hepatic procoagulant factor II remained unaffected. These data suggest pneumonia-induced extrahepatic vitamin K depletion leading to accelerated elastic fiber damage and thrombosis in severe COVID-19 due to impaired activation of MGP and endothelial protein S, respectively.

Adjunctive treatment with oral dexamethasone in non-ICU patients hospitalised with community-acquired pneumonia: a randomised clinical trial.

BACKGROUND: Adjunctive intravenous corticosteroid treatment has been shown to reduce length of stay (LOS) in adults hospitalised with community-acquired pneumonia (CAP). We aimed to assess the effect of oral dexamethasone on LOS and whether this effect is disease severity dependent. METHODS: In this multicentre, stratified randomised, double-blind, placebo-controlled trial, immunocompetent adults with CAP were randomly assigned (1:1 ratio) to receive oral dexamethasone (6 mg once daily) or placebo for 4 days in four teaching hospitals in the Netherlands. Randomisation (blocks of four) was stratified by CAP severity (pneumonia severity index class I-III and IV-V). The primary outcome was LOS. RESULTS: Between December 2012 and November 2018, 401 patients were randomised to receive dexamethasone (n=203) or placebo (n=198). Median LOS was shorter in the dexamethasone group (4.5 days, 95% CI 4.0-5.0 days) than in the placebo group (5.0 days, 95% CI 4.6-5.4 days; p=0.033). Within both CAP severity subgroups, differences in LOS between treatment groups were not statistically significant. The secondary ICU admission rate was lower in the dexamethasone arm (5 (3%) versus 14 (7%); p=0.030); 30-day mortality did not differ between groups. In the dexamethasone group the rate of hospital readmission tended to be higher (20 (10%) versus 9 (5%); p=0.051) and hyperglycaemia (14 (7%) versus 1 (1%); p=0.001) was more prevalent. CONCLUSION: Oral dexamethasone reduced LOS and ICU admission rate in adults hospitalised with CAP. It remains unclear for which patients the risk-benefit ratio is optimal.

Enhanced lung inflammatory response in whole-body compared to nose-only cigarette smoke-exposed mice.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by a progressive and abnormal inflammatory response in the lungs, mainly caused by cigarette smoking. Animal models exposed to cigarette smoke (CS) are used to mimic human COPD but the use of different CS protocols makes it difficult to compare the immunological and structural consequences of using a nose-only or whole-body CS exposure system. We hypothesized that when using a standardized CS exposure protocol based on particle density and CO (carbon monoxide) levels, the whole-body CS exposure system would generate a more severe inflammatory response than the nose-only system, due to possible sensitization by uptake of CS-components through the skin or via grooming. METHODS: In this study focusing on early COPD, mice were exposed twice daily 5 days a week to CS either with a nose-only or whole-body exposure system for 14 weeks to assess lung function, remodeling and inflammation. RESULTS: At sacrifice, serum cotinine levels were significantly higher in the whole-body (5.3 (2.3-6.9) ng/ml) compared to the nose-only ((2.0 (1.8-2.5) ng/ml) exposure system and controls (1.0 (0.9-1.0) ng/ml). Both CS exposure systems induced a similar degree of lung function impairment, while inflammation was more severe in whole body exposure system. Slightly more bronchial epithelial damage, mucus and airspace enlargement were observed with the nose-only exposure system. More lymphocytes were present in the bronchoalveolar lavage (BAL) and lymph nodes of the whole-body exposure system while enhanced IgA and IgG production was found in BAL and to a lesser extent in serum with the nose-only exposure system. CONCLUSION: The current standardized CS-exposure protocol resulted in a higher internal load of serum cotinine in the whole-body exposure system, which was associated with more inflammation. However, both exposure systems resulted in a similar lung function impairment. Data also highlighted differences between the two models in terms of lung inflammation and remodelling, and potential sensitization to CS. Researchers should be aware of these differences when designing their future studies for an early intervention in COPD.

Prior use of therapeutic anticoagulation does not protect against COVID-19 related clinical outcomes in hospitalized patients: A propensity score-matched cohort study.

The hypercoagulable state observed in COVID-19 could be responsible for morbidity and mortality. In this retrospective study we investigated whether therapeutic anticoagulation prior to infection has a beneficial effect in hospitalized COVID-19 patients. This study included 1154 COVID-19 patients admitted to 6 hospitals in the Netherlands between March and May 2020. We applied 1:3 propensity score matching to evaluate the association between prior therapeutic anticoagulation use and clinical outcome, with in hospital mortality as primary endpoint. In total, 190 (16%) patients used therapeutic anticoagulation prior to admission. In the propensity score matched analyses, we observed no associations between prior use of therapeutic anticoagulation and overall mortality (risk ratio 1.02 [95% confidence interval; 0.80-1.30]) or length of hospital stay (7.0 [4-12] vs. 7.0 [4-12] days, P = .69), although we observed a lower risk of pulmonary embolism (0.19 [0.05-0.80]). This study shows that prior use of therapeutic anticoagulation is not associated with improved clinical outcome in hospitalized COVID-19 patients.

Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019.

Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes. Vitamin K plays a crucial role in the activation of both pro- and anticlotting factors in the liver and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention. However, the role of vitamin K extends beyond coagulation. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation. Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates. This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2-induced proteolysis. In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors. We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity. Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively. Intervention trials should be conducted to assess whether vitamin K administration plays a role in the prevention and treatment of severe Covid-19.

Can sodium MRI be used as a method for mapping of cartilage stiffness?

OBJECTIVE: Sodium concentration is responsible for (at least part of) the stiffness of articular cartilage due to the osmotic pressure it generates. Therefore, we hypothesized that we could use sodium MRI to approximate the stiffness of cartilage to assess early cartilage degeneration. METHODS: Four human tibial plateaus were retrieved from patients undergoing total knee replacement (TKR), and their cartilage stiffness mapped with indentation testing, after which samples were scanned in a 7 T MRI to determine sodium concentration. The relation of biomechanical parameters to MRI sodium and glycosaminoglycan (GAG) concentration was explored by a linear mixed model. RESULTS: Weak correlations of GAG concentration with apparent peak modulus (p = 0.0057) and apparent equilibrium modulus (p = 0.0181) were observed and lack of correlation of GAG concentration versus MRI sodium concentration was observed. MRI sodium concentration was not correlated with apparent peak modulus, though a moderate correlation of MRI sodium concentration with permeability was shown (p = 0.0014). DISCUSSION AND CONCLUSION: Although there was correlation between GAG concentration and cartilage stiffness, this was not similar with sodium concentration as measured by MRI. Thus, if the correlation between MRI sodium imaging and GAG concentration could be resolved, this strategy for assessing cartilage functional quality still holds promise.

Translation and transcultural validation of the Dutch hospital for special surgery paediatric functional activity brief scale (HSS Pedi-FABS).

BACKGROUND: There is a need for a validated simple Dutch paediatric activity scale. The purpose was to translate and transculturally validate the Dutch Hospital for Special Surgery Paediatric Functional Activity Brief Scale (HSS Pedi-FABS) questionnaire in healthy children and adolescents. METHODS: The original HSS Pedi-FABS was translated forward and backward and was transculturally adapted after performing a pilot study among children and professionals. The final version of the Dutch HSS Pedi-FABS was validated in healthy children and adolescents aged 10 to 18 years old. Children who had any condition or injury limiting their normal physical activity were excluded. The interval between the first questionnaire T0 (HSS Pedi-FABS, Physical Activity Questionnaire for children or adolescents (PAQ-C/A) and Tegner activity scale) and the second questionnaire T1 (HSS Pedi-FABS) was 2 weeks. Construct validity, interpretability and reliability were evaluated. Content validity was evaluated through cognitive interviews among a smaller group of children and through a questionnaire among professionals. RESULTS: To evaluate content validity, 9 children and adolescents were interviewed, and 30 professionals were consulted. Content validity among professionals showed a relevance of less than 85% for most items on construct. However, content validity among children was good with a 92% score for item relevance. Readability was scored at a reading level of 11- to 12-year-olds. The validation group consisted of 110 healthy children and adolescents (mean age of 13.9 years ±2.6). Construct validity was considered good as 8 out of 10 hypotheses were confirmed. The Dutch HSS Pedi-FABS showed no floor or ceiling effect. Analysis of the internal consistency in the validation group resulted in a Cronbach's alpha of 0.82. Test-retest reliability was evaluated among 69 children and adolescents and revealed an Intraclass Correlation Coefficient (ICC) of 0.76. CONCLUSION: The Dutch HSS Pedi-FABS showed good psychometric properties in a healthy Dutch paediatric and adolescent population. Limitations of the current Dutch HSS Pedi-FABS are content validity on construct of items reported by professionals.

Conserved NPPB+ Border Zone Switches From MEF2- to AP-1-Driven Gene Program.

BACKGROUND: Surviving cells in the postinfarction border zone are subjected to intense fluctuations of their microenvironment. Recently, border zone cardiomyocytes have been specifically implicated in cardiac regeneration. Here, we defined their unique transcriptional and regulatory properties, and comprehensively validated new molecular markers, including Nppb, encoding B-type natriuretic peptide, after infarction. METHODS: Transgenic reporter mice were used to identify the Nppb-positive border zone after myocardial infarction. Transcriptome analysis of remote, border, and infarct zones and of purified cardiomyocyte nuclei was performed using RNA-sequencing. Top candidate genes displaying border zone spatial specificity were histologically validated in ischemic human hearts. Mice in which Nppb was deleted by genome editing were subjected to myocardial infarction. Chromatin accessibility landscapes of border zone and control cardiomyocyte nuclei were assessed by using assay for transposase-accessible chromatin using sequencing. RESULTS: We identified the border zone as a spatially confined region transcriptionally distinct from the remote myocardium. The transcriptional response of the border zone was much stronger than that of the remote ventricular wall, involving acute downregulation of mitochondrial oxidative phosphorylation, fatty acid metabolism, calcium handling, and sarcomere function, and the activation of a stress-response program. Analysis of infarcted human hearts revealed that the transcriptionally discrete border zone is conserved in humans, and led to the identification of novel conserved border zone markers including NPPB, ANKRD1, DES, UCHL1, JUN, and FOXP1. Homozygous Nppb mutant mice developed acute and lethal heart failure after myocardial infarction, indicating that B-type natriuretic peptide is required to preserve postinfarct heart function. Assay for transposase-accessible chromatin using sequencing revealed thousands of cardiomyocyte lineage-specific MEF2-occupied regulatory elements that lost accessibility in the border zone. Putative injury-responsive enhancers that gained accessibility were highly associated with AP-1 (activator protein 1) binding sites. Nuclear c-Jun, a component of AP-1, was observed specifically in border zone cardiomyocytes. CONCLUSIONS: Cardiomyocytes in a discrete zone bordering the infarct switch from a MEF2-driven homeostatic lineage-specific to an AP-1-driven injury-induced gene expression program. This program is conserved between mouse and human, and includes Nppb expression, which is required to prevent acute heart failure after infarction.

Development of Preoperative Prediction Models for Pain and Functional Outcome After Total Knee Arthroplasty Using The Dutch Arthroplasty Register Data.

BACKGROUND: One of the main determinants of treatment satisfaction after total knee arthroplasty (TKA) is the fulfillment of preoperative expectations. For optimal expectation management, it is useful to accurately predict the treatment result. Multiple patient factors registered in the Dutch Arthroplasty Register (LROI) can potentially be utilized to estimate the most likely treatment result. The aim of the present study is to create and validate models that predict residual symptoms for patients undergoing primary TKA for knee osteoarthritis. METHODS: Data were extracted from the LROI of all TKA patients who had preoperative and postoperative patient-reported outcome measures registered. Multivariable logistic regression analyses were performed to construct predictive algorithms for satisfaction, treatment success, and residual symptoms concerning pain at rest and during activity, sit-to-stand movement, stair negotiation, walking, performance of activities of daily living, kneeling, and squatting. We assessed predictive performance by examining measures of calibration and discrimination. RESULTS: Data of 7071 patients could be included for data analysis. Residual complaints on kneeling (female 72%/male 59%) and squatting (female 71%/male 56%) were reported most frequently, and least residual complaints were scored for walking (female 16%/male 12%) and pain at rest (female 18%/male 14%). The predictive algorithms were presented as clinical calculators that present the probability of residual symptoms for an individual patient. The models for residual symptoms concerning sit-to-stand movement, stair negotiation, walking, activities of daily living, and treatment success showed acceptable discriminative values (area under the curve 0.68-0.74). The algorithms for residual complaints regarding kneeling, squatting, pain, and satisfaction showed less favorable results (area under the curve 0.58-0.64). The calibration curves showed adequate calibration for most of the models. CONCLUSION: A considerable proportion of patients have residual complaints after TKA. The present study showed that demographic and patient-reported outcome measure data collected in the LROI can be used to predict the probability of residual symptoms after TKA. The models developed in the present study predict the chance of residual symptoms for an individual patient on 10 specific items concerning treatment success, functional outcome, and pain relief. This prediction can be useful for individualized expectation management in patients planned for TKA.

Artificial intelligence outperforms pulmonologists in the interpretation of pulmonary function tests.

The interpretation of pulmonary function tests (PFTs) to diagnose respiratory diseases is built on expert opinion that relies on the recognition of patterns and the clinical context for detection of specific diseases. In this study, we aimed to explore the accuracy and interrater variability of pulmonologists when interpreting PFTs compared with artificial intelligence (AI)-based software that was developed and validated in more than 1500 historical patient cases.120 pulmonologists from 16 European hospitals evaluated 50 cases with PFT and clinical information, resulting in 6000 independent interpretations. The AI software examined the same data. American Thoracic Society/European Respiratory Society guidelines were used as the gold standard for PFT pattern interpretation. The gold standard for diagnosis was derived from clinical history, PFT and all additional tests.The pattern recognition of PFTs by pulmonologists (senior 73%, junior 27%) matched the guidelines in 74.4±5.9% of the cases (range 56-88%). The interrater variability of κ=0.67 pointed to a common agreement. Pulmonologists made correct diagnoses in 44.6±8.7% of the cases (range 24-62%) with a large interrater variability (κ=0.35). The AI-based software perfectly matched the PFT pattern interpretations (100%) and assigned a correct diagnosis in 82% of all cases (p<0.0001 for both measures).The interpretation of PFTs by pulmonologists leads to marked variations and errors. AI-based software provides more accurate interpretations and may serve as a powerful decision support tool to improve clinical practice.

Pedi-IKDC or KOOS-child: which questionnaire should be used in children with knee disorders?

BACKGROUND: The Pedi International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) child are validated questionnaires for children with knee disorders. The aim of this study was to translate these questionnaires in Dutch and to recommend which questionnaires should - based on their psychometric properties - be used in clinical practice. METHODS: The English Pedi-IKDC and KOOS-Child were translated by the forward-backward procedure. Subsequently, content validity of the Pedi-IKDC and KOOS-Child was evaluated by both patients (n = 18) and experts (n = 18). To evaluate construct validity and interpretability participants with knee disorders (n = 100) completed the Numeric Rating Scale Pain, Lysholm Knee Scoring Scale, EuroQol-5 Dimension, Pedi-IKDC and KOOS-Child at baseline. Participants completed the anchor question, Pedi-IKDC and KOOS-child two weeks (n = 54) and one year (n = 71) after baseline, for evaluating the test-retest reliability and responsiveness. Psychometric properties were interpreted following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. RESULTS: The Pedi-IKDC showed adequate test-retest reliability (intraclass correlation coefficient (ICC) 0.9; standard error of measurement (SEM) 8.6; smallest detectable change (SDC) 23.8), adequate content validity (> 75% relevant), adequate construct validity (75% confirmed hypotheses), low floor or ceiling effects (scores between 5 and 95) and adequate responsiveness (> 75% confirmed hypotheses). The KOOS-Child showed an adequate test-retest reliability (ICC 0.8-0.9; SEM 8.9-16.9; SDC 24.7-46.9), adequate content validity (> 75% relevant, except KOOS-Child subscale ADL), adequate construct validity (75% confirmed hypotheses), low floor and ceiling effects (scores between 5 and 95, except KOOS-Child subscale activities of daily living and Sport/play) and moderate responsiveness (40% confirmed hypotheses). CONCLUSIONS: The Pedi IKDC showed better psychometric properties than the KOOS-Child and should therefore be used in children with knee disorders.

Validation of Simendo Knee Arthroscopy Virtual Reality Simulator.

PURPOSE: To determine the face and construct validity as well as educational value and user-friendliness of the Simendo knee arthroscopy virtual reality simulator. METHODS: Sixty participants were recruited and equally divided into novices (0 arthroscopic procedures), intermediates (1-59 arthroscopic procedures), and experts (60 or more arthroscopic procedures). Participants were excluded if they had previously trained with the studied simulator. Construct validity, that is, the ability to discriminate between different levels of expertise, was examined by a navigation task. All participants were asked to perform 5 navigation trials within 10 minutes. Face validity, educational value, and user-friendliness were examined by questionnaires before and after the navigation trials. Face validity is the subjective impression of how closely the simulation replicates the real environment. RESULTS: The novices were significantly slower than the intermediates in the first (P < .001) and the third (P = .031) trial. The novices were significantly slower than the experts in all trials (P = .016), except for the fifth (P = .054). The experts were significantly faster than the intermediates in every trial except for the fourth (P = .069). Median task time for the fifth trial was 63 seconds (44-80 seconds) for novices, 58 seconds (46-80 seconds) for intermediates, and 41 seconds (33-55 seconds) for experts. Ninety-two percent of all participants agreed that the simulator can be used to train for surgical inspection, and 95% indicated sufficient user-friendliness. CONCLUSIONS: Based on the results, this knee simulator can be applied to train the basic arthroscopic hand-eye coordination skills at the start of resident education programs. Further testing is necessary to determine whether the skills are retained. CLINICAL RELEVANCE: The simulator is partly validated, which contributes to training of basic arthroscopic skills without compromising patient safety.

Measurement properties of the OARSI core set of performance-based measures for hip osteoarthritis: a prospective cohort study on reliability, construct validity and responsiveness in 90 hip osteo-arthritis patients.

Background and purpose - Improvement of physical function is one of the main treatment goals in severe hip osteoarthritis (OA) patients. The Osteoarthritis Research Society International (OARSI) has identified a core set of performance-based tests to assess the construct physical function: 30-s chair stand test (30-s CST), 4x10-meter fast-paced walk test (40 m FPWT), and a stair-climb test. Despite this recommendation, available evidence on the measurement properties is limited. We evaluated the reliability, validity, and responsiveness of these performance-based measures in patients with hip OA scheduled for total hip arthroplasty (THA). Patients and methods - Baseline and 12-month follow-up measurements were prospectively obtained in 90 end-stage hip OA patients who underwent THA. As there is no gold standard for comparison, the hypothesis testing method was used for construct validity and responsiveness analysis. A test can be assumed valid if ≥75% of predefined hypotheses are confirmed. A subgroup (n = 30) underwent test-retest measurements for reliability analysis. The Oxford Hip Score, Hip injury and Osteoarthritis Outcome Score-Physical Function Short Form, pain during activity score, and muscle strength were used as comparator instruments. Results - Test-retest reliability was appropriate; intraclass correlation coefficient values exceeded 0.70 for all 3 tests. None of the performance-based measures reached 75% hypothesis confirmation for the construct validity or responsiveness analysis. Interpretation - The performance-based tests have good reliability in the assessment of physical function. Construct validity and responsiveness, using patient-reported measures and muscle strength as comparator instruments, could not be confirmed. Therefore, our findings do not justify their use for clinical practice.

Increased circulating desmosine and age-dependent elastinolysis in idiopathic pulmonary fibrosis.

Although chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) seem to be opposite entities from a clinical perspective, common initial pathogenic steps have been suggested in both lung diseases. Emphysema is caused by an elastase/anti-elastase imbalance leading to accelerated elastin degradation. Elastinolysis is however, also accelerated in the IPF patients' lungs. The amino acids desmosine and isodesmosine (DES) are unique to elastin. During the degradation process, elastases liberate DES from elastin fibers. Blood DES levels consequently reflect the rate of systemic elastinolysis and are increased in COPD. This is the first report describing elevated DES levels in IPF patients. We also demonstrated that the age-related increment of DES concentrations is enhanced in IPF. Our current study suggests that elastinolysis is a shared pathogenic step in both COPD and IPF. Further investigation is required to establish the relevance of accelerated elastin degradation in IPF and to determine whether decelerating this process leads to slower progression of lung fibrosis and better survival for patients with IPF.

Susceptibility allele-specific loss of miR-1324-mediated silencing of the INO80B chromatin-assembly complex gene in pre-eclampsia.

In humans, the elucidation of the genetics underlying multifactorial diseases such as pre-eclampsia remains complex. Given the current day availability of genome-wide linkage- and expression data pools, we applied pathway-guided genome-wide meta-analysis guided by the premise that the functional network underlying these multifactorial syndromes is under selective genetic pressure. This approach drastically reduced the genomic region of interest, i.e. 2p13 linked with pre-eclampsia in Icelandic families, from 8 679 641 bp (region with linkage) to 45 264 bp (coding exons of prioritized genes) (0.83%). Mutation screening of the candidate genes (n = 13) rapidly reduced the minimal critical region and showed the INO80B gene, encoding a novel winged helix domain (pfam14465) and part of the chromatin-remodeling complex, to be linked to pre-eclampsia. The functional defect in placental cells involved a susceptibility allele-dependent loss-of-gene silencing due to increased INO80B RNA stability as a consequence of differential binding of miR-1324 to the susceptibility allele of rs34174194. This risk allele is located at position 1 in an absolutely conserved 7-mer (UUGUCUG) in the 3-UTR of INO80B immediately downstream of a variant Pumillio Recognition Element (UGUANAAG). These data support that pre-eclampsia genes affect a conserved fundamental mechanism that evolved as a consequence of hemochorial placentation. Functionally, this involves founder-dependent, placentally expressed paralogous genes that regulate an essential trophoblast differentiation pathway but act at different entry points.