Prioritization of Adverse Consequences After Total Knee Arthroplasty Contributing to a Poor Response: A Best-Worst Scaling Exercise Among Total Knee Arthroplasty Patients and Knee Specialists.

BACKGROUND: Total knee arthroplasty (TKA) can have a number of adverse consequences for patients that might contribute to a poor outcome. This study aimed to prioritize these consequences, from the perspective of patients and knee specialists. METHODS: There were 95 TKA patients and 63 knee specialists who prioritized a set of 29 adverse consequences, based on a previous qualitative study, using a Maximum Difference Scaling method. A hierarchical Bayesian analysis was used to calculate relative importance scores. Differences and agreements between patients versus knee specialists and satisfied versus dissatisfied patients were analyzed using Mann-Whitney-U tests and Kendall's coefficients of concordance. RESULTS: There were 4 out of 5 items in the top-5 of both patients and knee specialists that were similar, however, the ranking was different. The highest-ranked consequence for patients was: "Inability to do normal activities such as walking, cycling, swimming and heavy household chores", while knee specialists ranked: "No improvement in pain during the day" as the highest. "No improvement in walking" was in the patients' top-5, but was not ranked in the top-5 of knee specialists. For satisfied and dissatisfied patients, the top-5 of consequences was similar. CONCLUSION: Comparable perspectives were found for patients versus knee specialists and satisfied versus dissatisfied patients on the importance of adverse consequences after TKA. However, when looking in more detail, differences in ranking of specific subitems suggest that patients place slightly more importance on the inability to perform valued activities, while knee specialists prioritize lack of pain relief to a higher degree.

Inadequate Classification of Poor Response After Total Knee Arthroplasty: A Comparative Analysis of 15 Definitions Using Data From the Dutch Arthroplasty Register and the Osteoarthritis Initiative Database.

BACKGROUND: Variations in defining poor response to total knee arthroplasty (TKA) impede comparisons of response after TKA over time and across hospitals. This study aimed to compare the prevalence, overlap, and discriminative accuracy of 15 definitions of poor response after TKA using 2 databases. METHODS: Data of patients one year after primary TKA from the Dutch Arthroplasty Register (n = 12,275) and the Osteoarthritis Initiative database (n = 204) were used to examine the prevalence, overlap (estimated by Cohen's kappa), and discriminative accuracy (sensitivity, specificity, positive predictive value, negative predictive value, and Youden index) of 15 different definitions of poor response after TKA. In the absence of a gold standard for measuring poor response to TKA, the numeric rating scale satisfaction (≤ 6 'poor responder') and the global assessment of knee impact (dichotomized: ≥ 4 'poor responder') were used as anchors for assessing discriminative accuracy for the Dutch Arthroplasty Register and Osteoarthritis Initiative dataset, respectively. These anchors were chosen based on a prior qualitative study that identified (dis)satisfaction as a central theme of poor responses to TKA by patients and knee specialists. RESULTS: The median (25th to 75th percentile) prevalence of poor responders in the examined definitions was 18.5% (14.0 to 25.5%), and the median Cohen's kappa for the overlap between pairs of definitions was 0.41 (0.32 to 0.59). Median (25th to 75th percentile) sensitivity was 0.45 (0.39 to 0.54), specificity was 0.86 (0.82 to 0.94), positive predictive value was 0.45 (0.34 to 0.62), negative predictive value was 0.89 (0.87 to 0.89), and the Youden index was 0.36 (0.20 to 0.43). CONCLUSIONS: This study found a lack of overlap between different definitions of poor response to TKA. None of the examined definitions adequately classified poor responders to TKA. In contrast, the absence of a poor response could be classified with confidence.

First step in implementation of opportunistic salpingectomy for prevention of ovarian cancer: Current care and its determinants.

INTRODUCTION: Opportunistic salpingectomy (OS) refers to additional removal of the fallopian tubes during abdominal surgery performed for another medical indication, as prevention for ovarian cancer. As OS has been inconsistently implemented, its clinical practice varies worldwide. To reduce this variation, insight is required into current clinical practice and its determinants. Therefore, the study aim was to determine the implementation of counseling and performance of OS between 2015 and 2018, and its patient, surgical, physician, and hospital characteristics. MATERIAL AND METHODS: Retrospective study using electronic medical records from six different Dutch hospitals: two academic, two large teaching, and two non-teaching hospitals. Patients were considered eligible for OS if they underwent elective non-obstetric abdominal surgery for a gynecological indication from January 2015 through December 2018. Primary outcomes were uptake of counseling and performance of OS. Multilevel multivariable logistic regression analyses were conducted to identify characteristics associated with OS. RESULTS: A total of 3214 patients underwent elective non-obstetric abdominal surgery for a gynecological indication and were eligible for OS. Counseling on OS increased significantly from 2.9% in 2015 to 29.4% in 2018. In this period, 440 patients were counseled on OS, of which 95.9% chose OS. Performance of OS increased significantly from 6.9% in 2015 to 44.5% in 2018. Counseling for and performance of OS were more likely in patients who had surgery by laparoscopic approach, were counseled by a gynecological resident, or had more than three contact moments before surgery. Additionally, OS was less likely in patients who had vaginal surgery. CONCLUSIONS: Although the uptake of OS increased from 2015 to 2018, the majority of patients who were eligible for OS were not counseled and did not undergo OS. Its clinical practice varies on patient, surgery, and physician characteristics. Therefore, an implementation strategy tailored to associated determinants is recommended.

Acceptable migration of a fully cemented rotating hinge-type knee revision system measured in 20 patients with model-based RSA with a 2-year follow-up.

BACKGROUND AND PURPOSE: Rotating hinged knee implants are highly constrained prostheses used in cases in which adequate stability is mandatory. Due to their constraint nature, multidirectional stresses are directed through the bone-cement-implant interface, which might affect fixation and survival. The goal of this study was to assess micromotion of a fully cemented rotating hinged implant using radiostereometric analysis (RSA). PATIENTS AND METHODS: 20 patients requiring a fully cemented rotating hinge-type implant were included. RSA images were taken at baseline, 6 weeks, and 3, 6, 12, and 24 months postoperatively. Micromotion of femoral and tibial components referenced to markers in the bone was assessed with model-based RSA software, using implant CAD models. Total translation (TT), total rotation (TR), and maximal total point motion (MTPM) were calculated (median and range). RESULTS: At 2 years, TTfemur was 0.38 mm (0.15-1.5), TRfemur was 0.71° (0.37-2.2), TTtibia was 0.40 mm (0.08-0.66), TRtibia was 0.53° (0.30-2.4), MTPMfemur was 0.87 mm (0.54-2.8), and MTPMtibia was 0.66 mm (0.29-1.6). Femoral components showed more outliers (> 1 mm, > 1°) compared with tibial components. CONCLUSION: Fixation of this fully cemented rotating hinge-type revision implant seems adequate in the first 2 years after surgery. Femoral components showed more outliers, in contrast to previous RSA studies on condylar revision total knee implants.

Primary prevention of ovarian cancer: a patient decision aid for opportunistic salpingectomy.

BACKGROUND: The discovery of the fallopian tube epithelium as the origin of high-grade serous ovarian cancer has brought a new option for ovarian cancer prevention. The fallopian tubes have no known function after completion of childbearing and can be removed to reduce the lifetime risk of ovarian cancer. Although the lifetime risk in the general population does not justify preventive surgery in itself, salpingectomy can be performed during abdominal surgery for other indications, also known as an opportunistic salpingectomy. The popularity of opportunistic salpingectomy is increasing worldwide; however, the variation between gynecologists and hospitals in their advice on opportunistic salpingectomy occurs because of the remaining uncertainty of evidence. Therefore, whether a woman can make her own decision depends on the hospital or gynecologist she visits. We aimed to lower this practice variation by providing standardized and unbiased counseling material. OBJECTIVE: We aimed to develop and test a patient decision aid for opportunistic salpingectomy in women undergoing pelvic gynecologic surgery to either retain the ovaries or opt for sterilization. STUDY DESIGN: We followed a systematic development process based on the International Patient Decision Aid Standards. Data were collected between June 2019 and June 2020, using both qualitative and quantitative methods. The development process that occurred in collaboration with patients and healthcare professionals was overseen by a multidisciplinary steering group and was divided into 4 phases: (1) assessment of decisional needs using individual telephone interviews and questionnaires; (2) development of content and format based on decisional needs, current literature, and guidelines; (3) alpha testing and the first revision round; and (4) alpha testing and the second revision round. RESULTS: An outline of the patient decision aid was developed on the basis of decisional needs, current literature, and guidelines. It became clear that the decision aid should consist of 2 separate paths: one with information specifically for salpingectomy in addition to abdominal surgery and one for salpingectomy as a sterilization method. Both paths contained information on the anatomy and function of ovaries and fallopian tubes, risk reduction of ovarian cancer, and potential benefits and risks of opportunistic salpingectomy. Moreover, the sterilization path contains information on various sterilization methods and risks of unwanted pregnancy. The patient decision aid was developed as an online tool that includes information chapters, a knowledge quiz, consideration statements, and a summary detailing the patient's preferences and considerations. Adjustments were made following alpha testing round 1. The improved patient decision aid was subjected to usability tests (alpha testing round 2), in which it scored an "excellent" in tests with patients and a "good" in tests with gynecologists. Furthermore, our patient decision aid met the requirements of 45 of 49 applicable items from the International Patient Decision Aid Standards criteria. CONCLUSION: In collaboration with patients and healthcare professionals, a patient decision aid was developed on opportunistic salpingectomy and salpingectomy as a sterilization method. Both patients and gynecologists believed it is a useful tool that supports patients in making an informed decision whether to undergo an opportunistic salpingectomy and supports the counseling process by gynecologists.

External validation of Risk of Malignancy Index compared to IOTA Simple Rules.

BACKGROUND: Mathematical predictive models for ovarian tumors have an advantage over subjective assessment due to their relative simplicity, and therefore usefulness for less experienced sonographers. It is currently unclear which predictive model is best at predicting the nature of an ovarian tumor. PURPOSE: To compare the diagnostic predictive accuracy of the International Ovarian Tumour Analysis Simple Rules (IOTA SR) with Risk of Malignancy Index (RMI), to differentiate between benign and malignant ovarian tumors. MATERIAL AND METHODS: A total of 202 women diagnosed with ovarian tumor(s) were included. Preoperatively, patients were examined through transvaginal ultrasonography and CA-125 (U/mL) levels were measured. RMI and IOTA SR were determined, and where possible compared to definitive histopathological diagnosis. RESULTS: Of the 202 women with ovarian tumors, 168 women were included in this cohort study. Of these tumors, 118 (70.2%) were benign, 17 (10.1%) were borderline, and 33 (19.7%) were malignant. The sensitivity, specificity, and area under the curve for the RMI were 72.0%, 90.7%, and 0.896, respectively. For the IOTA SR, these were 90.0%, 68.6%, and 0.793, respectively. CONCLUSION: This cohort study shows that the RMI is a relatively useful diagnostic model in characterizing ovarian tumors, compared to the IOTA SR. However, due to the relatively low sensitivity of the RMI and high rate of inconclusive results of the IOTA SR, both diagnostic tests do not seem discriminative enough. Therefore, alternative diagnostic models are necessary.

Patients' and professionals' perspectives on implementation of opportunistic salpingectomy: a mixed-method study.

BACKGROUND: To prevent ovarian cancer, several international societies have issued guidelines which recommend to discuss opportunistic salpingectomy with women undergoing pelvic surgery after completion of childbearing. The opportunistic salpingectomy refers to the additional removal of Fallopian tubes during pelvic surgery for another indication to reduce the risk of developing ovarian cancer. These recommendations emphasize the importance of counselling on benefits and risks of opportunistic salpingectomy but offer no guidance on their implementation in daily practice. The lack of a tailored implementation strategy has resulted in a wide variation in current practice. To reduce this practice variation, we identified influencing factors on implementing opportunistic salpingectomy from patients' and professionals' perspectives. METHODS: We conducted a mixed-method study between 2019 and 2020 throughout the Netherlands. In a qualitative phase, we conducted interviews with gynecologic patients (N = 11) and their professionals (N = 20) to explore barriers and facilitators, using an interview guide. In the quantitative phase, we quantified these barriers and facilitators among patients who underwent a hysterectomy or sterilization and were counselled on the opportunistic salpingectomy (N = 77), and members of the Dutch Society of Obstetrics and Gynecology (N = 204), using questionnaires. For both phases, barriers and facilitators were classified into the following domains: innovation, patient, healthcare professional, social setting, organization, and economic and political context. RESULTS: For patients, main barriers were lack of knowledge about: the existence of the opportunistic salpingectomy (45%), size of the surgery (44%) and its associated possible disadvantages (37%). In addition, patients attributed their reluctance to concerns about the removal of healthy organs (46%). For professionals, main barriers were: patients' lack of knowledge of the size of surgery (85%) and its associated possible disadvantages (77%), the gap in evidence on long term risks and benefits (43%), the lack of feasibility in certain patients and during vaginal surgery (66%). Both patients (41%) and professionals (67%) identified the need for counselling material as facilitator. CONCLUSION: To reduce the variety in care regarding opportunistic salpingectomy, consensus and uniform counselling is needed. Including the opportunistic salpingectomy in gynecological guidelines and a decision aid for counselling could serve as tools to facilitate implementation.

Translation, cross-cultural adaptation, reliability and construct validity of the Dutch Oxford Knee Score - Activity and Participation Questionnaire.

BACKGROUND: Patients undergoing total knee arthroplasty (TKA) tend to be younger and tend to receive TKA at an earlier stage compared to 20 years ago. The Oxford Knee Score - Activity and Participation (OKS-APQ) questionnaire evaluates higher levels of activity and participation, reflecting activity patterns of younger or more active people. The purpose of this study was to translate the OKS-APQ questionnaire into Dutch, and to evaluate its measurement properties in pre- and postoperative TKA patients. METHODS: The OKS-APQ was translated and adapted according to the forward-backward translation multi step approach and tested for clinimetric quality. Floor and ceiling effects, structural validity, construct validity, internal consistency and test-retest reliability were evaluated using COSMIN quality criteria. The OKS-APQ, the Oxford Knee Score (OKS), the Short Form-36 (SF-36), a Visual Analogue Scale (VAS) for pain and the Forgotten Joint Score (FJS) were assessed in 131 patients (72 preoperative and 59 postoperative TKA patients), and the OKS-APQ was administered twice in 50 patients (12 preoperative and 38 postoperative TKA patients), after an interval of minimal 2 weeks. RESULTS: Floor effects were observed in preoperative patients. Confirmatory factor analyses (CFA) indicated a good fit of a 1-factor model by the following indices: (Comparative Fit Index (CFI): 0.97, Tucker-Lewis Index (TLI): 0.96 and Standardized Root Mean Square Residual (SRMR): 0.03). Construct validity was supported as > 75% of the hypotheses were confirmed. Internal consistency (Cronbach α's from 0.81 to 0.95) was good in the pooled and separate pre- and postoperative samples and test-retest reliability (Intraclass Correlation Coefficients (ICCs) from 0.63 - 0.85) were good in postoperative patients and moderate in preoperative patients. The standard Error of Measurements (SEMs) ranged from 8.5 - 12.2 and the Smallest Detectable Changes in individuals (SDCind) ranged from 23.5 - 34.0 (on a scale from 0 to 100). CONCLUSIONS: Preliminary findings suggest that the Dutch version of the OKS-APQ is reliable and valid for a Dutch postoperative TKA patient sample. However, in a preoperative TKA sample, the OKS-APQ seems less suitable, because of floor effects and lower test-retest reliability. The Dutch version of the OKS-APQ can be used alongside the OKS to discriminate among levels of activity and participation in postoperative patients.

Definitions of poor outcome after total knee arthroplasty: an inventory review.

BACKGROUND: A significant proportion of patients experiences poor response (i.e. no or little improvement) after total knee arthroplasty (TKA) because of osteoarthritis. It is difficult to quantify the proportion of patients who experiences poor response to TKA, as different definitions of, and perspectives (clinician's and patient's) on poor response are being used. The aim of this study was therefore to review the literature and summarize definitions of poor response to TKA. METHODS: A systematic search was performed to identify and review studies that included dichotomous definitions of poor outcome after primary TKA. The type, amount and combination of domains (e.g. functioning), outcome measures, type of thresholds (absolute/relative, change/cut-off), values and moments of follow-up used in definitions were summarized. RESULTS: A total of 47 different dichotomous definitions of poor response to TKA were extracted from 2163 initially identified studies. Thirty-six definitions incorporated one domain, seven definitions comprised two domains and four definitions comprised three domains. Eight different domains were used in identified definitions: pain, function, physical functioning, quality of life (QoL), patient satisfaction, anxiety, depression and patient global assessment. The absolute cut-off value was the most common type of threshold, with large variety in value and timing of follow-up. CONCLUSIONS: Our inventory review shows that definitions of poor response to TKA are heterogeneous. Our findings stresses the need for an unambiguous definition of poor response to draw conclusions about the prevalence of poor-responders to TKA across hospitals and countries, and to identify patients at risk.

Mid-flexion laxity in the asymptomatic native knee is predominantly present on the lateral side.

PURPOSE: During total knee arthroplasty (TKA), an orthopaedic surgeon is focused on soft-tissue balance in extension (0°) and in flexion (90°). Patients with instability problems of the knee often report a feeling of instability during daily life activities, at around 30° knee flexion. There are no reference values available for knee laxity of healthy subjects in mid-flexion (30°) and flexion (90°) for comparison with the TKA population. Therefore, the aim was to quantify varus and valgus knee laxity in extension, mid-flexion and flexion in the asymptomatic native knee. METHODS: In 40 healthy volunteers matched for age, gender and BMI with the TKA-population, varus and valgus knee laxity in extension (0°), mid-flexion (30°) and flexion (90°) was measured on low-dose radiographs. For each subject, one randomly selected knee was stressed in extension, mid-flexion and flexion (with 15 Nm) using a stress device. RESULTS: Varus laxity in mid-flexion was higher than in extension and flexion (p < 0.01). Valgus laxity tended to be highest in mid-flexion laxity; however, no differences in knee laxity between flexion angles were seen (n.s.). Varus knee laxity in extension was higher in females than in males (p < 0.05). CONCLUSIONS: Mid-flexion laxity in the native knee is more prominent on the lateral side of the knee, while the medial side is more stable and constrained. Varus knee laxity in extension was shown to be higher in females than in males. LEVEL OF EVIDENCE: Prognostic Level II.

Associations of adipose and muscle tissue parameters at colorectal cancer diagnosis with long-term health-related quality of life.

PURPOSE: Increased visceral adiposity (visceral obesity) and muscle wasting (sarcopenia) at colorectal cancer (CRC) diagnosis, quantified by computed tomography (CT) image analysis, have been unfavorably associated with short-term clinical outcomes and survival, but associations with long-term health-related quality of life (HRQoL) have not been investigated. We studied associations of visceral adiposity, muscle fat infiltration, muscle mass, and sarcopenia at CRC diagnosis with HRQoL 2-10 years post-diagnosis. METHODS: A cross-sectional study was conducted in 104 stage I‒III CRC survivors, diagnosed at Maastricht University Medical Center+, the Netherlands (2002-2010). Diagnostic CT images at the level of the third lumbar vertebra were analyzed to retrospectively determine visceral adipose tissue area (cm2); intermuscular adipose tissue area (cm2) and mean muscle attenuation (Hounsfield units) as measures of muscle fat infiltration; and skeletal muscle index (SMI, cm2/m2) as measure of muscle mass and for determining sarcopenia. RESULTS: Participants showed a large variation in body composition parameters at CRC diagnosis with a mean visceral adipose tissue area of 136.1 cm2 (standard deviation: 93.4) and SMI of 47.8 cm2/m2 (7.2); 47% was classified as being viscerally obese, and 32% as sarcopenic. In multivariable linear regression models, associations of the body composition parameters with long-term global quality of life, physical, role and social functioning, disability, fatigue, and distress were not significant, and observed mean differences were below predefined minimal important differences. CONCLUSIONS: Although visceral obesity and sarcopenia are relatively common at CRC diagnosis, we found no significant associations of these parameters with long-term HRQoL in stage I-III CRC survivors.

Exploration of adverse consequences of total knee arthroplasty by patients and knee specialists: a qualitative study.

Objectives: A successful outcome according to the knee specialist is not a guarantee for treatment success as perceived by patients. In this study, we aimed to explore outcome expectations and experiences of patients with OA before and after total knee arthroplasty (TKA) surgery and knee specialists that might contribute to the negative appraisal of its effect, and differences in views between patients and knee specialists. Methods: Semi-structured interviews were held in Belgium and the Netherlands. Twenty-five patients (2 without indications for TKA, 11 on the waiting list for TKA and 12 postoperative TKA) and 15 knee specialists (9 orthopaedic surgeons, 1 physician assistant, 1 nurse practitioner and 4 physiotherapists) were interviewed. Conversations were audio recorded, transcribed verbatim, and analysed using thematic analysis following the grounded theory approach. Separate analyses were conducted for patients and knee specialists. Results: Patients were focused on the arduous process of getting used to the prosthesis, lingering pain, awareness of the artificial knee and limitations they experience during valued and daily activities, whereas knee specialists put emphasis on surgical failure, unexplained pain, limited walking ability and impairments that limit the physical functioning of patients. Conclusion: This study provides a comprehensive overview of potential adverse consequences from the perspective of both patients and knee specialists. Improving patients' awareness and expectations of adaptation to the knee prosthesis needs to be considered.

STop OVarian CAncer (STOPOVCA) young: Protocol for a multicenter follow-up study to determine the long-term effects of opportunistic salpingectomy on age at menopause.

BACKGROUND: Opportunistic salpingectomy comprises additional bilateral salpingectomy during abdominal surgery as a prophylactic method to reduce the risk of ovarian cancer. However, opportunistic salpingectomy may potentially damage (micro)blood circulation to the ovaries, resulting in earlier onset of menopause. PRIMARY OBJECTIVE: To evaluate the long-term effects of opportunistic salpingectomy on the onset of menopause in women who underwent sterilization through salpingectomy compared with a control group who underwent sterilization by tubal ligation or no surgery at all. STUDY HYPOTHESIS: Opportunistic salpingectomy does not lower the mean age at onset of menopause. TRIAL DESIGN: In a multicenter observational noninferiority study, we will prospectively compare the age at menopause of women initially aged 35-45 who underwent sterilization through opportunistic salpingectomy with a similarly aged control group who underwent sterilization by tubal ligation or no sterilization. Participants will be asked to complete an annual questionnaire on onset of menopause to eventually determine whether there is more than a one-year decrease in mean age at onset of menopause in the opportunistic salpingectomy group. Follow-up will last until determination of menopause, with a maximum of 15 years. MAJOR INCLUSION/EXCLUSION CRITERIA: Inclusion criteria: pre-menopausal; age between 35 and 45; intact ovaries. EXCLUSION CRITERIA: post-menopausal; previous bilateral salpingectomy or oophorectomy; previous hysterectomy; abnormal karyotype; previous or current chemotherapy or pelvic radiation. PRIMARY ENDPOINT(S): Determination of age of menopause measured by annual questionnaire. SAMPLE SIZE: 1200 (400 intervention group; 800 control group). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: It is estimated that recruitment will be completed by 2023 and results will be published by 2039. GOV IDENTIFIER: NCT04757922 PROTOCOL VERSION: : Version 1, February 2021.

Prediction models in gynaecology: Transparent reporting needed for clinical application.

The clinical application of prediction models is increasing within the field of gynaecology and obstetrics. This is mostly due to the fact that clinicians and patients prefer individualized counselling and person specific, more objective outcome assessment. To prevent using inadequate models, it is important to construct and perform prediction model studies correctly. Therefore, the TRIPOD statement (the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) was developed. The aim of this review is to obtain an overview of the existing published prediction models for benign gynaecology and to investigate to what extent these studies meet the TRIPOD criteria. We performed a literature search in the databases PubMed, Embase and Cochrane Library from inception to August 2020. Searching the cross-references of the relevant studies within our search identified additional articles. Publications were included if the aim of the study was to develop a multivariable prediction model within the field of benign gynaecology. Two independent reviewers extracted the data. Analysis of the studies was performed by using a checklist derived from the TRIPOD criteria. Based on our search, 2487 studies were selected, including potential duplications. Eventually, a total of twenty-two studies were selected. 91% of these studies handled their predictors by univariable analysis before developing a multivariable prediction model. Fifteen studies described having missing data, but not all of them (9%) handled these missing data. Four different internal validation methods were used in twenty studies. Fifteen studies (68%) had prediction models with a C-index ≥ 0.7, which indicates a good model. Half of the studies (50%) did not measure the calibration, overall performance was described in two studies (9%). External validation was performed in 9% of the studies. The correct development of a prediction model within benign gynaecology and subsequent transparent reporting of the model development is important to facilitate clinical use. Without transparent reporting, wrong assumptions can be made leading to incorrect application of a specific prediction model. This overview shows that excepting carrying out an external validation, only one article met all the criteria. Therefore, we strongly recommend use of the TRIPOD criteria for developing and validating a prediction model (study). In addition, prior to publication, content experts should critically and statistically review the prediction model. If too many criteria are not met, refusing publication should be considered.

Mechano-Hypoxia Conditioning of Engineered Human Meniscus.

Meniscus fibrochondrocytes (MFCs) experience simultaneous hypoxia and mechanical loading in the knee joint. Experimental conditions based on these aspects of the native MFC environment may have promising applications in human meniscus tissue engineering. We hypothesized that in vitro "mechano-hypoxia conditioning" with mechanical loading such as dynamic compression (DC) and cyclic hydrostatic pressure (CHP) would enhance development of human meniscus fibrocartilage extracellular matrix in vitro. MFCs from inner human meniscus surgical discards were pre-cultured on porous type I collagen scaffolds with TGF-ß3 supplementation to form baseline tissues with newly formed matrix that were used in a series of experiments. First, baseline tissues were treated with DC or CHP under hypoxia (HYP, 3% O2) for 5 days. DC was the more effective load regime in inducing gene expression changes, and combined HYP/DC enhanced gene expression of fibrocartilage precursors. The individual treatments of DC and HYP regulated thousands of genes, such as chondrogenic markers SOX5/6, in an overwhelmingly additive rather than synergistic manner. Similar baseline tissues were then treated with a short course of DC (5 vs 60 min, 10-20% vs 30-40% strain) with different pre-culture duration (3 vs 6 weeks). The longer course of loading (60 min) had diminishing returns in regulating mechano-sensitive and inflammatory genes such as c-FOS and PTGS2, suggesting that as few as 5 min of DC was adequate. There was a dose-effect in gene regulation by higher DC strains, whereas outcomes were inconsistent for different MFC donors in pre-culture durations. A final set of baseline tissues was then cultured for 3 weeks with mechano-hypoxia conditioning to assess mechanical and protein-level outcomes. There were 1.8-5.1-fold gains in the dynamic modulus relative to baseline in HYP/DC, but matrix outcomes were equal or inferior to static controls. Long-term mechano-hypoxia conditioning was effective in suppressing hypertrophic markers (e.g., COL10A1 10-fold suppression vs static/normoxia). Taken together, these results indicate that appropriately applied mechano-hypoxia conditioning can support meniscus fibrocartilage development in vitro and may be useful as a strategy for developing non-hypertrophic articular cartilage using mesenchymal stem cells.

The role of concomitant ligament injury in the development of post-traumatic osteoarthritis after distal radius fractures: a protocol for a systematic review.

INTRODUCTION: Treatment of distal radius fractures (DRFs) aims to restore anatomic position of the fracture fragments and congruity of the articular surface to optimise functional outcomes and prevent osteoarthritis in the long term. While ligament injury of the wrist is often associated with DRFs and sole ligament injuries of the wrist lead to osteoarthritis, it is plausible that concomitant ligament injury in DRFs may aggravate degenerative changes of the wrist. The relationship between concomitant ligament injury and post-traumatic osteoarthritis in patients with DRFs is unclear. This study aims to identify the types of associated ligament injury in patients with a DRF and to elucidate the association of ligament injury on the development of post-traumatic osteoarthritis. METHODS AND ANALYSIS: This protocol is written in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) guidelines. An electronic search in MEDLINE, Embase, Web of Science, Cochrane Central Register of Trials and Google Scholar has been created and performed by a Health Sciences librarian with expertise in systematic review searching. Original research articles in English literature, which report on concomitant ligament injury of the wrist in relation to post-traumatic osteoarthritis, patient-reported outcome measures or clinician-reported outcome measures in patients (aged ≥18 years) with DRFs will be included. Two reviewers will independently screen and appraise articles and perform data extraction. In case of any disagreements, a third reviewer will be consulted. A systematic qualitative synthesis will be performed using text and tables. ETHICS AND DISSEMINATION: No ethical approval is required, since this is a protocol for a systematic review. The systematic review will be submitted for publication in a peer-reviewed scientific journal and for presentation at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42020165007.

A novel test for assessment of anterolateral rotatory instability of the knee: the tibial internal rotation test (TIR test).

BACKGROUND: Rotational instability of the knee may persist after anterior cruciate ligament (ACL) reconstruction, which may be due to insufficiency of anterolateral stabilizing structures. However, no reliable diagnostic tool or physical examination test is available for identifying patients with anterolateral rotatory instability (ALRI). As shown in cadaveric studies, static internal rotation of the knee is increased in higher flexion angles of the knee after severing the anterolateral structures. This might also be the case in patients with an ACL-deficient knee and concomitant damage to the anterolateral structures. The objective of this study is to assess anterolateral rotatory instability of the knee during physical examination with a tibial internal rotation test. METHODS: ACL-injured knees of 52 patients were examined by two examiners and side-to-side differences were compared. Both lower legs were internally rotated by applying manual internal rotation torque to both feet in prone position with the knees in 30°, 60° and 90° of flexion. For quantification of the amount of rotation in degrees, a torque adapter on a booth was used. Intra-rater, inter-rater and rater-device agreement were determined by calculating kappa (κ) for the tibial internal rotation test. RESULTS: Tibial internal rotation is increased in 19.2% of the patients with ACL injury according to the tibial internal rotation test. Good intra-rater agreement was found for the tibial internal rotation test, κC = 0.63 (95%CI -0.02-1.28), p = 0.015. Fair inter-rater agreement was found, κF = 0.29 (95%CI 0.02-0.57), p = 0.038. Good rater-device agreement was found, κC = 0.62 (95%CI 0.15-1.10), p = 0.001. CONCLUSION: The tibial internal rotation test shows increased tibial internal rotation in a small amount of patients with ACL injury. Even though no gold standard for assessment of increased tibial internal rotation of the knee is available yet, the test can be of additional value. It can be used for assessment of internal rotatory laxity of the knee as part of ALRI in addition to the pivot shift test. No clinical implications should yet be based on this test alone.

Rater agreement reliability of the dial test in the ACL-deficient knee.

BACKGROUND: Posterolateral rotatory instability (PLRI) of the knee can easily be missed, because attention is paid to injury of the cruciate ligaments. If left untreated this clinical instability may persist after reconstruction of the cruciate ligaments and may put the graft at risk of failure. Even though the dial test is widely used to diagnose PLRI, no validity and reliability studies of the manual dial test are yet performed in patients. This study focuses on the reliability of the manual dial test by determining the rater agreement. METHODS: Two independent examiners performed the dial test in knees of 52 patients after knee distorsion with a suspicion on ACL rupture. The dial test was performed in prone position in 30°, 60° and 90° of flexion of the knees. ≥10° side-to-side difference was considered a positive dial test. For quantification of the amount of rotation in degrees, a measuring device was used with a standardized 6 Nm force, using a digital torque adapter on a booth. The intra-rater, inter-rater and rater-device agreement were determined by calculating kappa (κ) for the dial test. RESULTS: A positive dial test was found in 21.2% and 18.0% of the patients as assessed by a blinded examiner and orthopaedic surgeon respectively. Fair inter-rater agreement was found in 30° of flexion, κF = 0.29 (95% CI: 0.01 to 0.56), p = 0.044 and 90° of flexion, κF = 0.38 (95% CI: 0.10 to 0.66), p = 0.007. Almost perfect rater-device agreement was found in 30° of flexion, κC = 0.84 (95% CI: 0.52 to 1.15), p < 0.001. Moderate rater-device agreement was found in 30° and 90° combined, κC = 0.50 (95% CI: 0.13 to 0.86), p = 0.008. No significant intra-rater agreement was found. CONCLUSIONS: Rater agreement reliability of the manual dial test is questionable. It has a fair inter-rater agreement in 30° and 90° of flexion.

Twelve novel mutations in the tissue-nonspecific alkaline phosphatase gene (ALPL) in patients with various forms of hypophosphatasia.

Hypophosphatasia is a rare inherited disorder characterized by defective bone mineralization and deficiency of serum and tissue liver/bone/kidney tissue alkaline phosphatase (L/B/K ALP) activity. We report here the characterization of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 11 families affected by various forms of hypophosphatasia. Nineteen distinct mutations were found, 7 of which were previously reported. Eleven of the 12 new mutations were missense mutations (Y11C, A34V, R54H, R135H, N194D, G203V, E218G, D277Y, F310G, A382S, V406A), the last one (998-1G>T) was a mutation affecting acceptor splice site.