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Bone & Joint Research
Vol. 13, Issue 2 | Pages 66 - 82
5 Feb 2024
Zhao D Zeng L Liang G Luo M Pan J Dou Y Lin F Huang H Yang W Liu J

Aims

This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

Methods

Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization.


The Bone & Joint Journal
Vol. 106-B, Issue 2 | Pages 203 - 211
1 Feb 2024
Park JH Won J Kim H Kim Y Kim S Han I

Aims. This study aimed to compare the performance of survival prediction models for bone metastases of the extremities (BM-E) with pathological fractures in an Asian cohort, and investigate patient characteristics associated with survival. Methods. This retrospective cohort study included 469 patients, who underwent surgery for BM-E between January 2009 and March 2022 at a tertiary hospital in South Korea. Postoperative survival was calculated using the PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models. Model performance was assessed with area under the curve (AUC), calibration curve, Brier score, and decision curve analysis. Cox regression analyses were performed to evaluate the factors contributing to survival. Results. The SORG model demonstrated the highest discriminatory accuracy with AUC (0.80 (95% confidence interval (CI) 0.76 to 0.85)) at 12 months. In calibration analysis, the PATHfx3.0 and OPTIModel models underestimated survival, while the SPRING13 and IOR models overestimated survival. The SORG model exhibited excellent calibration with intercepts of 0.10 (95% CI -0.13 to 0.33) at 12 months. The SORG model also had lower Brier scores than the null score at three and 12 months, indicating good overall performance. Decision curve analysis showed that all five survival prediction models provided greater net benefit than the default strategy of operating on either all or no patients. Rapid growth cancer and low serum albumin levels were associated with three-, six-, and 12-month survival. Conclusion. State-of-art survival prediction models for BM-E (PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models) are useful clinical tools for orthopaedic surgeons in the decision-making process for the treatment in Asian patients, with SORG models offering the best predictive performance. Rapid growth cancer and serum albumin level are independent, statistically significant factors contributing to survival following surgery of BM-E. Further refinement of survival prediction models will bring about informed and patient-specific treatment of BM-E. Cite this article: Bone Joint J 2024;106-B(2):203–211


Bone & Joint 360
Vol. 12, Issue 4 | Pages 16 - 20
1 Aug 2023

The August 2023 Knee Roundup360 looks at: Curettage and cementation of giant cell tumour of bone: is arthritis a given?; Anterior knee pain following total knee arthroplasty: does the patellar cement-bone interface affect postoperative anterior knee pain?; Nickel allergy and total knee arthroplasty; The use of artificial intelligence for the prediction of periprosthetic joint infection following aseptic revision total knee arthroplasty; Ambulatory unicompartmental knee arthroplasty: development of a patient selection tool using machine learning; Femoral asymmetry: a missing piece in knee alignment; Needle arthroscopy – a benefit to patients in the outpatient setting; Can lateral unicompartmental knees be done in a day-case setting?


The Bone & Joint Journal
Vol. 105-B, Issue 6 | Pages 702 - 710
1 Jun 2023
Yeramosu T Ahmad W Bashir A Wait J Bassett J Domson G

Aims. The aim of this study was to identify factors associated with five-year cancer-related mortality in patients with limb and trunk soft-tissue sarcoma (STS) and develop and validate machine learning algorithms in order to predict five-year cancer-related mortality in these patients. Methods. Demographic, clinicopathological, and treatment variables of limb and trunk STS patients in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2004 to 2017 were analyzed. Multivariable logistic regression was used to determine factors significantly associated with five-year cancer-related mortality. Various machine learning models were developed and compared using area under the curve (AUC), calibration, and decision curve analysis. The model that performed best on the SEER testing data was further assessed to determine the variables most important in its predictive capacity. This model was externally validated using our institutional dataset. Results. A total of 13,646 patients with STS from the SEER database were included, of whom 35.9% experienced five-year cancer-related mortality. The random forest model performed the best overall and identified tumour size as the most important variable when predicting mortality in patients with STS, followed by M stage, histological subtype, age, and surgical excision. Each variable was significant in logistic regression. External validation yielded an AUC of 0.752. Conclusion. This study identified clinically important variables associated with five-year cancer-related mortality in patients with limb and trunk STS, and developed a predictive model that demonstrated good accuracy and predictability. Orthopaedic oncologists may use these findings to further risk-stratify their patients and recommend an optimal course of treatment. Cite this article: Bone Joint J 2023;105-B(6):702–710


Bone & Joint Open
Vol. 4, Issue 6 | Pages 399 - 407
1 Jun 2023
Yeramosu T Ahmad W Satpathy J Farrar JM Golladay GJ Patel NK

Aims. To identify variables independently associated with same-day discharge (SDD) of patients following revision total knee arthroplasty (rTKA) and to develop machine learning algorithms to predict suitable candidates for outpatient rTKA. Methods. Data were obtained from the American College of Surgeons National Quality Improvement Programme (ACS-NSQIP) database from the years 2018 to 2020. Patients with elective, unilateral rTKA procedures and a total hospital length of stay between zero and four days were included. Demographic, preoperative, and intraoperative variables were analyzed. A multivariable logistic regression (MLR) model and various machine learning techniques were compared using area under the curve (AUC), calibration, and decision curve analysis. Important and significant variables were identified from the models. Results. Of the 5,600 patients included in this study, 342 (6.1%) underwent SDD. The random forest (RF) model performed the best overall, with an internally validated AUC of 0.810. The ten crucial factors favoring SDD in the RF model include operating time, anaesthesia type, age, BMI, American Society of Anesthesiologists grade, race, history of diabetes, rTKA type, sex, and smoking status. Eight of these variables were also found to be significant in the MLR model. Conclusion. The RF model displayed excellent accuracy and identified clinically important variables for determining candidates for SDD following rTKA. Machine learning techniques such as RF will allow clinicians to accurately risk-stratify their patients preoperatively, in order to optimize resources and improve patient outcomes. Cite this article: Bone Jt Open 2023;4(6):399–407


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 5 - 5
23 Feb 2023
Jadresic MC Baker J
Full Access

Numerous prediction tools are available for estimating postoperative risk following spine surgery. External validation studies have shown mixed results. We present the development, validation, and comparative evaluation of novel tool (NZSpine) for modelling risk of complications within 30 days of spine surgery. Data was gathered retrospectively from medical records of patients who underwent spine surgery at Waikato Hospital between January 2019 and December 2020 (n = 488). Variables were selected a priori based on previous evidence and clinical judgement. Postoperative adverse events were classified objectively using the Comprehensive Complication Index. Models were constructed for the occurrence of any complication and significant complications (based on CCI >26). Performance and clinical utility of the novel model was compared against SpineSage (. https://depts.washington.edu/spinersk/. ), an extant online tool which we have shown in unpublished work to be valid in our local population. Overall complication rate was 34%. In the multivariate model, higher age, increased surgical invasiveness and the presence of preoperative anemia were most strongly predictive of any postoperative complication (OR = 1.03, 1.09, 2.1 respectively, p <0.001), whereas the occurrence of a major postoperative complication (CCI >26) was most strongly associated with the presence of respiratory disease (OR = 2.82, p <0.001). Internal validation using the bootstrapped models showed the model was robust, with an AUC of 0.73. Using sensitivity analysis, 80% of the model's predictions were correct. By comparison SpineSage had an AUC of 0.71, and in decision curve analysis the novel model showed greater expected benefit at all thresholds of risk. NZSpine is a novel risk assessment tool for patients undergoing acute and elective spine surgery and may help inform clinicians and patients of their prognosis. Use of an objective tool may help to provide uniformity between DHBs when completing the “clinician assessment of risk” section of the national prioritization tool


Bone & Joint 360
Vol. 12, Issue 1 | Pages 36 - 39
1 Feb 2023

The February 2023 Trauma Roundup360 looks at: Masquelet versus bone transport in infected nonunion of tibia; Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multicentre randomized clinical trial; Is the T-shaped acetabular fracture really a “T”?; What causes cut-out of proximal femur nail anti-rotation device in intertrochanteric fractures?; Is the common femoral artery at risk with percutaneous fragility pelvis fixation?; Anterior pelvic ring pattern predicts displacement in lateral compression fractures; Differences in age-related characteristics among elderly patients with hip fractures.


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1011 - 1016
1 Sep 2022
Acem I van de Sande MAJ

Prediction tools are instruments which are commonly used to estimate the prognosis in oncology and facilitate clinical decision-making in a more personalized manner. Their popularity is shown by the increasing numbers of prediction tools, which have been described in the medical literature. Many of these tools have been shown to be useful in the field of soft-tissue sarcoma of the extremities (eSTS). In this annotation, we aim to provide an overview of the available prediction tools for eSTS, provide an approach for clinicians to evaluate the performance and usefulness of the available tools for their own patients, and discuss their possible applications in the management of patients with an eSTS.

Cite this article: Bone Joint J 2022;104-B(9):1011–1016.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 548 - 560
17 Aug 2022
Yuan W Yang M Zhu Y

Aims. We aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism. Methods. Five datasets were obtained from the Gene Expression Omnibus database. Unsupervised consensus cluster analysis was used to determine new PMOP subtypes. To determine the central genes and the core modules related to PMOP, the weighted gene co-expression network analysis (WCGNA) was applied. Gene Ontology enrichment analysis was used to explore the biological processes underlying key genes. Logistic regression univariate analysis was used to screen for statistically significant variables. Two algorithms were used to select important PMOP-related genes. A logistic regression model was used to construct the PMOP-related gene profile. The receiver operating characteristic area under the curve, Harrell’s concordance index, a calibration chart, and decision curve analysis were used to characterize PMOP-related genes. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of the PMOP-related genes in the gene signature. Results. We identified three PMOP-related subtypes and four core modules. The muscle system process, muscle contraction, and actin filament-based movement were more active in the hub genes. We obtained five feature genes related to PMOP. Our analysis verified that the gene signature had good predictive power and applicability. The outcomes of the GSE56815 cohort were found to be consistent with the results of the earlier studies. qRT-PCR results showed that RAB2A and FYCO1 were amplified in clinical samples. Conclusion. The PMOP-related gene signature we developed and verified can accurately predict the risk of PMOP in patients. These results can elucidate the molecular mechanism of RAB2A and FYCO1 underlying PMOP, and yield new and improved treatment strategies, ultimately helping PMOP monitoring. Cite this article: Bone Joint Res 2022;11(8):548–560


Bone & Joint 360
Vol. 8, Issue 6 | Pages 35 - 36
1 Dec 2019


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_12 | Pages 68 - 68
1 Oct 2019
Bedair HS
Full Access

Background. Postoperative recovery after routine total hip arthroplasty (THA) can lead to the development of prolonged opioid use but there are few tools for predicting this adverse outcome. The purpose of this study was to develop machine learning algorithms for preoperative prediction of prolonged post-operative opioid use after THA. Methods. A retrospective review of electronic health records was conducted at two academic medical centers and three community hospitals to identify adult patients who underwent THA for osteoarthritis between January 1. st. , 2000 and August 1. st. , 2018. Prolonged postoperative opioid prescriptions were defined as continuous opioid prescriptions after surgery to at least 90 days after surgery. Five machine learning algorithms were developed to predict this outcome and were assessed by discrimination, calibration, and decision curve analysis. Results. Overall, 5507 patients underwent THA, of which 345 (6.3%) had prolonged postoperative opioid prescriptions. The factors determined for prediction of prolonged postoperative opioid prescriptions were: age, duration of pre-operative opioid exposure, preoperative hemoglobin, and certain preoperative medications (anti-depressants, benzodiazepines, non-steroidal anti-inflammatory drugs, and beta-2-agonists). The elastic-net penalized logistic regression model achieved the best performance across discrimination (c-statistic = 0.77), calibration, and decision curve analysis. This model was incorporated into a digital application able to provide both predictions and explanations; available here: . https://sorg-apps.shinyapps.io/thaopioid/. Conclusion. If externally validated in independent populations, the algorithms developed in this study could improve preoperative screening and support for THA patients at high-risk for prolonged postoperative opioid use. Early identification and intervention in high-risk cases may mitigate the long-term adverse consequence of opioid dependence. For any tables or figures, please contact the authors directly


Background. Metastatic bone patients who require surgery needs to be evaluated in order to maximise quality of life and avoiding functional impairment, minimising the risks connected to the surgical procedures. The best surgical procedure needs to be tailored on survival estimation. There are no current available tool or method to evaluate survival estimation with accuracy in patients with bone metastasis. We recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable skeletal metastases. After making it publicly available on . www.PATHFx.org. , we attempted to externally validate it using independent, international data. Methods. We collected data from patients treated at 13 Italian orthopaedic oncology referral centers between 2008 and 2012, then applied to PATHFx, which generated a probability of survival at three and 12-months for each patient. We assessed accuracy using the area under the receiver-operating characteristic curve (AUC), clinical utility using Decision Curve Analysis DCA), and compared the Italian patient data to the training set (United States) and first external validation set (Scandinavia). Results. The Italian dataset contained 287 records with at least 12 months follow-up information. The AUCs for the three-month and 12-month estimates was 0.80 and 0.77, respectively. There were missing data, including the surgeon's estimate of survival that was missing in the majority of records. Physiologically, Italian patients were similar to patients in the training and first validation sets. However notable differences were observed in the proportion of those surviving three and 12-months, suggesting differences in referral patterns and perhaps indications for surgery. Conclusions. PATHFx was successfully validated in an Italian dataset containing missing data. This study demonstrates its broad applicability to European patients, even in centers with differing treatment philosophies from those previously studied


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_9 | Pages 83 - 83
1 May 2017
Spinelli M Piccioli A Maccauro G Forsberg J Wedin R
Full Access

Background. Metastatic bone patients who require surgery needs to be evaluated in order to maximise quality of life and avoiding functional impairment, minimising the risks connected to the surgical procedures. The best surgical procedure needs to be tailored on survival estimation. There are no current available tool or method to evaluate survival estimation with accuracy in patients with bone metastasis. We recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable skeletal metastases. After making it publicly available on . www.PATHFx.org. , we attempted to externally validate it using independent, international data. Methods. We collected data from patients treated at 13 Italian orthopaedic oncology referral centers between 2008 and 2012, then applied to PATHFx, which generated a probability of survival at three and 12-months for each patient. We assessed accuracy using the area under the receiver-operating characteristic curve (AUC), clinical utility using Decision Curve Analysis DCA), and compared the Italian patient data to the training set (United States) and first external validation set (Scandinavia). Results. The Italian dataset contained 287 records with at least 12 months follow-up information. The AUCs for the three-month and 12-month estimates was 0.80 and 0.77, respectively. There were missing data, including the surgeon's estimate of survival that was missing in the majority of records. Physiologically, Italian patients were similar to patients in the training and first validation sets. However notable differences were observed in the proportion of those surviving three and 12-months, suggesting differences in referral patterns and perhaps indications for surgery. Conclusions. PATHFx was successfully validated in an Italian dataset containing missing data. This study demonstrates its broad applicability to European patients, even in centers with differing treatment philosophies from those previously studied. Level of Evidence. IV. None of the authors have financial disclosures or conflicts of interest to declare. The study presented did not need the approval by ethics committee