Does the Presence of Missing Data Affect the Performance of the SORG Machine-learning Algorithm for Patients With Spinal Metastasis? Development of an Internet Application Algorithm.

BACKGROUND: The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA) was developed to predict the survival of patients with spinal metastasis. The algorithm was successfully tested in five international institutions using 1101 patients from different continents. The incorporation of 18 prognostic factors strengthens its predictive ability but limits its clinical utility because some prognostic factors might not be clinically available when a clinician wishes to make a prediction. QUESTIONS/PURPOSES: We performed this study to (1) evaluate the SORG-MLA's performance with data and (2) develop an internet-based application to impute the missing data. METHODS: A total of 2768 patients were included in this study. The data of 617 patients who were treated surgically were intentionally erased, and the data of the other 2151 patients who were treated with radiotherapy and medical treatment were used to impute the artificially missing data. Compared with those who were treated nonsurgically, patients undergoing surgery were younger (median 59 years [IQR 51 to 67 years] versus median 62 years [IQR 53 to 71 years]) and had a higher proportion of patients with at least three spinal metastatic levels (77% [474 of 617] versus 72% [1547 of 2151]), more neurologic deficit (normal American Spinal Injury Association [E] 68% [301 of 443] versus 79% [1227 of 1561]), higher BMI (23 kg/m2 [IQR 20 to 25 kg/m2] versus 22 kg/m2 [IQR 20 to 25 kg/m2]), higher platelet count (240 × 103/µL [IQR 173 to 327 × 103/µL] versus 227 × 103/µL [IQR 165 to 302 × 103/µL], higher lymphocyte count (15 × 103/µL [IQR 9 to 21× 103/µL] versus 14 × 103/µL [IQR 8 to 21 × 103/µL]), lower serum creatinine level (0.7 mg/dL [IQR 0.6 to 0.9 mg/dL] versus 0.8 mg/dL [IQR 0.6 to 1.0 mg/dL]), less previous systemic therapy (19% [115 of 617] versus 24% [526 of 2151]), fewer Charlson comorbidities other than cancer (28% [170 of 617] versus 36% [770 of 2151]), and longer median survival. The two patient groups did not differ in other regards. These findings aligned with our institutional philosophy of selecting patients for surgical intervention based on their level of favorable prognostic factors such as BMI or lymphocyte counts and lower levels of unfavorable prognostic factors such as white blood cell counts or serum creatinine level, as well as the degree of spinal instability and severity of neurologic deficits. This approach aims to identify patients with better survival outcomes and prioritize their surgical intervention accordingly. Seven factors (serum albumin and alkaline phosphatase levels, international normalized ratio, lymphocyte and neutrophil counts, and the presence of visceral or brain metastases) were considered possible missing items based on five previous validation studies and clinical experience. Artificially missing data were imputed using the missForest imputation technique, which was previously applied and successfully tested to fit the SORG-MLA in validation studies. Discrimination, calibration, overall performance, and decision curve analysis were applied to evaluate the SORG-MLA's performance. The discrimination ability was measured with an area under the receiver operating characteristic curve. It ranges from 0.5 to 1.0, with 0.5 indicating the worst discrimination and 1.0 indicating perfect discrimination. An area under the curve of 0.7 is considered clinically acceptable discrimination. Calibration refers to the agreement between the predicted outcomes and actual outcomes. An ideal calibration model will yield predicted survival rates that are congruent with the observed survival rates. The Brier score measures the squared difference between the actual outcome and predicted probability, which captures calibration and discrimination ability simultaneously. A Brier score of 0 indicates perfect prediction, whereas a Brier score of 1 indicates the poorest prediction. A decision curve analysis was performed for the 6-week, 90-day, and 1-year prediction models to evaluate their net benefit across different threshold probabilities. Using the results from our analysis, we developed an internet-based application that facilitates real-time data imputation for clinical decision-making at the point of care. This tool allows healthcare professionals to efficiently and effectively address missing data, ensuring that patient care remains optimal at all times. RESULTS: Generally, the SORG-MLA demonstrated good discriminatory ability, with areas under the curve greater than 0.7 in most cases, and good overall performance, with up to 25% improvement in Brier scores in the presence of one to three missing items. The only exceptions were albumin level and lymphocyte count, because the SORG-MLA's performance was reduced when these two items were missing, indicating that the SORG-MLA might be unreliable without these values. The model tended to underestimate the patient survival rate. As the number of missing items increased, the model's discriminatory ability was progressively impaired, and a marked underestimation of patient survival rates was observed. Specifically, when three items were missing, the number of actual survivors was up to 1.3 times greater than the number of expected survivors, while only 10% discrepancy was observed when only one item was missing. When either two or three items were omitted, the decision curves exhibited substantial overlap, indicating a lack of consistent disparities in performance. This finding suggests that the SORG-MLA consistently generates accurate predictions, regardless of the two or three items that are omitted. We developed an internet application (https://sorg-spine-mets-missing-data-imputation.azurewebsites.net/) that allows the use of SORG-MLA with up to three missing items. CONCLUSION: The SORG-MLA generally performed well in the presence of one to three missing items, except for serum albumin level and lymphocyte count (which are essential for adequate predictions, even using our modified version of the SORG-MLA). We recommend that future studies should develop prediction models that allow for their use when there are missing data, or provide a means to impute those missing data, because some data are not available at the time a clinical decision must be made. CLINICAL RELEVANCE: The results suggested the algorithm could be helpful when a radiologic evaluation owing to a lengthy waiting period cannot be performed in time, especially in situations when an early operation could be beneficial. It could help orthopaedic surgeons to decide whether to intervene palliatively or extensively, even when the surgical indication is clear.

Effects of a Hybrid Teaching Program on Lower Limb Muscle Strength, Knee Function, and Depression in Older Adults After Total Knee Replacement: A Randomized Controlled Trial.

The aim of the current study was to evaluate the effects of a nurse-led hybrid teaching program on lower limb strength, knee function, and depression in older adults after total knee replacement (TKR). This was a single-blind, randomized controlled trial. Fifty-two patients who underwent TKR were randomly assigned to either the experimental group (EG; n = 26), which received routine care plus 16 weeks of home rehabilitation through a hybrid teaching program, or the control group (CG; n = 26), which received routine care only. The intervention included pre-discharge face-to-face education, video instructions to follow at home after discharge, and four monthly telephone-based follow ups during the 16 weeks post-surgery. After the 16-week intervention, participants in the EG exhibited improved quadriceps strength, hamstring strength, and Knee Injury and Osteoarthritis Outcome Score (KOOS) compared to those in the CG. Generalized estimating equation analyses revealed a significant group-by-time interaction effect on quadriceps strength, overall KOOS score, and Geriatric Depression Scale-Short Form score. Findings suggest that a nurse-led hybrid teaching program enhances physical and psychological function after TKR when compared to routine care. This hybrid teaching program, involving exercise and postoperative education, proves to be a feasible and cost-effective intervention for improving outcomes in older adults following TKR. Health care teams should consider it as a viable home rehabilitation option for older adults who undergo TKR. [Research in Gerontological Nursing, 17(1), 31-40.].

Application of tomosynthesis for vertebral compression fracture diagnosis and bone healing assessment in fracture liaison services.

Early identification of vertebral compression fractures (VCFs) is crucial for successful secondary fracture prevention. Tomosynthesis, a low-dose tomographic imaging technique, may facilitate the evaluation and long-term follow-up of VCFs in patients with osteoporosis. Herein, we compared the performances of plain radiography and tomosynthesis for VCF diagnosis and healing assessment in patients enrolled in fracture liaison services in our hospital. Forty-nine patients with new VCFs at the T10-L5 levels were prospectively recruited between August 2018 and May 2020; all patients underwent thoracolumbar plain radiography and tomosynthesis. We evaluated the accuracy of the VCF diagnosis, image quality, and VCFs healing process. Tomosynthesis identified 90 levels of VCF in 49 patients, while plain radiography revealed only 87.8% (79/90) of them. There were 44.9% (22/49) patients with neglected chronic VCFs as seen on tomosynthesis. Tomosynthesis images had improved VCF diagnostic accuracy up to 12.2% and showed significantly more anatomic details than plain radiography. For diagnosis of VCFs, the performance of plain radiographs was poorer than that of tomosynthesis images (plain radiographs: sensitivity 84%, specificity 93.5%, false positive rate 6.5%, and false negative rate 16%; tomosynthesis: sensitivity 93.2%, specificity 100%, false positive rate 0%, and false negative 6.8%), using magnetic resonance imaging (MRI) as gold standard. The Kappa coefficient between Tomosynthesis and MRI is 0.956 while between radiography and MRI is 0.704. Tomosynthesis showed significantly more anatomic details than plain radiography and all the examiners revealed a clear preference for tomosynthesis. Tomosynthesis scored 3.3 times higher on the fracture healing assessment at the 3-month follow-up than plain radiographs. Tomosynthesis is a promising tool for VCF screening and diagnosis in patients with osteoporosis and for monitoring fracture healing status at a low radiation dose and cost.

A machine learning algorithm for predicting prolonged postoperative opioid prescription after lumbar disc herniation surgery. An external validation study using 1,316 patients from a Taiwanese cohort.

BACKGROUND CONTEXT: Preoperative prediction of prolonged postoperative opioid prescription helps identify patients for increased surveillance after surgery. The SORG machine learning model has been developed and successfully tested using 5,413 patients from the United States (US) to predict the risk of prolonged opioid prescription after surgery for lumbar disc herniation. However, external validation is an often-overlooked element in the process of incorporating prediction models in current clinical practice. This cannot be stressed enough in prediction models where medicolegal and cultural differences may play a major role. PURPOSE: The authors aimed to investigate the generalizability of the US citizens prediction model SORG to a Taiwanese patient cohort. STUDY DESIGN: Retrospective study at a large academic medical center in Taiwan. PATIENT SAMPLE: Of 1,316 patients who were 20 years or older undergoing initial operative management for lumbar disc herniation between 2010 and 2018. OUTCOME MEASURES: The primary outcome of interest was prolonged opioid prescription defined as continuing opioid prescription to at least 90 to 180 days after the first surgery for lumbar disc herniation at our institution. METHODS: Baseline characteristics were compared between the external validation cohort and the original developmental cohorts. Discrimination (area under the receiver operating characteristic curve and the area under the precision-recall curve), calibration, overall performance (Brier score), and decision curve analysis were used to assess the performance of the SORG ML algorithm in the validation cohort. This study had no funding source or conflict of interests. RESULTS: Overall, 1,316 patients were identified with sustained postoperative opioid prescription in 41 (3.1%) patients. The validation cohort differed from the development cohort on several variables including 93% of Taiwanese patients receiving NSAIDS preoperatively compared with 22% of US citizens patients, while 30% of Taiwanese patients received opioids versus 25% in the US. Despite these differences, the SORG prediction model retained good discrimination (area under the receiver operating characteristic curve of 0.76 and the area under the precision-recall curve of 0.33) and good overall performance (Brier score of 0.028 compared with null model Brier score of 0.030) while somewhat overestimating the chance of prolonged opioid use (calibration slope of 1.07 and calibration intercept of -0.87). Decision-curve analysis showed the SORG model was suitable for clinical use. CONCLUSIONS: Despite differences at baseline and a very strict opioid policy, the SORG algorithm for prolonged opioid use after surgery for lumbar disc herniation has good discriminative abilities and good overall performance in a Han Chinese patient group in Taiwan. This freely available digital application can be used to identify high-risk patients and tailor prevention policies for these patients that may mitigate the long-term adverse consequence of opioid dependence: https://sorg-apps.shinyapps.io/lumbardiscopioid/.

Simultaneous Bilateral Total Knee Arthroplasty Becomes Safer after Institution of Optimal Perioperative Management: A Longitudinal Cohort Study.

Simultaneous bilateral total knee arthroplasty (SBTKA) increases the rates of procedure-related complications and mortality compared with unilateral TKA. There are no well-defined guidelines for selecting patients to avoid mortality and proposing an upgrade treatment to decrease complication rates. This study aimed to evaluate whether optimal perioperative management could improve the safety of SBTKA. From 2005 to 2017, 1,166 cases of SBTKA were identified from 14,209 TKA procedures. We retrospectively examined the SBTKA patients' demographics, comorbidity profiles, procedure-related complications, and perioperative management during two time periods. Optimal perioperative workup for managing SBTKA significantly decreased the incidences of major complication from 6.2 to 2.4% (p = 0.001) and minor complications from 28.9 to 21.5% (p = 0.004) during period I and period II, respectively. The efficiency of less tourniquet use along with intraarticular tranexamic acid injection was demonstrated by the decreases of hemoglobin (Hb) change in the first 2 days after surgery (p = 0.005) and blood transfusion requirement (p = 0.035) during the SBTKA. Furthermore, the less tourniquet use group had less thigh pain (visual analog scale decreased from 6.0 to 4.2, p = 0.003), shorter duration of hospital stay (decreased from 7.8 to 7.1, p < 0.001), and lower coagulation time (decrease from 3.5 to 2.9, p < 0.001) than the routine tourniquet use group. Patient's screening must be performed carefully for cardiopulmonary compromise in patients aged >80 years and with an American Society of Anesthesiologists score of 3. Additionally, hospitalists should consider developing methods for the eligibility, testing, and perioperative monitoring of patients who undergo SBTKA with the aim of avoiding complications and improving outcomes.

A Multi-Institutional Randomized Controlled Trial to Investigate Whether Zoledronate Prevents Bone Loss After Discontinuation of Denosumab: The Study Protocol of Denosumab Sequential Therapy (DST) Trial.

Background: Though denosumab is an effective treatment for osteoporosis, the rebound effect after discontinuation has drawn investigators' attention. It includes a dramatic loss of gained bone mineral density (BMD) and an increased risk of vertebral fractures. This prospective multi-institutional randomized controlled trial aims to investigate whether zoledronate prevents loss of BMD after discontinuation of denosumab. The trial was registered as Denosumab Sequential Therapy (DST) trial in March 2019 at clinicaltrials.gov, with the identifier NCT03868033. Methods: The study is conducted at National Taiwan University Hospital and its branches. Patients who have continuously received denosumab treatment for two or more years are surveyed for eligibility. Baseline characteristics and questionnaires of life quality are recorded after recruitment. BMD, circulating levels of bone turnover markers (BTMs), including serum N-terminal propeptide of type 1 collagen (P1NP) and C-terminal telopeptide (CTX), are checked before the stratified randomization to 4 groups. Biological sex and the T-scores are used to create 4 strata. The participants in group 1 adhere to regular denosumab therapy for another 2 years. All the other patients receive on-time zoledronate treatment in the first year. The participants in group 2, 3, and 4 have on-time denosumab, on-time zoledronate and drug holiday in the second year, respectively. BMDs are checked annually. Pre-scheduled checkpoints of BTMs are also arranged. For patient safety, rescue treatment with another injection of zoledronate will be applied to the patients on drug holiday if the CTX levels raise above the pre-specified threshold, 0.573 ng/mL for women and 0.584 ng/mL for men. The primary outcomes are the percentage changes of BMDs in lumbar spine, total hip and femoral neck. The secondary outcomes include the changes of serum level of the BTMs, new osteoporotic fractures, extra zoledronate injections needed in group 4 and the differences of quality of life. Discussion: We aim to provide evidence whether zoledronate prevents bone loss after denosumab cessation. To our knowledge, the study has the largest sample size. No other randomized controlled study included all the three different treatment strategies and a positive control. It is also the first associated randomized controlled trial outside Europe.

Decorin inhibits the insulin-like growth factor I signaling in bone marrow mesenchymal stem cells of aged humans.

Aging impairs the IGF-I signaling of bone marrow mesenchymal stem cells (bmMSCs), but the mechanism is unclear. Here, we found that the ability to auto-phosphorylate IGF-I receptor (IGF-IR) in response to IGF-I was decreased in the bmMSCs of aged donors. Conversely, data showed that decorin (DCN) expression was prominently increased in aged bmMSCs, and that under IGF-I treatment, DCN knockdown in serum-starved aged bmMSCs potentiated their mitogenic activity and IGF-IR auto-phosphorylation, whereas DCN overexpression in serum-starved adult bmMSCs decreased both activities. Co-immunoprecipitation assays suggested that IGF-I and DCN bound to IGF-IR in a competitive manner. Online MethPrimer predicted 4 CpG islands (CGIs) in the introns of DCN gene. RT-qPCR and bisulfite sequencing showed that dimethyloxalylglycine, an inhibitor of DNA demethylation, increased DCN mRNA expression and CGI-I methylation in adult bmMSCs, whereas 5-aza-2'-deoxycytidine, a DNA methylation inhibitor, decreased DCN mRNA expression and CGI-I methylation in aged bmMSCs, and ultimately enhanced the proliferation of serum-starved aged bmMSCs under IGF-I stimulation. Thus, IGF-IR could be the prime target of aging in down-regulating the IGF-I signaling of bmMSCs, where DCN could be a critical mediator.

A Spine Robotic-Assisted Navigation System for Pedicle Screw Placement.

Pedicle screw implantation has excellent treatment effects and is often used by surgeons in spinal fusion surgery. However, due to the complexity of human body anatomy, this surgical procedure is difficult and challenging, especially in minimally invasive surgery or patients with congenital anomalies and kyphoscoliosis deformity. In addition to the abovementioned factors, the surgical experience and technique of the surgeon also affect the recovery rates and complications of the patients after the surgical operation. Therefore, accurately performing pedicle screw implantation has is a constant topic of common concern for surgeons and patients. In recent years, with the technological development, robot-assisted navigation systems have gradually become adopted. These robot-assisted navigation systems provide surgeons with complete preoperative planning before surgery. The system provides 3D reconstructed images of each vertebra, allowing surgeons to understand the patient's physiological characteristics more quickly. It also provides 2D images of sagittal, coronal, axial and oblique planes so that surgeons can accurately perform pedicle screw placement plan. Previous studies have demonstrated the effectiveness of robot-assisted navigation systems for pedicle screw implantation procedures, including accuracy and safety assessments. This step-by-step protocol aims to outline a standardized surgical technique note for robotic-assisted pedicle screw placement.

Results of using robotic-assisted navigational system in pedicle screw placement.

Recent technical developments have resulted in robotic-assisted pedicle screw placement techniques. However, the use of robotic-assisted navigational techniques is still subject to controversy. This study aims to assess the accuracy and safety of a self-developed navigation system, the point spine navigation system (PSNS), for robotic-assisted pedicle screw placement surgery. Fifty-nine pedicle screws were implanted in three porcine vertebrae at the T6-T10 and L1-L5 levels, with the assistance of the PSNS. The navigation and planning system provides virtual surgical guide images, including sagittal, coronal, axial, oblique planes, and customized three-dimensional reconstructions for each vertebra to establish accurate pedicle screw trajectories and placement tracts. After pedicle screw placement, post-operative spiral computer tomographic scans were performed and screws were evaluated using the Gertzbein-Robbins classification. Differences between the actual pedicle screw position and pre-operative planning paths, including the angle, shortest distance, and entry trajectory were recorded. The 59 pedicle screw placements were all within a safe zone, and there was no spinal canal perforation or any other damage under postoperative computed tomography image data. Fifty-one screws were categorized as group A, seven screws were noted as group B, and one screw was identified as group E under the Gertzbein-Robbins classification. The mean entry point deviation was 2.71 ± 1.72°, mean trajectory distance was 1.56 ± 0.66 mm, and average shortest distance between two paths was 0.96 ± 0.73 mm. Pedicle placement remains a challenging procedure with high reported incidences of nerve and vascular injuries. The implementation of a robotic-assisted navigational system yields an acceptable level of accuracy and safety for the pedicle screw placement surgery.

Functional Studies of Anodic Oxidized ß-Ti-28Nb-11Ta-8Zr Alloy for Mechanical, In-vitro and Antibacterial Capability.

We developed an osseocompatible ß-type Ti-28Nb-11Ta-8Zr (TNTZ) alloy that displays the excellent elastic modulus, cellular response, corrosion resistance and antibacterial capability demanded for bone-mimetic materials. The TNTZ alloy exhibited an elastic modulus of 49 GPa, which approximates that of human bones and prevent stress shielding effects. A further anodic oxidation and subsequent post-annealing modification formed a crystalline nanoporous TNTZ oxide layer (NPTNTZO(c)) on the alloy surface, potentially promoting interlocking with the extracellular matrix of bone cells and cell proliferation. Osteoblast viability tests also verified that NPTNTZO(c) enhanced cell growth more significantly than that of flat TNTZ. In addition, potentiodynamic polarization tests in Hanks' balanced salt solution (HBSS) revealed that both TNTZ and NPTNTZO(c) exhibited better corrosion resistance than commercial pure titanium. Finally, NPTNTZO(c) reinforced with silver nanoparticles (NPTNTZO

Novel Passive Two-Stage Magnetic Targeting Devices for Distal Locking of Interlocking Nails.

Interlocking nailing is a common surgical operation to stabilize fractures in long bones. One of the difficult parts of the surgery is how to locate the position and direction of a screw hole on the interlocking nail, which is invisible to the naked eye after insertion of the nail into the medullary canal. Here, we propose a novel two-stage targeting process using two passive magnetic devices to locate the position and direction of the screw hole without radiation for the locking screw procedure. This involves a ring-shape positioning magnet inside the nail to generate a magnetic field for targeting. From the accuracy test results of these two-stage targeting devices, the search region can be identified in less than 20 seconds by the 1st-stage targeting device, while the total targeting time to locate the drilling position and direction takes less than 4 minutes, with 100% successful rate in 50 attempts. The drilling test further combines the two-stage targeting process and drilling process on the swine tibia, and it is shown that a 100% successful rate is achieved in all 10 attempts, where the total time needed is less than 5 minutes.

Role of femoral ring allograft in anterior interbody fusion of the spine.

A review was carried out on 59 patients (10 males and 49 females) who had anterior interbody fusion performed with femoral ring allograft packed with autograft bone chips with a minimum follow up of 2 years. The average age at the time of surgery was 49.1 year old (26 to 75). The total number of levels grafted was 141. The diagnosis consisted of multiple degenerative disease in 6, degenerative change below the long segment of fusion for scoliosis in 9, osteoporosis with collapsed fracture in 3, pseudarthrosis after posterior laminectomy and fusion in 35, congenital scoliosis in 3, scoliosis in 2 and paralytic scoliosis due to multiple sclerosis in one. The distribution of levels fused was T12-L1 in 6, L1-2 in 12, L2-3 in 17, L3-4 in 22, L4-5 in 35 and L5-S1 in 39. The remaining 10 levels were in the lower thoracic areas (T7-T12). The operations were performed as anterior fusion alone in 13 patients, one-stage anterior and posterior fusion in 26 patients and two-stage surgery in 20 patients. Anterior instrumentation was used in all 141 levels. At average follow-up (33.7 months) there was no significant change in allograft angles (average = 1.6 degrees ). Fusion of the allograft was classified by Bridwell's grading system. At 24 months of the follow up, 97 % of the allografts were in grade I (fully incorporated) and 3% were in grade II (partially incorporated). Compared to 12 months follow-up only 76.2% of the grafts were in grade I, 28 % were in grade II and 0.8% were in grade III. Two patients had deep posterior infections which required further surgery (without resorption of the allograft anteriorly). One patient had a screw migration anteriorly which required removal. Three patients had persistence of radiolucent line at one of the vertebral end plates - graft interfaces but no subsidence of the graft or pain. In conclusion, the femoral ring allograft appeared to benefit the anterior interbody fusion in complex spinal surgery.