Adipokine dysregulation as an underlying pathology for diffuse ectopic ossification of spinal posterior longitudinal ligament in patients with obesity.

Growing evidence suggests that obesity is implicated in the progression of heterotopic ossification of the posterior longitudinal ligament of the spine (OPLL), a major cause of myelopathy in Asians. However, it remains unclear whether dysregulation of adipokine production due to fat accumulation contributes to OPLL progression. To determine whether adipose-derived biochemical signals are associated with OPLL development or severity. A nationwide, multicenter, case-control study. Patients with symptomatic thoracic OPLL (T-OPLL) who received treatment between June 2017 and March 2021 and 111 controls without OPLL. OPLL severity index based on whole-spine computed tomography. Serum concentrations of adipokines, including leptin (Lep), tumor necrosis factor α (TNFα), and adiponectin (Adpn), as well as the Adpn/Lep ratio-an indicator of adipokine production dysregulation-were compared between the multiple-region OPLL and the single-region OPLL groups. Regression analysis was performed to examine the correlation between adipokine concentrations and OPLL severity index, which was calculated using whole-spine computed tomography images of 77 patients with T-OPLL within 3 years of onset. Using propensity score matching, the adipokine profiles of 59 patients with T-OPLL were compared with those of 59 non-OPLL controls. Patients with multiple-region OPLL exhibited a higher body mass index (BMI), lower serum Adpn/Lep ratio, and higher serum concentration of osteocalcin (OCN) than those with single-region OPLL. The OPLL severity index exhibited a weak positive correlation with BMI and serum Lep levels and a weak negative correlation with the Adpn/Lep ratio. Serum TNFα and OCN concentrations were significantly higher in patients with T-OPLL than in controls with similar age, sex, and BMI. Patients with diffuse OPLL over the entire spine are often metabolically obese with low Adpn/Lep ratios. In patients with OPLL, TNFα and OCN serum concentrations were essentially elevated regardless of obesity, suggesting a potential association with OPLL development. Considering the absence of therapeutic drugs for OPLL, the findings presented herein offer valuable insights that can aid in identifying therapeutic targets and formulating strategies to impede its progression.

Takahata M ，Koike Y ，Endo T ，Ikegawa S ，Imagama S ，Kato S ，Kanayama M ，Kobayashi K ，Kaito T ，Sakai H ，Kawaguchi Y ，Oda I ，Terao C ，Kanto T ，Taneichi H ，Iwasaki N ... -  《-》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》

Importance of gap evaluation in the ossification of posterior longitudinal ligament lesions using 3-dimensional computed tomography.

Evaluating the gaps within the ossification of the posterior longitudinal ligament (OPLL) lesions, which may contribute to neurological symptoms, using conventional imaging techniques is challenging. This study aimed to investigate the importance of evaluating gaps using 3-dimensional computed tomography (3D-CT) and their association with the occurrence of magnetic resonance imaging (MRI) T2 high intensity in the spinal cord. Retrospective cohort study. Retrospective analysis of 116 patients diagnosed with cervical OPLL. Presence of gaps in OPLL, presence of T2 high intensity in the cervical spinal cord, and OPLL thickness were evaluated. Lateral X-ray, CT, and reconstructed 3D-CT images were reviewed to assess lesion characteristics and the presence of gaps. MRI was used to evaluate the change in spinal cord signal intensity. The relationship among gap presence, lesion morphology, and MRI T2 high intensity in the spinal cord was examined. A significant difference in gap detection accuracy was observed between CT and 3D-CT (p=.0054). CT demonstrated false-positive results in the detection of gaps as compared with 3D-CT. The presence of gaps was significantly associated with an increased likelihood of MRI T2 high intensity in the spinal cord (p=.037). Patients with thicker lesions and smaller space available for the spinal cord (SAC) were more likely to exhibit T2 high intensity. Meanwhile, patients with gaps co-occurring with T2 high intensity exhibited significantly thinner lesions (p=.011) and larger SACs (p=.0002). Patients with gaps had a significantly lower JOA scores (p=.0035), which indicates that patient with gaps are likely to exhibit more severe clinical neurological symptoms. 3D-CT showed superiority in accurately identifying gaps within OPLL lesions, while CT demonstrated false-positive results in the detection of gaps. Furthermore, the gap presence was a risk factor for MRI T2 high intensity in the spinal cord, independent of lesion thickness. In addition, gaps are related to more severe clinical symptoms. This study highlighted the importance of evaluating gaps within OPLL lesions using 3D-CT to clarify neurological pathogenesis.

Alaa H ，Tung NTC ，Ueno T ，Makino H ，Futakawa H ，Seki S ，Kawaguchi Y ... -  《-》

Far Posterior Approach for Rib Fracture Fixation: Surgical Technique and Tips.

The present video article describes the far posterior or paraspinal approach to posterior rib fractures. This approach is utilized to optimize visualization intraoperatively in cases of far-posterior rib fractures. This technique is also muscle-sparing, and muscle-sparing posterolateral, axillary, and anterior approaches have been shown to return up to 95% of periscapular strength by 6 months postoperatively1. Like most fractures, the skin incision depends on the fracture position. The vertical incision is made either just medial to a line equidistant between the palpable spinous processes and medial scapular border or directly centered over the fracture line in this region. The incision and superficial dissection must be extended cranially and caudally, approximately 1 or 2 rib levels past the planned levels of instrumentation, in order to allow muscle elevation and soft-tissue retraction. Superficial dissection reveals the trapezius muscle, with its fibers coursing from inferomedial to superolateral caudal to the scapular spine, and generally coursing transversely above this level. The trapezius is split in line with its fibers (or elevated proximally at the caudal-most surface), and the underlying layer will depend on the location of the incision. The rhomboid minor muscle overlies ribs 1 and 2, the rhomboid major muscle overlies ribs 3 to 7, and the latissimus dorsi overlies the remaining rib levels. To avoid muscle transection, the underlying muscle is also split in line with its fibers. Next, the thoracolumbar fascia is encountered and sharply incised, revealing the erector spinae muscles, which comprise the spinalis thoracis, longissimus thoracis, and iliocostalis thoracis muscles. These muscles and their tendons must be sharply elevated from lateral to midline; electrocautery is useful for this because there is a robust blood supply in this region. Medially, while retracting the paraspinal musculature, visualization with this approach can extend to the head and neck of the rib, and even to the spine. Following deep dissection, the fractures are now visualized. During fracture reduction, it is critical to assess reduction of both the costovertebral joint and the costotransverse joint. With fractures closer to the spine, it is recommended to have at least 2 cm between the rib head and tubercle in order to allow 2 plate holes to be positioned on the neck of the rib; if comminution exists and plating onto the transverse process is needed, several screws are required here for stability as well. For appropriate stability if plating onto the spine is not required, a minimum of 3 locking screws on each side of the fracture are recommended. Contouring of the plates to match the curvature of the rib and to allow for proper apposition may be required with posterior rib fractures. Screws must be placed perpendicular to the rib surface. Following operative stabilization of the rib fractures, a layered closure is performed, and a soft dressing is applied. Nonoperative alternatives include non-opioid and opioid medications as well as corticosteroid injections for pain control. Supportive mechanical ventilation and physiotherapy breathing exercises can also be implemented as needed. Operative alternatives include open reduction and internal fixation utilizing conventional locking plates and screws. Rib fractures are often treated nonoperatively when nondisplaced because of the surrounding soft-tissue support2,3. According to Chest Wall Injury Society guidelines, contraindications to surgical fixation of rib fractures include patients requiring ongoing resuscitation; rib fractures involving ribs 1, 2, 11, or 12, which are relative contraindications; severe traumatic brain injury; and acute myocardial infarction. Patient age of <18 years is also a relative contraindication for the operative treatment of rib fractures. The current literature does not recommend surgical fixation in this age group because these fractures typically heal as the patient ages; however, fracture-dislocations may require the use of instrumentation to prevent displacement. Currently, the U.S. Food and Drug Administration does not approve most plating systems for patients <18 years old4. In certain cases, including those with substantial displacement, persistent respiratory distress, pain, or fracture nonunion, stabilization with open reduction and internal fixation may be appropriate5-7. In cases of flail chest injuries, surgery is often indicated6. Flail chest injuries have been noted in the literature to have an incidence of approximately 150 cases per 100,000 injuries and have been shown to carry a mortality rate of up to 33%8,9. Surgical treatment of rib fractures has been shown to be associated with a decreased hospital length of stay and mortality rate in patients with major trauma1. Expected outcomes of this procedure include low complication rates, decreased hospital and intensive care unit length of stay, and reduced mechanical ventilation time10,11. However, as with any procedure, there are also risks involved, including iatrogenic lung injury from long screws or an aortic or inferior vena cava injury with aggressive manipulation of displaced fractured fragments, especially on the left side of the body. During open reduction, there is also a risk of injuring the neurovascular bundle. Tanaka et al. demonstrated a significant reduction in the rate of postoperative pneumonia in their operative group (22%) compared with their nonoperative group (90%)12. Schuette et al. demonstrated a 23% rate of postoperative pneumonia, 0% mortality at 1 year, an average of 6.2 days in the intensive care unit, an average total hospital length of stay of 17.3 days, and an average total ventilator time of 4 days in the operative group10. Prins et al. reported a significantly lower incidence of pneumonia in operative (24%) versus nonoperative patients (47.3%; p = 0.033), as well as a significantly lower 30-day mortality rate (0% versus 17.7%; p = 0.018)3. This procedure utilizes a muscle-sparing technique, which has demonstrated successful results in the literature on the use of the posterolateral, axillary, and anterior approaches, returning up to 95% of periscapular strength, compared with the uninjured shoulder, by 6 months postoperatively1. The use of a muscle-sparing technique with the far-posterior approach represents a topic that requires further study in order to compare the results with the successful results previously shown with other approaches. The ipsilateral extremity can be prepared into the field to allow its intraoperative manipulation in order to achieve scapulothoracic motion and improved subscapular access.For costovertebral fracture-dislocations, the vertical incision line is made just medial to a line equidistant between the palpable spinous processes and medial scapular border.Lateral decubitus positioning can be utilized to allow for simultaneous access to fractures that extend more laterally and warrant a posterolateral approach; however, it is generally more difficult to access the fracture sites near the spine with this approach.This muscle-sparing technique is recommended to optimize postoperative periscapular strength, as previously demonstrated with other approaches.Incision and superficial dissection must be extended cranially and caudally approximately 1 or 2 rib levels past the planned levels of instrumentation in order to allow muscle elevation and soft-tissue retraction.To avoid muscle transection during surgical dissection, the underlying muscle is split in line with its fibers.During deep dissection, it can be difficult to delineate underlying muscles because these muscles have fibers that do not run in line with the trapezius, and some, like the rhomboid major, run nearly perpendicular to it.Electrocautery is useful while elevating the erector spinae muscles and tendons, as there is a robust blood supply in this region.The erector spinae muscle complex is relatively tight and adherent to the underlying ribs, which may make it difficult to achieve adequate visualization; therefore, at least 3 rib levels must be elevated to access a rib for reduction and instrumentation.Although internal rotation deformities are more common in this region, any external displacement of a fracture can lead to a muscle injury that can be utilized for access.During fracture reduction, it is critical to assess reduction of both the costovertebral joint and the costotransverse joint.Special attention must be given to contouring the implants because there are not any commercially available precontoured implants for this region at this time, and plating onto the spine remains an off-label use of any currently available implant.For the more challenging fracture patterns, the use of a right-angled power drill and screwdriver is recommended.Generally, the incision is utilized as previously described to provide access as far medial as the transverse process if needed. However, in cases in which this approach does not allow proper visualization with rib fracture-dislocations involving the posterior ribs or spine, a midline spinal incision can be utilized while working in combination with a spine surgeon.With fractures closer to the spine, it is recommended to have at least 2 cm between the rib head and tubercle in order to allow 2 plate holes to be positioned on the neck of the rib.If comminution exists and plating onto the transverse process is needed, several screws are required for stability.When measuring the length of screws to be placed in the transverse process, preoperative CT scans can be utilized. CT = computed tomographyCWIS = Chest Wall Injury SocietyIVC = inferior vena cava.

Manes TJ ，DeGenova DT ，Taylor BC ，Patel JN ... -  《-》

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.

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. 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. 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/m 2 [IQR 20 to 25 kg/m 2 ] versus 22 kg/m 2 [IQR 20 to 25 kg/m 2 ]), higher platelet count (240 × 10 3 /µL [IQR 173 to 327 × 10 3 /µL] versus 227 × 10 3 /µL [IQR 165 to 302 × 10 3 /µL], higher lymphocyte count (15 × 10 3 /µL [IQR 9 to 21× 10 3 /µL] versus 14 × 10 3 /µL [IQR 8 to 21 × 10 3 /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. 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. 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. 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.

Huang CC ，Peng KP ，Hsieh HC ，Groot OQ ，Yen HK ，Tsai CC ，Karhade AV ，Lin YP ，Kao YT ，Yang JJ ，Dai SH ，Huang CC ，Chen CW ，Yen MH ，Xiao FR ，Lin WH ，Verlaan JJ ，Schwab JH ，Hsu FM ，Wong T ，Yang RS ，Yang SH ，Hu MH ... -  《-》