Risk Factors for Adjacent Vertebral Fractures Following Cement Vertebroplasty: The Clinical Significance of Multiple Preexisting Vertebral Compression Fractures.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The study retrospectively analyzed the factors associated with the development of adjacent vertebral fractures. SUMMARY OF BACKGROUND DATA: Adjacent vertebral fractures (AVF) may occur following cement vertebroplasty, and several risk factors have been reported with controversies. METHODS: A total of 123 patients, with a mean age of 79.2 years, who underwent single-level vertebroplasty were included in the investigation. We systematically collected data encompassing baseline demographics, osteoporosis parameters, surgical details, radiologic measurements, and Hounsfield unit (HU) values in the lumbar spine. Subsequently, univariable, followed by multivariable logistic regression analyses, were employed to identify the risk factors of AVFs. RESULTS: Thirty of 123 patients had AVFs within 6 months following vertebroplasty. The AVF group exhibited a higher percentage of multiple preexisting vertebral compression fractures (P=0.006), a greater volume of injected cement (P=0.032), and a more pronounced reduction in local kyphosis (P=0.007). Multivariable logistic regression analysis revealed multiple preexisting vertebral compression fractures and a reduction in local kyphosis exceeding 8 degrees were independent risk factors for AVFs (P=0.008 and 0.003, respectively), with odds ratios of 3.78 (95% confidence interval: 1.41-10.12) and 4.16 (95% CI: 1.65-10.50), respectively. Subgroup analysis showed that patients with multiple preexisting vertebral compression fractures (VCFs) had significantly lower bone mineral density Z-score, T-score, and HU values compared with those without preexisting VCFs (P<0.05). Conversely, there were no significant differences in T-score or HU values between patients with no VCFs and those with a single VCF. CONCLUSION: This study demonstrated that both bone strength and local alignment are key factors associated with adjacent vertebral fractures. Specifically, having multiple preexisting vertebral compression fractures and a reduction in local kyphosis exceeding 8 degrees are independent risk factors. The presence of more than one previous vertebral compression fracture serves as a significant clinical indicator of advanced bone density reduction in patients with osteoporosis, offering a quick and straightforward method for identifying high-risk patients. Patients exhibiting these risk factors should be monitored more closely for favorable clinical outcomes. LEVEL OF EVIDENCE: Level III-retrospective nonexperimental study.

Activated dormant stem cells recover spermatogenesis in chemoradiotherapy-induced infertility.

Male infertility is a recognized side effect of chemoradiotherapy. Extant spermatogonial stem cells (SSCs) may act as originators for any subsequent recovery. However, which type of SSCs, the mechanism by which they survive and resist toxicity, and how they act to restart spermatogenesis remain largely unknown. Here, we identify a small population of Set domain-containing protein 4 (Setd4)-expressing SSCs that occur in a relatively dormant state in the mouse seminiferous tubule. Extant beyond high-dose chemoradiotherapy, these cells then activate to recover spermatogenesis. Recovery fails when Setd4+ SSCs are deleted. Confirmed to be of fetal origin, these Setd4+ SSCs are shown to facilitate early testicular development and also contribute to steady-state spermatogenesis in adulthood. Upon activation, chromatin remodeling increases their genome-wide accessibility, enabling Notch1 and Aurora activation with corresponding silencing of p21 and p53. Here, Setd4+ SSCs are presented as the originators of both testicular development and spermatogenesis recovery in chemoradiotherapy-induced infertility.

Comparison of Classically and Machine Learning Generated Survival Prediction Models for Patients With Spinal Metastasis - A meta-Analysis of Two Recently Developed Algorithms.

STUDY DESIGN: A systemic review and a meta-analysis. We also provided a retrospective cohort for validation in this study. OBJECTIVE: (1) Using a meta-analysis to determine the pooled discriminatory ability of The Skeletal Oncology Research Group (SORG) classical algorithm (CA) and machine learning algorithms (MLA); and (2) test the hypothesis that SORG-CA has less variability in performance than SORG-MLA in non-American validation cohorts as SORG-CA does not incorporates regional-specific variables such as body mass index as input. METHODS: After data extraction from the included studies, logit-transformation was applied for extracted AUCs for further analysis. The discriminatory abilities of both algorithms were directly compared by their logit (AUC)s. Further subgroup analysis by region (America vs non-America) was also conducted by comparing the corresponding logit (AUC). RESULTS: The pooled logit (AUC)s of 90-day SORG-CA was .82 (95% confidence interval [CI], .53-.11), 1-year SORG-CA was 1.11 (95% CI, .74-1.48), 90-day SORG-MLA was 1.36 (95% CI, 1.09-1.63), and 1-year SORG-MLA was 1.57 (95% CI, 1.17-1.98). All the algorithms performed better in United States than in Taiwan (P < .001). The performance of SORG-CA was less influenced by a non-American cohort than SORG-MLA. CONCLUSION: These observations might highlight the importance of incorporating region-specific variables into existing models to make them generalizable to racially or geographically distinct regions.

Risk Factors of Failed Conservative Treatment for Adjacent Vertebral Fractures Following Percutaneous Vertebroplasty.

STUDY DESIGN: A retrospective, single-center, observational study. OBJECTIVE: This study investigated the risk factors associated with the failure of conservative treatment for adjacent vertebral fractures (AVFs). SUMMARY OF BACKGROUND DATA: Adjacent vertebral fractures following vertebroplasty for osteoporotic vertebral compression fractures are not uncommon. Presently, there is a lack of consensus regarding the management of adjacent vertebral fractures. METHODS: We included patients who developed adjacent vertebral fractures within two years post single-level vertebroplasty between January 2013 and December 2020. All patients initially underwent six weeks of conservative treatment, including pain medications, bracing, and physical therapy. Surgical intervention was offered to those with intractable back pain due to AVFs. Baseline demographics, AVF characteristics, and radiological measurements were systematically collected, and sequential univariable and multivariable logistic regression analyses were conducted to explore the risk factors. RESULTS: Of the 114 patients with a mean age of 78.6 years, two-thirds (76 patients) tolerated conservative treatment well, while 38 required surgical interventions for adjacent vertebral fractures. Both groups demonstrated similar baseline demographics and radiological parameters regarding AVFs (P>0.05). The multivariable logistic regression analyses revealed that the development of AVFs later than six months post-vertebroplasty and their caudal location to the index vertebroplasty were the independent risk factors of unsuccessful conservative treatment, with odds ratios of 3.57 (95% confidence interval [CI]: 1.14-11.1, P=0.029) and 2.50 (95% CI: 1.09-5.88, P=0.032), respectively. CONCLUSION: Adjacent vertebral fractures following percutaneous vertebroplasty generally have favorable outcomes under conservative treatment. However, the timing and the relative anatomical location of adjacent vertebral fractures are associated with treatment efficacy. Adjacent vertebral fractures occurring later than six months following the initial vertebroplasty or situated in the caudal location to the index vertebroplasty may exhibit reduced responsiveness to conservative treatment. These patients might benefit from a more aggressive therapeutic approach. LEVEL OF EVIDENCE: 3.

Determining patients with spinal metastases suitable for surgical intervention: A cost-effective analysis.

BACKGROUND: Both nonoperative and operative treatments for spinal metastasis are expensive interventions. Patients' expected 3-month survival is believed to be a key factor to determine the most suitable treatment. However, to the best of our knowledge, no previous study lends support to the hypothesis. We sought to determine the cost-effectiveness of operative and nonoperative interventions, stratified by patients' predicted probability of 3-month survival. METHODS: A Markov model with four defined health states was used to estimate the quality-adjusted life years (QALYs) and costs for operative intervention with postoperative radiotherapy and radiotherapy alone (palliative low-dose external beam radiotherapy) of spine metastases. Transition probabilities for the model, including the risks of mortality and functional deterioration, were obtained from secondary and our institutional data. Willingness to pay thresholds were prespecified at $100,000 and $150,000. The analyses were censored after 5-year simulation from a health system perspective and discounted outcomes at 3% per year. Sensitivity analyses were conducted to test the robustness of the study design. RESULTS: The incremental cost-effectiveness ratios were $140,907 per QALY for patients with a 3-month survival probability >50%, $3,178,510 per QALY for patients with a 3-month survival probability <50%, and $168,385 per QALY for patients with independent ambulatory and 3-month survival probability >50%. CONCLUSIONS: This study emphasizes the need to choose patients carefully and estimate preoperative survival for those with spinal metastases. In addition to reaffirming previous research regarding the influence of ambulatory status on cost-effectiveness, our study goes a step further by highlighting that operative intervention with postoperative radiotherapy could be more cost-effective than radiotherapy alone for patients with a better survival outlook. Accurate survival prediction tools and larger future studies could offer more detailed insights for clinical decisions.

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.

A Machine Learning Algorithm for Predicting 6-Week Survival in Spinal Metastasis: An External Validation Study Using 2,768 Taiwanese Patients.

INTRODUCTION: There are predictive algorithms for predicting 3-month and 1-year survival in patients with spinal metastasis. However, advance in surgical technique, immunotherapy, and advanced radiation therapy has enabled shortening of postoperative recovery, which returns dividends to the overall quality-adjusted life-year. As such, the Skeletal Oncology Research Group machine learning algorithm (SORG-MLA) was proposed to predict 6-week survival in patients with spinal metastasis, whereas its utility for patients treated with nonsurgical treatment was untested externally. This study aims to validate the survival prediction of the 6-week SORG-MLA for patients with spinal metastasis and provide the measurement of model consistency (MC). METHODS: Discrimination using area under the receiver operating characteristic curve, calibration, Brier score, and decision curve analysis were conducted to assess the model's performance in the Taiwanese-based cohort. MC was also applied to detect the proportion of paradoxical predictions among 6-week, 3-month, and 1-year survival predictions. The long-term prognosis should not be better than the shorter-term prognosis in that of an individual. RESULTS: The 6-week survival rate was 84.2%. The SORG-MLA retained good discrimination with an area under the receiver operating characteristic curve of 0.78 (95% confidence interval, 0.75 to 0.80) and good prediction accuracy with a Brier score of 0.11 (null model Brier score 0.13). There is an underestimation of the 6-week survival rate when the predicted survival rate is less than 50%. Decision curve analysis showed that the model was suitable for use over all threshold probabilities. MC showed suboptimal consistency between 6-week and 90-day survival prediction (78%). CONCLUSIONS: The results of this study supported the utility of the algorithm. The online tool ( https://sorg-apps.shinyapps.io/spinemetssurvival/ ) can be used by both clinicians and patients in informative decision-making discussion before management of spinal metastasis.

Reducing lipid peroxidation attenuates stress-induced susceptibility to herpes simplex virus type 1.

Psychological stress increases the susceptibility to herpes simplex virus type 1 (HSV-1) infection. There is no effective intervention due to the unknown pathogenesis mechanisms. In this study we explored the molecular mechanisms underlying stress-induced HSV-1 susceptibility and the antiviral effect of a natural compound rosmarinic acid (RA) in vivo and in vitro. Mice were administered RA (11.7, 23.4 mg·kg-1·d-1, i.g.) or acyclovir (ACV, 206 mg·kg-1·d-1, i.g.) for 23 days. The mice were subjected to restraint stress for 7 days followed by intranasal infection with HSV-1 on D7. At the end of RA or ACV treatment, mouse plasma samples and brain tissues were collected for analysis. We showed that both RA and ACV treatment significantly decreased stress-augmented mortality and alleviated eye swelling and neurological symptoms in HSV-1-infected mice. In SH-SY5Y cells and PC12 cells exposed to the stress hormone corticosterone (CORT) plus HSV-1, RA (100 µM) significantly increased the cell viability, and inhibited CORT-induced elevation in the expression of viral proteins and genes. We demonstrated that CORT (50 µM) triggered lipoxygenase 15 (ALOX15)-mediated redox imbalance in the neuronal cells, increasing the level of 4-HNE-conjugated STING, which impaired STING translocation from the endoplasmic reticulum to Golgi; the abnormality of STING-mediated innate immunity led to HSV-1 susceptibility. We revealed that RA was an inhibitor of lipid peroxidation by directly targeting ALOX15, thus RA could rescue stress-weakened neuronal innate immune response, thereby reducing HSV-1 susceptibility in vivo and in vitro. This study illustrates the critical role of lipid peroxidation in stress-induced HSV-1 susceptibility and reveals the potential for developing RA as an effective intervention in anti-HSV-1 therapy.

Nonalcoholic Fatty Liver Disease Is Associated With Decreased Bone Mineral Density in Adults: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to investigate the effect of nonalcoholic fatty liver disease (NAFLD) on bone mineral density (BMD) and the risk of osteoporosis and osteoporotic fracture in adults. We searched PubMed, MEDLINE, Embase, CINAHL, Web of Science, Cochrane Library, and Scopus for observational studies published from inception to January 2023 that reported adjusted effect sizes of NAFLD on BMD, osteopenia/osteoporosis, and osteoporotic fracture. The data were synthesized using multilevel and random-effects models. A total of 19 studies were included; of these, nine (21,294 participants) evaluated the effect of NAFLD on BMD, six (133,319 participants) investigated the risk of osteoporosis, and five (227,901 participants) assessed the risk of osteoporotic fracture. This meta-analysis showed that NAFLD was associated with decreased BMD (mean difference -0.019 g/cm2 , 95% confidence interval [CI] -0.036 to -0.002, I2 = 93%) and increased risks of osteoporosis (adjusted risk ratio [RR] = 1.28, 95% CI 1.08 to 1.52, I2 = 84%) and osteoporotic fractures (adjusted RR = 1.17, 95% CI 1.00 to 1.37, I2 = 67%). Subgroup analyses revealed that NAFLD had a significantly detrimental effect on BMD in men and on the BMD of the femoral neck and total hip. Stratified analyses by ethnicity demonstrated that NAFLD was not associated with BMD, osteoporosis, or osteoporotic fracture in non-Asian populations. The publication bias of all included studies was low; however, there was considerable heterogeneity among the studies, warranting a careful interpretation of the findings. Overall, our results suggest that NAFLD is associated with decreased BMD and an increased risk of osteoporosis or osteoporotic fractures. Male sex and the BMD of the femoral neck and total hip may be potential risk factors for decreased BMD in adults with NAFLD. Additionally, ethnic disparities were observed between Asian and non-Asian populations regarding BMD and osteoporotic fractures. © 2023 American Society for Bone and Mineral Research (ASBMR).

Distal Junctional Kyphosis after Posterior Spinal Fusion in Lenke 1 and 2 Adolescent Idiopathic Scoliosis-Exploring Detailed Features of the Sagittal Stable Vertebra Concept.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To investigate the factors contributing to the development of postoperative distal junctional kyphosis (DJK) in adolescent idiopathic scoliosis (AIS) patients who underwent posterior spinal fusion (PSF) with lowest instrumented vertebrae (LIV) at or above L1. METHODS: Patients with Lenke type 1 or 2 curves who underwent PSF with LIV at or above L1 with a minimum follow-up of 2 years were evaluated. The primary outcome measure was the occurrence of postoperative DJK. Radiographic parameters of sagittal alignment and inclusion/exclusion of sagittal stable vertebra (SSV) in PSF were analyzed to determine their associations with the occurrence of postoperative DJK. RESULTS: Overall, 122 patients (mean age: 15.1 ± 3.2 years) were included. The overall incidence of postoperative DJK was 6.6%. DJK was observed in 19.0% (8/42) of patients whose SSV was not included in PSF and not in patients with SSV included in PSF (n = 80). In the SSV-excluded group, univariate analysis found two significant risk factors for DJK: postoperative thoracic kyphosis (TK, T5-12) and postoperative thoracolumbar kyphosis (TLK, T11-L2). The ROC curve revealed that postoperative TK ≥ 25° and TLK ≥ 10° best predicted the occurrence of postoperative DJK in the SSV-excluded group. The incidence was significantly higher in cases with postoperative TK ≥ 25° or TLK ≥ 10° (7/13 = 53.8%) than in those with postoperative TK < 25° and TLK < 10° (1/29 = 3.4%). CONCLUSIONS: The current study revealed that postoperative TK ≥ 25° or postoperative TLK ≥ 10° with SSV excluded from PSF were related to DJK after PSF for Lenke type 1 and type 2 AIS. When the SSV is intended to be spared from PSF to save more motion segments, TK and TLK should be carefully evaluated and attained in a lesser magnitude (TK < 25°, TLK < 10°) after surgery.

Cognitive behaviour therapy in adults with spinal cord injury: A scoping review.

AIM: The aim of this study is to report on the extent and range of the research evaluating cognitive behaviour therapy (CBT) in adults with spinal cord injury. BACKGROUND: Spinal cord injury is a devastating event that can lead to permanent neurologic deficit. Compared with the average person, spinal cord injury (SCI) patients are at twice the risk of developing mood disorders, highlighting vulnerability of SCI patients' mental states which can be easily hurt. CBT is the most commonly used psychosocial intervention. DESIGN: This was a scoping review. REVIEW METHOD: Five electronic databases (MEDLINE, CINAHL, EMBASE, PsycINFO and Airiti Library) were searched for articles published between 1990 and 2021. Google Scholar was utilized to search additional articles listed in the reference lists of included articles. RESULTS: Overall, 16 articles met the inclusion criteria, with the majority reporting on CBT, that focused on psychological distress and neuropathic pain. The core concept of intervention included disease identification, cognitive distortion/modification and coping strategies. CONCLUSIONS: There were significant knowledge gaps on the interventions' content and effectiveness for psychological distress of persons with SCI. Development of multifaceted cognitive behaviour interventions, especially to strengthen self-identity and to inspire patients' hope, is needed. Further research is required to investigate the long-term effectiveness of CBT.

Quantitative evaluation of correlation between lumbosacral lordosis and pelvic incidence in standing position among asymptomatic Asian adults: a prospective study.

The determination of lumbopelvic alignment is essential for planning adult spinal deformity surgery and for ensuring favorable surgical outcomes. This prospective study investigated the correlation between the lumbar section of lumbar spine lordosis and increasing pelvic incidence in 324 Asian adults with a mean age of 55 ± 13 years (range: 20-80 years), comprising 115 male and 209 female volunteers. Participants were divided into three groups based on pelvic incidence (G1, G2, and G3 had pelvic incidence of < 45°, 45-55°, and ≥ 55°, respectively). We determined that distal and proximal lumbar lordosis contributed differentially to the increase in pelvic incidence, whereas the lordosis ratio of the L3-L4 and L4-L5 segments mostly remained constant. The mean contribution ratio of the segmental lordosis from L1 to S1 was as follows: L1-L2, 2.3%; L2-L3, 11.7%; L3-L4, 18.1%; L4-L5, 25.2%; and L5-S1, 42.7%. Pelvic incidence had a stronger correlation with proximal lumbar lordosis than did distal lumbar lordosis. The ratios of proximal lumbar lordosis to distal lumbar lordosis were 37.8% in G1, 45.8% in G2, and 55.9% in G3. These findings serve as a reference for future lumbar spine correction or fusion surgery for Asian adults.

Implementing the evidence translation-based resilience care model on family caregivers of stroke patients: a best-practice implementation project.

OBJECTIVES: The aim of this project was to promote for the family caregivers of stroke patients the resilience evidence translation care model in the community. INTRODUCTION: Stroke is the main cause of disability among many patients with chronic diseases. Resilience helps family caregivers facing the consequences of adversity and stress to have a positive outcome. METHODS: The study utilized clinical audit strategies under the JBI Practical Application of Clinical Evidence System module. Three audit criteria for the caregivers of stroke patients were considered. A preimplementation audit was conducted with eight nurses and 30 caregivers to measure compliance between current practice and best practice. From that audit we identified barriers and facilitators to practice change by undertaking a Getting Research into Practice analysis. A postimplementation audit was conducted using the same number of samples at 8 weeks for the caregivers to evaluation, and the outcomes using follow-up audit. RESULTS: The three criteria showed an improvement: nurses who received education about resilience care protocols, criterion 1 from 0 to 100%, criterion 2 from 0 to 100%, criterion 3 from 0 to 90%. The results showed that the average resilience of caregivers increased from 17.47 (SD ±â€Š1.94) to 18.33 (SD ±â€Š1.54). The resilience scale of pretest and posttest scores were significantly improved ( P  ≤ 0.001). CONCLUSION: The implementation of best practice for enhancing resilience of the family caregivers of stroke patients on the resilience evidence translation care model: a best practice implementation project in community settings is possible. The results indicate that evidence-based practice is an effective method for enhancing the resilience of family caregivers. The strategies contributed to the success of this project, such as scenario simulation education, Objective Structured Clinical Examination, regular weekly audits, and collaboration with project leaders when carrying out caregiver case discussion during clinical practice.

Optimization of Tokuhashi Scoring System to Improve Survival Prediction in Patients with Spinal Metastases.

INTRODUCTION: Predicting survival time for patients with spinal metastases is important in treatment choice. Generally speaking, six months is a landmark cutoff point. Revised Tokuhashi score (RTS), the most widely used scoring system, lost its accuracy in predicting 6-month survival, gradually. Therefore, a more precise scoring system is urgently needed. OBJECTIVE: The aim of this study is to create a new scoring system with a higher accuracy in predicting 6-month survival based on the previously used RTS. METHODS: Data of 171 patients were examined to determine factors that affect prognosis (reference group), and the remaining (validation group) were examined to validate the reliability of a new score, adjusted Tokuhashi score (ATS). We compared their discriminatory abilities of the prediction models using area under receiver operating characteristic curve (AUC). RESULTS: Target therapy and the Z score of BMI (Z-BMI), which adjusted to the patients' sex and age, were additional independent prognostic factors. Patients with target therapy use are awarded 4 points. The Z score of BMI could be added directly to yield ATS. The AUCs were 0.760 for ATS and 0.636 for RTS in the validation group. CONCLUSION: Appropriate target therapy use can prolong patients' survival. Z-BMI which might reflect nutritional status is another important influencing factor. With the optimization, surgeons could choose a more individualized treatment for patients.

Multilayer Electrospun-Aligned Fibroin/Gelatin Implant for Annulus Fibrosus Repair: An In Vitro and In Vivo Evaluation.

Annulus fibrosus (AF) damage is proven to prompt intervertebral disc (IVD) degeneration, and unrepaired AF lesions after surgical discectomy may boost herniation of the nucleus pulposus (NP) which may lead to further compression of neural structures. Moreover, vascular and neural ingrowth may occur within the defect which is known as a possible reason for discogenic pain. Due to a limited healing capacity, an effective strategy to repair and close the AF defect is necessary. In this study, using electrospinning technology, two nature polymers, silk fibroin and gelatin, were linked to imitate the unique lamellae structure of native AF. Our findings revealed that a multilayer electrospun-aligned fibroin/gelatin scaffold with mechanical and morphological properties mimicking those of native AF lamellae have been developed. The average diameter of the nanofiber is 162.9 ± 38.8 nm. The young's modulus is around 6.70 MPa with an ultimate tensile strength of around 1.81 MP along preferred orientation. The in vitro test confirmed its biocompatibility and ability to maintain cell viability and colonization. Using a porcine model, we demonstrated that the multilayer-aligned scaffold offered a crucial microenvironment to induce collagen fibrous tissue production within native AF defect. In the implant-repaired AF, H&E staining showed homogeneous fibroblast-like cell infiltration at the repaired defect with very little vascular ingrowth, which was confirmed by magnetic resonance imaging findings. Picrosirius red staining and immunohistochemical staining against type I collagen revealed positively stained fibrous tissue in an aligned pattern within the implant-integrated site. Relative to the intact control group, the disc height index of the serial X-ray decreased significantly in both the injury control and implant group at 4 weeks and 8 weeks (p < 0.05) which indicated this scaffold may not reverse the degenerative process. However, the results of the discography showed that the effectiveness of annulus repair of the implant group is much superior to that of the untreated group. The scaffold, composed with nature fibroin/gelatin polymers, could potentially enhance AF healing that could prevent IVD recurrent herniation, as well as neural and neovascular ingrowth after discectomy surgeries.

Prognostic significance of lab data and performance comparison by validating survival prediction models for patients with spinal metastases after radiotherapy.

BACKGROUND AND PURPOSE: Well-performing survival prediction models (SPMs) help patients and healthcare professionals to choose treatment aligning with prognosis. This retrospective study aims to investigate the prognostic impacts of laboratory data and to compare the performances of Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy (METSSS) model, New England Spinal Metastasis Score (NESMS), and Skeletal Oncology Research Group machine learning algorithm (SORG-MLA) for spinal metastases (SM). MATERIALS AND METHODS: From 2010 to 2018, patients who received radiotherapy (RT) for SM at a tertiary center were enrolled and the data were retrospectively collected. Multivariate logistic and Cox-proportional-hazard regression analyses were used to assess the association between laboratory values and survival. The area under receiver-operating characteristics curve (AUROC), calibration analysis, Brier score, and decision curve analysis were used to evaluate the performance of SPMs. RESULTS: A total of 2786 patients were included for analysis. The 90-day and 1-year survival rates after RT were 70.4% and 35.7%, respectively. Higher albumin, hemoglobin, or lymphocyte count were associated with better survival, while higher alkaline phosphatase, white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, or international normalized ratio were associated with poor prognosis. SORG-MLA has the best discrimination (AUROC 90-day, 0.78; 1-year 0.76), best calibrations, and the lowest Brier score (90-day 0.16; 1-year 0.18). The decision curve of SORG-MLA is above the other two competing models with threshold probabilities from 0.1 to 0.8. CONCLUSION: Laboratory data are of prognostic significance in survival prediction after RT for SM. Machine learning-based model SORG-MLA outperforms statistical regression-based model METSSS model and NESMS in survival predictions.

SETD4 cells contribute to brain development and maintain adult stem cell reservoir for neurogenesis.

Cellular quiescence facilitates maintenance of neural stem cells (NSCs) and their subsequent regenerative functions in response to brain injury and aging. However, the specification and maintenance of NSCs in quiescence from embryo to adulthood remain largely unclear. Here, using Set domain-containing protein 4 (SETD4), an epigenetic determinant of cellular quiescence, we mark a small but long-lived NSC population in deep quiescence in the subventricular zone of adult murine brain. Genetic lineage tracing shows that SETD4+ cells appear before neuroectoderm formation and contribute to brain development. In the adult, conditional knockout of Setd4 resulted in quiescence exit of NSCs, generating newborn neurons in the olfactory bulb and contributing to damage repair. However, long period deletion of SETD4 lead to exhaustion of NSC reservoir or SETD4 overexpression caused quiescence entry of NSCs, leading to suppressed neurogenesis. This study reveals the existence of long-lived deep quiescent NSCs and their neurogenetic capacities beyond activation.

Simultaneous Hypercorrection of Lowest Instrumented Vertebral Tilt and Main Thoracic Curve is Associated With Progression of Residual Lumbar Curve in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To determine radiographic parameters, including the lowest instrumented vertebral (LIV) tilt, related to the postoperative magnitude and progression of residual lumbar curves (LCs) in adolescent idiopathic scoliosis patients who underwent posterior spinal fusion with LIV at or above L1. SUMMARY OF BACKGROUND DATA: Although several guidelines have been proposed for thoracic curve fusion, factors related to the postoperative magnitude and potential progression of unfused LCs remained undetermined. The effect of the LIV tilt on residual LCs is also unclear. MATERIALS AND METHODS: Patients with Lenke type 1 to 4 curves who underwent posterior spinal fusion with LIV at or above L1 with a minimum follow-up period of 2 years were evaluated. Prediction models for residual LCs were developed using multivariate linear regressions with selected radiographic parameters. Subgroup analyses, followed by sensitivity tests, were then performed for variables best predicting the progression of residual LCs. RESULTS: A total of 130 patients were included. Multivariate linear regression analysis showed that the immediate postoperative LIV-tilt angle was associated with the immediate postoperative LCs and the prediction model for residual LCs, with high accuracy ( R =0.93 and 0.77, respectively). Sensitivity tests revealed immediate postoperative LIV-tilt angle <10° and correction rate of main thoracic curve Cobb angle >53% as predictors for progression of residual LCs, and they reached moderate discrimination when combined together as one criterion (odds ratio=16.3, 95% confidence interval=5.3-50.1; sensitivity=89%, specificity=67%, positive predicted value=51%, negative predicted value=94%). CONCLUSION: The current study revealed that LIV tilt, as an operable factor during surgery, is not only a determinant in prediction models showing high correlation with the magnitude of postoperative LCs but a predictor for progression of residual LCs. "Immediate postoperative LIV-tilt angle <10° and correction rate of main thoracic curve Cobb angle >53%," as a united criterion, could serve as a predictor for progression of residual LCs.

Exosomal DEK removes chemoradiotherapy resistance by triggering quiescence exit of breast cancer stem cells.

Tumor therapeutics often target the primary tumor bulk but fail to eradicate therapy-resistant cancer stem cells (CSCs) in quiescent state. These can then become activated to initiate recurrence and/or metastasis beyond therapy. Here, we identified and isolated chemoradiotherapy-resistant CSCs in quiescent state with high capacity of tumor-initiation and tumorsphere formation from three types of breast tumors in mice. Experiments of knockdown and rescue revealed DEK, a nuclear protein, as essential for CSC activation. Exogenous DEK was then used to trigger quiescence exit of CSCs. ChIP-seq and ATAC-seq showed that DEK directly binds to chromatin, facilitating its genome-wide accessibility. The resulting epigenetic events upregulate the expression of cellular activation-related genes including MYC targets, whereas cellular quiescence-related genes including the p53 signaling pathway are silenced. However, twinned with DEK-induced activation, formerly resistant CSCs were then destroyed by chemotherapy in vitro. In mice, traditional chemoradiotherapy concurrent with the injection of DEK-containing exosomes resulted in eradication of primary tumors together with formerly resistant CSCs without recurrence or metastasis. Our findings advance knowledge of the mechanism of quiescent CSC activation and may provide novel clinical opportunities for removal of quiescence-linked therapy resistance.

Decreased psoas muscle area is a prognosticator for 90-day and 1-year survival in patients undergoing surgical treatment for spinal metastasis.

BACKGROUND AND AIMS: Survival estimation for patients with spinal metastasis is crucial to treatment decisions. Psoas muscle area (PMA), a surrogate for total muscle mass, has been proposed as a useful survival prognosticator. However, few studies have validated the predictive value of decreased PMA in an Asian cohort or its predictive value after controlling for existing preoperative scoring systems (PSSs). In this study, we aim to answer: (1) Is PMA associated with survival in Han Chinese patients with spinal metastasis? (2) Is PMA a good prognosticator according to concordance index (c-index) and decision curve analysis (DCA) after controlling for six existing and commonly used PSSs? METHODS: This study included 180 adult (≥18 years old) Taiwanese patients with a mean age of 58.3 years (range: 22-85) undergoing surgical treatment for spinal metastasis. A patient's PMA was classified into decreased, medium, and large if it fell into the lower (0-33%), middle (33-67%), and upper (67-100%) 1/3 in the study cohort, respectively. We used logistic and cox proportional-hazard regressions to assess whether PMA was associated with 90-day, 1-year, and overall survival. The model performance before and after addition of PMA to six commonly used PSSs, including Tomita score, original Tokuhashi score, revised Tokuhashi score, modified Bauer score, New England Spinal Metastasis Score, and Skeletal Oncology Research Group machine learning algorithms (SORG-MLAs), was compared by c-index and DCA to determine if PMA was a useful survival prognosticator. RESULTS: Patients with a larger PMA is associated with better 90-day, but not 1-year, survival. The model performance of 90-day survival prediction improved after PMA was incorporated into all PSSs except SORG-MLAs. PMA barely improved the discriminatory ability (c-index, 0.74; 95% confidence interval [CI], 0.67-0.82 vs. c-index, 0.74; 95% CI, 0.66-0.81) and provided little gain of clinical net benefit on DCA for SORG-MLAs' 90-day survival prediction. CONCLUSIONS: PMA is a prognosticator for 90-day survival and improves the discriminatory ability of earlier-proposed PSSs in our Asian cohort. However, incorporating PMA into more modern PSSs such as SORG-MLAs did not significantly improve its prediction performance.