A plasma protein-based risk score to predict hip fractures.
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ABSTRACT:
SUBMITTER: Austin TR
PROVIDER: S-EPMC11333168 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
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A plasma protein-based risk score to predict hip fractures.
Austin Thomas R TR Nethander Maria M Fink Howard A HA Törnqvist Anna E AE Jalal Diana I DI Buzkova Petra P Barzilay Joshua I JI Carbone Laura L Gabrielsen Maiken E ME Grahnemo Louise L Lu Tianyuan T Hveem Kristian K Jonasson Christian C Kizer Jorge R JR Langhammer Arnulf A Mukamal Kenneth J KJ Gerszten Robert E RE Psaty Bruce M BM Robbins John A JA Sun Yan V YV Skogholt Anne Heidi AH Kanis John A JA Johansson Helena H Åsvold Bjørn Olav BO Valderrabano Rodrigo J RJ Zheng Jie J Richards J Brent JB Coward Eivind E Ohlsson Claes C
Nature aging 20240527 8
As there are effective treatments to reduce hip fractures, identification of patients at high risk of hip fracture is important to inform efficient intervention strategies. To obtain a new tool for hip fracture prediction, we developed a protein-based risk score in the Cardiovascular Health Study using an aptamer-based proteomic platform. The proteomic risk score predicted incident hip fractures and improved hip fracture discrimination in two Trøndelag Health Study validation cohorts using the s ...[more]
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Project description:Femoral neck width (FNW) derived from DXA scans may provide a useful adjunct to hip fracture prediction. Therefore, we investigated whether FNW is related to hip fracture risk independently of femoral neck bone mineral density (FN-BMD), using a genetic approach. FNW was derived from points automatically placed on the proximal femur using hip DXA scans from 38 150 individuals (mean age 63.8 yr, 48.0% males) in UK Biobank (UKB). Genome-wide association study (GWAS) identified 71 independent genome-wide significant FNW SNPs, comprising genes involved in cartilage differentiation, hedgehog, skeletal development, in contrast to SNPs identified by FN-BMD GWAS which primarily comprised runx1/Wnt signaling genes (MAGMA gene set analyses). FNW and FN-BMD SNPs were used to generate genetic instruments for multivariable Mendelian randomization. Greater genetically determined FNW increased risk of all hip fractures (odds ratio [OR] 1.53; 95% CI, 1.29-1.82 per SD increase) and femoral neck fractures (OR 1.58;1.30-1.92), but not trochanteric or forearm fractures. In contrast, greater genetically determined FN-BMD decreased fracture risk at all 4 sites. FNW and FN-BMD SNPs were also used to generate genetic risk scores (GRSs), which were examined in relation to incident hip fracture in UKB (excluding the FNW GWAS population; n = 338 742, 3222 cases) using a Cox proportional hazards model. FNW GRS was associated with increased risk of all incident hip fractures (HR 1.08;1.05-1.12) and femoral neck fractures (hazard ratio [HR] 1.10;1.06-1.15), but not trochanteric fractures, whereas FN-BMD GRS was associated with reduced risk of all hip fracture types. We conclude that the underlying biology regulating FNW and FN-BMD differs, and that DXA-derived FNW is causally related to hip fractures independently of FN-BMD, adding information beyond FN-BMD for hip fracture prediction. Hence, FNW derived from DXA analyses or a FNW GRS may contribute clinically useful information beyond FN-BMD for hip fracture prediction.
| S-EPMC11240160 | biostudies-literature
Project description:BackgroundPost-hip fracture surgery delirium (PHFD) is a significant clinical problem in older patients, but an adequate, simple risk prediction model for use in the preoperative period has not been developed.MethodsThe 2016 American College of Surgeons National Surgical Quality Improvement Program Hip Fracture Procedure Targeted Participant Use Data File was used to obtain a cohort of patients ≥60 years of age who underwent hip fracture surgery (n = 8871; randomly assigned to derivation [70%] or validation [30%] cohorts). A parsimonious prediction model for PHFD was developed in the derivation cohort using stepwise multivariable logistic regression with further removal of variables by evaluating changes in the area under the receiver operator characteristic curve (AUC). A risk score was developed from the final multivariable model.ResultsOf 6210 patients in the derivation cohort, PHFD occurred in 1816 (29.2%). Of 32 candidate variables, 9 were included in the final model: (1) preoperative delirium (adjusted odds ratio [aOR], 8.32 [95% confidence interval {CI}, 6.78-10.21], 8 risk score points); (2) preoperative dementia (aOR, 2.38 [95% CI, 2.05-2.76], 3 points); (3) age (reference, 60-69 years of age) (age 70-79: aOR, 1.60 [95% CI, 1.20-2.12], 2 points; age 80-89: aOR, 2.09 [95% CI, 1.59-2.74], 2 points; and age ≥90: aOR, 2.43 [95% CI, 1.82-3.23], 3 points); (4) medical comanagement (aOR, 1.43 [95% CI, 1.13-1.81], 1 point); (5) American Society of Anesthesiologists (ASA) physical status III-V (aOR, 1.40 [95% CI, 1.14-1.73], 1 point); (6) functional dependence (aOR, 1.37 [95% CI, 1.17-1.61], 1 point); (7) smoking (aOR, 1.36 [95% CI, 1.07-1.72], 1 point); (8) systemic inflammatory response syndrome/sepsis/septic shock (aOR, 1.34 [95% CI, 1.09-1.65], 1 point); and (9) preoperative use of mobility aid (aOR, 1.32 [95% CI, 1.14-1.52], 1 point), resulting in a risk score ranging from 0 to 20 points. The AUCs of the logistic regression and risk score models were 0.77 (95% CI, 0.76-0.78) and 0.77 (95% CI, 0.76-0.78), respectively, with similar results in the validation cohort.ConclusionsA risk score based on 9 preoperative risk factors can predict PHFD in older adult patients with fairly good accuracy.
| S-EPMC6917900 | biostudies-literature
Project description:Despite continual efforts to establish pre-operative prognostic model of gastric cancer by using clinical and pathological parameters, a staging system that reliably separates patients with early and advanced gastric cancer into homogeneous groups with respect to prognosis does not exist. With use of microarray and quantitative RT-PCR technologies, we exploited series of experiments in combination with complementary data analyses on tumor specimens from 161 gastric cancer patients. Various statistical analyses were applied to gene expression data to uncover subgroups of gastric cancer, to identify potential biomarkers associated with prognosis, and to construct molecular predictor of risk from identified prognostic biomarkers.Two subgroups of gastric cancer with strong association with prognosis were uncovered. The robustness of prognostic gene expression signature was validated in independent patient cohort with use of support vector machines prediction model. For easy translation of our finding to clinics, we develop scoring system based on expression of six genes that can predict the likelihood of recurrence after curative resection of tumors. In multivariate analysis, our novel risk score was an independent predictor of recurrence (P=0.004) in cohort of 96 patients, and its robustness was validated in two other independent cohorts. We identified novel prognostic subgroups of gastric cancer that are distinctive in gene expression patterns. Six-gene signature and risk score derived from them has been validated for predicting the likelihood of survival at diagnosis. 65 primary gastric adenocarcinoma, 6 GIST and 19 surrounding normal fresh frozen tissues were used for microarray. All the tissues were obtained after curative resection after pathologic confirm at Yonsei cancer center(Seoul, Korea). Microarray experiment and data analysis were done at Dept. of systems biology, MDACC DNA microarray (Illumina human V3)
2011-07-18 | E-GEOD-13861 | biostudies-arrayexpress
Project description:Nowadays, there are different ICU scoring systems to predict the likelihood of mortality, such as Acute Physiology And Chronic Health Condition (APACHE), Sequential Organ Failure Assessment (SOFA), and SAPS (Simplified Acute Physiology Score). Theses risk scores are based on the use of physiologic and other clinical data. However, the use of these score systems depend on the clinical trust in the reliability and predictions by physicians. In this work, we have evaluated the expression profile by microarray analysis from postsurgical patients with the aim of proposing a candidate set genes as a mortality risk score.
2020-05-05 | GSE132897 | GEO
Project description:Introduction: Vertebral compression fractures (VCFs) pose a considerable healthcare burden and are linked to elevated morbidity and mortality. Despite available anti-osteoporotic treatments (AOTs), guideline adherence is lacking. This study aims to evaluate subsequent hip fracture incidence after index VCF and to elucidate AOT prescribing patterns in VCF patients, further assessing the impact of surgical interventions on these patterns. Materials and Methods: Patients with index VCFs between 2010 and 2021 were identified using the PearlDiver database. Diagnostic and procedural data were recorded using International Classification of Diseases (ICD-9, ICD-10) and Current Procedural Terminology (CPT) codes. Patients under age 50 and follow-up <one year following index VCF were excluded. Patients were categorized based on whether they received AOT within one year, preceding and after index VCF, and were subsequently propensity-matched 1:3 based on age, sex, and Elixhauser Comorbidity Index (ECI) score to compare hip fracture incidence following index VCF. Sub-analysis was performed for operatively managed VCFs (kyphoplasty/vertebroplasty). Statistical tests included Chi-squared for categorical outcomes, and Kruskal-Wallis for continuous measures. Results: Of 637,701 patients, 72.6% were female. The overall subsequent hip fracture incidence was 2.6% at one year and 12.9% for all-time follow-up. Propensity-matched analysis indicated higher subsequent hip fracture rates in patients initiated on AOT post-index VCF (one year: 3.8% vs. 3.5%, p = 0.0013; all-time: 14.3% vs. 13.0%, p < 0.0001). Conclusions: The study reveals an unexpected increase in subsequent hip fractures among patients initiated on AOT post-index VCF, likely due to selection bias. These findings highlight the need for refined osteoporosis-management strategies to improve guideline adherence, thereby mitigating patient morbidity and mortality.
| S-EPMC11355522 | biostudies-literature
Project description:BackgroundPeriprosthetic fractures are a devastating complication of total hip arthroplasty (THA) and are associated with significantly higher mortality rates in the postoperative period. Given the strain that periprosthetic fractures place on the patient as well as the healthcare system, identifying and optimizing medical comorbidities is essential in reducing complications and improving outcomes.MethodsAll THA with primary indications of osteoarthritis from 2007 to 2020 were queried from the National Surgical Quality Improvement Program database. Demographic data, preoperative laboratory values, medical comorbidities, hospital course, and acute complications were collected and compared between patients with and without readmission for a periprosthetic fracture. A multivariate logistic regression analysis was performed to determine associated independent risk factors for periprosthetic fractures after index THA.ResultsThe analysis included 275,107 patients, of which 2539 patients were readmitted for periprosthetic fractures. Patients with postoperative fractures were more likely to be older (>65 years), females, BMI >40, and increased medical comorbidities. Preoperative hypoalbuminemia, hyponatremia, and abnormal estimated glomerular filtration rates were independent risk factors for sustaining a periprosthetic fracture and readmission within 30 days. Modifiable patient-related factors of concurrent smoking and chronic steroid use at the time of index THA were also independent risk factors for periprosthetic fractures. Inpatient metrics of longer length of stay, operative time, and discharge to rehab predicted postarthroplasty fracture risk. Readmitted fracture patients subsequently had increased risks of developing a surgical site infection, urinary tract infection, and requiring blood transfusions.ConclusionsPatients with hypoalbuminemia, hyponatremia, and abnormal estimated glomerular filtration rate are at increased risk for sustaining periprosthetic fractures after THA. Preoperative optimization with close monitoring of metabolic markers and modifiable risk factors may help not only prevent acute periprosthetic fractures but also associated infection and bleeding risk with fracture readmission.
| S-EPMC9860454 | biostudies-literature
Project description:BackgroundThe Radiographic Union Score for Hip (RUSH) is a previously validated outcome instrument designed to improve intra- and interobserver reliability when describing the radiographic healing of femoral neck fractures. The ability to identify fractures that have not healed is important for defining nonunion in clinical trials and predicting patients who will likely require additional surgery to promote fracture healing. We sought to investigate the utility of the RUSH score to define femoral neck fracture nonunion.Questions/purposes(1) What RUSH score threshold yields at least 98% specificity to diagnose nonunion at 6 months postinjury? (2) Using the threshold identified, are patients below this threshold at greater risk of reoperation for nonunion and for other indications?MethodsA representative sample of 250 out of a cohort of 725 patients with adequate 6-month hip radiographs was analyzed from a multinational elderly hip fracture trial (FAITH). All patients had a femoral neck fracture and were treated with either multiple cancellous screws or a sliding hip screw. Two reviewers independently determined the RUSH score based on the 6-month postinjury radiographs and interrater reliability was assessed with the interclass correlation coefficient (ICC). There was substantial reliability between the reviewers assigning the RUSH scores (ICC, 0.81; 95% confidence interval [CI], 0.76-0.85). The RUSH score is a checklist-based system that quantifies four measures of healing: cortical bridging, cortical fracture disappearance, trabecular consolidation, and trabecular fracture disappearance.. Fracture healing was determined by two independent methods: (1) concurrently by the treating surgeon using both clinical and radiographic assessments as per routine clinical care; and (2) retrospectively by a Central Adjudication Committee using complete obliteration of the fracture line on radiographs alone. Receiver operating characteristic tables were used to define a RUSH threshold score that was > 98% specific for fracture nonunion.ResultsA threshold score of < 18 was associated with a 100% specificity (95% CI, 97%-100%) and a positive predictive value of 100% (95% CI, 73%-100%) for radiographic nonunion. In contrast, using the fracture healing assessments of the treating surgeons failed to identify a useful discriminatory nonunion threshold and the highest positive predictive value was 43%. With respect to complications, patients with RUSH scores below 18 had greater risk of undergoing reoperation for nonunion (reoperation when < 18: six of 13 [46%]; reoperation when ≥ 18: 11 of 237 [54%]; relative risk [RR], 9.9 [95% CI, 4.4-22.7]; p < 0.001) and for all indications (reoperation when < 18: eight of 13 [62%]; reoperation when ≥ 18: 54 of 237 [38%]; RR, 2.7 [95% CI, 1.7-4.4]; p = 0.004).ConclusionsThe 6-month RUSH score is a reliable method for assessing radiographic healing. Our results highlight the discordance between radiographic determinations and clinician assessments of fracture healing and stress the need for clinical data to be incorporated in research studies evaluating fracture healing.Level of evidenceLevel III, diagnostic study.
| S-EPMC4868173 | biostudies-literature
Project description:Despite continual efforts to establish pre-operative prognostic model of gastric cancer by using clinical and pathological parameters, a staging system that reliably separates patients with early and advanced gastric cancer into homogeneous groups with respect to prognosis does not exist. With use of microarray and quantitative RT-PCR technologies, we exploited series of experiments in combination with complementary data analyses on tumor specimens from 161 gastric cancer patients. Various statistical analyses were applied to gene expression data to uncover subgroups of gastric cancer, to identify potential biomarkers associated with prognosis, and to construct molecular predictor of risk from identified prognostic biomarkers.Two subgroups of gastric cancer with strong association with prognosis were uncovered. The robustness of prognostic gene expression signature was validated in independent patient cohort with use of support vector machines prediction model. For easy translation of our finding to clinics, we develop scoring system based on expression of six genes that can predict the likelihood of recurrence after curative resection of tumors. In multivariate analysis, our novel risk score was an independent predictor of recurrence (P=0.004) in cohort of 96 patients, and its robustness was validated in two other independent cohorts. We identified novel prognostic subgroups of gastric cancer that are distinctive in gene expression patterns. Six-gene signature and risk score derived from them has been validated for predicting the likelihood of survival at diagnosis.
2011-07-19 | GSE13861 | GEO
Project description:BackgroundStudies have shown that the clinical efficacy of TBS (Trabecular Bone Score) of DXA in hip fracture patients. This study aimed to investigate the difference of TBS in trochanteric fractures and femoral neck fractures in hip fracture patients.MethodsData were derived from the University affiliated hospital, the participants included 249 patients aged 60 years or older who were available of TBS prescribe by DXA. 89 femoral neck fracture patients and 160 trochanteric fractures were enrolled. Spine T- score, hip T- score (neck), hip T- score (total), lowest T- score in hip, L1-L4 TBS. TBS Z-score, L1-L4 BMD(g/cm²), L1-L4 BMD T-score, L1 TBS, L1 BMD(g/cm2), L1 BMD T-score, L2 TBS, L2 BMD(g/cm2), L2 BMD T-score, L3 TBS, L3 BMD(g/cm2), L3 BMD T-score, L4 TBS, L4 BMD(g/cm2), L4 BMD T-score, lowest TBS score, highest TBS score were analyzed.ResultsDemographic data (age, sex, height, weight, BMI) and T-score of hip and spine in two groups showed no significant difference. TBS in spine in two groups revealed higher TBS in femoral neck fracture groups.ConclusionThere is no difference of age, sex, and BMI in two groups. The T-score was not statistically significant in comparison of bone quality in hip fracture groups. The TBS in femoral neck fracture group is higher than trochanteric fractures. The TBS in spine can be more valuable than T-score of DXA for the proper evaluation of bone quality in the hip fracture patients.
| S-EPMC11562483 | biostudies-literature
Project description:BackgroundWith the aging of the world's population, the social and economic implications of osteoporotic fractures are at epidemic proportions. This study was performed to test the hypothesis that a proximal humeral fracture is an independent risk factor for a subsequent hip fracture and that the risk of the subsequent hip fracture is highest within the first five years after the humeral fracture.MethodsA cohort of 8049 older white women with no history of a hip or humeral fracture who were enrolled in the Study of Osteoporotic Fractures was followed for a mean of 9.8 years. The risk of hip fracture after an incident humeral fracture was estimated with use of age-adjusted Cox proportional hazards regression analysis with time-varying variables; women without a humeral fracture were the reference group. Cox regression analysis was used to evaluate the timing between the proximal humeral and subsequent hip fracture. Risk factors were determined on the basis of a review of the current literature, and we chose the variables that were most predictive and easily ascertained in a clinical setting.ResultsThree hundred and twenty-one women sustained a proximal humeral fracture, and forty-four of them sustained a subsequent hip fracture. After adjustment for age and bone mineral density, the hazard ratio for hip fracture for subjects with a proximal humeral fracture relative to those without a proximal humeral fracture was 1.83 (95% confidence interval = 1.32 to 2.53). After multivariate adjustment, this risk appeared attenuated but was still significant (hazard ratio = 1.57; 95% confidence interval = 1.12 to 2.19). The risk of a subsequent hip fracture after a proximal humeral fracture was highest within one year after the proximal humeral fracture, with a hazard ratio of 5.68 (95% confidence interval = 3.70 to 8.73). This association between humeral and hip fracture was not significant after the first year, with hazard ratios of 0.87 (95% confidence interval = 0.48 to 1.59) between one and five years after the humeral fracture and 0.58 (95% confidence interval = 0.22 to 1.56) after five years.ConclusionsIn this cohort of older white women, a proximal humeral fracture independently increased the risk of a subsequent hip fracture more than five times in the first year after the humeral fracture but was not associated with a significant increase in the hip fracture risk in subsequent years.
| S-EPMC2669747 | biostudies-literature