Category-free Net Reclassification Improvement Research Articles

A CT texture-based nomogram for predicting futile reperfusion in patients with intraparenchymal hyperdensity after endovascular thrombectomy for acute anterior circulation large vessel occlusion.

Post-thrombectomy intraparenchymal hyperdensity (PTIH) in patients with acute anterior circulation large vessel occlusion is a common CT sign associated with a higher incidence of futile reperfusion (FR). We aimed to develop a nomogram to predict FR specifically in patients with PTIH. We retrospectively collected information on patients with acute ischemic stroke who underwent endovascular thrombectomy (EVT) at two stroke centers. A total of 398 patients with PTIH were included to develop and validate the nomogram, including 214 patients in the development cohort, 92 patients in the internal validation cohort and 92 patients in the external validation cohort. The nomogram was developed according to the independent predictors obtained from multivariate logistic regression analysis, including clinical factors and CT texture features extracted from hyperdense areas on CT images within half an hour after EVT. The performance of the nomogram was evaluated with integrated discrimination improvement (IDI), category-free net reclassification improvement (NRI), the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analyses for discrimination, calibration ability, and clinical net benefits, respectively. Our nomogram was constructed based on three clinical factors (age, NIHSS score and ASPECT score) and two CT texture features (entropy and kurtosis), with AUC-ROC of 0.900, 0.897, and 0.870 in the development, internal validation, and external validation cohorts, respectively. NRI and IDI further validated the superior predictive ability of the nomogram compared to the clinical model. The calibration plot revealed good consistency between the predicted and the actual outcome. The decision curve indicated good positive net benefit and clinical validity of the nomogram. The nomogram enables clinicians to accurately predict FR specifically in patients with PTIH within half an hour after EVT and helps to formulate more appropriate treatment plans in the early post-EVT period.

Triglyceride-glucose index is associated with recurrent revascularization in patients with type 2 diabetes mellitus after percutaneous coronary intervention

BackgroundThe Triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, is independently associated with the severity of coronary artery lesions and the prognosis of coronary heart disease. The investigation aimed to explore the relationship between the TyG index and recurrent revascularization in individuals with type 2 diabetes mellitus (T2DM) resulting from the progression of lesions or in-stent restenosis (ISR) after percutaneous coronary intervention (PCI).MethodA total of 633 patients who met the inclusion and exclusion criteria were enrolled and divided into three groups based on the tertiles of the TyG index. The primary endpoint was recurrent revascularization resulting from the progression of lesions or ISR. All-cause death was considered as the competing risk event. Competing risk analysis and Cox regression analysis for predicting recurrent revascularization after PCI were conducted stepwise. Variables were standardized to make the hazard ratio (HR), subdistribution hazard ratio (SHR) and corresponding 95% CI more consistent prior to being used for fitting the multivariate risk model. The predictive ability of the TyG index was evaluated using several measures, including the ROC curve, likelihood ratio test, Akaike’s information criteria, category-free continuous net reclassification improvement (cNRI > 0), and integrated discrimination improvement (IDI). Internal validation was conducted through bootstrapping with 1000 resamples.ResultsDuring a median follow-up period of 18.33 months, a total of 64 (10.11%) patients experienced recurrent revascularization, including 55 cases of lesion progression and 9 cases of in-stent restenosis. After controlling for competitive risk events, the TyG index was independently associated with a higher risk of recurrent revascularization [SHR:1.4345, (95% CI 1.1458–1.7959), P = 0.002]. The likelihood ratio test and Akaike’s information criteria showed that the TyG index significantly improves the prognostic ability. Additionally, adding the TyG index improved the ability of the established risk model in predicting recurrent revascularization, indicated by a C-index of 0.759 (95% CI 0.724–0.792, P < 0.01), with a cNRI > 0 of 0.170 (95% CI 0.023–0.287, P < 0.05), and an IDI of 0.024 (95% CI 0.009–0.039, P = 0.002). These results remained consistent when the models containing TyG index were confirmed using an internal bootstrap validation method.ConclusionThe findings highlight the potential of the TyG index as a predictor of recurrent revascularization. Lesion progression emerged as the primary contributor to recurrent revascularization instead of in-stent restenosis. The incorporation of the TyG index into risk prediction models is likely to be beneficial for accurate risk stratification in order to improve prognosis.

Plasma NGAL levels in stable kidney transplant recipients and the risk of allograft loss.

The objective of this study was to investigate the utility of neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin (CPT) to predict long-term graft survival in stable kidney transplant recipients (KTR). A total of 709 stable outpatient KTR were enrolled >2 months post-transplant. The utility of plasma and urinary NGAL (pNGAL, uNGAL) and plasma and urinary CPT at enrollment to predict death-censored graft loss was evaluated during a 58-month follow-up. Among biomarkers, pNGAL showed the best predictive ability for graft loss and was the only biomarker with an area under the curve (AUC)>0.7 for graft loss within 5 years. Patients with graft loss within 5 years (n=49) had a median pNGAL of 304 [interquartile range (IQR) 235-358] versus 182 (IQR 128-246) ng/mL with surviving grafts (P<.001). Time-dependent receiver operating characteristic analyses at 58 months indicated an AUC for pNGAL of 0.795, serum creatinine-based Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) had an AUC of 0.866. pNGAL added to a model based on conventional risk factors for graft loss with death as competing risk (age, transplant age, presence of donor-specific antibodies, presence of proteinuria, history of delayed graft function) had a strong independent association with graft loss {subdistribution hazard ratio (sHR) for binary log-transformed pNGAL [log2(pNGAL)] 3.4, 95% confidence interval (CI) 2.24-5.15, P<.0001}. This association was substantially attenuated when eGFR was added to the model [sHR for log2(pNGAL) 1.63, 95% CI 0.92-2.88, P=.095]. Category-free net reclassification improvement of a risk model including log2(pNGAL) in addition to conventional risk factors and eGFR was 54.3% (95% CI 9.2%-99.3%) but C-statistic did not improve significantly. pNGAL was an independent predictor of renal allograft loss in stable KTR from one transplant center but did not show consistent added value when compared with baseline predictors including the conventional marker eGFR. Future studies in larger cohorts are warranted.

Erector spinae muscle-based nomogram for predicting in-hospital mortality among older patients with severe community-acquired pneumonia

BackgroundNo multivariable model incorporating erector spinae muscle (ESM) has been developed to predict clinical outcomes in older patients with severe community-acquired pneumonia (SCAP). This study aimed to construct a nomogram based on ESM to predict in-hospital mortality in patients with SCAP.MethodsPatients aged ≥ 65 years with SCAP were enrolled in this prospective observational study. Least absolute selection and shrinkage operator and multivariable logistic regression analyses were used to identify risk factors for in-hospital mortality. A nomogram prediction model was constructed. The predictive performance was evaluated using the concordance index (C-index), calibration curve, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis.ResultsA total of 490 patients were included, and the in-hospital mortality rate was 36.1%. The nomogram included the following independent risk factors: mean arterial pressure, peripheral capillary oxygen saturation, Glasgow Coma Scale score (GCS), lactate, lactate dehydrogenase, blood urea nitrogen levels, and ESM cross-sectional area. Incorporating ESM into the base model with other risk factors significantly improved the C-index from 0.803 (95% confidence interval [CI], 0.761–0.845) to 0.836 (95% CI, 0.798–0.873), and these improvements were confirmed by category-free NRI and IDI. The ESM-based nomogram demonstrated a high level of discrimination, good calibration, and overall net benefits for predicting in-hospital mortality compared with the combination of confusion, urea, respiratory rate, blood pressure, and age ≥ 65 years (CURB-65), Pneumonia Severity Index (PSI), Acute Physiology and Chronic Health Evaluation II (APACHEII), and Sequential Organ Failure Assessment (SOFA).ConclusionsThe proposed ESM-based nomogram for predicting in-hospital mortality among older patients with SCAP may help physicians to promptly identify patients prone to adverse outcomes.Trial registrationThis study was registered at www.chictr.org.cn (registration number Chi CTR-2300070377).

Association of urinary liver-type fatty acid–binding protein with outcomes after adrenalectomy for unilateral primary aldosteronism

Background and AimsThis study explored the association between urinary liver-type fatty acid-binding protein to creatinine (uL-FABP-cre) ratio and postoperative clinical failure in unilateral primary aldosteronism (PA) patients undergoing adrenalectomy. Materials and MethodsData from the Taiwan Primary Aldosteronism Investigation Group database were analyzed, including patients with unilateral PA who had adrenalectomy between December 2015 and October 2018. Statistical methods included generalized additive modeling, logistic regression analysis, net reclassification improvement (NRI), and the C statistic. ResultsIn the study cohort of 131 patients (mean age 52.3 ± 10.8 years; 43.5% male), 117 achieved clinical success, while 14 experienced clinical failure. A uL-FABP-cre ratio ≥5 predicted clinical failure (odds ratio: 6.22, p = 0.005). Subgroup analysis revealed its efficacy in predicting clinical failure in patients with BMI ≥ 24 kg/m2, normokalemia, or <5 years of hypertension.Furthermore, incorporating uL-FABP-cre ratio into the Primary Aldosteronism Surgical Outcome (PASO) score significantly improved predictive ability. The addition increased the C statistic from 0.671 to 0.762 (p < 0.01) and improved category-free NRI by 0.675 (p = 0.014). ConclusionA uL-FABP-cre ratio ≥5 accurately predicted clinical failure post-adrenalectomy in unilateral PA, enhancing PASO score's identification of high-risk patients for postoperative clinical failure.

Preoperative Risk Stratification in Esophageal Cancer Surgery: Comparing Risk Models with the Clinical Judgment of the Surgeon

BackgroundNumerous prediction models estimating the risk of complications after esophagectomy exist but are rarely used in practice. The aim of this study was to compare the clinical judgment of surgeons using these prediction models.MethodsPatients with resectable esophageal cancer who underwent an esophagectomy were included in this prospective study. Prediction models for postoperative complications after esophagectomy were selected by a systematic literature search. Clinical judgment was given by three surgeons, indicating their estimated risk for postoperative complications in percentage categories. The best performing prediction model was compared with the judgment of the surgeons, using the net reclassification improvement (NRI), category-free NRI (cfNRI), and integrated discrimination improvement (IDI) indexes.ResultsOverall, 159 patients were included between March 2019 and July 2021, of whom 88 patients (55%) developed a complication. The best performing prediction model showed an area under the receiver operating characteristic curve (AUC) of 0.56. The three surgeons had an AUC of 0.53, 0.55, and 0.59, respectively, and all surgeons showed negative percentages of cfNRIevents and IDIevents, and positive percentages of cfNRInonevents and IDIevents. This indicates that in the group of patients with postoperative complications, the prediction model performed better, whereas in the group of patients without postoperative complications, the surgeons performed better. NRIoverall was 18% for one surgeon, while the remainder of the NRIoverall, cfNRIoverall and IDIoverall scores showed small differences between surgeons and the prediction models.ConclusionPrediction models tend to overestimate the risk of any complication, whereas surgeons tend to underestimate this risk. Overall, surgeons’ estimations differ between surgeons and vary between similar to slightly better than the prediction models.

Association between the triglyceride-glucose index and stroke in middle-aged and older non-diabetic population: A prospective cohort study

Background and aimsData regarding the association between insulin resistance (IR) and stroke among the non-diabetic population is still limited and inconsistent. This study aimed to investigate the association between IR measured by the triglyceride-glucose (TyG) index and the risk of stroke among the middle-aged and elderly Chinese without diabetes. Methods and resultsA total of 17,708 middle-aged and elderly (main respondents≥45 years) individuals without diabetes were enrolled from the China Health and Retirement Longitudinal Study. Participants were divided into 4 categories according to quartiles of the TyG index. During a median follow-up of 7.00 years, a total of 305 (3.93%) incident strokes occurred. With the increase in the TyG index quartiles, stroke incidence increased substantially, compared with the Q1 group, the fully adjusted hazard ratios (HRs) were 1.64 (95% confidence interval [CI], 1.13–2.38), 1.65 (95% CI, 1.10–2.46), and 1.76 (95% CI, 1.21–2.57) for Q2, Q3, and Q4 groups, respectively. The cutoff value we determined for the TyG index was 8.28. Furthermore, the addition of the TyG index to a conventional risk model had an incremental effect on the predictive value for stroke (integrated discrimination improvement 0.17%, P = 0.0025; category-free net reclassification improvement 17.91%, P = 0.0025). ConclusionTyG index was significantly associated with a higher risk of stroke among the middle-aged and elderly non-diabetic population. Our findings indicated that the TyG index may be a good tool in the prediction of stroke risk for clinical and public health fields.

Plasma sDPP4 (Soluble Dipeptidyl Peptidase-4) and Cognitive Impairment After Noncardioembolic Acute Ischemic Stroke.

DPP4 (dipeptidyl peptidase-4) inhibitors have been proven to promote neuronal regeneration, reverse the development of cognitive deficits. However, the association of circulating soluble form (sDPP4 [soluble DPP4]) with poststroke cognitive impairment (PSCI) is unclear. We aimed to investigate the association between plasma sDPP4 levels and PSCI in patients with ischemic stroke. A total of 600 noncardioembolic stroke patients were included based on a preplanned ancillary study from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). We used the Montreal Cognitive Assessment to evaluate cognitive function at 3 months follow-up after ischemic stroke. Binary logistic regression analyses were performed to investigate the association of plasma sDPP4 levels with subsequent PSCI. We further calculated integrated discrimination improvement and category-free net reclassification improvement to investigate the incremental prognostic effect of plasma sDPP4 beyond the basic model with conventional risk factors. Plasma sDPP4 was inversely associated with PSCI after ischemic stroke, and the adjusted odds ratio (95% CI) for the highest versus lowest quartile of sDPP4 was 0.49 (0.29-0.81; P for trend=0.011). Each 1-SD increase of logarithm-transformed plasma sDPP4 concentration was associated with 17% (odds ratio, 0.83 [95% CI, 0.70-0.99]) lower risk of PSCI. Adding plasma sDPP4 to the basic model notably improved risk reclassification for PSCI, as shown by a category-free net reclassification improvement of 19.10% (95% CI, 2.52%-35.68%; P=0.03) and integrated discrimination improvement of 0.79% (95% CI, 0.13%-1.46%; P=0.02). Higher plasma sDPP4 levels were associated with decreased risk of cognitive impairment after noncardioembolic ischemic stroke.

Associations of SCORE2, circulating cardiovascular biomarkers and carotid intima-media-thickness in a population-based cohort

Abstract Background The updated SCORE2 model to estimate the 10-year risk of fatal and non-fatal cardiovascular disease (CVD) was recently introduced, which is based solely on traditional cardiovascular risk factors. Purpose We aimed to investigate the associations of SCORE2-predicted risk with four circulating cardiovascular biomarkers (high-sensitivity troponin I [hs-cTnI], N-terminal pro B-type natriuretic peptide [NT-proBNP], cystatin C-derived estimated glomerular filtration rate [eGFR] and high-sensitivity C-reactive protein [hs-CRP]) as well as mean carotid intima-media-thickness (cIMT) in a prospective, population-based German cohort. Methods In the first set of 10,000 participants, who were aged 45–74 years and recruited between 2016 and 2019, the SCORE2 model was applied in a cross-sectional manner. Individuals with prevalent CVD were excluded for this purpose. Eligible individuals were then categorized into five risk groups (&amp;lt;2.5%, 2–&amp;lt;5%, 5–&amp;lt;10%, 10–&amp;lt;15%, and ≥15%) according to SCORE2. To test for the associations of circulating biomarkers and cIMT with SCORE2, we created box plots and computed Pearson's correlation coefficients (R). Considering cIMT as a biological surrogate for incident CVD, we explored the incremental utility of circulating biomarkers to predict cIMT beyond SCORE2 by multivariable logistic regression analysis with stepwise selection of variables, quantified by Beta-coefficients per one standard deviation (SD) increase with respective 95% confidence intervals (CI). Discrimination (C-index) and category-free net reclassification improvement (NRI) for predicting mean cIMT &amp;gt;1mm were calculated for this extended model in comparison to SCORE2 alone as the reference. Results In 8,518 individuals free of CVD, median estimated 10-year risk of CVD based on SCORE2 was 6.1 (interquartile range [IQR] 3.2, 9.9) %. All four investigated biomarkers (hs-cTnI, R=0.41; NT-proBNP, R=0.21; hs-CRP, R=0.22; eGFR, R=−0.44; all P&amp;lt;0.001), and mean cIMT (R=0.42, P&amp;lt;0.001) correlated strongly with the continuous SCORE2 risk and the respective SCORE2 risk categories (Figure 1). In multivariable regression analysis, all four circulating biomarkers remained significant independent predictors of mean cIMT when added to SCORE 2 (Figure 2). When compared to SCORE2 as the reference model (C-index 0.763, 95% CI 0.742–0.784) to predict mean cIMT &amp;gt;1mm, the joint addition of all four stepwise-selected investigated biomarkers led to a small but significant improvement of discrimination (C-index 0.770, 95% CI 0.749–0.791, P&amp;lt;0.001) and reclassification yield (NRI 0.154, 95% CI 0.059–0.250, P=0.002). Conclusions All four investigated circulating biomarkers depicting different pathophysiological pathways and mean cIMT correlate strongly with the cardiovascular risk estimated by SCORE2. Circulating biomarkers may further improve CVD-risk prediction when added to the traditional cardiovascular risk factors currently considered by SCORE2. Funding Acknowledgement Type of funding sources: None.

Serum glycated albumin is associated with in-stent restenosis in patients with acute coronary syndrome after percutaneous coronary intervention with drug-eluting stents: An observational study.

BackgroundPrevious studies have confirmed the predicted value of serum glycated albumin (GA) in atherosclerotic cardiovascular disease. However, the relationship between GA and the development of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation has not been verified in patients with acute coronary syndrome (ACS).Materials and methodsIn this study, 797 patients diagnosed with ACS who underwent re-coronary angiography more than 6 months after the first successful DES-based percutaneous coronary intervention (PCI) were eventually included. Patients were categorized into two groups based on the median GA levels of 14.94%. Moreover, multivariate logistic regression analysis models and the net reclassification improvement and integrated differentiation improvement risk models were constructed to assess the relationship between the GA and DES-ISR in patients with ACS.ResultsThe GA was significantly associated with an increased risk of DES-ISR, upon adjusting for confounding factors (as nominal variate: OR 1.868, 95% CI 1.191–2.932, P = 0.007; as continuous variate: OR 1.109, 95% CI 1.040–1.183, P = 0.002). The addition of GA to a baseline risk model had an incremental effect on the predictive value for DES-ISR (AUC: GA vs. baseline model, 0.714 vs. 0.692, comparison P = 0.017; category-free net reclassification improvement (NRI) 0.080, P = 0.035; integrated discrimination improvement (IDI) 0.023, P < 0.001).ConclusionGA level was significantly associated with a high risk of DES-ISR in patients with ACS treated with PCI. Moreover, the addition of the GA to a baseline risk model has an incremental effect on the predictive potential for DES-ISR.

Triglyceride glucose index and its combination with the Get with the Guidelines-Heart Failure score in predicting the prognosis in patients with heart failure.

BackgroundHeart failure (HF) is associated with generalized insulin resistance (IR). Recent studies demonstrated that triglyceride glucose (TyG) is an effective alternative index of IR. However, the relationship between the TyG index and in-hospital mortality in patients with HF is unclear. In the present study, we aimed to clarify the association between the TyG index and in-hospital mortality in patients with HF.MethodsA retrospective study consisting of 4,411 patients diagnosed with HF from 2015 to 2018 was conducted. All-cause mortality during hospitalization was the primary endpoint. The association between the TyG index and in-hospital mortality was assessed using the logistic regression analysis.ResultsThe risk of in-hospital mortality was significantly associated with increased TyG index (OR: 1.886, 95% CI: 1.421–2.501, p < 0.001) under logistic regression with multivariable adjustment. When divided into three groups based on the TyG index, Tertile 3 demonstrated significantly higher in-hospital mortality than the other two Tertiles (OR: 2.076, 95% CI: 1.284–3.354, p = 0.001). Moreover, the TyG index improved the prediction efficiency of the Get with the Guidelines-Heart Failure (GWTG-HF) score (absolute integrated discrimination improvement = 0.006, p < 0.001; category-free net reclassification improvement = 0.075, p = 0.005). In subgroup analysis, the TyG index exhibited similar predictive performance of in-hospital mortality when groups were stratified based on type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD).ConclusionTyG is a potential index for predicting in-hospital mortality in patients with HF, independent of T2DM or CAD status. The TyG index may be combined with the GWTG-HF score to further improve its predictive efficacy.

Comparison of three frailty screening instruments for prediction of adverse outcomes among older adults in the emergency department.

To compare the predictive abilities of the FRAIL scale (FS), frailty screening questionnaire (FSQ) and clinical frailty scale (CFS) for adverse outcomes in older adults in the emergency department. In total, 317 older adults aged ≥65 years attending emergency department was screened for frailty using the FS, FSQ and CFS. Outcome measures included all-cause 28-day mortality and intensive care unit readmission. Cox proportional hazards model was used for survival comparison. Logistic regression was used to analyze risk factors for readmissions. In addition, we calculated the C-statistic, net reclassification improvement and integrated discrimination improvement to evaluate the predictive value of three scales. The prevalence of frailty was 55.2% (FS), 47.0% (FSQ) and 69.4% (CFS). Cox regression and logistic regression analysis revealed that frailty screening by FS, FSQ and CFS was an independent risk factor for all-cause 28-day mortality and 30- and 90-day readmission after adjustment. Incorporation of FS, FSQ and CFS into a basic model with other risk factors significantly improved C-statistic. For all-cause 28-day mortality, the model including FS had the highest C-statistic from 0.786 (95% confidence interval: 0.706-0.865) to 0.854 (95% confidence interval: 0.802-0.907) and the improvements in risk prediction were also confirmed by category-free net reclassification improvement and integrated discrimination improvement, suggesting FS was significantly better than CFS and FSQ. The three tools had a low predictive ability for readmission (all C-statistics <0.7). All three frailty scales showed a predictive ability for 28-day mortality and readmission but FS may be the most valid tool in the emergency department. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2022; 22: 851-856.

High triglyceride-glucose index in young adulthood is associated with incident cardiovascular disease and mortality in later life: insight from the CARDIA study

BackgroundThis study aimed to investigate the associations between the triglyceride-glucose (TyG) index in young adulthood with incident cardiovascular disease (CVD) and mortality.MethodsWe included 4,754 participants from the Coronary Artery Risk Development in Young Adults study at baseline. The TyG index was calculated as ln (fasting TG [mg/dl] × fasting glucose [mg/dl]/2), and the TyG index trajectories were identified by using the latent class growth mixture model. We evaluated the association between the baseline and trajectories of the TyG index with incident CVD events and all-cause mortality using Cox proportional hazards regression analysis. The added value of the TyG index included in pooled cohort equations for CVD prediction was also analyzed.ResultsAmong 4754 participants (mean age 24.72 years, 45.8% male, 51.2% black), there were 158 incident CVD events and 246 all-cause mortality during a median 25 years follow-up. After adjusting for multiple confounding variables, each one-unit increase in the TyG index was associated with a 96% higher CVD risk (hazard ratio [HR] 1.96, 95% confidence interval [CI] 1.44–2.66) and a 85% higher all-cause mortality risk (HR 1.85, 95% CI 1.45–2.36). Three distinct trajectories of the TyG index along the follow-up duration were identified: low (44.0%), moderate (45.5%), and high (10.5%). Compared with those participants in the low TyG index trajectory group, those in the high TyG index trajectory group had a greater risk of CVD events (HR 2.35, 95% CI 1.34–4.12) and all-cause mortality (HR 3.04, 95% CI 1.83–5.07). The addition of baseline TyG index to pooled cohort equations for CVD improved the C-statistics (P < 0.001), integrated discrimination improvement value (P < 0.001), and category-free net reclassification improvement value (P = 0.003).ConclusionsHigher baseline TyG index levels and higher long-term trajectory of TyG index during young adulthood were significantly associated with an increased risk of incident CVD events and all-cause mortality in later life.

Predictive ability of the total score of the Kihon checklist for the incidence of functional disability in older Japanese adults: An 8-year prospective study.

To investigate the association between the total score of the Kihon checklist (t-KCL score) and functional disability over an 8-year follow-up period, and to examine whether the t-KCL score in the basic model with risk factors contributes to the incremental predictive ability for functional disability among older adults. We followed 2209 older adults aged ≥65 years without functional disability at baseline. The t-KCL score was determined using a baseline survey questionnaire. Functional disability was defined based on information from long-term care certifications. The association between the t-KCL score and functional disability was examined using the Cox proportional hazards model. The incremental predictive ability of the t-KCL score for functional disability was evaluated by the difference of the C-statistic, category-free net reclassification improvement (NRI), and integrated discrimination improvement (IDI). The median follow-up period was 7.8 years, and 557 participants developed functional disability. The adjusted hazard ratio (95% confidence interval [CI]) of functional disability for a 1-point increase of the t-KCL score was 1.08 (1.06-1.10). Adding the t-KCL score to the basic model significantly improved the C-statistic (95% CI) from 0.747 (0.728-0.768) to 0.760 (0.741-0.781). When the t-KCL score was added to the basic model, the NRI and IDI were 0.187 (95% CI: 0.095-0.287) and 0.020 (95% CI: 0.012-0.027), respectively. The t-KCL score had an independent positive association with functional disability over an 8-year follow-up. Furthermore, adding the t-KCL score to the basic model improved the predictive ability for functional disability. Geriatr Gerontol Int 2022; 22: 723-729.

Predictive Ability of the Five-time Chair Stand Test for Postoperative Pneumonia after Minimally Invasive Esophagectomy for Esophageal Cancer

The revised sarcopenia guidelines proposed handgrip strength (HGS) and five-time chair stand test (5-CST) as the primary parameters of muscle function. HGS and 5-CST are associated with pulmonary function among community-dwelling people, although few reports have described an association between these parameters and surgical outcomes in carcinomas. We examined the predictive ability of 5-CST for postoperative pneumonia after minimally invasive esophagectomy (MIE) compared with that of HGS. This retrospective, single-center, observational study evaluated 222 male patients who underwent MIE for esophageal cancer between February 2018 and October 2020. Sarcopenia parameters included 5-CST, HGS, and skeletal muscle index. Postoperative pneumonia predictors were determined by using multivariate logistic regression analysis. We assessed the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) to analyze the predictive ability of 5-CST and HGS. MIE was performed for squamous cell carcinoma (n = 179), adenocarcinoma (n = 38), and other cancers (n = 5). Forty-nine (22.1%) patients developed postoperative pneumonia. Multivariate logistic regression showed that age (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.01-1.10; p = 0.027), 5-CST (OR, 1.19; 95% CI 1.00-1.40; p = 0.046), and recurrent laryngeal nerve palsy (RLNP) (OR, 3.37; 95% CI 1.60-7.10; p = 0.001) significantly predicted postoperative pneumonia. Category-free NRI and IDI showed that adding 5-CST in the prediction model with age and RLNP resulted in significantly greater reclassification and discrimination abilities than did HGS. The 5-CST significantly predicted postoperative pneumonia after MIE. NRI and IDI analyses suggested that 5-CST had significantly better predictive ability for postoperative pneumonia than did HGS.

Prognostic value of plasma high mobility group box 1 protein and histone H3 levels in patients with disseminated intravascular coagulation: a multicenter prospective cohort study

BackgroundWe compared the prognostic value of plasma high mobility group box 1 protein (HMGB1) and histone H3 levels with the International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) scores for 28-day in-hospital mortality in patients with DIC caused by various underlying diseases.MethodsWe conducted a multicenter prospective cohort study including two hematology departments, four emergency departments, and one general medicine department in Japan, between August 2017 and July 2021. We included patients diagnosed with DIC by the ISTH DIC scoring system.ResultsOverall, 104 patients were included: 50 with hematopoietic disorders, 41 with infections, and 13 with the other diseases. The 28-day in-hospital mortality rate was 21%. The receiver operator characteristic (ROC) curve showed that a DIC score of 6 points, plasma HMGB1 level of 8 ng/mL, and plasma histone H3 level of 2 ng/mL were the optimal cutoff points. The odds ratios of more than these optimal cutoff points of the DIC score, plasma HMGB1, and histone H3 levels were 1.58 (95% confidence interval [CI]: 0.60 to 4.17, p = 0.36), 5.47 (95% CI: 1.70 to 17.6, p = 0.004), and 9.07 (95% CI: 2.00 to 41.3, p = 0.004), respectively. The area under the ROC curve of HMGB1 (0.74, 95% CI: 0.63 to 0.85) was better than that of the ISTH DIC scores (0.55, 95% CI: 0.43 to 0.67, p = 0.03), whereas that of histone H3 was not (0.71, 95% CI: 0.60 to 0.82, p = 0.07). Calibration and net reclassification plots of HMGB1 identified some high-risk patients, whereas the ISTH DIC scores and histone H3 did not. The category-free net reclassification improvement of HMGB1 was 0.45 (95% CI: 0.01 to 0.90, p = 0.04) and that of histone H3 was 0.37 (95% CI: − 0.05 to 0.78, p = 0.08).ConclusionsPlasma HMGB1 levels have a prognostic value for mortality in patients with DIC. This finding may help physicians develop treatment strategies.

Novel Usefulness of Krebs von den Lungen 6 (KL-6) with Hemoglobin and Lactate Dehydrogenase for Assessing Bone Marrow Fibrosis.

Bone marrow fibrosis (BMF) is manually assessed by reticulin and trichrome stain of bone marrow (BM) biopsy and graded on a semi-quantitative scale. Krebs von den Lungen 6 (KL-6) and Mac-2 binding protein glycosylation isomer (M2BPGi) are known to be associated with lung and liver fibrosis, respectively. We explored the usefulness of KL-6 and M2BPGi to assess BMF. A total of 250 patients who underwent BM biopsy with hematologic or non-hematologic diseases were included, and 42 patients with lung and liver diseases were excluded. The patients’ data, including age, sex, diagnosis, white blood cell, hemoglobin (Hb), platelet, and lactate dehydrogenase (LDH) were collected. Measured KL-6 and M2BPGi levels were compared with reticulin grade (RG) (grade 0–3). KL-6 levels were significantly elevated with an increase in RG, but M2BPGi did not show a significant difference. Hb, LDH, or KL-6 were independent predictors for BMF (odds ratio: 1.96, 2.26, 2.91, respectively), but showed poor predictive ability (area under the curve [AUC] 0.62, 0.61, 0.60, respectively). The combination of Hb, LDH, and KL-6 showed a significantly improved predictive ability for BMF (AUC 0.73; integrated discrimination improvement 0.057; category-free net reclassification improvement 0.625). This is the first study to evaluate the usefulness of KL-6 for assessing BMF. The combination of Hb, LDH, and KL-6 would be an objective and relevant biomarker approach and be applied to risk stratification for BMF.

Prediction models for the risk of total knee replacement: development and validation using data from multicentre cohort studies.

Few prognostic prediction models for total knee replacement are available, and the role of radiographic findings in predicting its use remains unclear. We aimed to develop and validate predictive models for total knee replacement and to assess whether adding radiographic findings improves predictive performance. We identified participants with recent knee pain (in the past 3 months) in the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI). The baseline visits of MOST were initiated in 2003 and of OAI were initiated in 2004. We developed two predictive models for the risk of total knee replacement within 60 months of follow-up by fitting Cox proportional hazard models among participants in MOST. The first model included sociodemographic and anthropometric factors, medical history, and clinical measures (referred to as the clinical model). The second model added radiographic findings into the predictive model (the radiographic model). We evaluated each model's discrimination and calibration performance and assessed the incremental value of radiographic findings using both category-free net reclassification improvement (NRI) and integrated discrimination improvement (IDI). We tuned the models and externally validated them among participants in OAI. We included 2658 participants from MOST (mean age 62·4 years [SD 8·1], 1646 [61·9%] women) in the training dataset and 4060 participants from OAI (mean age 60·9 years [9·1], 2379 [58·6%] women) in the validation dataset. 290 (10·9%) participants in the training dataset and 174 (4·3%) in the validation dataset had total knee replacement. The retained predictive variables included in the clinical model were age, sex, race, history of knee arthroscopy, frequent knee pain, current use of analgesics, current use of glucosamine, body-mass index, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, and the most predictive factors were age, race, and WOMAC pain score. The retained predictive variables in the radiographic model were age, sex, race, frequent knee pain, current use of analgesics, WOMAC pain score, and Kellgren-Lawrence grade, and the most predictive factors were Kellgren-Lawrence grade, race, and age. The C-statistic was 0·79 (95% CI 0·76-0·81) for the clinical model and 0·87 (0·85-0·99) for the radiographic model in the training dataset. The calibration slope was 0·95 (95% CI 0·86-1·05) and 0·96 (0·87-1·04), respectively. Adding radiograph findings significantly improved predictive performance with an NRI of 0·43 (95% CI 0·38-0·50) and IDI of 0·14 (95% CI: 0·10-0·18). Both models, with tuned coefficients, showed a good predictive performance among participants in the validation dataset. The risk of total knee replacement can be predicted based on common risk factors with good discrimination and calibration. Additionally, adding radiographic findings of knee osteoarthritis into the model substantially improves its predictive performance. National Natural Science Foundation of China, National Key Research and Development Program, and Beijing Municipal Science & Technology Commission.

Left Ventricular Structure is Associated with Postoperative Death After Coronary Artery Bypass Grafting in Patients with Heart Failure with Reduced Ejection Fraction

BackgroundThe relationship between abnormal left ventricular (LV) structure and adverse outcomes has been confirmed in diverse patient groups in previous studies. However, it remains uncertain whether LV structure has predictive implications in heart failure with reduced ejection fraction (HFrEF) patients with coronary artery bypass grafting (CABG).MethodsThis study retrospectively enrolled patients who had HFrEF and underwent CABG between January 2013 and July 2019. According to LV hypertrophy (LVH) and LV enlargement (LVE) assessed by echocardiography, patients were classified into four LV structure types: (-)LVH/(-)LVE, (+)LVH/(-)LVE, (-)LVH/(+)LVE, and (+)LVH/(+)LVE.ResultsA total of 435 consecutive patients (mean age: 59.4 ± 9.6 years; 14.9% female) were enrolled in the present study. Examined independently, either LVH (p < 0.001) or LVE (p < 0.001) was independently associated with postoperative mortality in multivariate analysis. When LVH and LVE were analyzed in combination, the risk of mortality after CABG was lowest in (-)LVH/(-)LVE and increased with (+)LVH/(-)LVE (odds ratio [OR]: 7.525; 95% confidence interval [CI]: 1.827–30.679, p = 0.004), (-)LVH/(+)LVE (OR: 7.253; 95% CI: 1.950–27.185, p = 0.003), and (+)LVH/(+)LVE (OR: 9.547; 95% CI: 2.726–34.805, p < 0.001), independent of other risk factors. Adding LV structural types to the baseline model gained an incremental effect on the predictive value for postoperative mortality (AUC: baseline model, 0.838 vs baseline model + LV structural types, 0.901, p for comparison = 0.010; category‐free net reclassification improvement (NRI): 0.764, p < 0.001; integrated discrimination improvement (IDI): 0.061, p = 0.007).ConclusionLVH and LVE were associated with an increased risk of postoperative mortality after CABG in patients with HFrEF. Categorizing LV structural patterns with LVH and LVE contributes to risk stratification and provides incremental predictive ability. Routine echocardiographic assessment of LVH and LVE is needed in clinical practice.

Computed Tomography-Derived Skeletal Muscle Radiodensity Is an Early, Sensitive Marker of Age-Related Musculoskeletal Changes in Healthy Adults.

BackgroundA decrease in computed tomography (CT)-derived skeletal muscle radiodensity (SMD) reflects age-related ectopic fat infiltration of muscle, compromising muscle function and metabolism. We investigated the age-related trajectory of SMD and its association with vertebral trabecular bone density in healthy adults.MethodsIn a cohort of healthy adult kidney donors aged 19 to 69 years (n=583), skeletal muscle index (SMI, skeletal muscle area/height2), SMD, and visceral-to-subcutaneous fat (V/S) ratio were analyzed at the level of L3 from preoperative CT scans. Low bone mass was defined as an L1 trabecular Hounsfield unit (HU) <160 HU.ResultsL3SMD showed constant decline from the second decade (annual change –0.38% and –0.43% in men and women), whereas the decline of L3SMI became evident only after the fourth decade of life (–0.37% and –0.18% in men and women). One HU decline in L3SMD was associated with elevated odds of low bone mass (adjusted odds ratio, 1.07; 95% confidence interval, 1.02 to 1.13; P=0.003), independent of L3SMI, age, sex, and V/S ratio, with better discriminatory ability compared to L3SMI (area under the receiver-operating characteristics curve 0.68 vs. 0.53, P<0.001). L3SMD improved the identification of low bone mass when added to age, sex, V/S ratio, and L3SMI (category-free net reclassification improvement 0.349, P<0.001; integrated discrimination improvement 0.015, P=0.0165).ConclusionL3SMD can be an early marker for age-related musculoskeletal changes showing linear decline throughout life from the second decade in healthy adults, with potential diagnostic value for individuals with low bone mass.