Development and validation of multimorbidity index predicting mortality among Chinese older adults

This study aimed to construct a multimorbidity index among Chinese older adults. Participants aged 65-84 years (n=11,757) from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Fourteen self-reported chronic conditions were assessed at baseline. Outcome was all-cause mortality within five-year follow-up. We used restrictive association rules mining to identify the patterns of multiple chronic conditions associated with mortality. The weights of conditions and disease combinations were assigned using logistic regression adjusted by age and sex in training set. Multimorbidity index (MI) with individual diseases and multimorbidity index incorporating disease combinations (MIDC) were developed. We compared the performance of MI and MIDC with condition count and XGBoost algorithm in the validation set. There were no significant differences of c-statistics between condition count (0.687) and MI (0.692) or MIDC (0.689). The c-statistic of XGBoost algorithm (0.675) was the lowest among all models. The Integrated Discrimination Improvement (IDI) and categorical Net Reclassification Index (NRI) for MI (IDI: 0.01, P < 0.001; NRI: 0.01, P = 0.127), MIDC (IDI: 0.004, p = 0.002; NRI: 0.02, P = 0.033), and XGBoost model (IDI: 0.02, P < 0.001; NRI: 0.03, P = 0.004) were significantly positive compared with condition count. However, no significant differences for IDI and NRI were observed between MI and MIDC. Among Chinese older adults, weighted multimorbidity index with individual disease can better predict five-year mortality risk over condition count. There was little improvement in the predictive performance of the index after considering the joint effects of disease combinations.

A 3-Biomarker 2-Point-Based Risk Stratification Strategy in Acute Heart Failure

Introduction and Objectives: Most multi-biomarker strategies in acute heart failure (HF) have only measured biomarkers in a single-point time. This study aimed to evaluate the prognostic yielding of NT-proBNP, hsTnT, Cys-C, hs-CRP, GDF15, and GAL-3 in HF patients both at admission and discharge.Methods: We included 830 patients enrolled consecutively in a prospective multicenter registry. Primary outcome was 12-month mortality. The gain in the C-index, calibration, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) was calculated after adding each individual biomarker value or their combination on top of the best clinical model developed in this study (C-index 0.752, 0.715–0.789) and also on top of 4 currently used scores (MAGGIC, GWTG-HF, Redin-SCORE, BCN-bioHF).Results: After 12-month, death occurred in 154 (18.5%) cases. On top of the best clinical model, the addition of NT-proBNP, hs-CRP, and GDF-15 above the respective cutoff point at admission and discharge and their delta during compensation improved the C-index to 0.782 (0.747–0.817), IDI by 5% (p < 0.001), and NRI by 57% (p < 0.001) for 12-month mortality. A 4-risk grading categories for 12-month mortality (11.7, 19.2, 26.7, and 39.4%, respectively; p < 0.001) were obtained using combination of these biomarkers.Conclusion: A model including NT-proBNP, hs-CRP, and GDF-15 measured at admission and discharge afforded a mortality risk prediction greater than our clinical model and also better than the most currently used scores. In addition, this 3-biomarker panel defined 4-risk categories for 12-month mortality.

Delayed neurological improvement is predictive to long-term clinical outcome on endovascular thrombectomy patients

Objectives This study aims at exploring the 3-month outcome predicting ability of delayed neurological improvement and the cause of delayed neurological improvement. Materials and methods Early neurological improvement and delayed neurological improvement were calculated to represent the neurological improvements. Good functional outcome was defined as a 90-day modified Rankin Scale score 0–2. We used multivariant logistic regression to explore the influential factors of good functional outcome as well as delayed neurological improvement. We applied net reclassification improvement and integrated discrimination improvement to assess the quantitative improvement of the predictive model. Results Early neurological improvement was observed in 50 (23%) patients and delayed neurological improvement exhibited in 67 (30%) patients. Early neurological improvement and delayed neurological improvement were both independent predictive factors to good functional outcome. In the basic model (adjusted for age, admission glucose level, baseline National Institute of Health Stroke Scale, and complications and number of retrieval attempts), early neurological improvement and delayed neurological improvement statistically improved the predictive ability (early neurological improvement: net reclassification improvement = 0.34, 95% confidence interval, 95% confidential interval (0.06, 0.69); integrated discrimination improvement = 0.05, p < 0.001; delayed neurological improvement: net reclassification improvement = 0.79, 95% confidential interval (0.47, 1.12); integrated discrimination improvement = 0.14, p < 0.001) delayed neurological improvement could predict clinical outcomes more accurately than early neurological improvement (early neurological improvement vs. delayed neurological improvement: integrated discrimination improvement = 0.09, p < 0.001). Moreover, delayed neurological improvement was affected by hypertension (odds ratio = 0.40, 95% CI (0.18, 0.88), p = 0.02), early neurological improvement (odds ratio = 20.10, 95% confidential interval (8.24, 19.02), p < 0.001), number of retrieval attempts (odds ratio = 0.39, 95% confidential interval (0.24, 0.66), p < 0.001), and complication (odds ratio = 0.25, 95% confidential interval (0.12, 0.54), p < 0.001). Conclusions Delayed neurological improvement could predict clinical outcomes more accurately than early neurological improvement. Hypertension, early neurological improvement, numbers of retrieval attempts, and complications were all predicting factors to delayed neurological improvement.

Polygenic Risk Score to Identify Subclinical Coronary Heart Disease Risk in Young Adults

Background: Polygenic risk scores (PRS) may enhance risk stratification for coronary heart disease among young adults. Whether a coronary heart disease PRS improves prediction beyond modifiable risk factors in this population is not known. Methods: Genotyped adults aged 18 to 35 years were selected from the CARDIA study (Coronary Artery Risk Development in Young Adults; n=1132) and FOS (Framingham Offspring Study; n=663). Systolic blood pressure, total and HDL (high-density lipoprotein) cholesterol, triglycerides, smoking, and waist circumference or body mass index were measured at the visit 1 exam of each study, and coronary artery calcium, a measure of coronary atherosclerosis, was assessed at year 15 (CARDIA) or year 30 (FOS). A previously validated PRS for coronary heart disease was computed for each subject. The C statistic and integrated discrimination improvement were used to compare Improvements in prediction of elevated coronary artery calcium between models containing the PRS, risk factors, or both. Results: There were 62 (5%) and 93 (14%) participants with a coronary artery calcium score >20 (CARDIA) and >300 (FOS), respectively. At these thresholds, the C statistic changes of adding the PRS to a risk factor–based model were 0.015 (0.004–0.028) and 0.020 (0.001–0.039) in CARDIA and FOS, respectively. When adding risk factors to a PRS-based model, the respective changes were 0.070 (0.033–0.109) and 0.051 (0.017–0.079). The integrated discrimination improvement, when adding the PRS to a risk factor model, was 0.027 (−0.006 to 0.054) in CARDIA and 0.039 (0.0005–0.072) in FOS. Conclusions: Among young adults, a PRS improved model discrimination for coronary atherosclerosis, but improvements were smaller than those associated with modifiable risk factors.

Role of handgrip strength in predicting new-onset diabetes: findings from the survey of health, ageing and retirement in Europe

Background Diabetes is a major concern for the global health burden. This study aimed to investigate the relationship between handgrip strength (HGS) and the risk of new-onset diabetes and to compare the predictive abilities between relative HGS and dominant HGS. Methods This longitudinal study used data from the Survey of Health, Ageing and Retirement in Europe (SHARE), including 66,100 European participants aged 50 years or older free of diabetes at baseline. The Cox proportional hazard model was used to analyze the relationship between HGS and diabetes, and the Harrell’s C index, net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to evaluate the predictive abilities of different HGS expressions. Results There were 5,661 diabetes events occurred during follow-up. Compared with individuals with lowest quartiles, the hazard ratios (95 % confidence intervals) of the 2nd-4th quartiles were 0.88 (0.81–0.94), 0.82 (0.76–0.89) and 0.85 (0.78–0.93) for dominant HGS, and 0.95 (0.88–1.02), 0.82 (0.76–0.89) and 0.60 (0.54–0.67) for relative HGS. After adding dominant HGS to an office-based risk score (including age, gender, body mass index, smoking, and hypertension), the incremental values of the Harrell’s C index, NRI, IDI of relative HGS were all slightly higher than those of dominant HGS in both training and validation sets. Conclusions Our findings supported that HGS was an independent predictor of new-onset diabetes in the middle-aged and older European population. Moreover, relative HGS exhibited a slightly higher predictive ability than dominant HGS.

FGF21/adiponectin ratio predicts deterioration in glycemia: a 4.6-year prospective study in China

Background The fibroblast growth factor (FGF) 21-adiponectin pathway is involved in the regulation of insulin resistance. However, the relationship between the FGF21-adiponectin pathway and type 2 diabetes in humans is unclear. Here, we investigated the association of FGF21/adiponectin ratio with deterioration in glycemia in a prospective cohort study. Methods We studied 6361 subjects recruited from the prospective Shanghai Nicheng Cohort Study in China. The association between baseline FGF21/adiponectin ratio and new-onset diabetes and incident prediabetes was evaluated using multiple logistic regression analysis. Results At baseline, FGF21/adiponectin ratio levels increased progressively with the deterioration in glycemic control from normal glucose tolerance to prediabetes and diabetes (p for trend < 0.001). Over a median follow-up of 4.6 years, 195 subjects developed new-onset diabetes and 351 subjects developed incident prediabetes. Elevated baseline FGF21/adiponectin ratio was a significant predictor of new-onset diabetes independent of traditional risk factors, especially in subjects with prediabetes (odds ratio, 1.367; p = 0.001). Moreover, FGF21/adiponectin ratio predicted incident prediabetes (odds ratio, 1.185; p = 0.021) while neither FGF21 nor adiponectin were independent predictors of incident prediabetes (both p > 0.05). Furthermore, net reclassification improvement and integrated discrimination improvement analyses showed that FGF21/adiponectin ratio provided a better performance in diabetes risk prediction than the use of FGF21 or adiponectin alone. Conclusions FGF21/adiponectin ratio independently predicted the onset of prediabetes and diabetes, with the potential to be a useful biomarker of deterioration in glycemia.

Development and Validation of a Prognostic Nomogram Based on the Systemic Immune-Inflammation Index for Resectable Gallbladder Cancer to Predict Survival and Chemotherapy Benefit

ObjectivesTo investigate the prognostic significance of the systemic immune-inflammation index (SII) in patients after radical cholecystectomy for gallbladder cancer (GBC) using overall survival (OS) as the primary outcome measure.MethodsBased on data from a multi-institutional registry of patients with GBC, significant prognostic factors after radical cholecystectomy were identified by multivariate Cox proportional hazards model. A novel staging system was established, visualized as a nomogram. The response to adjuvant chemotherapy was compared between patients in different subgroups according to the novel staging system.ResultsOf the 1072 GBC patients enrolled, 691 was randomly selected in the discovery cohort and 381 in the validation cohort. SII&gt;510 was found to be an independent predictor of OS (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.42-2.54). Carbohydrate antigen 199(CA19-9), tumor differentiation, T stage, N stage, margin status and SII were involved in the nomogram. The nomogram showed a superior prediction compared with models without SII (1-, 3-, 5-year integrated discrimination improvement (IDI):2.4%, 4.1%, 5.4%, P&lt;0.001), and compared to TNM staging system (1-, 3-, 5-year integrated discrimination improvement (IDI):5.9%, 10.4%, 12.2%, P&lt;0.001). The C-index of the nomogram in predicting OS was 0.735 (95% CI 0.683-0.766). The novel staging system based on the nomogram showed good discriminative ability for patients with T2 or T3 staging and with negative lymph nodes after R0 resection. Adjuvant chemotherapy offered significant survival benefits to these patients with poor prognosis.ConclusionsSII was an independent predictor of OS in patients after radical cholecystectomy for GBC. The new staging system identified subgroups of patients with T2 or T3 GBC with negative lymph nodes who benefited from adjuvant chemotherapy.Clinical Trial RegistrationClinicalTrials.gov, identifier (NCT04140552).

Comparison of metabolic phenotypes and BMI as indicators of recurrent stroke in Chinese hospitalized stroke patients: a retrospective study

Background Metabolic status and body mass index (BMI) are known as apparent risk factors of recurrent stroke, but which one is more likely related to recurrent stroke remains uncertain. This study aimed to compare the metabolic phenotypes and BMI as indicators of recurrent stroke in Chinese hospitalized stroke patients. Methods In this retrospective population-based study, 856 hospitalized stroke patients from the Third Affiliated Hospital of Soochow University were enrolled. Recurrent stroke was defined as newly-onset stroke patients with a history of previous stroke. Metabolic phenotypes were based on Adult Treatment Panel III criteria. BMI ≥ 25kg/m2 was defined as obesity. Results Among the hospitalized stroke patients, the prevalence of recurrent stroke was 21.9%. Metabolic phenotypes rather than BMI were significantly associated with recurrent stroke. Compared with metabolically healthy patients, metabolically unhealthy ones had 72% (odds ratio [OR] = 1.72, 95% confidence interval [CI] 1.01–2.68) increased recurrent stroke, regardless of BMI and other confounding factors. Whereas, no statistical association between BMI and recurrent stroke were found. Metabolic status improved risk prediction of recurrent stroke when adding to conventional risk factors (net reclassification index 17.6%, P = 0.0047; integrated discrimination improvement 0.7%, P = 0.014), while BMI did not. Conclusions Recurrent stroke was likely associated with poor metabolic status rather than with BMI, suggesting that controlling metabolic abnormalities could be an important method for recurrent stroke prevention.

Choice of CTO scores to predict procedural success in clinical practice. A comparison of 4 different CTO PCI scores in a comprehensive national registry including expert and learning CTO operators

Background We aimed to compare the performance of the recent CASTLE score to J-CTO, CL and PROGRESS CTO scores in a comprehensive database of percutaneous coronary intervention of chronic total occlusion procedures. Methods Scores were calculated using raw data from 1,342 chronic total occlusion procedures included in REBECO Registry that includes learning and expert operators. Calibration, discrimination and reclassification were evaluated and compared. Results Mean score values were: CASTLE 1.60±1.10, J-CTO 2.15±1.24, PROGRESS 1.68±0.94 and CL 2.52±1.52 points. The overall percutaneous coronary intervention success rate was 77.8%. Calibration was good for CASTLE and CL, but not for J-CTO or PROGRESS scores. Discrimination: the area under the curve (AUC) of CASTLE (0.633) was significantly higher than PROGRESS (0.557) and similar to J-CTO (0.628) and CL (0.652). Reclassification: CASTLE, as assessed by integrated discrimination improvement, was superior to PROGRESS (integrated discrimination improvement +0.036, p<0.001), similar to J-CTO and slightly inferior to CL score (– 0.011, p = 0.004). Regarding net reclassification improvement, CASTLE reclassified better than PROGRESS (overall continuous net reclassification improvement 0.379, p<0.001) in roughly 20% of cases. Conclusion Procedural percutaneous coronary intervention difficulty is not consistently depicted by available chronic total occlusion scores and is influenced by the characteristics of each chronic total occlusion cohort. In our study population, including expert and learning operators, the CASTLE score had slightly better overall performance along with CL score. However, we found only intermediate performance in the c-statistic predicting chronic total occlusion success among all scores.

Selected nasogastric lavage in patients with nonvariceal upper gastrointestinal bleeding

Background Risk stratification before endoscopy is crucial for proper management of patients suspected as having upper gastrointestinal bleeding (UGIB). There is no consensus regarding the role of nasogastric lavage for risk stratification. In this study, we investigated the usefulness of nasogastric lavage to identify patients with UGIB requiring endoscopic examination. Methods From January 2017 to December 2018, patients who visited the emergency department with a clinical suspicion of UGIB and who underwent nasogastric lavage before endoscopy were eligible. Patients with esophagogastric variceal bleeding were excluded. The added predictive ability of nasogastric lavage to the Glasgow–Blatchford score (GBS) was estimated using category-free net reclassification improvement and integrated discrimination improvement. Results Data for 487 patients with nonvariceal UGIB were analyzed. The nasogastric aspirate was bloody in 67 patients (13.8 %), coffee-ground in 227 patients (46.6 %), and clear in 193 patients (39.6 %). The gross appearance of the nasogastric aspirate was associated with the presence of UGIB. Model comparisons showed that addition of nasogastric lavage findings to the GBS improved the performance of the model to predict the presence of UGIB. Subgroup analysis showed that nasogastric lavage improved the performance of the prediction model in patients with the GBS ≤ 11, whereas no additive value was found when the GBS was greater than 11. Conclusions Nasogastric lavage is useful for predicting the presence of UGIB in a subgroup of patients, while its clinical utility is limited in high-risk patients with a GBS of 12 or more.