Objective:To explore the relationship between serum urea nitrogen to creatinine ratio (UCR) and cardiac function in elderly patients with severe pneumonia.Methods:A prospective selection of 100 elderly patients with severe pneumonia admitted to Group Wanbei General Hospital of Wanbei Coal Power from May 2020 to April 2023 was conducted as the case group, and an additional 50 patients who underwent health examinations in the hospital during the same period were selected as the control group. Serum urea nitrogen (BUN), creatinine (Cr), UCR value, myocardial injury indexes: cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-ProBNP), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), and cardiac function indexes: left ventricular ejection fraction (LVEF), cardiac output (CO), stroke volume (SV) and cardiac output index (CI) were detected in the two groups. The patients in the case group were divided into two subgroups based on the occurrence of heart failure during hospitalization: the heart failure subgroup and the normal heart function subgroup. The serum UCR, myocardial injury and cardiac function indexes were compared between the case group and the control group. The general data, myocardial injury and cardiac function indexes were compared between the heart failure group and the normal heart function group. The relationship between serum UCR and cardiac function in patients with severe pneumonia was analyzed by bivariate Pearson correlation. Logistic regression model was used to analyze the influencing factors of cardiac dysfunction in patients with severe pneumonia, and using receiver operating characteristic (ROC) curve to analyze the value of serum UCR in predicting cardiac dysfunction in patients with severe pneumonia.Results:The values of BUN, UCR, cTnI, NT-ProBNP, CK and CK-MB in the case group were higher than those in the control group: (8.72 ± 1.14) μmol/L vs. (6.41 ± 0.76) μmol/L, 125.00 ± 19.75 vs. 86.12 ± 12.02, 0.04 (0.03, 0.05) μg/L vs. 0.04 (0.03, 0.05) μg/L, (185.49 ± 20.59) ng/L vs. (147.76 ± 20.85) ng/L, (104.78 ± 14.98) U/L vs. (99.33 ± 15.07) U/L, (31.59 ± 6.23) U/L vs. (29.13 ± 5.76) U/L. The values of Cr, LVEF, CO, SV and CI in the observation group were lower than those in the control group: (70.22 ± 5.76) μmol/L vs. (74.75 ± 5.12) μmol/L, (59.72 ± 2.41)% vs. (61.78 ± 2.16)%, (3.93 ± 0.43) L/min vs. (4.53 ± 0.62) L/min, (59.82 ± 6.12) ml vs. (62.23 ± 7.22) ml, (2.95 ± 0.30) L/(min·m 2) vs. (3.06 ± 0.33) L/(min·m 2), with a statistical significant difference ( P<0.05). In the case group, 21 patients had heart failure during hospitalization, accounting for 21.00%. The pneumonia severity index score on admission in the heart failure subgroup was higher than that in the normal heart function subgroup: (172.76 ± 9.18) points vs. (168.24 ± 8.81) points. The serum BUN and UCR levels were higher than those in the normal heart function subgroup: (9.51 ± 0.79) mmol/L vs. (8.51 ± 1.13) mmol/L, 141.62 ± 9.89 vs. 120.59 ± 19.39. The serum Cr level was lower than that in the normal heart function subgroup: (67.26 ± 5.34) μmol/L vs. (71.00 ± 5.65) μmol/L, with a significant statistical difference ( P<0.05). There was no significant statistical difference in other data between the two subgroups ( P>0.05). The bivariate Pearson correlation analysis showed that serum UCR was positively correlated with cardiac function indicators cTnI, NT-ProBNP, CK and CK-MB levels in severe pneumonia ( r = 0.40, 0.27, 0.32 and 0.33; P<0.05), and negatively correlated with LVEF, CO, SV and CI levels ( r = - 0.37, - 0.21, - 0.25 and - 0.21; P<0.05). Univariate and multivariate Logistic regression analysis showed that the occurrence of cardiac dysfunction in elderly patients with severe pneumonia may be related to the pneumonia severity index score on admission and the abnormal expression of serum BUN, UCR and Cr levels ( P<0.05). ROC curve analysis found that the area under the curve for predicting the occurrence of cardiac dysfunction during hospitalization in severe pneumonia patients with serum UCR on admission was 0.85 (95% CI 0.77 to 0.92), which had certain predictive value. Conclusions:Elderly patients with severe pneumonia are accompanied by a certain degree of elevated serum UCR levels, and the higher the serum UCR level, the more severe the cardiac function damage and the greater the risk of cardiac dysfunction.

Objective:To perform a prospective cohort study to identify individual susceptibility of glucocorticoid (GC) -associated osteonecrosis of the femoral head (GA-ONFH) and their clinical and genetic risk factors. Methods:The present prospective cohort study enrolled patients who received their first GC therapy between July 2015 and January 2018 at Zhongshan Hospital. All patients did not receive any GC treatment before enrollment. Further, they planned to start GC treatment with the dose (equivalent prednisone) of ≥30 mg/d, lasted ≥3 weeks, or pulse dose ≥200 mg/d, lasted ≥3 d. Blood samples were collected before GC treatment to evaluate bone metabolism and its released factors. Hip MRI was performed at the 1st, 3rd, 6th, 12th and 24th month to diagnose GA-ONFH. All patients were followed-up for ≥2 years. The endpoint was regarded as diagnosis of GA-ONFH or completion of 2 years follow-up. Lasso regression was performed to determine which clinical features were associated with GA-ONFH. A nested case-control sub-cohort (A, n=12) was established prospectively based on the main cohort by 1∶1 matching. Whole exome sequencing was performed to screen differential and functional candidate single nucleotide polymorphisms and insertion-deletions (SNP/InDels). Another sub-cohort (B, n=50) was constructed retrospectively in patients with GA-ONFH and non-ONFH patients received standard high dose GC treatment for more than two years. The candidate SNP/InDels were verified by Sanger sequencing based on the patients from sub-cohort B. Results:A total of 96 patients were enrolled of which 88 of them (32 males and 56 females, mean age 42.30 years) completed follow-up. Eight cases (9.1%) were diagnosed with GA-ONFH. The median time from the start of GC therapy to the diagnosis of ONFH was 53.00(34.00,13.50) days. The baseline characteristics, such as age, sex and body mass index, indicated no significant difference between the ONFH group and the non-ONFH group. The cumulative GC dose of the ONFH patients in the first month was higher than that of non-ONFH [32.74(29.55, 47.05) mg/kg vs. 24.00(21.10, 29.45) mg/kg, Z=-2.410, P=0.016]. However, there was no significant difference of patients who underwent pulse therapy (37.5% vs. 10.0%, adjusted χ 2=2.829, P=0.093). The ratio of serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) in patients with ONFH was higher than that in non-ONFH group before GC use [0.95(0.80, 1.50) vs. 0.70(0.60, 0.80), Z=-2.875, P=0.000]. Due to the multicollinearity, Lasso regression model was performed to reduce overfitting. All variables were included in the model. The results suggested that higher ApoB/ApoA1 ratio, lower serum β-c-terminal telopeptide (β-CTX) and higher cumulative GC dose in the first month were the top three risk factors of GA-ONFH. This model had an accuracy of 0.982 in internal validation. Seven differential candidate SNP/InDels were found by whole exome sequencing of sub-cohort A. We further verified these SNP/InDels in sub-cohort B. The patients with COLEC12 mutation (rs2305027, G1816A) were at risk of GA-ONFH ( OR=6.00, 95% CI: 1.17, 30.73). Conclusion:Higher first-month GC dose, lower serum β-CTX level before treatment, higher ApoB/ApoA1 ratio and COLEC12 mutation (rs2305027, G1816A) could increase the risk of GA-ONFH.