Performance of various pneumonia severity models for predicting adverse outcomes in elderly inpatients with community acquired pneumonia.

OBJECTIVE: We aimed to assess the performance of common pneumonia severity scores, including Pneumonia Severity Index (PSI), CURB-65, CRB-65, A-DROP and SMART-COP, in predicting adverse outcomes in an elderly community-acquired pneumonia (CAP) cohort and to determine the optimal scoring system for specific outcomes of interest. METHODS: A total of 822 elderly inpatients were included in the retrospective cohort study. Clinical and laboratory results on admission were used to calculate above scores. The primary outcome was 30-day mortality. Secondary outcomes were in-hospital mortality, need for mechanical ventilation (MV) and intensive care unit (ICU) admission. Model discrimination was evaluated by the area under receiver operating characteristic curves (AUCs). RESULTS: The 30-day and in-hospital mortality rates were 6.8% (56/822) and 8.6% (71/822), respectively. One hundred and ninety-eight (24.0%) received MV and 111 (13.5%) were admitted to the ICU. All five scoring systems showed the same trend of increasing rates of each adverse outcome with increasing risk groups (all p<0.001). PSI had the highest AUC, sensitivity, and negative predictive value (NPV) in predicting 30-day mortality and in-hospital mortality. SMART-COP had the highest AUC for predicting the need for MV and ICU admission, but PSI had the highest sensitivity and NPV for these two outcomes. CONCLUSIONS: PSI performed well in identifying elderly patients at risk for 30-day mortality and its high NPV is helpful in excluding patients who are not at risk. Considering the effectiveness and simplicity, SMART-COP and CURB-65 are easier to perform in clinical practice than PSI.

Association between trough serum vancomycin concentration and vancomycin-associated acute kidney injury and 30-day mortality in critically ill elderly adults.

BACKGROUND: Vancomycin-associated acute kidney injury (VA-AKI) is the most clinically relevant side effect of vancomycin. The objective of this study was to investigate the association between VTC and VA-AKI as well as 30-day mortality in critically ill elderly adults. METHOD: Elderly patients with trough serum vancomycin concentration records(VTC) in the Medical Information Mart-IV (MIMIC-IV) and eICU databases were retrospectively studied. RESULTS: A total of 3,146 critically ill elderly adults were finally enrolled. The incidence of VA-AKI in the elderly population was 76.5%. Logistic regression analysis revealed significant relationships between VA-AKI and various factors, including VTC, comorbidities, and laboratory indicators, and SOFA, and GCS score. For each mg/L increase, the OR for VA-AKI increased by 2.5%. The association between VTC and 30-day mortality was found to be statistically significant (odds ratio (OR): 1.021, 95% CI: 1.010-1.031), P < 0.001). The Restricted cubic splines (RCS) curves revealed that VTC ranged of 19.67 to 35.72 mg/l for AKI and 19.17 to 42.86 mg/l for 30-day mortality exhibit OR with 95% CI above 1, indicating statistically significant associations with an increased risk of AKI and 30-day mortality, respectively. In the subgroup analysis, VTC was identified as a risk factor for VA-AKI in specific patient groups, including white individuals, female patients, those with shock, patients with SOFA > 6, patients with baseline creatinine > 1.2 mg/dl and patients with or without exposed to other nephrotoxic medications. CONCLUSION: This study found the significant association between VTC and the incidence of VA-AKI and 30-day mortality in critically ill elderly adults. The RCS curves indicated concentration ranges for AKI (19.67-35.72 mg/L) and 30-day mortality (19.17-42.86 mg/L), signifying increased risk.

Clinical success of anti-infective combination therapy compare to monotherapy in patients with carbapenem-resistant Pseudomonas aeruginosa infection: a 10-years retrospective study.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection has become a major public health concern. The recommendations for monotherapy and combination therapy in the current guidelines lack sufficient evidence to support them. The primary objective of this study is to determine the effectiveness of anti-Infective combination therapy compared to monotherapy in achieving clinical success in patients with CRPA infection and risk factors of clinical failure of monotherapy. METHODS: A retrospective study from Medical Information Mart for Intensive Care IV (MIMIC-IV) was conducted. We included adults with infections caused by CRPA. The outcomes of this study were clinical success, complete clinical success, and 28-day all-cause mortality. RESULTS: A total of 279 subjects were finally enrolled. The rate of clinical success for combination therapy was higher than that for monotherapy (73.1% versus 60.4%, p=0.028). Compared to clinical failure patients, patients in the clinical success group were more likely to die within 28 days after CRPA was found (48.3% versus 3.6%, p<0.001). In a multivariate logistic regression analysis, monotherapy was found to be significantly correlated with clinical success (OR, 0.559, 95% CI, 0.321-0.976; p = 0.041). CONCLUSION: Combination therapy is more effective for CRPA infection patients, especially those whose SOFA score is ≥ 2 or whose Charlson comorbidity index is ≥ 6.

Cathelicidin LL-37 restoring glucocorticoid function in smoking and lipopolysaccharide-induced airway inflammation in rats.

BACKGROUND: Glucocorticoids have been widely used to treat patients with chronic obstructive pulmonary disease (COPD). Nevertheless, corticosteroid insensitivity is a major barrier to the effective treatment of COPD and its mechanism remains unclear. This study aimed to evaluate the effect of cathelicidin LL-37 on corticosteroid insensitivity in COPD rat model, and to explore the involved mechanisms. METHODS: COPD model was established by exposing male Wistar rats to cigarette smoke combined with intratracheal instillation of lipopolysaccharide (LPS). Inhaled budesonide and LL-37 were consequently applied to COPD models separately or collectively to confirm the effects on inflammatory cytokines (tumor necrosis factor [TNF]-α and transforming growth factor [TGF]-ß) by enzyme-linked immunosorbent assay (ELISA) and lung tissue histopathological morphology. Expression of histone deacetylase-2 (HDAC2) and phosphorylation of Akt (p-AKT) in lung were also measured. RESULTS: Briefly, COPD model rats showed an increased basal release of inflammatory cytokines (lung TNF-α: 45.7 ±â€Š6.1 vs. 20.1 ±â€Š3.8 pg/mL, P < 0.01; serum TNF-α: 8.9 ±â€Š1.2 vs. 6.7 ±â€Š0.5 pg/mL, P = 0.01; lung TGF-ß: 122.4 ±â€Š20.8 vs. 81.9 ±â€Š10.8 pg/mL, P < 0.01; serum TGF-ß: 38.9 ±â€Š8.5 vs. 20.6 ±â€Š2.3 pg/mL, P < 0.01) and COPD related lung tissue histopathological changes, as well as corticosteroid resistance molecular profile characterized by an increase in phosphoinositide 3-kinase (PI3K)/Akt (0.5 ±â€Š0.1 fold of control vs. 0.2 ±â€Š0.1 fold of control, P = 0.04) and a decrease in HDAC2 expression and activity (expression: 13.1 ±â€Š0.4 µmol/µg vs. 17.4 ±â€Š1.1 µmol/µg, P < 0.01; activity: 1.1 ±â€Š0.1 unit vs. 1.4 ±â€Š0.1 unit, P < 0.01), compared with control group. In addition, LL-37 enhanced the anti-inflammatory effect of budesonide in an additive manner. Treatment with combination of inhaled corticosteroids (ICS) and LL-37 led to a significant increase of HDAC2 expression and activity (expression: 15.7 ±â€Š0.4 µmol/µg vs. 14.1 ±â€Š0.9 µmol/µg, P < 0.01; activity: 1.3 ±â€Š0.1 unit vs. 1.0 ±â€Š0.1 unit, P < 0.01), along with decrease of p-AKT compared to budesonide monotherapy (0.1 ±â€Š0.0 fold of control vs. 0.3 ±â€Š0.1 fold of control, P < 0.01). CONCLUSIONS: This study suggested that LL-37 could improve the anti-inflammatory activity of budesonide in cigarette smoke and LPS-induced COPD rat model by enhancing the expression and activity of HDAC2. The mechanism of this function of LL-37 might involve the inhibition of PI3K/Akt pathway.