Associations of cold-inducible RNA-binding protein with bacterial load, proinflammatory cytokines and mortality from pneumonia.

Cold-inducible RNA-binding protein (CIRP) is a damage-associated molecular pattern that plays a critical role in triggering inflammatory responses. It remains unknown whether CIRP is strongly associated with bacterial load, inflammatory response, and mortality in sepsis model. Pneumonia was induced in specific pathogen-free 8-9-week old male rats by injecting bacteria via puncture of the tracheal cartilage. The expressions of CIRP and proinflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß] in lung tissues, alveolar macrophages (AMs), plasma, and bronchoalveolar lavage fluid (BALF) were determined by reverse transcription-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The numbers of bacteria recovered from the lungs were correlated with the bacterial loads injected and mortality. The expressions of CIRP increased sharply as the bacterial loads increased in the lung tissues and AMs. The amounts of TNF-α, IL-6 and IL-1ß proteins synthesized were dependent on the bacterial load in the lung tissues. Releases of CIRP, TNF-α, IL-6, and IL-1ß increased with the bacterial load in the blood plasma. The proteins confirmed similar patterns in the BALF. CIRP was strongly associated with the releases of TNF-α, IL-6, and IL-1ß in the lung tissues, blood plasma, and BALF, and showed a close correlation with mortality. CIRP demonstrated a strong association with bacterial load, which is new evidence, and close correlations with proinflammatory cytokines and mortality of pneumonia in rats, suggesting that it might be an interesting pneumonic biomarker for monitoring host response and predicting mortality, and a promising target for immunotherapy.

Updating cut-off values of severity scoring systems for community-acquired pneumonia to orchestrate more predictive accuracy.

Background: The assessment of severity is crucial in the management of community-acquired pneumonia (CAP). It remains unknown whether updating cut-off values of severity scoring systems orchestrate improvement in predictive accuracy.Methods: 3,212 patients with CAP were recruited to two observational prospective cohort studies. Three bettered scoring systems were derived from the corresponding well-established and extensively used pneumonia-specific severity scoring systems, i.e. pneumonia severity index, minor criteria and CURB-65 (confusion, urea >7 mmol/L, respiratory rate ≥30/min, low blood pressure, and age ≥65 years) score, with the updating cut-off values for tachypnea and low blood pressure. Cronbach α was employed to determine construct validity. Discrimination was valued by calculating the area under the receiver operating characteristic curve (AUROC) and net reclassification improvement (NRI).Results: Respiratory rate ≥22/min and systolic blood pressure ≤100 mm Hg were performed better than respiratory rate ≥30/min and hypotension for predicting mortality in the derivation cohort, respectively (AUROC, 0.823 vs 0.519, 0.688 vs 0.622; NRI, 0.61, 0.13). Bettered scoring systems orchestrated higher convergences, indicated by greater Cronbach α and more decrease in Cronbach α if the updating cut-off values were deleted. The six scoring systems agreed well with one another. Bettered- pneumonia severity index, minor criteria and CURB-65 score showed higher associations with severity and mortality rates and demonstrated greater predictive accuracies for mortality compared with the corresponding original systems (AUROC, 0.939 vs 0.883, 0.909 vs 0.871, 0.913 vs 0.859; NRI, 0.113, 0.076, 0.108; respectively). The validation cohort confirmed a similar pattern.Conclusions: Updating cut-off values of severity scoring systems for CAP orchestrate improvement in predictive accuracy, suggesting that it may facilitate the rationalization of clinical triage decision-making and further reduce mortality. The current studies provide the first known prospective evidence of potential benefit of the updating cut-off values of severity scoring systems for CAP in predictive accuracy.Key messagesUpdating cut-off values were performed better for predicting mortality.Bettered scoring systems orchestrated higher convergences.Bettered scoring systems demonstrated greater predictive accuracies for mortality.

qSOFA predicted pneumonia mortality better than minor criteria and worse than CURB-65 with robust elements and higher convergence.

BACKGROUND: Limited data are available on the discriminatory capacity of quick sequential [sepsis-related] organ failure assessment (qSOFA) versus IDSA/ATS minor criteria for predicting mortality in patients with community-acquired pneumonia (CAP). METHODS: An observational prospective cohort study of 2116 patients with CAP was performed. Construct validity was determined using Cronbach α. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC) and net reclassification improvement (NRI). RESULTS: Overall in-hospital mortality was 6.43%. Mortality was 25.96% for patients with a qSOFA score of 2 or higher versus 3.05% for those with a qSOFA score less than 2 (odds ratio for mortality 6.57, P < 0.0001), and 13.85% for patients with at least 3 minor criteria versus 2.03% for those with 2 or fewer minor criteria (odds ratio for mortality 2.27, P < 0.0001). qSOFA had a higher correlation with mortality than minor criteria, as well as higher internal consistency (Cronbach alpha 0.43 versus 0.14) and diagnostic values of individual elements (larger AUROCs and higher Youden's indices). qSOFA ≥2 was less sensitive but more specific for predicting mortality than ≥3 minor criteria (qSOFA sensitivity 59.6%, specificity 88.3% and positive likelihood ratio 5.11 versus ≥3 minor criteria sensitivity 80.1%, specificity 65.8% and positive likelihood ratio 2.34). The predictive validity of qSOFA was good for mortality (AUROC = 0.868), was statistically greater than minor criteria, was equal to pneumonia severity index, and was inferior compared with CURB-65 (AUROC, 0.824, 0.902, 0.919; NRI, 0.088, -0.068, -0.103; respectively). CONCLUSIONS: The qSOFA predicted mortality in CAP better than IDSA/ATS minor criteria and worse than CURB-65 with robust elements and higher convergence. qSOFA as a bedside prompt might be positioned as a proxy for minor criteria and increase the recognition and thus merit more appropriate management of CAP patients likely to fare poorly, which might have implications for more accurate clinical triage decisions.

Cold-inducible RNA-binding protein might determine the severity and the presences of major/minor criteria for severe community-acquired pneumonia and best predicted mortality.

BACKGROUND: Severity of community-acquired pneumonia (CAP) depends on microbial pathogenicity, load and virulence, and immune responses. The Infectious Disease Society of America and the American Thoracic Society (IDSA/ATS) minor criteria responsible for clinical triage of patients with CAP are of unequal weight in predicting mortality. It is unclear whether the IDSA/ATS major/minor criteria might be strongly and positively associated with the immune responses. It is warranted to explore this intriguing hypothesis. METHODS: A prospective cohort study of 404 CAP patients was performed. Cold-inducible RNA-binding protein (CIRP) levels were measured using a sandwich-based enzyme-linked immunosorbent assay. The receiver operating characteristic curves were created and the areas under the curves were calculated to illustrate and compare the accuracy of the indices. RESULTS: Severe CAP patients meeting the major criteria had the highest plasma concentrations of CIRP. The more the number of most predictive minor criteria strongly associated to mortality, i.e. arterial oxygen pressure/fraction inspired oxygen ≤ 250 mmHg, confusion, and uremia, present, the higher the CIRP level. Interestingly, the patients with non-severe CAP meeting the most predictive minor criteria demonstrated unexpectedly higher CIRP level compared with the patients with severe CAP not fulfilling the criteria. Procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP), sequential organ failure assessment (SOFA) and pneumonia severity index (PSI) scores, and mortality confirmed similar intriguing patterns. CIRP was strongly linked to PCT, IL-6, CRP, minor criteria, SOFA and PSI scores, and mortality (increased odds ratio 3.433). The pattern of sensitivity, specificity, positive predictive value, and Youden's index of CIRP ≥ 3.50 ng/mL for predicting mortality was the optimal. The area under the receiver operating characteristic curve of CIRP was the highest among the indices. CONCLUSIONS: CIRP levels were strongly correlated with the IDSA/ATS major/minor criteria. CIRP might determine the severity and the presences of major/minor criteria and best predicted mortality, and a CIRP of ≥ 3.50 ng/mL might be more valuable cut-off value for severe CAP, suggesting that CIRP might be a novel and intriguing biomarker for pneumonia to monitor host response and predict mortality, which might have implications for more accurate clinical triage decisions.

Weighted Epworth sleepiness scale predicted the apnea-hypopnea index better.

BACKGROUND: The relationship between the Epworth sleepiness scale (ESS) and the apnea-hypopnea index (AHI) is uncertain and even poor. The major problem associated with the ESS might be a lack of consideration of weight in prediction in clinical practice. Would awarding different item-scores to the four scales of ESS items to develop a weighted ESS scoring system improve the accuracy of the AHI prediction? It is warranted to explore the intriguing hypotheses. METHODS: Seven hundred fifty-six adult patients with suspicion of obstructive sleep apnoea syndrome (OSAS) were prospectively recruited to a derivation cohort. This was tested against a prospective validation cohort of 810 adult patients with suspected OSAS. Each ESS item's increased odds ratio for the corresponding AHI was calculated using univariate logistic regression. The receiver operating characteristic curves were created and the areas under the curves (AUCs) were calculated to illustrate and compare the accuracy of the indices. RESULTS: The higher the ESS item-score, the closer the relationship with the corresponding AHI. The odds ratios decreased as a result of the increased AHI. The ESS items were of unequal weight in predicting the corresponding AHI and a weighted ESS was developed. The coincidence rates with the corresponding AHI, body mass indices, and neck circumferences rose as the scores increased, whereas nocturnal nadir oxygen saturations decreased, and the weighted ESS was more strongly associated with these indices, compared with the ESS. The capability in predicting the patients without OSAS or with severe OSAS was strong, especially the latter, and the weighted ESS orchestrated manifest improvement in screening the patients with simple snoring. The patterns of sensitivities, specificities, and Youden's indices of the four ranks of weighted ESS for predicting the corresponding AHI were better than those of the ESS, and the AUCs of weighted ESS were greater than the corresponding areas of ESS in the two cohorts. CONCLUSIONS: The weighted ESS orchestrated significant improvement in predicting the AHI, indicating that the capability in predicting the patients without OSAS or with severe OSAS was strong, which might have implications for clinical triage decisions to prioritize patients for polysomnography.

Correction to: Scored minor criteria for severe community-acquired pneumonia predicted better.

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Scored minor criteria for severe community-acquired pneumonia predicted better.

BACKGROUND: Infectious Disease Society of America/American Thoracic Society (IDSA/ATS) minor criteria for severe community-acquired pneumonia (CAP) are of unequal weight in predicting mortality, but the major problem associated with IDSA/ATS minor criteria might be a lack of consideration of weight in prediction in clinical practice. Would awarding different points to the presences of the minor criteria improve the accuracy of the scoring system? It is warranted to explore this intriguing hypothesis. METHODS: A total of 1230 CAP patients were recruited to a retrospective cohort study. This was tested against a prospective two-center cohort of 1749 adults with CAP. 2 points were assigned for the presence of PaO2/FiO2 ≤ 250 mmHg, confusion, or uremia on admission and 1 point for each of the others. RESULTS: The mortality rates, and sequential organ failure assessment (SOFA) and pneumonia severity index (PSI) scores increased significantly with the numbers of IDSA/ATS minor criteria present and minor criteria scores. The correlations of the minor criteria scores with the mortality rates were higher than those of the numbers of IDSA/ATS minor criteria present. As were the correlations of the minor criteria scores with SOFA and PSI scores, compared with the numbers of IDSA/ATS minor criteria present. The pattern of sensitivity, specificity, positive predictive value, and Youden's index of scored minor criteria of ≥2 scores or the presence of 2 or more IDSA/ATS minor criteria for prediction of mortality was the best in the retrospective cohort, and the former was better than the latter. The validation cohort confirmed a similar pattern. The area under the receiver operating characteristic curve of scored minor criteria was higher than that of IDSA/ATS minor criteria in the retrospective cohort, implying higher accuracy of scored version for predicting mortality. The validation cohort confirmed a similar paradigm. CONCLUSIONS: Scored minor criteria orchestrated improvements in predicting mortality and severity in patients with CAP, and scored minor criteria of ≥2 scores or the presence of 2 or more IDSA/ATS minor criteria might be more valuable cut-off value for severe CAP, which might have implications for more accurate clinical triage decisions.

Priority for Treatment and Intensive Care of Patients With Non-Severe Community-Acquired Pneumonia.

BACKGROUND: The Infectious Disease Society of America/the American Thoracic Society (IDSA/ATS) minor criteria for severe community-acquired pneumonia (CAP) are of unequal weight in predicting mortality. It is unclear whether the patients with non-severe CAP meeting the minor criteria most strongly associated to mortality should have the priority for treatment and intensive care. It is warranted to explore this intriguing hypothesis. METHODS: A retrospective cohort study of 1230 patients with CAP was performed. This was tested against a prospective 2-center cohort of 1749 adults with CAP. RESULTS: The patients with CAP fulfilling the predictive findings most strongly associated to mortality, i.e. PaO2/FiO2 ≤ 250 mm Hg, confusion, and uremia, showed higher mortality rates than those not fulfilling the predictive findings in subgroup analyses of the retrospective cohort. The more the number of predictive findings present, the higher the mortality rates. The prospective cohort confirmed a similar pattern. Interestingly, the patients with non-severe CAP meeting the predictive findings demonstrated unexpectedly higher mortality rates compared with the patients with severe CAP not meeting the predictive findings in the prospective cohort (P = 0.003), although there only existed death of an uptrend in the retrospective cohort. Two similar and intriguing paradigms about sequential organ failure assessment (SOFA) scores and pneumonia severity index (PSI) scores were confirmed in the 2 cohorts. CONCLUSIONS: The patients with non-severe CAP fulfilling the predictive findings most strongly associated to mortality demonstrated higher SOFA and PSI scores and mortality rates, and might have the priority for treatment and intensive care.

Modified IDSA/ATS Minor Criteria for Severe Community-Acquired Pneumonia Best Predicted Mortality.

It is not clear whether the IDSA/ATS minor criteria for severe community-acquired pneumonia (CAP) could be simplified or even be modified to orchestrate improvements in predicting mortality.A retrospective cohort study of 1230 CAP patients was performed to simplify and to modify the scoring system by excluding 4 noncontributory or infrequent variables (leukopenia, hypothermia, hypotension, and thrombocytopenia) and by excluding these variables and then adding age ≥65 years, respectively. The simplification and modification were tested against a prospective 2-center validation cohort of 1409 adults with CAP.The increasing numbers of IDSA/ATS, simplified, and modified minor criteria present in the retrospective cohort were positively associated with the mortality, showing significant increased odds ratios for mortality of 2.711, 4.095, and 3.755, respectively. The validation cohort confirmed a similar pattern. The sensitivity, specificity, positive predictive value, and Youden index of modified minor criteria for mortality prediction were the best pattern in the retrospective cohort. High values of corresponding indices were confirmed in the validation cohort. The highest accuracy of the modified version for predicting mortality in the retrospective cohort was illustrated by the highest area under the receiver operating characteristic curve of 0.925 (descending order: modified, simplified, and IDSA/ATS minor criteria). The validation cohort confirmed a similar paradigm.The IDSA/ATS minor criteria could be simplified to 5 variables and then be modified to orchestrate improvements in predicting mortality in CAP patients. The modified version best predicted mortality. These were more suitable for clinic and emergency department.

CUR-65 Score for Community-Acquired Pneumonia Predicted Mortality Better Than CURB-65 Score in Low-Mortality Rate Settings.

BACKGROUND: It is not clear whether low-blood pressure criterion could be removed from CURB-65 (confusion, urea >7 mmol/L, respiratory rate ≥30/min, low blood pressure and age ≥65 years) score to orchestrate an improvement in identifying patients with community-acquired pneumonia (CAP) in low-mortality rate settings. METHODS: A retrospective cohort study of 1,230 CAP patients was performed to simplify the CURB-65 scoring system by excluding low-blood pressure variable. The simplification was validated in a prospective 2-center cohort of 1,409 adults with CAP. RESULTS: The hospital mortalities were 1.3% and 3.8% in the retrospective and prospective cohorts, respectively. The mortality rates in the 2 cohorts increased directly with the increasing scores, showing significant increased odds ratios for mortality. The pattern of sensitivity, specificity, positive predictive value and Youden's index of a CUR-65 (Confusion, Urea >7 mmol/L, Respiratory rate ≥30/min and age ≥65 years) score of ≥2 for prediction of mortality was better than that of a CURB-65 score of ≥3 in the retrospective cohort. Higher values of corresponding indices were confirmed in the validation cohort. The higher accuracy of CUR-65 score for predicting mortality was illustrated by the area under the receiver operating characteristic curve of 0.937, compared with 0.915 for CURB-65 score in the retrospective cohort (P = 0.0073). The validation cohort confirmed a similar paradigm (0.953 versus 0.907, P = 0.0002). CONCLUSIONS: CURB-65 score could be simplified by removing low blood pressure to orchestrate an improvement in predicting mortality in CAP patients who have a low risk of death. A CUR-65 score of ≥2 might be a more valuable cutoff value for severe CAP.

Mortality among severe community-acquired pneumonia patients depends on combinations of 2007 IDSA/ATS minor criteria.

OBJECTIVES: The individual 2007 Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) minor criteria for severe community-acquired pneumonia (CAP) are of unequal weight in predicting mortality. It is not clear whether the combinations of predictive findings might imply diverse severities or different mortalities. METHODS: A prospective two centre cohort study was performed of 385 severe CAP patients fulfilling three or more IDSA/ATS minor criteria amongst 1430 patients. RESULTS: Hospital mortality rose sharply from 5.7%, 9.9%, and 16.5%, respectively, for patients with none of three predictive findings most strongly associated to mortality (PaO2/FiO2 ≤ 250mm Hg, confusion and uraemia), one of those, and two of those to 38.6% for patients with all those (p<0.001). The number of three predictive findings present had a significantly increased odds ratio for mortality of 2.796 (p<0.001), and had the degree of positive association with sequential organ failure assessment scores at 72hours, incurring significantly longer hospital stay and higher costs. CONCLUSIONS: Different combinations of 2007 IDSA/ATS minor criteria for severe CAP were associated to diverse severities and different mortalities. The combination of PaO2/FiO2 ≤ 250mm Hg, confusion and uraemia predicted more severity and higher mortality compared with others.