The Glycemic Gap and 90-Day Mortality in Community-acquired Pneumonia. A Prospective Cohort Study.

Rationale: Hyperglycemia is associated with mortality in patients with community-acquired pneumonia (CAP), and hyperglycemia may be a biomarker of severity. However, hyperglycemia has a major disadvantage because the association is diminished in patients with diabetes mellitus (DM). This hampers the use of hyperglycemia as a biomarker. Accounting for habitual glucose levels could overcome this disadvantage.Objectives: We hypothesized that the glycemic gap (the difference between plasma glucose and the estimated average glucose) may be associated with mortality irrespective of DM.Methods: Among 1,933 adults with CAP included in a prospective multicenter cohort, we investigated the association between the glycemic gap and 90-day mortality. Hemoglobin A1c was used to estimate the average glucose. The association was assessed with Cox proportional hazard models after adjustment for age, sex, CURB-65 (Confusion, urea >7 mmol/L, respiratory rate ≥30 breaths/minute, systolic blood pressure <90 mmHg or diastolic blood pressure ≤60 mmHg and age ≥65 years), and comorbidities. In the prespecified analysis the absolute and relative glycemic gaps were used as a continuous variable. In a post hoc analysis, the absolute and relative glycemic gaps were used as a categorical variable grouped according to quartiles.Results: In the post hoc analysis, patients with the lowest (negative) and highest (positive) absolute glycemic gap quartiles had increased risk of 90-day mortality (hazard ratio, 2.6; 95% confidence interval, 1.02-6.65; and hazard ratio, 2.5; 95% confidence interval, 1.01-6.06, respectively). A similar association was found for the relative glycemic gap. The associations were independent of age, CURB-65 score, sex, or number of comorbidities and not modified by DM.Conclusions: Patients with the highest and lowest glycemic gap may have an increased risk of 90-day mortality, and the association was not modified by DM. These associations were found in an exploratory post hoc analysis and should be validated in other populations before further conclusions can be made.

Is chronic obstructive pulmonary disease a risk factor for death in patients with community acquired pneumonia?

BACKGROUND: It is still a matter of debate whether the outcome of community acquired pneumonia is more severe in patients with chronic obstructive pulmonary disease. We aimed to determine whether chronic obstructive pulmonary disease was associated with increased mortality and to identify risk-factors for mortality in patients with community acquired pneumonia and chronic obstructive pulmonary disease. METHODS: Retrospective cohort study comparing patients with community acquired pneumonia and chronic obstructive pulmonary disease to patients without chronic obstructive pulmonary disease. We included 1309 patients with community acquired pneumonia admitted from 2011 until 2012 (243 patients with chronic obstructive pulmonary disease and 1066 without chronic obstructive pulmonary disease). RESULTS: At admission patients with community acquired pneumonia and chronic obstructive pulmonary disease presented with more severe pneumonia as measured by CURB-65 score compared to patients without chronic obstructive pulmonary disease. Mortality on day 30 was generally high, and higher among patients with community acquired pneumonia and chronic obstructive pulmonary disease compared to those without chronic obstructive pulmonary disease (16.0% versus 11.3%, p = .04). In an adjusted analysis, however, chronic obstructive pulmonary disease was not independently associated with 30-d mortality (odds ratio 0.94, confidence interval 95% 0.59-1.50). Factors related to mortality in patients with community acquired pneumonia and chronic obstructive pulmonary disease were age, premorbid condition, severity of pneumonia as determined by CURB-65 score, and pleural effusion and multi-lobular infiltrate on chest X-ray. CONCLUSIONS: Chronic obstructive pulmonary disease was not independently associated with 30-d mortality in patients with community acquired pneumonia.

The inflamed sputum in lower respiratory tract infection: l-lactate levels are correlated to neutrophil accumulation.

Lower respiratory tract infections (LRTI) are common, but little is known about the response of biomarkers of inflammation in the lungs. Therefore, our primary aim was to compare the concentration of l-lactate to the concentration of neutrophils in sputum and systemic markers of infection. Because it is difficult to differentiate viral and bacterial infection on the basis of clinical presentation in LRTI, our secondary aim was to evaluate if l- and d-lactate may serve as markers of local inflammation as representatives of neutrophils and bacteria, respectively. METHODS: Patients with acute LRTI were prospectively recruited. Sputum samples were collected and analysed for neutrophil count, l-lactate and d-lactate. We had data on pathogens from sputum cultures and polymerase chain reaction (PCR) (atypical bacteria, virus) and C-reactive protein (CRP) from blood. RESULTS: In 44 sputum samples from 32 patients, the median (interquartile range (IQR)) sputum neutrophil granulocyte count was 0.615 × 107  cells/mL (0.236-1.575). The sputum neutrophil granulocyte count was associated with sputum l-lactate (p = 0.011) and CRP (p = 0.018), but not with d-lactate (p = 0.177). There was a strong association between sputum d-lactate and l-lactate (p < 0.0001). CONCLUSION: As l-lactate in sputum is closely correlated to sequestration of neutrophils in the lungs, l-lactate is a marker for local inflammation in LRTI and a potential biomarker in clinical management of LRTI. On expectorated sputum, d-lactate had no clinical relevance.

Cerebrospinal fluid pleocytosis in infectious and noninfectious central nervous system disease: A retrospective cohort study.

Cerebrospinal fluid (CSF) analysis is the most important tool for assessing central nervous system (CNS) disease. An elevated CSF leukocyte count rarely provides the final diagnosis, but is almost always an indicator of inflammation within the CNS.The present study investigated the variety of diseases associated with CSF pleocytosis.CSF analyses were identified through the biochemical database used in the capital region of Denmark in the period from 2003 to 2010. In patients >15 years, clinical diagnoses associated with the finding of a CSF leukocyte count >10 × 10 cells/L were obtained from discharge records and patient files.A total of 1058 CSF samples from 1054 patients were included in the analysis. The median age was 50 (interquartile range: 36-67) and 53% were male. Eighty-one different diagnoses were identified in 1058 cases with an elevated CSF leukocyte count, besides unknown causes. Infections were the most common cause of CSF pleocytosis (61.4%) followed by miscellaneous causes (12.7%), vascular (9.7%), neurodegenerative (7%), neoplastic (5%), and inflammatory conditions (4.2%). Only infections presented with leukocyte counts >10,000 × 10/L. Infections represented 82.6% of all cases with a leukocyte count >100 × 10/L whereas 56.3% of cases with at leukocyte counts <100 × 10/L were dominated by disease not related to infection.The present study may serve as a reminder to clinicians of what diseases and disease categories to suspect when patients present with CSF biochemistry indicating CNS inflammation.

Failure of CRP decline within three days of hospitalization is associated with poor prognosis of Community-acquired Pneumonia.

BACKGROUND: C-reactive protein (CRP) is a well-known acute phase protein used to monitor the patient's response during treatment in infectious diseases. Mortality from Community-acquired Pneumonia (CAP) remains high, particularly in hospitalized patients. Better risk prediction during hospitalization could improve management and ultimately reduce mortality levels. The aim of this study was to evaluate CRP on the 3rd day (CRP3) of hospitalization as a predictor for 30 days mortality. METHODS: A retrospective multicentre cohort study of adult patients admitted with CAP at three Danish hospitals. Predictive associations of CRP3 (absolute levels and relative decline) and 30 days mortality were analysed using receiver operating characteristics and logistic regression. RESULTS: Eight hundred and fourteen patients were included and 90 (11%) died within 30 days. The area under the curve for CRP3 level and decline for predicting 30 days mortality were 0.64 (0.57-0.70) and 0.71 (0.65-0.76). Risk of death was increased in patients with CRP3 level >75 mg/l (OR 2.44; 95%CI 1.36-4.37) and in patients with a CRP3 decline <50% (OR 4.25; 95%CI 2.30-7.83). In the multivariate analysis, the highest mortality risk was seen in patients who failed to decline by 50%, irrespective of the actual level of CRP (OR 7.8; 95%CI 3.2-19.3). Mortality risk increased significantly according to CRP decline for all strata of CURB-65 score. CONCLUSIONS: CRP responses day 3 is a valuable predictor of 30 days mortality in hospitalized CAP patients. Failure to decline in CRP was associated with a poor prognosis irrespective of the actual level of CRP or CURB-65.