Normoferremia in Patients with Acute Bacterial Infections-A Hitherto Unexplored Field of the Dichotomy between CRP and Ferritin Expression in Patients with Hyper Inflammation and Failure to Increase Ferritin.

Ferritin is an acute phase response protein, which may not rise as expected in acute bacterial infections. This could be due to the time required for its production or to a lack of response of ferritin to the bacterial inflammatory process. Medical records of hospitalized patients with acute hyper inflammation were retrieved and studied, looking closely at two acute phase proteins: C-reactive protein (CRP) and ferritin. The estimated time between symptom onset and the procurement of blood tests was also measured. 225 patients had a median ferritin level of 109.9 ng/mL [IQR 85.1, 131.7] and a median CRP level of 248.4 mg/L [IQR 221, 277.5]. An infectious inflammatory process was identified in 195 patients. Ferritin levels were relatively low in comparison with the CRP in each group, divided according to time from symptom onset until the procurement of blood tests. The discrepancy between high CRP and low ferritin suggests that these two acute phase response proteins utilize different pathways, resulting in a failure to increase ferritin concentrations in a documented state of hyperinflammation. A new entity of normoferremic inflammation accounts for a significant percentage of patients with acute bacterial infections, which enables bacteria to better survive the inflammation and serves as a new "inflammatory stamp".

The potential benefit of a second C-reactive protein measurement in patients with gram-negative bacteraemia presenting to the emergency medicine department.

BACKGROUND: Low C-reactive protein in acute bacterial infections could convey the erroneous impression of a mild infection. We focussed on gram-negative bacteraemia, a phenomenon frequently seen at the emergency room. METHODS: Of 2200 patients with gram-negative bacteraemia, 460 patients with first C-reactive protein <30 mg/L and 460 patients with C-reactive protein >187 mg/L were reviewed. Following exclusions, we finally investigated 229 and 289 patients with low and high C-reactive protein concentrations, respectively. RESULTS: The cohort was divided into low and high C-reactive protein groups. Median first C-reactive protein was 13.6 and 219.9 mg/L, respectively (interquartile range 6.4-21.6 and 195-270.1). Compared to patients with first high C-reactive protein, patients with first low C-reactive protein concentrations had a significant five-fold higher C-reactive protein level with their second test. CONCLUSIONS: Patients with gram-negative bacteraemia can present with C-reactive protein within the range of apparently healthy individuals. A second C-reactive protein might help to avoid an erroneous decision regarding the severity of the infection.

Grapefruit juice prolongs the QT interval of healthy volunteers and patients with long QT syndrome.

BACKGROUND: The list of medications linked to drug-induced long QT syndrome (LQTS) is diverse. It is possible that food products too have QT-prolonging potential. OBJECTIVE: We tested the effects of grapefruit juice on the QT interval with the methodology used by the pharmaceutical industry to test new drugs. METHODS: This was an open-label, randomized, crossover study with blinded outcome evaluation, a thorough QT study of grapefruit juice performed according to the Guidelines for the Clinical Evaluation of QT/QTc for Non-antiarrhythmic Drugs. Thirty healthy volunteers and 10 patients with congenital LQTS were studied. Healthy volunteers drank 2 L of grapefruit juice (in divided doses), or received 400 mg oral moxifloxacin, in a randomized crossover study. Patients with LQTS were tested with only grapefruit. Repeated baseline, off-drug, and on-drug (grapefruit or moxifloxacin) electrocardiograms were scanned and coded. QT measurements were done with electronic calipers. RESULTS: In comparison to off-drug electrocardiograms, grapefruit juice led to significant rate-corrected QT (QTc) prolongation. The absolute net QTc prolongation from grapefruit was 14.0 ms (95% confidence interval 6.2-21.7 ms; P < .001). The QT-prolonging effects of grapefruit in healthy volunteers were comparable with those of moxifloxacin. The QT-prolonging effects of grapefruit juice were greater in female patients and particularly marked in patients with LQTS (net QTc prolongation 21.8 ms; 95% confidence interval 3.4-35.3 ms; P = .034). CONCLUSION: Grapefruit juice, at doses tested, prolongs the QT interval. The effect is significant in healthy volunteers, greater in female patients, and more so in patients with LQTS.

Septic patients presenting with apparently normal C-reactive protein: A point of caution for the ER physician.

The presentation of septic patients with low C-reactive protein (CRP) concentrations to the emergency room (ER) might convey an erroneous impression regarding the severity of the disease.We analyzed a retrospective study of septic patients admitted to the internal medicine departments of a relatively large tertiary medical center, following admission to the ER. These patients had CRP concentrations of <31.9 mg/L, the determined cut-off for CRP concentrations in a large cohort of apparently healthy individuals in the community (n = 17,214, upper limit of mean + 3 standard deviations).By processing the electronic medical records, we found 2724 patients with a diagnosis of sepsis, 476 of whom had an admission CRP concentration of <31.9 mg/L. Following further analysis of these records, we found that 34 of the 175 patients (19.4%) who fulfilled the definition of sepsis, died within 1 week of hospitalization. Of special interest was the finding that within <24 h, a significant increment from a median CRP of 16.1 mg/L (IQR 7.9-22.5) to 58.6 mg/L (IQR 24.2-134.4), (P < .001) was noted, accompanied by a velocity change from 0.4 ±â€Š0.29 to 8.3 ±â€Š24.2 mg/L/h following antibiotic administration (P < .001).ER physicians should take into consideration that septic patients with a high in-hospital mortality rate can present with CRP concentrations that are within the range observed in apparently healthy individuals in the community. A second CRP test obtained within 24 h following antibiotic administration might influence attitudes regarding the severity of the disease.

Erythrocyte adhesiveness/aggregation: a novel biomarker for the detection of low-grade internal inflammation in individuals with atherothrombotic risk factors and proven vascular disease.

BACKGROUND: We have introduced a concept of using the erythrocyte as a sensor for the detection of enhanced inflammation-sensitive protein concentrations. We presently evaluated the capability of this new biomarker to detect the presence of inflammation in individuals with a history of a vascular disease as opposed to individuals with atherothrombotic risk factors but no clinically evident vascular disease. METHODS: The degree of erythrocyte adhesiveness/aggregation was determined in the peripheral venous blood by using a simple blood test. Blood was drawn into a syringe containing sodium citrate and trickled onto a slide at an angle of 30 degrees. The slides were than scanned by a blinded technician by using an image analyzer to determine the area that is covered by the erythrocytes. RESULTS: One hundred fifty-six subjects (61 women and 95 men) of 2586 (1238 women and 1348 men) met the criteria of a definite vascular disease (history of stroke, myocardial infarction, coronary artery bypass grafting, or peripheral vascular disease). The degree of erythrocyte aggregation was significantly (P = .008) higher in men, but not in women, with vascular disease as opposed to these without a vascular disease. The results of receiver operating characteristic curve analysis confirmed the diagnostic superiority of the erythrocyte aggregation biomarker over other commonly used markers of the acute phase in men. Similar results were obtained by using discriminant analysis. Finally, a significant correlation was found between the degree of erythrocyte aggregation and other markers of the acute phase suggesting its relevance for the detection and quantitation of low-grade inflammation in individuals with atherothrombosis. CONCLUSION: Erythrocyte adhesiveness/aggregation may be a useful biomarker to detect internal inflammation in individuals with atherothrombosis.

Superiority of a functional leukocyte adhesiveness/aggregation test over the white blood cell count to discriminate between mild and significant inflammatory response in patients with acute bacterial infections.

Electronic cell counters may underestimate the white blood cell count (WBCC) in the presence of aggregated leukocytes. In the present study we focused on the possibility of using a functional, as opposed to an anatomic, count to circumvent this eventual underestimation. A model of bacterial infection was used because of the importance of leukocytosis in the physician's clinical decision-making process. There were 35 patients with low C-reactive protein (CRP) concentrations (0.5-4.9 mg/dL), 45 with intermediate (5-9.9 mg/dL), and 120 with relatively high (>10 mg/dL) CRP concentrations. A significant (P=0.008) difference was noted between the state of leukocyte adhesiveness/aggregation in the peripheral blood of individuals with low CRP concentrations (3.5%+/-4.3%) and those with high CRP concentrations (7.4%+/-8%), while there was no significant difference in the respective number of WBCs per cubic millimeter (cmm) (11,600 +/- 5,500 and 14,000 +/- 7,200, respectively). We raise the possibility that a functional test might be superior over an anatomic count in patients with acute bacterial infection and a significant acute phase response.