Cornelis P. C. de Jager

Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit

IntroductionAbsolute lymphocytopenia has been reported as a predictor of bacteremia in medical emergencies. Likewise, the neutrophil-lymphocyte count ratio (NLCR) has been shown a simple promising method to evaluate systemic inflammation in critically ill patients.MethodsWe retrospectively evaluated the ability of conventional infection markers, lymphocyte count and NLCR to predict bacteremia in adult patients admitted to the Emergency Department with suspected community-acquired bacteremia. The C-reactive protein (CRP) level, white blood cell (WBC) count, neutrophil count, lymphocyte count and NLCR were compared between patients with positive blood cultures (n = 92) and age-matched and gender-matched patients with negative blood cultures (n = 92) obtained upon Emergency Department admission.ResultsSignificant differences between patients with positive and negative blood cultures were detected with respect to the CRP level (mean ± standard deviation 176 ± 138 mg/l vs. 116 ± 103 mg/l; P = 0.042), lymphocyte count (0.8 ± 0.5 × 109/l vs. 1.2 ± 0.7 × 109/l; P < 0.0001) and NLCR (20.9 ± 13.3 vs. 13.2 ± 14.1; P < 0.0001) but not regarding WBC count and neutrophil count. Sensitivity, specificity, positive and negative predictive values were highest for the NLCR (77.2%, 63.0%, 67.6% and 73.4%, respectively). The area under the receiver operating characteristic curve was highest for the lymphocyte count (0.73; confidence interval: 0.66 to 0.80) and the NLCR (0.73; 0.66 to 0.81).ConclusionsIn an emergency care setting, both lymphocytopenia and NLCR are better predictors of bacteremia than routine parameters like CRP level, WBC count and neutrophil count. Attention to these markers is easy to integrate in daily practice and without extra costs.

Biomarkers and Molecular Analysis to Improve Bloodstream Infection Diagnostics in an Emergency Care Unit

Molecular pathogen detection from blood is still expensive and the exact clinical value remains to be determined. The use of biomarkers may assist in preselecting patients for immediate molecular testing besides blood culture. In this study, 140 patients with ≥ 2 SIRS criteria and clinical signs of infection presenting at the emergency department of our hospital were included. C-reactive protein (CRP), neutrophil-lymphocyte count ratio (NLCR), procalcitonin (PCT) and soluble urokinase plasminogen activator receptor (suPAR) levels were determined. One ml EDTA blood was obtained and selective pathogen DNA isolation was performed with MolYsis (Molzym). DNA samples were analysed for the presence of pathogens, using both the MagicPlex Sepsis Test (Seegene) and SepsiTest (Molzym), and results were compared to blood cultures. Fifteen patients had to be excluded from the study, leaving 125 patients for further analysis. Of the 125 patient samples analysed, 27 presented with positive blood cultures of which 7 were considered to be contaminants. suPAR, PCT, and NLCR values were significantly higher in patients with positive blood cultures compared to patients without (p < 0.001). Receiver operating characteristic curves of the 4 biomarkers for differentiating bacteremia from non-bacteremia showed the highest area under the curve (AUC) for PCT (0.806 (95% confidence interval 0.699–0.913)). NLCR, suPAR and CRP resulted in an AUC of 0.770, 0.793, and 0.485, respectively. When compared to blood cultures, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for SepsiTest and MagicPlex Sepsis Test were 11%, 96%, 43%, 80%, and 37%, 77%, 30%, 82%, respectively. In conclusion, both molecular assays perform poorly when one ml whole blood is used from emergency care unit patients. NLCR is a cheap, fast, easy to determine, and rapidly available biomarker, and therefore seems most promising in differentiating BSI from non-BSI patients for subsequent pathogen identification using molecular diagnostics.

The neutrophil-lymphocyte count ratio in patients with community-acquired pneumonia.

Study Objective The neutrophil-lymphocyte count ratio (NLCR) has been identified as a predictor of bacteremia in medical emergencies. The aim of this study was to investigate the value of the NLCR in patients with community-acquired pneumonia (CAP). Methods and Results Consecutive adult patients were prospectively studied. Pneumonia severity (CURB-65 score), clinical characteristics, complications and outcomes were related to the NLCR and compared with C-reactive protein (CRP), neutrophil count, white blood cell (WBC) count. The study cohort consisted of 395 patients diagnosed with CAP. The mean age of the patients was 63.4±16.0 years. 87.6% (346/395) of the patients required hospital admission, 7.8% (31/395) patients were admitted to the Intensive Care Unit (ICU) and 5.8% (23/395) patients of the study cohort died. The NLCR was increased in all patients, predicted adverse medical outcome and consistently increased as the CURB-65 score advanced. NLCR levels (mean ± SD) were significantly higher in non-survivors (23.3±16.8) than in survivors (13.0±11.4). The receiver-operating characteristic (ROC) curve for NLCR predicting mortality showed an area under the curve (AUC) of 0.701. This was better than the AUC for the neutrophil count, WBC count, lymphocyte count and CRP level (0.681, 0.672, 0.630 and 0.565, respectively). Conclusion Admission NLCR at the emergency department predicts severity and outcome of CAP with a higher prognostic accuracy as compared with traditional infection markers.

Embolization as treatment of choice for bleeding peptic ulcers in high-risk patients.

Background/Aim: Peptic ulcers are the most common cause of acute upper gastrointestinal bleedings in the digestive tract. Most patients are poor surgical candidates. The aim was to describe the efficacy of embolization as the treatment of choice for bleeding peptic ulcers in high-risk patients when endoscopic treatment failed. Methods: All patients who underwent a selective embolization of branches of the superior mesenteric artery and/or branches of the gastroduodenal artery for a bleeding peptic ulcer in the period January 2004 until December 2007 were included in this retrospective descriptive study. We examined the known risk factors for surgery and mortality in upper gastrointestinal bleeding due to peptic ulcers and describe the clinical course and outcome. Primary endpoints were the primary technical success and the clinical success rates. The secondary endpoint was the 30-day mortality. Results: 16 patients were included. All patients had at least two risk factors for surgery and mortality. The clinical success rate was 81% (13/16). The first embolization failed in 3 patients, 1 was successful re-embolized and 2 were operated upon without re-embolization. The primary technical success rate, i.e. bleedings controlled by radiologic intervention, was 88% (14/16). 6 patients died due to non-embolization-related problems; 5 of them developed upper gastrointestinal bleeding during a stay in the hospital. Conclusion: Embolization was a successful, minimal invasive alternative for surgical intervention in high-risk patients with upper gastrointestinal bleeding after failure of endoscopic treatment.

Dynamic light application therapy to reduce the incidence and duration of delirium in intensive-care patients: a randomised controlled trial

BACKGROUND Disturbed circadian rhythm is a potentially modifiable cause of delirium among patients in intensive-care units (ICUs). Bright-light therapy in the daytime can realign circadian rhythm and reduce the incidence of delirium. We investigated whether a high-intensity dynamic light application (DLA) would reduce ICU-acquired delirium. METHODS This was a randomised, controlled, single-centre trial of medical and surgical patients admitted to the ICU of a teaching hospital in the Netherlands. Patients older than 18 years, expected to stay in the ICU longer than 24 h and who could be assessed for delirium were randomised to DLA or normal lighting (control), according to a computer-generated schedule. The DLA was administered through ceiling-mounted fluorescent tubes that delivered bluish-white light up to 1700 lux between 0900 h and 1600 h, except for 1130-1330 h, when the light was dimmed to 300 lux. The light could only be turned off centrally by investigators. Control light levels were 300 lux and lights could be turned on and off from inside the room. The primary endpoint was the cumulative incidence of ICU-acquired delirium. Analyses were by intention to treat and per protocol. The study was terminated prematurely after an interim analysis for futility. This study is registered with Clinicaltrials.gov, number NCT01274819. FINDINGS Between July 1, 2011, and Sept 9, 2013, 734 patients were enrolled, 361 in the DLA group and 373 in the control group. Delirium occurred in 137 (38%) of 361 DLA patients and 123 (33%) of 373 control patients (odds ratio 1·24, 95% CI 0·92-1·68, p=0·16). No adverse events were noted in patients or staff. INTERPRETATION DLA as a single intervention does not reduce the cumulative incidence of delirium. Bright-light therapy should be assessed as part of a multicomponent strategy. FUNDING None.

Noise pollution in the ICU: time to look into the mirror

No abstract

Dynamics of peripheral blood lymphocyte subpopulations in the acute and subacute phase of Legionnaires' disease

Study Objective Absolute lymphocytopenia is recognised as an important hallmark of the immune response to severe infection and observed in patients with Legionnaires’ disease. To explore the immune response, we studied the dynamics of peripheral blood lymphocyte subpopulations in the acute and subacute phase of LD. Methods and Results EDTA-anticoagulated blood was obtained from eight patients on the day the diagnosis was made through detection of L. pneumophila serogroup 1 antigen in urine. A second blood sample was obtained in the subacute phase. Multiparametric flow cytometry was used to calculate lymphocyte counts and values for B-cells, T-cells, NK cells, CD4+ and CD8+ T-cells. Expression of activation markers was analysed. The values obtained in the subacute phase were compared with an age and gender matched control group. Absolute lymphocyte count (×109/l, median and range) significantly increased from 0.8 (0.4–1.6) in the acute phase to 1.4 (0.8–3.4) in the subacute phase. B-cell count showed no significant change, while T-cell count (×106/l, median and range) significantly increased in the subacute phase (495 (182–1024) versus 979 (507–2708), p = 0.012) as a result of significant increases in both CD4+ and CD8+ T-cell counts (374 (146–629) versus 763 (400–1507), p = 0.012 and 119 (29–328) versus 224 (107–862), p = 0.012). In the subacute phase of LD, significant increases were observed in absolute counts of activated CD4+ T-cells, naïve CD4+ T-cells and memory CD4+ T-cells. In the CD8+ T-cell compartment, activated CD8+ T-cells, naïve CD8+ T-cell and memory CD8+ T-cells were significantly increased (p<0.05). Conclusion The acute phase of LD is characterized by absolute lymphocytopenia, which recovers in the subacute phase with an increase in absolute T-cells and re-emergence of activated CD4+ and CD8+ T cells. These observations are in line with the suggested role for T-cell activation in the immune response to LD.

“Benign” superior vena cava syndrome

A 41-year-old man, known to have congenital antithrombin (AT)-III deficiency, presented to the emergency department with progressive dyspnea, facial swelling, generalized edema, and hypotension. A viral gastroenteritis, several weeks before the admission, resulted in subtherapeutic international normalized ratio (INR) levels. Echocardiography showed inflow obstruction of the right ventricle with preserved left ventricular function. Computed tomography (CT) confirmed ‘‘benign’’ superior vena cava thrombosis with several collateral veins (Fig. 1). Endovascular stenting was carried out as a minimally invasive and simple procedure, restoring venous return with immediate relief of symptoms in our patient (Figs. 2, 3). Long-term anticoagulation was intensified, and he is currently doing well, 5 years after this complication of his AT-III deficiency.

Reducing sensory input in critically ill patients: are eyemasks a blind spot?

We read with interest the article by Van Rompaey and colleagues [1] reporting that earplugs may be useful in the prevention of delirium in non-ventilated ICU patients. Unfortunately, they did not report any potentially negative effects of earplugs related to sensory deprivation - for example, restlessness, discomfort, or anxiety. In non-ventilated critical care patients the combination of earplugs and eyemasks were effective to improve sleep [2], and the use of eyemasks, in healthy volunteers, in a simulated ICU environment led to improved nighttime sleep and higher nocturnal melatonin levels [3]. Whether or not these positive results also apply to intubated ICU patients is not known and the mentioned possible disadvantages might especially occur in this vulnerable patient group. Nevertheless, the Dutch guideline on delirium management states that the use of nighttime eyemasks should be considered [4]. As the use of eyemasks in intubated patients could very well lead to a feeling of sensorial deprivation and its feasibility in critically ill patients is not clear, we analyzed 18 ICU patients who were offered the choice of wearing a nightmask from 10 p.m. to 6 a.m. (Table ​(Table1).1). The need for informed consent was waived since the use of eyemasks is a part of national delirium guidelines and participation was on a voluntary basis. Table 1 Patient characteristics Eleven patients (61%) were willing to wear a nightmask on average on 28% (median 4 nights, range 1 to 5) of nights on the ICU. In these patients self-perceived quality of sleep, using a visual analog scale (VAS), improved from 6.6 (5.9 to 8.2) to 7.5 (7.0 to 8.0) (P = 0.041) when the mask was worn. In 72% of cases, the mask was refused or taken off prematurely due to restlessness (30%), discomfort (20%), or anxiety (11%). While eyemasks might improve sleep in selected patients, it also may lead to feelings of discomfort and anxiety in mechanically ventilated ICU patients and therefore its standardized use should be used with caution and only on a voluntary basis in this specific group.

Association between the Hanging Chin Sign and Mortality in Critically Ill Patients, a Retrospective Observational Study

Purpose: Define a new sign called the ‘Hanging Chin Sign’ (HCS) and discuss its clinical significance by evaluating if it is associated with poor hospital outcome in critically ill patients.Methods: A retrospective observational study was performed. 331 adult patients presenting to the emergency department (ED) between 1 April 2011 and 31 July 2013, for which an Intensive Care Unit (ICU) physician was consulted and a supine chest X-ray was taken, were included. HCS was defined as radiological projection of the jawbone (os mandibula) over one or more ribs on the chest X-ray. In-hospital mortality, ICU admission and hospital length of stay (LOS) was compared between patients with and without a HCS.Results: In patients presenting with a HCS, mortality was significantly higher. After case mix correction for age, gender, Glascow Coma Scale and neurological pathology, there was no significant independent association between the HCS and mortality, ICU admission, hospital LOS, ICU LOS and APACHE II score.Conclusion: Critically ill patients presenting to the ED with a HCS have higher in-hospital mortality. Although there is no independent association between the HCS and severity of disease, it can be used as an additional clinical marker for mortality and frailty.