The diagnostic and prognostic significance of monitoring blood levels of immature neutrophils in patients with systemic inflammation

IntroductionIn this cohort study, we investigated whether monitoring blood levels of immature neutrophils (myelocytes, metamyelocytes and band cells) differentiated patients with sepsis from those with the non-infectious (N-I) systemic inflammatory response syndrome (SIRS). We also ascertained if the appearance of circulating immature neutrophils was related to adverse outcome.MethodsBlood samples were routinely taken from 136 critically ill patients within 48 hours of ICU entry and from 20 healthy control subjects. Clinical and laboratory staff were blinded to each other’s results, and patients were retrospectively characterised into those with SIRS (n = 122) and those without SIRS (n = 14). The patients with SIRS were further subdivided into categories of definite sepsis (n = 51), possible sepsis (n = 32) and N-I SIRS (n = 39). Two established criteria were used for monitoring immature white blood cells (WBCs): one where band cells >10% WBCs and the other where >10% of all forms of immature neutrophils were included but with a normal WBC count. Immature neutrophils in blood smears were identified according to nuclear morphology and cytoplasmic staining.ResultsWith the first criterion, band cells were present in most patients with SIRS (mean = 66%) when compared with no SIRS (mean = 29%; P <0.01) and with healthy subjects (0%). The prevalence of band cells was higher in definite sepsis (mean = 82%) than in patients with possible sepsis (mean = 63%; P <0.05) or with N-I SIRS (mean = 39%; P <0.001), and they had a sensitivity of 84% and a specificity of 71% for the detection of definite sepsis. With the second criterion (that is, patients with normal WBC counts), we noted that immature neutrophils did not differentiate any of the patient groups from one another. Patients who died within 1 week of blood sample provision had higher levels of myelocytes and metamyelocytes (median = 9%; P <0.05) than patients who died at 2 to 4 weeks (median =0.5%).ConclusionsRaised blood levels of band cells have diagnostic significance for sepsis, provided that measurements are not confined to patients with normal WBC counts, whereas an increased prevalence of myelocytes and metamyelocytes may have prognostic application.     

Opening of small and intermediate calcium-activated potassium channels induces relaxation mainly mediated by nitric-oxide release in large arteries and endothelium-derived hyperpolarizing factor in small arteries from rat

This study was designed to investigate whether calcium-activated potassium channels of small (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1) conductance activated by 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) are involved in both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF)-type relaxation in large and small rat mesenteric arteries. Segments of rat superior and small mesenteric arteries were mounted in myographs for functional studies. NO was recorded using NO microsensors. SK(Ca) and IK(Ca) channel currents and mRNA expression were investigated in human umbilical vein endothelial cells (HUVECs), and calcium concentrations were investigated in both HUVECs and mesenteric arterial endothelial cells. In both superior (～1093 μm) and small mesenteric (～300 μm) arteries, NS309 evoked endothelium- and concentration-dependent relaxations. In superior mesenteric arteries, NS309 relaxations and NO release were inhibited by both N(G),N(G)-asymmetric dimethyl-l-arginine (ADMA) (300 μM), an inhibitor of NO synthase, and apamin (0.5 μM) plus 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) (1 μM), blockers of SK(Ca) and IK(Ca) channels, respectively. In small mesenteric arteries, NS309 relaxations were reduced slightly by ADMA, whereas apamin plus an IK(Ca) channel blocker almost abolished relaxation. Iberiotoxin did not change NS309 relaxation. HUVECs expressed mRNA for SK(Ca) and IK(Ca) channels, and NS309 induced increases in calcium, outward current, and NO release that were blocked by apamin and TRAM-34 or charybdotoxin. These findings suggest that opening of SK(Ca) and IK(Ca) channels leads to endothelium-dependent relaxation that is mediated mainly by NO in large mesenteric arteries and by EDHF-type relaxation in small mesenteric arteries. NS309-induced calcium influx appears to contribute to the formation of NO.     

Determination of optimal atrioventricular delay for cardiac resynchronization therapy using acute non-invasive blood pressure.

AIMS: In this study, we apply non-invasive blood pressure (BP) monitoring, by continuous finger photoplethysmography (Finometer), to detect directly haemodynamic responses during adjustment of the atrioventricular (AV) delay of cardiac resynchronization therapy (CRT), at different heart rates. METHODS AND RESULTS: Twelve patients were studied with six re-attending for reproducibility assessment. At each AV delay, systolic BP relative to a reference AV delay of 120 ms (SBPrel) was calculated. We found that at higher heart rates, altering the AV delay had a more pronounced effect on BP (average range of SBPrel=17.4 mmHg) compared with resting rates (average range of SBPrel=6.5 mmHg), P<0.0001. Secondly, peak AV delay differed between patients (minimum 120 ms, maximum 200 ms). Thirdly, small changes in AV delay had significant BP effects: programming AV delay 40 ms below the peak AV delay reduced SBPrel by 4.9 mmHg (P<0.003); having it 40 ms above the peak decreased SBPrel by 4.4 mmHg (P<0.0005). Finally, the peak AV delay is highly reproducible both on the same day and at 3 months (Bland-Altman difference: 3+/-8 ms). CONCLUSIONS: Continuous non-invasive arterial pressure monitoring demonstrates that even small changes in AV delay from its haemodynamic peak value have a significant effect on BP. This peak varies between individuals, is highly reproducible, and is more pronounced at higher heart rates than resting rates.     

A stable isotope aridity index for terrestrial environments

We use the oxygen isotopic composition of tooth enamel from multiple mammalian taxa across eastern Africa to present a proxy for aridity. Here we report tooth enamel delta(18)O values of 14 species from 18 locations and classify them according to their isotopic sensitivity to environmental aridity. The species are placed into two groups, evaporation sensitive (ES) and evaporation insensitive (EI). Tooth enamel delta(18)O values of ES animals increase with aridity, whereas the tooth enamel delta(18)O values of EI animals track local meteoric water delta(18)O values, demonstrating that bioapatite delta(18)O values of animals with different behaviors and physiologies record different aspects of the same environment. The enrichment between tooth enamel delta(18)O values of ES and EI animals records the degree of (18)O enrichment between evaporated water (ingested water or body water) and source water, which increases with environmental aridity. Recognition of the ES-EI distinction creates the opportunity to use the (18)O composition of bioapatite as an index of terrestrial aridity.     

Measurement of pulse wave velocity: site matters

BACKGROUND: Aortic pulse wave velocity (PWV) predicts mortality from cardiovascular disease, ischaemic heart disease and stroke. However, a comparison of associations between PWV measured at different sites and atherosclerosis in coronary, carotid and femoral arteries has not been made. METHODS: In 159 men (ages 45-82 years) with and without known coronary artery disease, PWV measurements were made between carotid-femoral, carotid-radial and femoral-posterior tibial sites, using an ultrasound technique. Coronary artery calcification (CAC) scores were measured by multislice computed tomography. Carotid and femoral intima-media thickness (IMT) and presence of plaque were determined by ultrasound. Known coronary artery disease was confirmed by angiography. Participants were grouped into four categories of CAC score: 0-10, 11-100, 101-400, > 400 Hounsfield Units (HU). Measurements of blood pressure, heart rate and fasting bloods were made in all individuals. RESULTS: Carotid-femoral PWV correlated positively with CAC score and increased with incremental coronary calcification category (median carotid-femoral PWV 16.8 m/s in those with CAC score > 400 HU and 13.8 m/s in those with CAC score < 10 HU; P = 0.003). Carotid-femoral PWV also correlated with carotid and femoral IMT (P < 0.001, P = 0.004, respectively) and with carotid and femoral plaque (P = 0.001, P = 0.038, respectively). Increased carotid-femoral PWV also correlated with increasing age (P < 0.001), systolic blood pressure (P < 0.001), mean arterial pressure and pulse pressure (P < 0.001). Carotid-radial and femoral-posterior tibial PWV were not significantly associated with CAC score, carotid or femoral IMT or carotid plaque. CONCLUSIONS: Carotid-femoral PWV is a better indicator of atherosclerosis than either carotid-radial or femoral-posterior tibial PWV, and should be used preferentially in studies of atherosclerosis and in stratifying risk in clinical settings.     

The ageing of the population: implications for multidisciplinary care in hospital

BACKGROUND: Comprehensive geriatric assessment and multidisciplinary intervention are of proven benefit in the care of older people. OBJECTIVE: To determine whether patients' multidisciplinary needs in hospital can be met by current service provision. DESIGN: A comprehensive census assessing the multidisciplinary needs of an entire inpatient population compared to available multidisciplinary therapy time. SETTING: A large teaching hospital Trust, comprising six hospital sites. METHODS: On census day, the age, Barthel Index score and multidisciplinary needs of all adult inpatients were documented. Each therapist completed a questionnaire regarding their direct patient contact time on census day. RESULTS: 889 of 1,324 eligible patients (69%) had multidisciplinary needs on census day. These patients were scattered throughout all 46 acute wards, 14 rehabilitation and 4 continuing care settings. Mean age was 65.3 years in acute wards, 73.5 in rehabilitation wards and 80.8 in continuing care. Age correlated inversely with Barthel Index score (r -0.255, P <0.01). The percentage of patients with multidisciplinary need increased with increasing age. The calculated number of minutes of therapy time per day available to each patient varied between therapies and across sites. Mean physiotherapy time available per patient needing physiotherapy on census day ranged from 17 minutes 41 seconds in acute wards to 26 minutes 24 seconds in rehabilitation wards. CONCLUSIONS: A high proportion of inpatients, particularly older patients, across all care settings have multidisciplinary needs. This needs to be expressly considered in the planning of future health services if multidisciplinary needs of older people in hospital are to be met.     

Evidence-based recommendations for PISA measurements in mitral regurgitation: systematic review,clinical and in-vitro study

Background

Guidelines for quantifying mitral regurgitation (MR) using “proximal isovelocity surface area” (PISA) instruct operators to measure the PISA radius from valve orifice to Doppler flow convergence “hemisphere”. Using clinical data and a physically-constructed MR model we (A) analyse the actually-observed colour Doppler PISA shape and (B) test whether instructions to measure a “hemisphere” are helpful.

Methods and results

In part A, the true shape of PISA shells was investigated using three separate approaches. First, a systematic review of published examples consistently showed non-hemispherical, “urchinoid” shapes. Second, our clinical data confirmed that the Doppler-visualized surface is non-hemispherical. Third, in-vitro experiments showed that round orifices never produce a colour Doppler hemisphere.In part B, six observers were instructed to measure hemisphere radius r_h and (on a second viewing) urchinoid distance (d_u) in 11 clinical PISA datasets; 6 established experts also measured PISA distance as the gold standard. r_h measurements, generated using the hemisphere instruction significantly underestimated expert values (− 28%, p < 0.0005), meaning r_h² was underestimated by approximately 2-fold. d_u measurements, generated using the non-hemisphere instruction were less biased (+ 7%, p = 0.03).Finally, frame-to-frame variability in PISA distance was found to have a coefficient of variation (CV) of 25% in patients and 9% in in-vitro data. Beat-to-beat variability had a CV of 15% in patients.

Conclusions

Doppler-visualized PISA shells are not hemispherical: we should avoid advising observers to measure a hemispherical radius because it encourages underestimation of orifice area by approximately two-fold. If precision is needed (e.g. to detect changes reliably) multi-frame averaging is essential.     

Regulation of Aedes aegypti Population Dynamics in Field Systems: Quantifying Direct and Delayed Density Dependence

Transgenic strains of Aedes aegypti have been engineered to help control transmission of dengue virus. Although resources have been invested in developing the strains, we lack data on the ecology of mosquitoes that could impact the success of this approach. Although studies of intra-specific competition have been conducted using Ae. aegypti larvae, none of these studies examine mixed age cohorts at densities that occur in the field, with natural nutrient levels. Experiments were conducted in Mexico to determine the impact of direct and delayed density dependence on Ae. aegypti populations. Natural water, food, and larval densities were used to estimate the impacts of density dependence on larval survival, development, and adult body size. Direct and delayed density-dependent factors had a significant impact on larval survival, larval development, and adult body size. These results indicate that control methods attempting to reduce mosquito populations may be counteracted by density-dependent population regulation.     

Impact of gastroesophageal reflux disease on patients' daily lives: a European observational study in the primary care setting

Background  

The impact of gastroesophageal reflux disease (GERD) on the daily lives of patients managed in primary care is not well known. We report the burden of GERD in a large population of patients managed in primary care, in terms of symptoms and impact on patients' daily lives.