Clinical decision support in the neonatal ICU

Clinical Decision Support (CDS) tools help the healthcare team diagnose, monitor, and treat patients more efficiently and consistently by executing clinical practice guidelines and recommendations. As a result, CDS has a direct impact on the delivery and healthcare outcomes. This review covers the fundamental concepts, as well as the infrastructure needed to create a CDS tool and examples of its use in the neonatal setting. This article also serves as a primer on what to think about when proposing the development of a new CDS tool, or when upgrading an existing one. We also highlight important elements that influence CDS development, such as informatics methodologies, data and device interoperability, and regulation.     

Endothelial hyperplasia and endothelial galectin-3 expression are prognostic factors in primary central nervous system lymphomas

Recently, considerable attention has been focused on the identification of clinically relevant prognostic markers for primary central nervous system lymphomas (PCNSL). The present study investigated whether three morphological features, i.e. necrosis, reactive perivascular T-cell infiltrate and endothelial hyperplasia, and galectin-1 and galectin-3 immunohistochemical expression have prognostic roles in a series of 58 PCNSL samples from 44 immunocompetent and 14 immunocompromised patients. The presence of endothelial hyperplasia (identified in 21% of the assessable cases) was identified as a bad prognostic factor for immunocompetent PCNSL patients, whereas the other morphological features were not associated with any prognostic value. Lymphomatous cells of eight PCNSL cases expressed galectin-3 without any prognostic value, and lymphomatous cells did not express galectin-1. In contrast, endothelial expression of galectin-3 was identified (by means of uni- and multi-variate analyses) as a bad prognostic factor for immunocompetent PCNSL patients. In addition, a combination of endothelial hyperplasia and/or endothelial galectin-3 expression was shown to be an independent prognostic factor for immunocompetent PCNSL patients treated with methotrexate-based chemotherapy. In summary, this study suggests that endothelial-related markers can identify risk groups of PCNSL patients and indicates that galectin-3 could be involved in PCNSL angiogenesis.     

The sympathetic response to euglycaemic hyperinsulinaemia

Summary Sympathetic nervous system activation by insulin has been suggested as a mechanism explaining the association between insulin resistance and hypertension. We further examined the effect of insulin by direct microneurographic muscle and skin nerve sympathetic activity recordings during euglycaemic insulin clamps in healthy subjects. The mean plasma insulin level was elevated from 5.3±0.7 to 92.2±2.2 mU/l in seven subjects during a 90-min one-step clamp. In six other subjects plasma insulin was further raised from 85.7±4.0 mU/l to 747±53 mU/l between 45–90 min (two-step clamp). Four of the latter subjects received a sham clamp with NaCl infusions only on a second recording session. At the low dose of insulin muscle nerve sympathetic activity increased from a resting level of 22.7±5.0 bursts per min to 27.7±5.0 bursts per min at 15 min (p<0.05). The increases in muscle nerve sympathetic activity were significant (p<0.001; ANOVA) throughout insulin infusion, with a slight further increase (from 29.2±1.6 to 32.3±1.9 bursts per min) at the supraphysiological insulin concentration. During sham clamps muscle nerve sympathetic activity did not increase. Both insulin clamps induced minor, but significant, increases in forearm venous plasma noradrenaline concentrations. Skin nerve sympathetic activity (n=3) did not change during insulin infusions. Heart rate increased slightly but significantly (p<0.005), during the insulin clamps. Blood pressure was not notably affected. In conclusion, hyperinsulinaemia was associated with increased vasoconstrictor nerve activity to skeletal muscle and with no change of sympathetic outflow to skin.     

血清新蝶呤水平与急性冠脉综合征的关系

急性冠脉综合征(ACS)是一种心血管系统急症,对其发病机制的研究对该病的治疗和预防都具有极为重要的意义。目前研究认为,免疫系统激活在ACS的发病过程中起到一定的作用。而新蝶呤作为一种细胞介导免疫激活的敏感标志物,其血清水平升高是心血管不良事件的独立预测指标。     

Heart Rate Variability: Measurement and Clinical Utility

Electrocardiographic RR intervals fluctuate cyclically, modulated by ventilation, baroreflexes, and other genetic and environmental factors that are mediated through the autonomic nervous system. Short term electrocardiographic recordings (5 to 15 minutes), made under controlled conditions, e.g., lying supine or standing or tilted upright can elucidate physiologic, pharmacologic, or pathologic changes in autonomic nervous system function. Long‐term, usually 24‐hour recordings, can be used to assess autonomic nervous responses during normal daily activities in health, disease, and in response to therapeutic interventions, e.g., exercise or drugs. RR interval variability is useful for assessing risk of cardiovascular death or arrhythmic events, especially when combined with other tests, e.g., left ventricular ejection fraction or ventricular arrhythmias.     

Pupil motility in long-term diabetes

Summary Employing infrared TV-videopupillography and the open loop stimulatory technique the ability of the pupil of the eye to react to rhythmic light stimuli of increasing frequencies was studied in 15 control subjects and 14 long-term juvenile diabetics. The degree of retinopathy varied from nil to proliferative changes. The visual acuity of all subjects studied was at least 6/9 and there were no ophthalmoscopic signs of retinopathy in the area stimulated by the light, thereby ensuring roughly uniform retinal sensitivity. The degree of neuropathy ranged from nil to moderate or severe as judged by vibratory perception threshold and pupil size. The pupil response (gain: fractional response to a unit light stimulus, and phase lag: latency period in number of stimulatory cycles) was the same in the group of diabetics as in the control group. The results show that the pupillary abnormalities of long-term diabetic patients (small size and a loss of spontaneous fluctuations) are probably] not due to stiffness of the iris tissues. It is suggested that diabetic autonomic neuropathy predominantly affects the sympathetic innervation to the dilator muscle, the parasympathetic innervation to the sphincter muscle being relatively spared.     

Pressure and frequency dependent linkage between motility and epithelial secretion in human proximal small intestine

BACKGROUND: Motor disturbances are sometimes associated with diarrhoea by unknown mechanisms. AIM: To determine if there is a quantitative link between intestinal motility and epithelial secretion. SUBJECTS: Experiments were performed in 21 healthy volunteers and three patients with villus atrophy. METHODS: Duodenal and jejunal motor activities were registered in the fasted state by open tip manometry. Secretion was measured directly by marker perfusion and indirectly by recording transmural potential difference (PD). RESULTS: A significant correlation was found between "low pass filtered" pressure and PD, but no correlation was found between amplitudes of isolated contractions and PD changes. During repeated phasic contractions (phase III of migrating motor complex), PD increased at a rate that was higher in the duodenum than in the jejunum, and higher in patients with villus atrophy than in healthy controls. After reaching a peak, PD decreased despite continuing phasic motor activity, provided that there was no concomitant increase in mean pressure. Fluid secretion increased roughly in parallel with PD, except at the very end of the cycle. CONCLUSIONS: To explain these findings, one has to postulate participation of at least two types of receptor: a slowly adapting pressure sensitive receptor and another mechanoreceptor, possibly a mucosal touch receptor, to account for the run down phenomenon. This model predicts that short lasting trains of contractions, so called discrete clusters, will be a particularly potent stimulus for activation of mucosal secretion.     

Torsade de pointes complicating acute myocardial infarction: the importance of autonomic dysfunction as assessed by heart rate variability.

Torsade de pointes is a polymorphic ventricular tachycardia associated with QT-interval prolongation rarely reported to occur in the setting of an acute myocardial infarction. Autonomic dysfunction has been implicated as a major stimulus for the development of this dysrhythmia. We describe the case of an 80-year-old woman who presented with an acute myocardial infarction and progressive QT-interval lengthening. An 89-beat run of torsade de pointes occurred during the time of the peak creatine phosphokinase (CPK) without electrolyte abnormalities or antiarrhythmic therapy. Assessment of autonomic tone using power spectral analysis of two consecutive 24-h Holter recordings was performed indicating that a transient decrease in heart rate variability and increase in sympathetic tone preceded the tachyarrhythmia. This case shows the potential usefulness of heart rate variability analysis as a marker for autonomic dysfunction and arrhythmogenesis, particularly during myocardial ischemia.     

Interleukin-6 levels are inversely correlated with heart rate variability in patients with decompensated heart failure

INTRODUCTION: Increased local and systemic elaboration of cytokines have an important role in the pathogenesis of congestive heart failure (CHF) through diverse mechanisms. Because cytokines are known to act at the neuronal level in both the peripheral and central nervous system, we sought to determine whether increased cytokine levels are associated with the autonomic dysfunction that characterizes CHF. METHODS AND RESULTS: We studied 64 patients admitted for decompensated CHF (mean age 59+/-12 years). Autonomic function was assessed using time- and frequency-domain heart rate variability (HRV) measures, obtained from 24-hour Holter recordings. In addition, norepinephrine, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured in all patients. TNF-alpha levels did not correlate with any of the HRV measures. IL-6 inversely correlated with the time-domain parameters of standard deviation of RR intervals (SDNN) (r = -0.36, P = 0.004) and standard deviation of all 5-minute mean RR intervals (SDANN) (r = -0.39, P = 0.001), and with the frequency-domain parameters of total power (TP) (r = -0.37, P = 0.003) and ultralow-frequency (ULF) power (r = -0.43, P = 0.001). No correlation was found between IL-6 and indices of parasympathetic modulation. Using multiple linear regression models, adjusting for clinical variables and drug therapies, the strong inverse relationship between IL-6 and SDNN (P = 0.006), SDANN (P = 0.001), TP (P = 0.04), and ULF power (P = 0.0007) persisted. CONCLUSION: Reduction of long-term HRV indices is associated with increased levels of IL-6 in patients with decompensated heart failure. The ability of long-term HRV parameters to better reflect activation of diverse hormonal systems may explain their greater prognostic power for risk stratification in patients with CHF.