Clinical review: Fever in septic ICU patients - friend or foe?

In recent years, fever control in critically ill patients by medications and/or external cooling has gained widespread use, notably in patients suffering from neurological injuries. Nevertheless, such a strategy in septic patients is not supported by relevant data. Indeed, in response to sepsis, experimental and clinical studies argue that fever plays a key role in increasing the clearance of microorganisms, the immune response and the heat shock response. Moreover, fever is a cornerstone diagnostic sign in clinical practice, which aids in early and appropriate therapy, and allows physicians to follow the infection course. After discussing the physiological aspects of fever production, the present review aims to delineate the advantages and drawbacks of fever in septic patients. Finally, the treatment of fever by pharmacological and/or physical means is discussed with regards to their drawbacks, which argues for their careful use in septic patients in the absence of clinical relevance.     

Abnormal Coronary Anatomy in Patients with Transposition of the Great Arteries and Atrial Switch: A Predictor of Serious Cardiac Adverse Events?

Sudden cardiac death and heart failure are well known long-term complications after atrial switch for D-transposition of the great arteries (D-TGA). Right systemic ventricular dysfunction is common and myocardial ischemia has been implicated as a putative mechanism for sudden death, with coronary anomalies prevalent in 30% of cases. We sought to assess an association between adverse events and coronary anomalies in patients with D-TGA and atrial switch surgery. An observational study was conducted in 3 tertiary centers (Montreal Heart Institute, Canada, Nationwide Children’s hospital, Chicago, USA and Hopital cardiologique Louis Pradel de Lyon, France). Adults with D-TGA and atrial switch surgery qualified for inclusion if they had a major adverse cardiovascular event (MACE), i.e., ventricular arrhythmia, sudden cardiac death, heart failure, cardiac transplantation, or cardiovascular death. The prevalence of coronary anomalies was compared to historical controls. Forty-five patients were included. Twenty-one (46.7%) patients experienced a ventricular arrhythmia and 35 (77.8%) suffered from symptomatic heart failure and/or severe right ventricular dysfunction. Twelve patients (26.7%) had congenitally abnormal coronary arteries. There was no difference in the prevalence of coronary anomalies between the cohort with a MACE and a pooled population of 647 historical controls with D-TGA (28.7%, p = 0.89). In conclusion, the prevalence of congenital coronary anomalies is not higher in patients with D-TGA and atrial switch surgery who had adverse cardiovascular events. It could be hypothesized that ischemic complications in this patient population are more likely to be related to a supply-demand mismatch of the distal microvasculature rather than proximal coronary anomalies.     

七情所伤的致病特点

目的研究七情致病的规律和特点,指导中医养生、预防和治疗。方法对50份精神障碍患者填写的提纲式作业进行质性分析研究。对问卷内容中情志导致症状的相关字段进行编码,并进行总结和分析。结果怒、思(怀念)、悲、恐四种情志可以导致症状,其中恐导致症状的频率最多;情志所导致的症状以失眠最为常见;不同情志所伤的脏腑没有显著差异(P0.05);思(思维)不能单独导致症状但可以与其他情志协同导致症状。结论研究结果不支持"恐伤肾"等"本情志伤本脏"学说;情志致病主要涉及心、肝两脏,其次为脾,病机以郁、火、虚、风等为特点;思在七情当中具有中心地位;临床上面对症状尤其是失眠需要谨慎考虑是否由情志因素所导致。     

Developmental defects in zebrafish for classification of EGF pathway inhibitors

One of the major challenges when testing drug candidates targeted at a specific pathway in whole animals is the discrimination between specific effects and unwanted, off-target effects. Here we used the zebrafish to define several developmental defects caused by impairment of Egf signaling, a major pathway of interest in tumor biology. We inactivated Egf signaling by genetically blocking Egf expression or using specific inhibitors of the Egf receptor function. We show that the combined occurrence of defects in cartilage formation, disturbance of blood flow in the trunk and a decrease of myelin basic protein expression represent good indicators for impairment of Egf signaling. Finally, we present a classification of known tyrosine kinase inhibitors according to their specificity for the Egf pathway.     

Speckle tracking analysis allows sensitive detection of stress cardiomyopathy in severe aneurysmal subarachnoid hemorrhage patients

Purpose

Stress cardiomyopathy is a common life-threatening complication after aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that left ventricular (LV) longitudinal strain alterations assessed with speckle tracking could identify early systolic function impairment.

Methods

This was an observational single-center prospective pilot controlled study conducted in a neuro-intensive care unit. Forty-six patients with severe SAH with a World Federation of Neurological Surgeons grade (WFNS) ≥III were included. Transthoracic echocardiography (TTE) was performed on day 1, day 3, and day 7 after the patient’s admission. A cardiologist blinded to the patient’s management analyzed the LV global longitudinal strain (GLS). The control group comprised normal subjects matched according to gender and age.

Results

On day 1 median (25th–75th percentile) GLS was clearly impaired in SAH patients compared to controls [?16.7 (?18.7/?13.7) % versus ?20 (?22/?19) %, p < 0.0001], whereas LVEF was preserved [65 (59?70) %]. GLS was severely impaired in patients with a WFNS score of V versus III–IV [?15.6 (?16.9/?12.3) % versus ?17.8 (?20.6/?15.8) %, p = 0.008]. Seventeen (37 %) patients had a severe GLS alteration (>?16 %). In these patients, GLS improved from day 1 [?12.4 (?14.8/?10.9) %] to last evaluation [?16.2 (?19/?14.6) %, p = 0.0007] in agreement with the natural evolution of stress cardiomyopathy.

Conclusions

On the basis of LV GLS assessment, we demonstrated for the first time that myocardial alteration compatible with a stress cardiomyopathy is detectable in up to 37 % of patients with severe SAH while LVEF is preserved. GLS could be used for sensitive detection of stress cardiomyopathy. This is critical because cardiac impairment remains a major cause of morbidity and mortality after SAH.

     

Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002–2010)

Purpose

To analyze trends in incidence and mortality of candidemia in intensive care units (ICUs) vs. non-ICU hospitalized patients and to determine risk factors for infection by specific species and for death.

Methods

Active hospital-based surveillance program of incident episodes of candidemia due to common species in 24 tertiary care hospitals in the Paris area, France between October 2002 and September 2010.

Results

Among 2,507 adult cases included, 2,571 Candida isolates were collected and species were C. albicans (56 %), C. glabrata (18.6 %), C. parapsilosis (11.5 %), C. tropicalis (9.3 %), C. krusei (2.9 %), and C. kefyr (1.8 %). Candidemia occurred in ICU in 1,206 patients (48.1 %). When comparing ICU vs. non-ICU patients, the former had significantly more frequent surgery during the past 30 days, were more often preexposed to fluconazole and treated with echinocandin, and were less frequently infected with C. parapsilosis. Risk factors and age remained unchanged during the study period. A significant increased incidence in the overall population and ICU was found. The odds of being infected with a given species in ICU was influenced by risk factors and preexposure to fluconazole and caspofungin. Echinocandins initial therapy increased over time in ICU (4.6 % first year of study, to 48.5 % last year of study, p < 0.0001). ICU patients had a higher day-30 death rate than non-ICU patients (odds ratio [OR] 2.12; 95 % confidence interval [CI] 1.66–2.72; p < 0.0001). The day-30 and early (p = 0.001) and 28.7–38.8 % (p = 0.0292), respectively). Independent risk factors for day-30 death in ICU were age, arterial catheter, Candida species, preexposure to caspofungin, and lack of antifungal therapy at the time of blood cultures results (p < 0.05).

Conclusions

The availability of new antifungals and the publication of numerous guidelines did not prevent an increase of candidemia and death in ICU patients in the Paris area.