Increased blood flow by insulin infusion targeting normoglycemia in patients with severe sepsis: friend or foe?

A small study in patients with severe sepsis suggested that insulin infused to normalize blood glucose levels increased forearm flow. This clinical observation supports the effect of insulin on the endothelium, as previously shown by in vitro studies and by in vivo animal models of critical illness, but the clinical consequences remain unclear

Is "safe effective glucose control" effective and safe?

Since tight glucose control (TGC) inevitably comes with a risk of hypoglycemia, Krinsley and Preiser [1] suggest the use of a stepwise approach to glucose control, which they call “safe, effective glucose control ” (SEGC), and that targets an intermediate blood glucose level (BGL). SEGC is intended to decrease the rate of hyperglycemia while reducing the adverse effects of severe hypoglycemia. Of note, the randomized controlled trials that showed a benefit from glucose control have tested only one and the same BGL target (4.4 to 6.1 mmol/l [80 to 110 mg/dl]) [2,3]. In addition, in these trials conventional insulin treatment was administered only when the BGL was>12 mmol/L (215 mg/dl), with insulin infusion gradually decreased and stopped when the BGL fell to <10 mmol/l (180 mg/dl). Accordingly, the average morning BGL of the conventional treatmen

Clinical review: Critical illness polyneuropathy and myopathy

Critical illness polyneuropathy (CIP) and myopathy (CIM) are major complications of severe critical illness and its management. CIP/CIM prolongs weaning from mechanical ventilation and physical rehabilitation since both limb and respiratory muscles can be affected. Among many risk factors implicated, sepsis, systemic inflammatory response syndrome, and multiple organ failure appear to play a crucial role in CIP/CIM. This review focuses on epidemiology, diagnostic challenges, the current understanding of pathophysiology, risk factors, important clinical consequences, and potential interventions to reduce the incidence of CIP/CIM. CIP/CIM is associated with increased hospital and intensive care unit (ICU) stays and increased mortality rates. Recently, it was shown in a single centre that intensive insulin therapy significantly reduced the electrophysiological incidence of CIP/CIM and the need for prolonged mechanical ventilation in patients in a medical or surgical ICU for at least 1 week. The electrophysiological diagnosis was limited by the fact that muscle membrane inexcitability was not detected. These results have yet to be confirmed in a larger patient population. One of the main risks of this therapy is hypoglycemia. Also, conflicting evidence concerning the neuromuscular effects of corticosteroids exists. A systematic review of the available literature on the optimal approach for preventing CIP/CIM seems warranted

Ingredients for adequate evaluation of blood glucose algorithms as applied to the critically ill

The article by Eslami and colleagues provides an overview of the indicators used to measure the quality of blood glucose control in patients admitted to the intensive care unit. Each indicator can be related to one or more of the following categories: blood glucose zones, blood glucose levels, time intervals, and features of the insulin titration algorithm. Some important issues (for instance those concerning the clarity of definitions used for glycaemic thresholds) are raised. This systematic review calls for a practical guide to advise the clinician how different blood glucose signals should (ideally) be evaluated and which steps should to be undertaken

Dynamics of need-supportive and need-thwarting teaching behavior : the bidirectional relationship with student engagement and disengagement in the beginning of a lesson

Background: According to the classroom ecology paradigm, teachers and students interpret, predict, and respond to each other repeatedly in a reciprocal way. Such a reciprocal relationship is reflected in bidirectional interactions between a teacher’s behavior and student (dis)engagement, an issue that has been confirmed in longitudinal studies including measures at different moments in a school year.Aims: Starting from the perspective of self-determination theory, the aim of the present study was to investigate bidirectional relationships between student (dis)engagement and need-supportive and need-thwarting teaching behavior during the first 15 min of a lesson.Sample & method: The first three 5-minute intervals of 100 videotaped physical education lessons taught by 100 different teachers (51.9% male,Mage ¼ 37.5 + 10.9 years) were observed and coded for need-supportive and need-thwarting teaching behavior, student engagement, and student disengagement. Correlations were calculated to explore relationships between student (dis)engagement and teaching behavior over the first 15 minutes of a PE lesson. Next, path analyses were conducted to analyze 5-to- 5 minute interactions between teaching behavior and student (dis)engagement.Results: Student engagement correlated positively and disengagement correlatednegatively with need support, while engagement correlated negatively anddisengagement correlated positively with need-thwarting over the first 15 minutes of the lesson. There were few significant relationships between student engagement and teachers’ behavior across and between each of the three 5-minute intervals. Only when teachers provided more need support during the first 5 minutes of the lesson, students were more engaged in the third 5 minutes of the lesson. When students were more disengaged during the first 5 minutes of the lesson, teachers displayed less need support in the following 10 minutes of the lesson. In contrast, student disengagement in the second 5 minutes of the lesson related to more need support in the next 5 minutes. Most of the within-interval relationships between student engagement and teachers’ behaviors were inconsistent, but we did find positive relationships between student disengagement and need-thwarting teaching behaviors in the first and third interval, suggesting a rather direct and momentary within 5-minute intervals interaction between teachers and students.Conclusions: Findings of the present observational study suggest that, although overall relationships between student (dis)engagement and teachers’ behavior were in the expected directions, the picture might become more complicated when relationships are investigated according to the timing of the lesson, an issue that has remained uncovered in self-reported studies. While student disengagement was related to less need support and more need-thwarting teaching behaviors, more detailed analyses showed that it was particularly student disengagement in the beginning of a lesson that elicited less positive teaching behaviors. When students display disengagement further along in the first 15 minutes of the lesson, teachers seemed to respond in a more need supportive way to student disengagement. Such findings provide interesting insights to build interventions for teachers around certain critical moments during the lesson, for example when dealing with student disengagement at a specific moment in the lesson

Critical illness-induced bone loss is related to deficient autophagy and histone hypomethylation

BACKGROUND Survivors of critical illness are at increased risk of fractures. This may be due to increased osteoclast formation during critical illness, leading to trabecular bone loss. Such bone loss has also been observed in Paget's disease, and has been related to deficient autophagy. Deficient autophagy has also been documented in vital organs and skeletal muscle of critically ill patients. The objective of this study was to investigate whether deficient autophagy can be linked to critical illness-induced bone loss. METHODS Osteoclasts grown in vitro and their precursor cells isolated from peripheral blood of critically ill patients and from matched healthy volunteers were analysed for the expression of autophagy genes (SQSTM1, Atg3 and Atg7), and proteins (p62, Atg-5, and microtubule-associated protein light chain 3-II (LC3-II)) and for autophagy and epigenetic signalling factors via PCR arrays and were treated with the autophagy inducer rapamycin. The effect of rapamycin was also investigated at the tissue level in an in vivo rabbit model of critical illness. RESULTS Many more osteoclasts formed in vitro from the blood precursor cells isolated from critically ill patients, which accumulated p62, and displayed reduced expression of Atg5, Atg7, and LC3-II compared to healthy controls, suggesting deficient autophagy, whilst addition of rapamycin reduced osteoclast formation. PCR arrays revealed a down-regulation of histone methyltransferases coupled with an up-regulation of negative regulators of autophagy. Critically ill rabbits displayed a reduction in trabecular and cortical bone, which was rescued with rapamycin. CONCLUSIONS Deficient autophagy in osteoclasts and their blood precursor cells at least partially explained aberrant osteoclast formation during critical illness and was linked to global histone hypomethylation. Treatment with the autophagy activator Rapamycin reduced patient osteoclast formation in vitro and reduced the amount of bone loss in critically ill rabbits in vivo. These findings may help to develop novel therapeutic targets to prevent critical illness-induced bone loss

Automated detection and classification of nuclei in immunohistochemical stainings for Fuchs' endothelial corneal dystrophy

Fuchs’ endothelial corneal dystrophy (FECD) is a degenerative disease that affects the elderly population, and which lacks a unifying pathogenic theory and tangible drug targets. Immunohistochemical stainings can be used to identify proteins involved in the pathogenesis of FECD. We introduce a method for the automatic quantification of the ratio of stained cells starting from full high-resolution cornea images. First, the endothelium is extracted using entropy information in a low-resolution resampling. Then, within the endothelium, we heuristically detect and classify nuclei based on their size, color, and the color of the surrounding cytoplasm. This method achieves comparable results to manual evaluation in a set of corneas of patients with and without FECD.status: publishe