Unilateral focal polymicrogyria in a patient with classical Aarskog-Scott syndrome due to a novel missense mutation in an evolutionary conserved RhoGEF domain of the faciogenital dysplasia gene FGD1

Faciogenital dysplasia or Aarskog-Scott syndrome (AAS) is an X-linked disorder characterized by craniofacial, skeletal, and urogenital malformations and short stature. Mutations in the only known causative gene FGD1 are found in about one-fifth of the cases with the clinical diagnosis of AAS. FGD1 is a guanine nucleotide exchange factor (GEF) that specifically activates the Rho GTPase Cdc42 via its RhoGEF domain. The Cdc42 pathway is involved in skeletal formation and multiple aspects of neuronal development. We describe a boy with typical AAS and, in addition, unilateral focal polymicrogyria (PMG), a feature hitherto unreported in AAS. Sequencing of the FGD1 gene in the index case and his mother revealed the presence of a novel mutation (1396A>G; M466V), located in the evolutionary conserved alpha-helix 4 of the RhoGEF domain. M466V was not found in healthy family members, in >300 healthy controls and AAS patients, and has not been reported in the literature or mutation databases to date, indicating that this novel missense mutation causes AAS, and possibly PMG. Brain cortex malformations such as PMG could be initiated by mutations in the evolutionary conserved RhoGEF domain of FGD1, by perturbing the signaling via Rho GTPases such as Cdc42 known to cause brain malformation.

Influence of oxygen therapy on glucose-lactate metabolism after diffuse brain injury

OBJECT: Severe traumatic brain injury (TBI) imposes a huge metabolic load on brain tissue, which can be summarized initially as a state of hypermetabolism and hyperglycolysis. In experiments O2 consumption has been shown to increase early after trauma, especially in the presence of high lactate levels and forced O2 availability. In recent clinical studies the effect of increasing O2 availability on brain metabolism has been analyzed. By their nature, however, clinical trauma models suffer from a heterogeneous injury distribution. The aim of this study was to analyze, in a standardized diffuse brain injury model, the effect of increasing the fraction of inspired O2 on brain glucose and lactate levels, and to compare this effect with the metabolism of the noninjured sham-operated brain. METHODS: A diffuse severe TBI model developed by Foda and Maramarou, et al., in which a 420-g weight is dropped from a height of 2 m was used in this study. Forty-one male Wistar rats each weighing approximately 300 g were included. Anesthesized rats were monitored by placing a femoral arterial line for blood pressure and blood was drawn for a blood gas analysis. Two time periods were defined: Period A was defined as preinjury and Period B as postinjury. During Period B two levels of fraction of inspired oxygen (FiO2) were studied: air (FiO2 0.21) and oxygen (FiO2 1). Four groups were studied including sham-operated animals: air-air-sham (AAS); air-O2-sham (AOS); air-air-trauma (AAT); and air-O2-trauma (AOT). In six rats the effect of increasing the FiO2 on serum glucose and lactate was analyzed. During Period B lactate values in the brain determined using microdialysis were significantly lower (p < 0.05) in the AOT group than in the AAT group and glucose values in the brain determined using microdialysis were significantly higher (p < 0.04). No differences were demonstrated in the other groups. Increasing the FiO2 had no significant effect on the serum levels of glucose and lactate. CONCLUSIONS: Increasing the FiO2 influences dialysate glucose and lactate levels in injured brain tissue. Using an FiO2 of 1 influences brain metabolism in such a way that lactate is significantly reduced and glucose significantly increased. No changes in dialysate glucose and lactate values were found in the noninjured brain.

SwissScoring--a nationwide survey of NEMS assessing practices and its accuracy.

BACKGROUND The nine equivalents of nursing manpower use score (NEMS) is used to evaluate critical care nursing workload and occasionally to define hospital reimbursements. Little is known about the caregivers' accuracy in scoring, about factors affecting this accuracy and how validity of scoring is assured. METHODS Accuracy in NEMS scoring of Swiss critical care nurses was assessed using case vignettes. An online survey was performed to assess training and quality control of NEMS scoring and to collect structural and organizational data of participating intensive care units (ICUs). Aggregated structural and procedural data of the Swiss ICU Minimal Data Set were used for matching. RESULTS Nursing staff from 64 (82%) of the 78 certified adult ICUs participated in this survey. Training and quality control of scoring shows large variability between ICUs. A total of 1378 nurses scored one out of 20 case vignettes: accuracy ranged from 63.7% (intravenous medications) to 99.1% (basic monitoring). Erroneous scoring (8.7% of all items) was more frequent than omitted scoring (3.2%). Mean NEMS per case was 28.0 ± 11.8 points (reference score: 25.7 ± 14.2 points). Mean bias was 2.8 points (95% confidence interval: 1.0-4.7); scores below 37.1 points were generally overestimated. Data from units with a greater nursing management staff showed a higher bias. CONCLUSION Overall, nurses assess the NEMS score within a clinically acceptable range. Lower scores are generally overestimated. Inaccurate assessment was associated with a greater size of the nursing management staff. Swiss head nurses consider themselves motivated to assure appropriate scoring and its validation.

Etomidate - a review of robust evidence for its use in various clinical scenarios

Etomidate is an intravenous hypnotic with a favourable clinical profile in haemodynamic high-risk scenarios. Currently, there is an active debate about the clinical significance of the drug's side effects and its overall risk-benefit ratio. Etomidate-induced transient adrenocortical suppression is well documented and has been associated with increased mortality in sepsis. In surgical patients at risk of hypotensive complications, however, a review of current literature provides no robust evidence to contraindicate a single-bolus etomidate induction. Large randomised controlled trials as well as additional observational data are required to compare safety of etomidate and its alternatives.

The impact of medical errors on Swiss anaesthesiologists: a cross-sectional survey.

BACKGROUND Clinicians involved in medical errors can experience significant distress. This study aims to examine (1) how medical errors impact anaesthesiologists in key work and life domains; (2) anaesthesiologists' attitudes regarding support after errors; (3) and which anaesthesiologists are most affected by errors. METHODS This study is a mailed cross-sectional survey completed by 281 of the 542 clinically active anaesthesiologists (52% response rate) working at Switzerland's five university hospitals between July 2012 and April 2013. RESULTS Respondents reported that errors had negatively affected anxiety about future errors (51%), confidence in their ability as a doctor (45%), ability to sleep (36%), job satisfaction (32%), and professional reputation (9%). Respondents' lives were more likely to be affected as error severity increased. Ninety per cent of respondents disagreed that hospitals adequately support them in coping with the stress associated with medical errors. Nearly all of the respondents (92%) reported being interested in psychological counselling after a serious error, but many identified barriers to seeking counselling. However, there were significant differences between departments regarding error-related stress levels and attitudes about error-related support. Respondents were more likely to experience certain distress if they were female, older, had previously been involved in a serious error, and were dissatisfied with their last error disclosure. CONCLUSION Medical errors, even minor errors and near misses, can have a serious effect on clinicians. Health-care organisations need to do more to support clinicians in coping with the stress associated with medical errors.

Neurohistological abnormalities during early porcine endotoxemia.

BACKGROUND Brain dysfunction is common in sepsis. We aimed to assess whether cerebral perfusion, oxygenation, and/or metabolism are abnormal during early endotoxemia, and how they may relate to potential neurohistological changes. METHODS In this prospective animal study, we included 12 pigs (weight: 42 ± 4 kg; mean ± SD) that were exposed to Escherichia coli lipopolysaccharide (E. coli LPS B0111 : B4, 0.4 μg/kg/h) or saline infusion (n = 6, each) for 10 h. Systemic hemodynamics, cerebral blood flow, intracranial pressure, and brain tissue oxygen tension were continuously measured. At the end of the experiment, formalin-fixed brains were cut in coronal sections and embedded in paraffin. Afterwards, the sections were cut at 5 microns and stained with hematoxylin and eosin. RESULTS Stable systemic hemodynamics in both groups were associated with higher carotid arterial blood flow after 10 h of endotoxemia (9.0 ± 2.2 ml/kg/min) compared to controls (6.6 ± 1.2 ml/kg/min; time-group interaction: P = 0.014). Intracranial pressure, cerebral perfusion pressure, brain oxygen consumption, and brain tissue oxygen tension were similar in both groups. In four of the six endotoxemic animals but in none of the controls, cerebral tissue lesions were found (encephalomalacia with spongy degeneration of white matter, axonal swelling, and ischemic neuronal thalamic necrosis), including significant venous vascular alterations, predominantly in the brainstem, in three of the four animals. CONCLUSIONS Early endotoxemia seems to be associated with histological signs of brain damage unrelated to systemic or cerebral hemodynamics or oxygenation.

Impact of a communication strategy on family satisfaction in the intensive care unit.

BACKGROUND Family satisfaction of critically ill patients has gained increased interest as important indicator to evaluate the quality of care in the intensive care unit (ICU). The family satisfaction in the ICU questionnaire (FS-ICU 24) is a well-established tool to assess satisfaction in such settings. We tested the hypothesis that an intervention, aiming at improved communication between health professionals and patients' next of kin in the ICU improves family satisfaction, as assessed by FS-ICU 24. METHODS Using a multicenter before-and-after study design, we evaluated medium-term effectiveness of VALUE, a recently proposed strategy aiming at improved communication. Satisfaction was assessed using the FS-ICU 24 questionnaire. Performance-importance plots were generated in order to identify items highly correlated with overall satisfaction but with low individual score. RESULTS A total of 163 completed family questionnaires in the pre-intervention and 118 in the post-intervention period were analyzed. Following the intervention, we observed: (1) a non-significant increase in family satisfaction summary score and sub-scores; (2) no decline in any individual family satisfaction item, and (3) improvement in items with high overall impact on satisfaction but quoted with low degree of satisfaction. CONCLUSION No significant improvement in family satisfaction of critically ill adult patients could be found after implementing the VALUE strategy. Whether these results are due to insufficient training of the new strategy or a missing effect of the strategy in our socio-economic environment remains to be shown.