Prognostic value of continuous EEG monitoring during therapeutic hypothermia after cardiac arrest.

Introduction: Continuous EEG (cEEG) is increasingly used to monitor brain function in neuro-ICU patients. However, its value in patients with coma after cardiac arrest (CA), particularly in the setting of therapeutic hypothermia (TH), is only beginning to be elucidated. The aim of this study was to examine whether cEEG performed during TH may predict outcome. Methods: From April 2009 to April 2010, we prospectively studied 34 consecutive comatose patients treated with TH after CA who were monitored with cEEG, initiated during hypothermia and maintained after rewarming. EEG background reactivity to painful stimulation was tested. We analyzed the association between cEEG findings and neurologic outcome, assessed at 2 months with the Glasgow-Pittsburgh Cerebral Performance Categories (CPC). Results: Continuous EEG recording was started 12 ± 6 hours after CA and lasted 30 ± 11 hours. Nonreactive cEEG background (12 of 15 (75%) among nonsurvivors versus none of 19 (0) survivors; P < 0.001) and prolonged discontinuous "burst-suppression" activity (11 of 15 (73%) versus none of 19; P < 0.001) were significantly associated with mortality. EEG seizures with absent background reactivity also differed significantly (seven of 15 (47%) versus none of 12 (0); P = 0.001). In patients with nonreactive background or seizures/epileptiform discharges on cEEG, no improvement was seen after TH. Nonreactive cEEG background during TH had a positive predictive value of 100% (95% confidence interval (CI), 74 to 100%) and a false-positive rate of 0 (95% CI, 0 to 18%) for mortality. All survivors had cEEG background reactivity, and the majority of them (14 (74%) of 19) had a favorable outcome (CPC 1 or 2). Conclusions: Continuous EEG monitoring showing a nonreactive or discontinuous background during TH is strongly associated with unfavorable outcome in patients with coma after CA. These data warrant larger studies to confirm the value of continuous EEG monitoring in predicting prognosis after CA and TH.

Pulse pressure variation-guided fluid therapy after cardiac surgery: A pilot before-and-after trial.

PURPOSE: The aim of this study is to study the feasibility, safety, and physiological effects of pulse pressure variation (PPV)-guided fluid therapy in patients after cardiac surgery. MATERIALS AND METHODS: We conducted a pilot prospective before-and-after study during mandatory ventilation after cardiac surgery in a tertiary intensive care unit. We introduced a protocol to deliver a fluid bolus for a PPV ≥13% for at least >10 minutes during the intervention period. RESULTS: We studied 45 control patients and 53 intervention patients. During the intervention period, clinicians administered a fluid bolus on 79% of the defined PPV trigger episodes. Median total fluid intake was similar between 2 groups during mandatory ventilation (1297 mL [interquartile range 549-1968] vs 1481 mL [807-2563]; P = .17) and the first 24 hours (3046 mL [interquartile range 2317-3982] vs 3017 mL [2192-4028]; P = .73). After adjusting for several baseline factors, PPV-guided fluid management significantly increased fluid intake during mandatory ventilation (P = .004) but not during the first 24 hours (P = .47). Pulse pressure variation-guided fluid therapy, however, did not significantly affect hemodynamic, renal, and metabolic variables. No serious adverse events were noted. CONCLUSIONS: Pulse pressure variation-guided fluid management was feasible and safe during mandatory ventilation after cardiac surgery. However, its advantages may be clinically small.

Epac contributes to cardiac hypertrophy and amyloidosis induced by radiotherapy but not fibrosis.

BACKGROUND: Cardiac toxicity is a side-effect of anti-cancer treatment including radiotherapy and this translational study was initiated to characterize radiation-induced cardiac side effects in a population of breast cancer patients and in experimental models in order to identify novel therapeutic target. METHODS: The size of the heart was evaluated in CO-HO-RT patients by measuring the Cardiac-Contact-Distance before and after radiotherapy (48months of follow-up). In parallel, fibrogenic signals were studied in a severe case of human radiation-induced pericarditis. Lastly, radiation-induced cardiac damage was studied in mice and in rat neonatal cardiac cardiomyocytes. RESULTS: In patients, time dependent enhancement of the CCD was measured suggesting occurrence of cardiac hypertrophy. In the case of human radiation-induced pericarditis, we measured the activation of fibrogenic (CTGF, RhoA) and remodeling (MMP2) signals. In irradiated mice, we documented decreased contractile function, enlargement of the ventricular cavity and long-term modification of the time constant of decay of Ca(2+) transients. Both hypertrophy and amyloid deposition were correlated with the induction of Epac-1; whereas radiation-induced fibrosis correlated with Rho/CTGF activation. Transactivation studies support Epac contribution in hypertrophy stimulation and showed that radiotherapy and Epac displayed specific and synergistic signals. CONCLUSION: Epac-1 has been identified as a novel regulator of radiation-induced hypertrophy and amyloidosis but not fibrosis in the heart.

Low molecular weight carboxylic acids in oxidizing porphyry copper tailings

The distribution of low molecular weight carboxylic acids (LMWCA) was investigated in pore water profiles from two porphyry copper tailings impoundments in Chile (Piuquenes at La Andina and Cauquenes at El Teniente mine). The objectives of this study were (1) to determine the distribution of LMWCA, which are interpreted to be the metabolic byproducts of the autotroph microbial community in this low organic carbon system, and (2) to infer the potential role of these acids in cycling of Fe and other elements in the tailings impoundments. The speciation and mobility of iron, and potential for the release of H+ via hydrolysis of the ferric iron, are key factors in the formation of acid mine drainage in sulfidic mine wastes. In the low-pH oxidation zone of the Piuquenes tailings, Fe(III) is the dominant iron species and shows high mobility. LMWCA, which occur mainly between the oxidation front down to 300 cm below the tailings surface at both locations (e.g., max concentrations of 0.12 mmol/L formate, 0.17 mmol/L acetate, and 0.01 mmol/L pyruvate at Piuquenes and 0.14 mmol/L formate, 0.14 mmol/L acetate, and 0.006 mmol/L pyruvate at Cauquenes), are observed at the same location as high Fe concentrations (up to 71.2 mmol/L Fe(II) and 16.1 mmol/L Fe(III), respectively). In this zone, secondary Fe(111) hydroxides are depleted. Our data suggest that LMWCA may influence the mobility of iron in two ways. First, complexation of Fe(III), through formation of bidentate Fe(III)-LMWCA complexes (e.g., pyruvate, oxalate), may enhance the dissolution of Fe(III) (oxy)hydroxides or may prevent precipitation of Fe(III) (oxy)hydroxides. Soluble Fe(III) chelate complexes which may be mobilized downward and convert to Fe(II) by Fe(III) reducing bacteria. Second, monodentate LMWCA (e.g., acetate and formate) can be used by iron-reducing bacteria as electron donors (e.g., Acidophilum spp.), with ferric iron as the electron acceptor. These processes may, in part, explain the low abundances of secondary Fe(III) hydroxide precipitates below the oxidation front and the high concentrations of Fe(II) observed in the pore waters of some low-sulfide systems. The reduction of Fe(III) and the subsequent increase of iron mobility and potential acidity transfer (Fe(II) oxidation can result in the release of H+ in an oxic environment) should be taken in account in mine waste management strategies.

Contemporary approach to neurologic prognostication of coma after cardiac arrest.

Coma after cardiac arrest (CA) is an important cause of admission to the ICU. Prognosis of post-CA coma has significantly improved over the past decade, particularly because of aggressive postresuscitation care and the use of therapeutic targeted temperature management (TTM). TTM and sedatives used to maintain controlled cooling might delay neurologic reflexes and reduce the accuracy of clinical examination. In the early ICU phase, patients' good recovery may often be indistinguishable (based on neurologic examination alone) from patients who eventually will have a poor prognosis. Prognostication of post-CA coma, therefore, has evolved toward a multimodal approach that combines neurologic examination with EEG and evoked potentials. Blood biomarkers (eg, neuron-specific enolase [NSE] and soluble 100-β protein) are useful complements for coma prognostication; however, results vary among commercial laboratory assays, and applying one single cutoff level (eg, > 33 μg/L for NSE) for poor prognostication is not recommended. Neuroimaging, mainly diffusion MRI, is emerging as a promising tool for prognostication, but its precise role needs further study before it can be widely used. This multimodal approach might reduce false-positive rates of poor prognosis, thereby providing optimal prognostication of comatose CA survivors. The aim of this review is to summarize studies and the principal tools presently available for outcome prediction and to describe a practical approach to the multimodal prognostication of coma after CA, with a particular focus on neuromonitoring tools. We also propose an algorithm for the optimal use of such multimodal tools during the early ICU phase of post-CA coma.

BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects.

Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterized by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor gene (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with (1) OFCD syndrome, (2) putative X-linked ('Lenz') microphthalmia syndrome, (3) isolated ocular defects and (4) laterality phenotypes. We present a new cohort of females with OFCD syndrome and null mutations in BCOR, supporting the hypothesis that BCOR is the sole molecular cause of this syndrome. We identify for the first time mosaic BCOR mutations in two females with OFCD syndrome and one apparently asymptomatic female. We present a female diagnosed with isolated ocular defects and identify minor features of OFCD syndrome, suggesting that OFCD syndrome may be mild and underdiagnosed. We have sequenced a cohort of males diagnosed with putative X-linked microphthalmia and found a mutation, p.P85L, in a single case, suggesting that BCOR mutations are not a major cause of X-linked microphthalmia in males. The absence of BCOR mutations in a panel of patients with non-specific laterality defects suggests that mutations in BCOR are not a major cause of isolated heart and laterality defects. Phenotypic analysis of OFCD and Lenz microphthalmia syndromes shows that in addition to the standard diagnostic criteria of congenital cataract, microphthalmia and radiculomegaly, patients should be examined for skeletal defects, particularly radioulnar synostosis, and cardiac/laterality defects.

Seed-specific silencing of OsMRP5 reduces seed phytic acid and weight in rice.

Phytic acid (PA) is poorly digested by humans and monogastric animals and negatively affects human/animal nutrition and the environment. Rice mutants with reduced PA content have been developed but are often associated with reduced seed weight and viability, lacking breeding value. In the present study, a new approach was explored to reduce seed PA while attaining competitive yield. The OsMRP5 gene, of which mutations are known to reduce seed PA as well as seed yield and viability, was down-regulated specifically in rice seeds by using an artificial microRNA driven by the rice seed specific promoter Ole18. Seed PA contents were reduced by 35.8-71.9% in brown rice grains of transgenic plants compared to their respective null plants (non-transgenic plants derived from the same event). No consistent significant differences of plant height or number of tillers per plant were observed, but significantly lower seed weights (up to 17.8% reduction) were detected in all transgenic lines compared to null plants, accompanied by reductions of seed germination and seedling emergence. It was observed that the silencing of the OsMRP5 gene increased the inorganic P (Pi) levels (up to 7.5 times) in amounts more than the reduction of PA-P in brown rice. This indicates a reduction in P content in other cellular compounds, such as lipids and nucleic acids, which may affect overall seed development. Put together, the present study demonstrated that seed specific silencing of OsMRP5 could significantly reduce the PA content and increase Pi levels in seeds; however, it also significantly lowers seed weight in rice. Discussions were made regarding future directions towards producing agronomically competitive and nutritionally valuable low PA rice.

Considerations for prenatal counselling of patients with cardiac rhabdomyomas based on their cardiac and neurologic outcomes.

Cardiac rhabdomyomas are benign cardiac tumours with few cardiac complications, but with a known association to tuberous sclerosis that affects the neurologic outcome of the patients. We have analysed the long-term cardiac and neurological outcomes of patients with cardiac rhabdomyomas in order to allow comprehensive prenatal counselling, basing our findings on the records of all patients seen prenatally and postnatally with an echocardiographic diagnosis of cardiac rhabdomyoma encountered from August, 1982, to September, 2007. We analysed factors such as the number and the location of the tumours to establish their association with a diagnosis of tuberous sclerosis, predicting the cardiac and neurologic outcomes for the patients.Cardiac complications include arrhythmias, obstruction of the ventricular outflow tracts, and secondary cardiogenic shock. Arrhythmias were encountered most often during the neonatal period, with supraventricular tachycardia being the commonest rhythm disturbance identified. No specific dimension or location of the cardiac rhabdomyomas predicted the disturbances of rhythm.The importance of the diagnosis of tuberous sclerosis is exemplified by the neurodevelopmental complications, with four-fifths of the patients showing epilepsy, and two-thirds having delayed development. The presence of multiple cardiac tumours suggested a higher risk of being affected by tuberous sclerosis. The tumours generally regress after birth, and cardiac-related problems are rare after the perinatal period. Tuberous sclerosis and the associated neurodevelopmental complications dominate the clinical picture, and should form an important aspect of the prenatal counselling of parents.

Psychotropic drug-induced weight gain and other metabolic complications in a Swiss psychiatric population.

PURPOSE: To describe the weight gain-related side-effects of psychotropic drugs and their consequences on metabolic complications (hypercholesterolemia, obesity) in a Swiss cohort of psychiatric patients. METHOD: This cross-sectional observational study was performed in an out-patient psychiatric division with patients having received for more than 3 months the following drugs: clozapine, olanzapine, quetiapine, risperidone, lithium, and/or valproate. Clinical measures and lifestyle information (smoking behaviour, physical activity) were recorded. RESULTS: 196 inclusions were completed. Weight gain (≥10% of initial weight) following drug treatment was reported in 47% of these patients. Prevalence of obesity (BMI ≥ 30), hypercholesterolemia (≥6.2 mmol/L) and low HDL-cholesterol (<1.0 mmol/L in men, <1.3 mmol/L in women) were present in 38%, 21%, and 27% of patients, respectively. A higher standardised dose, an increase of appetite following medication introduction, the type of medication (clozapine or olanzapine > quetiapine or risperidone > lithium or valproate), and the gender were shown to be significantly associated with evolution of BMI. CONCLUSION: High prevalence of obesity and hypercholesterolemia was found in an out-patient psychiatric population and confirms drug-induced weight gain complications during long-term treatment. The results support the recently published recommendations of monitoring of metabolic side-effects during treatment with atypical antipsychotics. Moreover, the weight gain predictors found in the present study could help to highlight patients with special health care management requirement.

Cardiac and pericardial fistulae associated with esophageal or gastric neoplasms: a literature review

Pericardial and cardiac fistulae secondary to esophageal or gastric tumors are considered exceptional. They have never been the object of a literature review. We reviewed the medical literature between 1881 and 2001, searching for all published cases of pericardial or cardiac fistulae developed from esophageal and gastric tumors or favored by the applied therapy to these tumors. The cases of metastasization, tumor spread, and neoplasic pericardial effusion without fistula were excluded. Fifty patients were identified, with one original case. More than half the cases (56%) occurred in the last 25 years. Substernal pain is the main symptom. The majority of patients present at least one condition favoring fistula formation. The auscultation of a water-wheel murmur may suggest a pneumopericardium and therefore a pericardial fistula, as does a purulent pericarditis. Arrhythmias, signs of ischemia, and hematemesis point toward a ventricular fistula. Neurological and hemostasis disorders may be suspect of an atrial lesion. Diagnosis should be made by the association of a scanner and a transit. Prognosis is bad: 76% of the patients die in the first month. Pericardial or cardiac fistulae are part of the differential diagnosis of thoracic pain in patients with esophageal or gastric tumors and in patients who were treated for these pathologies. The diagnosis must be as quick as possible. An operation (patients with a good prognosis) or the placement of a stent (patients with a bad prognosis) is the only chance of survival

Early parenteral lipids and growth velocity in extremely-low-birth-weight infants.

BACKGROUND & AIMS: Whether early parenteral lipids improve postnatal growth of preterm neonates remains unclear. We aimed to assess the effects of parenteral lipids on growth velocity in extremely-low-birth-weight infants. METHODS: This retrospective cohort study included 121 extremely-low-birth-weight infants. The associations between parenteral lipids (cumulative intakes during the first week and delays in their introduction) and growth velocities (weight, head circumference and length) up to 28 days of life and to 36 weeks of corrected age were analysed using uni- and multivariate linear regression. RESULTS: Univariate analyses showed a significant positive association between the cumulative intakes of parenteral lipids during the first week and i) weight gain up to day 28; ii) weight gain up to 36 weeks of corrected age; iii) head circumference growth up to day 28. There was a negative correlation between the delay in parenteral lipid introduction and weight gain up to day 28. In multivariate analyses, the association between the cumulative intakes of parenteral lipids and weight gain up to 28 days was independent of gestational age at birth, birth weight, sex, smallness for gestational age, and enteral intakes (regression coefficient: 0.19; 95% CI: 0.01-0.38) and, up to 36 weeks, independent of gestational age, birth weight, sex, smallness for gestational age and parenteral glucose and amino acids (0.16; 95% CI: 0.04-0.27). CONCLUSIONS: Parenteral lipids during the first week were positively associated with weight gain in extremely-low-birth-weight infants and could improve early nutritional support of preterm neonates.