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INTRODUCTION Rib fracture fixation is becoming more popular and widely accepted among trauma surgeons worldwide as the recommended treatment method for flail chest injury. Recent data demonstrate improved results when compared with non-operative treatment. Improved outcomes were reported regarding ICU stay, need for tracheostomy, length of hospital stay, ventilator-associated pneumonia (VAP), and even death. The objective of this study was to ascertain whether clinical respiratory para-meters are improved after rib fracture fixation procedure. MATERIAL AND METHODS This is a prospective study using a retrospective cohort for control, which took place at the Soroka University Medical Centre, Israel. Inclusion criteria included all patients over 18 years of age with flail chest injury or multiple ribs fractures, who were admitted to the General Intensive Care Unit (GICU). Between October 2015 and December 2018, we identified 24 patients who had their rib fractures operatively fixed and compared them to 61 patients with flail chest and multiple rib fractures, who were admitted to our GICU between the years 2010 and 2015 and were treated non-opera-tively. In all the surgical cases operations were performed within 72 hours of arrival in accordance with our treatment algorithm. All fractures were fixed using specialised anatomic locking plates/nails. Demographic data were collected, and respiratory parameters before and after the surgery were recorded and analysed. RESULTS We compared patients who had had their rib fractures fixed with a cohort group of patients who had been treated non-operatively in the past. No demographic differences were found between the 2 groups, nor were there any differences in their clinical trauma scoring, mechanical ventilation days, length of ICU stay, VAP, and death rates. The respiratory parameters (paO2/FiO2 ratio and chest wall compliance) were significantly higher during the 3 ensuing days after surgery and continued to improve in Group 1 (rib fixation group), in comparison to group 2 (non-operative) patients (P = 0.007 and P < 0.0001, respectively). The peak inspiratory pressure and PEEP para-meters were significantly lower in group 1 in comparison to group 2 during the 3 days, in favour of the operated group, with significant improvement noted over the 3 days post-surgery (P = 0.007 and P = 0.02, respectively). CONCLUSIONS We suggest that surgical treatment of flail chest and multiple rib fractures has clinical benefit and improves respiratory parameters even in the presence of multiple trauma injuries.

Here we evaluate an alternative protocol to histologically examine blood-brain barrier (BBB) breakdown, brain edema, and lesion volume following traumatic brain injury (TBI) in the same set of rodent brain samples. We further compare this novel histological technique to measurements determined by magnetic resonance imaging (MRI) and a neurological severity score (NSS). Sixty-six rats were randomly assigned to a sham-operated, mild TBI, moderate TBI, or severe TBI group. 48 h after TBI, NSS, MRI and histological techniques were performed to measure TBI severity outcome. Both the histological and MRI techniques were able to detect measurements of severity outcome, but histologically determined outcomes were more sensitive. The two most sensitive techniques for determining the degree of injury following TBI were NSS and histologically determined BBB breakdown. Our results demonstrate that BBB breakdown, brain edema, and lesion volume following TBI can be accurately measured by histological evaluation of the same set of brain samples.

Background Patients with GBS may develop hypoalbuminemia following treatment with Intravenous Immunoglobulin (IVIG), which is related to a poorer outcome. This report presents a patient with GBS and his clinical response to two courses of IVIG treatments in association with his albumin level. Case report: A previously healthy 21-year-old male was admitted to the GICU due to GBS with severity grade 5 (required assisted ventilation). IVIG treatment was initiated. Over the next two weeks there was no clinical improvement and Albumin level dropped from 4.5 gr/dL to a nadir of 2.3 gr/dL. A second course of IVIG was initiated. After initiation of the second course the patient’s albumin began rising to 3.0 gr/dL and a clinical improvement followed this rise. Subsequently, he was weaned from mechanical ventilation within a few days. Conclusions When considering a second course of IVIG treatment, serum albumin levels may be considered a biomarker as part of the decision algorithm.

Post-stroke depression (PSD) is a common and serious complication following stroke. Both stroke and depression have independently been associated with pathologically elevated glutamate levels in the brain's extra-cerebral fluid (ECF). Here we evaluate an alternative therapeutic approach to PSD with pyruvate. Rats were randomly assigned into one of 3 groups: Middle Cerebral Artery Occlusion (MCAO) plus pyruvate treatment, MCAO plus placebo treatment, and sham operated rats. Post-MCAO depressive and anxiety-like behavior was assessed, along with neurological status, brain infarct zone, brain edema, blood brain barrier (BBB) breakdown, cerebrospinal fluid and blood glutamate levels. Anxiety-like behavior and levels of blood alanine and α-ketoglutarate were measured in naive rats treated with pyruvate, as a control. Post-stroke neurological deficit with concurrent elevation in glutamate levels were demonstrated, with peak glutamate levels 24 h after MCAO. Treatment with pyruvate led to reduced glutamate levels 24 h after MCAO and improved neurologic recovery. Pyruvate treatment reduced lesion volume, brain edema and the extent of BBB permeability 24 h post-MCAO. Naive rats treated with pyruvate showed increased levels of α-ketoglutarate. Rats demonstrated post-stroke depressive behavior that was improved by the administration of pyruvate. There was less anxiety-like behavior in post-stroke rats treated with placebo in comparison to the post-stroke rats treated with pyruvate or sham operated rats. Glutamate scavenging with pyruvate appears to be an effective as a method in providing neuroprotection following stroke and as a therapeutic option for the treatment of PSD by reducing the consequent elevations in CNS glutamate levels.

Critically ill patients with severe hypoxemia are often treated in the intensive care unit (ICU) with inhaled nitric oxide (iNO). These patients are at higher risk when they require intrahospital transportation. In this study, we collected clinical and laboratory data from 221 patients who were hospitalized in the general ICU and treated with iNO at Soroka Medical Center, Israel, between January 2010 and December 2019. We retrospectively compared the 65 patients who received iNO during intrahospital transportation to the 156 patients who received iNO without transportation. Among critically ill patients who were transported while being administered iNO, only one patient had an adverse event (atrial fibrillation) on transport. We found that maximal iNO dosage during ICU stay, duration of mechanical ventilation, and percent of vasopressor support were the only independent risk factors for ICU mortality in both study groups. No difference in primary outcome of ICU mortality rate was found between the critically ill patients treated with iNO during intrahospital transportation and those who were treated with iNO but not transported during the ICU stay. We anticipate that this study will advise clinical decision-making in the ICU, especially when treating patients who are administered iNO.

For many species, where status is a vital motivator that can affect health, social hierarchies influence behavior. Social hierarchies that include dominant-submissive relationships are common in both animal and human societies. These relationships can be affected by interactions with others and with their environment, making them difficult to analyze in a controlled study. Rather than a simple dominance hierarchy, this formation has a complicated presentation that allows rats to avoid aggression. Status can be stagnant or mutable, and results in complex societal stratifications. Here we describe a complex diving-for-food task to investigate rodent social hierarchy and behavioral interactions. This animal model may allow us to assess the relationship between a wide range of mental illnesses and social organization, as well as to study the effectiveness of therapy on social dysfunction.

Since 2015, endovascular thrombectomy has been established as the standard of care for re-establishing cerebral blood flow in patients with acute ischemic stroke. Several retrospective observational studies and prospective clinical trials have investigated two anesthetic techniques for endovascular stroke therapy: general anesthesia (GA) and conscious sedation (CS). The recent randomized studies suggest that GA is associated with higher rates of successful recanalization and better functional independence at 3 months compared with the CS technique. However, CS techniques are highly variable, and there is currently a lack of consensus on which anesthetic approach is best in all patients. Numerous patient and procedural factors should ultimately guide the decision of whether GA or CS should be used for a particular patient.

Background Patients who undergo surgical procedures that impair the integrity of the chest wall frequently experience extremely severe postoperative pain. Opiates and weaker analgesics, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are not sufficiently effective in achieving control of severe pain and might cause respiratory and gastrointestinal complications. In the past decade, there has been an increased interest in the use of regional nerve blocks for post-thoracoscopy and post-thoracotomy analgesia. Methods This is a prospective, randomized, double-blind and single-center study. We recruited 104 patients who underwent elective thoracoscopy. Prior to surgery, the participating patients were randomized into one of two study groups: Group 1- the "standard control group" that received standard postoperative pain control with intravenous opioids, NSAIDs and acetaminophen (paracetamol) and Group 2- the "block group" that was treated by ultrasound-guided serratus anterior plane (SAP) block (a single injection of 0.25% bupivacaine hydrochloride 2 mg/kg plus dexamethasone 8 mg) with standard postoperative pain control regimen. We compared the clinical, laboratory, and postoperative pain assessment data of both groups. Results Patients in the SAP block Group 2 reported significantly lower levels of pain after thoracic surgery as assessed by their visual analog scale scores, as compared to the patients in the standard pain control Group 1 (P

Glucocorticoids might have significant influence on positive fluid balance, mostly due to their mineralocorticoid effect. We assessed the association between glucocorticoid therapy and fluid balance in septic patients, in the intensive care unit (ICU). We considered two definitions of exposure: daily exposure to glucocorticoids and glucocorticoid treatment at any time. Of 945 patients, 375 were treated with glucocorticoids in the ICU. We applied four regression models. In the first, fluid balance did not differ during days with and without glucocorticoid treatment, among patients treated and not treated with glucocorticoids in the ICU. In our second model, daily fluid balance was increased in patients who were ever treated with glucocorticoids during their ICU stay compared to untreated patients. In the third model, which included only patients treated with glucocorticoids during their ICU stay, glucocorticoid treatment days were not associated with daily fluid balance. In the last model, on "steroid-free days", patients who received glucocorticoid treatment during their ICU stay had a positive fluid balance compared to those who were never treated with steroids. Despite their known mineralocorticoid activity, glucocorticoids themselves appear not to contribute substantially to fluid retention. This work highlights the importance of precise selection of variables to mitigate biases.

Background Ischemic stroke is one of the leading causes of mortality and morbidity. The currently available non-invasive therapeutic options are not sufficiently efficacious. Post-ischemic brain is characterized by a prominent inflammatory response. Little is known about the involvement of cyclooxygenase (COX)-1 in the pathophysiology of ischemic stroke. Objective This study was undertaken to examine the effects of a highly selective COX-1 inhibitor – mofezolac – on clinical outcomes and brain inflammatory markers in post-stroke rats. Methods Stroke was induced by subjecting rats to permanent middle cerebral artery occlusion (MCAO). Control rats underwent a sham surgery. Rats were treated with mofezolac (50 mg/kg, intraperitoneally [ip]) once daily for 14 days. Control animals were treated with vehicle. Body temperature (BT), neurological score (NS) and cumulative mortality were monitored at different time points. At the end of the experiment, rats were euthanized and three brain regions (hypothalamus, hippocampus and frontal cortex) were extracted. Levels of interleukin (IL)-6, prostaglandin (PG)E2 and tumor necrosis factor (TNF)-α in these brain regions were determined by ELISA kits. Results BT, NS and cumulative mortality were all significantly higher in post-MCAO rats than in sham-operated rats, irrespective of the treatment given. BT, NS and mortality rate did not differ significantly between mofezolac-treated and vehicle-treated sham-operated animals. BT was significantly lower in mofezolac-treated as compared to vehicle-treated post-MCAO rats. Mofezolac did not significantly alter NS in post-MCAO rats at any time-point. Cumulative 14-day mortality was non-significantly higher in mofezolac-treated as compared to vehicle-treated post-MCAO rats (48 % vs. 21 %, respectively; P = 0.184). Mostly, IL-6 and TNF-α levels did not differ between post-MCAO and sham-operated rats and were not affected by mofezolac treatment. In contrast, mofezolac significantly decreased PGE2 levels in post-MCAO rats’ brains. Conclusion Overall, these results suggest that chronic treatment with the selective COX-1 inhibitor mofezolac did not reduce morbidity or mortality in post-stroke rats.

Acute liver injury (ALI) plays a crucial role in the development of hepatic failure, which is characterized by severe liver dysfunction including complications such as hepatic encephalopathy and impaired protein synthesis. Appropriate animal models are vital to test the mechanism and pathophysiology of ALI and investigate different hepatoprotective strategies. Due to its ability to perform chemical transformations, carbon tetrachloride (CCl4) is widely used in the liver to induce ALI through the formation of reactive oxygen species. CCl4 exposure can be performed intraperitoneally, by inhalation, or through a nasogastric or orogastric tube. Here, we describe a rodent model, in which ALI is induced by CCl4 exposure through an orogastric tube. This method is inexpensive, easily performed, and has minimal hazard risk. The model is highly reproducible and can be widely used to determine the efficacy of potential hepatoprotective strategies and assess markers of liver injury.

Background:Inadvertent hyperthermia during anaesthesia is a rare but life-threatening complication. We have encountered several cases of severe hyperthermia in paediatric patients undergoing anaesthesia for cochlear implantation.Methods:This study aimed to describe the clinical characteristics of children who developed hyperthermia while undergoing cochlear implantation, and to explore possible mechanisms and predisposing factors. The anaesthetic charts of all patients aged under 18 years who underwent cochlear implantation, or mastoid or ophthalmic surgery, between 1 January 2006 and 31 December 2009, at Soroka Medical Center in Beer Sheva, Israel, were reviewed. Patients undergoing mastoid and ophthalmic surgical procedures were used as controls.Results:A larger percentage of patients who underwent cochlear implant surgery (10 per cent) developed hyperthermia compared to controls (0.7 per cent, p < 0.05). In five of the seven cases, hyperthermia appeared in combination with tachycardia and hypercapnia, adhering to the clinical triad of malignant hyperthermia.Conclusion:Patients undergoing cochlear implantation are susceptible to developing intra-operative hyperthermia. This article describes the hyperthermic events that occur during paediatric cochlear implantation, and attempts to identify potential triggers of hyperthermia.

Serious complications in obstetric anesthesia are a rare occurrence. High neuraxial block, respiratory arrest in labor and delivery, and an unrecognized spinal catheter are among the most frequently reported serious complications. A serious complication occurs in approximately 1:3000 obstetric patients. Neuraxial hematoma after obstetric epidural analgesia or anesthesia is extremely rare. We present a case of a puerperal spinal epidural hematoma following epidural labor analgesia. The patient presented with foot drop, which resolved after conservative treatment. We reviewed the epidemiology, clinical manifestations and treatment options for this rare complication.

Background: Glucocorticoids (GCS) are commonly administered to critically ill patients. Due to their mineralocorticoid effect, GCS might have a substantial influence on a positive fluid balance. We assessed the association between glucocorticoids (GCS) therapy and fluid balance in critically ill patients with sepsis.Methods: This is a retrospective study of patients with sepsis hospitalized during 2006-2018 in a general intensive care unit (ICU) at a 1100-bed tertiary medical center.Results – We considered two definitions of exposure: daily exposure to GCS and GCS treatment at any time in the ICU. Of 945 patients with a diagnosis of sepsis, 375 were treated with GCS at any time and 570 were not. We applied four regression models to assess the association between GCS treatment and fluid balance; in our first model, fluid balance did not differ during days with GCS treatment, between patients who were and were not treated with GCS in the ICU (coefficient estimate 79.5 (-55.4 to 214.4), p=0.25). In our second model, daily fluid balance was increased by 139.8 ml (10.8 to 268.9; p=0.03) in patients who were ever treated with GCS during their ICU stay compared to untreated patients. In the third model, which included only patients treated with GCS during their ICU stay, GCS treatment days were not associated with daily fluid balance (coefficient estimate -190.6 (-485.1 to 103.9), p-value=0.21). In the last model, on "steroid free days", patients who received GCS treatment during their ICU stay had a positive fluid balance compared to those who were never treated with steroids (coefficient estimate 157.7 (-24.6 to 340.1), p-value=0.09).Conclusions – Despite their known mineralocorticoid activity, GCS themselves appear not to contribute substantially to fluid retention. The findings highlight the importance of a clear definition of exposure.

Post-stroke depression (PSD) is a major complication of stroke that significantly impacts functional recovery and quality of life. While the exact mechanism of PSD is unknown, recent attention has focused on the association of the glutamatergic system in its etiology and treatment. Minimizing secondary brain damage and neuropsychiatric consequences associated with excess glutamate concentrations is a vital part of stroke management. The blood glutamate scavengers, oxaloacetate and pyruvate, degrade glutamate in the blood to its inactive metabolite, 2-ketoglutarate, by the coenzymes glutamate–oxaloacetate transaminase (GOT) and glutamate–pyruvate transaminase (GPT), respectively. This reduction in blood glutamate concentrations leads to a subsequent shift of glutamate down its concentration gradient from the blood to the brain, thereby decreasing brain glutamate levels. Although there are not yet any human trials that support blood glutamate scavengers for clinical use, there is increasing evidence from animal research of their efficacy as a promising new therapeutic approach for PSD. In this review, we present recent evidence in the literature of the potential therapeutic benefits of blood glutamate scavengers for reducing PSD and other related neuropsychiatric conditions. The evidence reviewed here should be useful in guiding future clinical trials.

The brain undergoes significant physiologic changes during pregnancy. Pregnant women who are critically ill with obstetric disorders, such as eclampsia, preeclampsia, intracranial hemorrhage (ICH), and benign intracranial hypertension, and those with severe TBI or other disorders that need prolonged sedation in the ICU may require appropriate neuromonitoring during their ICU stay. Despite the variety of invasive and noninvasive neuromonitoring tools, daily clinical neurological examination (including Glasgow coma scoring, assessment of pupil size, and daily focal neurologic deficit evaluation) remains the cornerstone component of neuromonitoring during the ICU stay of such patients.

Stroke is a major cause of global morbidity and mortality. Middle cerebral artery occlusion (MCAO) has historically been the most common animal model of simulating ischemic stroke. The extent of neurological injury after MCAO is typically measured by cerebral edema, infarct zone, and blood-brain barrier (BBB) permeability. A significant limitation of these methods is that separate sets of brains must be used for each measurement. Here we examine an alternative method of measuring cerebral edema, infarct zone and BBB permeability following MCAO in the same set of brain samples. Ninety-six rats were randomly divided into three experimental groups. Group 1 (n = 27) was used for the evaluation of infarct zone and brain edema in rats post-MCAO (n = 17) vs. sham-operated controls (n = 10). Group 2 (n = 27) was used for the evaluation of BBB breakdown in rats post-MCAO (n = 15) vs. sham-operated controls (n = 10). In Group 3 (n = 42), all three parameters were measured in the same set of brain slices in rats post-MCAO (n = 26) vs. sham-operated controls (n = 16). The effect of Evans blue on the accuracy of measuring infarct zone by 2,3,5-triphenyltetrazolium chloride (TTC) staining was determined by measuring infarct zone with and without an applied blue filter. The effects of various concentrations of TTC (0, 0.05, 0.35, 0.5, 1, and 2%) on the accuracy of measuring BBB permeability was also assessed. There was an increase in infarct volume (p < 0.01), brain edema (p < 0.01) and BBB breakdown (p < 0.01) in rats following MCAO compared to sham-operated controls, whether measured separately or together in the same set of brain samples. Evans blue had an effect on measuring infarct volume that was minimized by the application of a blue filter on scanned brain slices. There was no difference in the Evans blue extravasation index for the brain tissue samples without TTC compared to brain tissue samples incubated in TTC. Our results demonstrate that measuring cerebral edema, infarct zone and BBB permeability following MCAO can accurately be measured in the same set of brain samples.

Background To compare covert closed-circuit television (CCTV) monitoring to standard overt observation in assessing the hand hygiene (HH) conduct of health care workers (HCWs) caring for patients infected with multidrug-resistant organisms (MDROs). This was a cross-sectional study in a general intensive care unit of a 1,000-bed university hospital. Methods Forty-six general intensive care unit HCWs (staff physicians, registered nurses, and auxiliary workers) caring for contact isolation MDRO-infected patients. The study incorporated the following 3 phases: phase 1, establishment of interrater reliability between 2 simultaneous observers using the overt observation method; phase 2, establishment of interrater reliability between 2 simultaneous observers using the CCTV method; and phase 3, simultaneous monitoring of HH by both methods to evaluate the suitability of CCTV as an alternative to direct observation of the HH conduct of HCWs caring for MDRO-infected patients. Results Overall, 1,104 opportunities to perform HH were documented during 49 observation sessions. The compliance rate observed by the overt method (37.3%) was significantly higher than that observed when only the covert method was used (26.5%). However, simultaneous overt-covert observations were found to have intraclass correlation coefficients of >0.85. Conclusions Covert CCTV observation of HCW HH compliance appears to provide a truer and more realistic picture than overt observation, probably because of its ability to neutralize the Hawthorne effect of overt observation. The high intraclass correlation coefficients between covert observation and overt observation supports this conclusion.

Post-stroke depression (PSD) is the most recurrent of all psychiatric complications resulting from an ischemic stroke. A greater majority (about 60%) of all ischemic stroke patients suffer from PSD, a disorder considered to be an ischemic stroke-related precursor for increased death and degradation in health. The pathophysiology of PSD is still obscure. To study the mechanism of development and occurrence of PSD further, and to find out a therapy, we attempted to develop a new protocol that requires occluding the middle cerebral artery (MCA) via the internal carotid artery (ICA) in rats. This protocol describes a model of PSD induced in rats through the middle cerebral artery occlusion (MCAO). Also used in the experiment are the Porsolt forced swim test and the sucrose preference test to confirm and evaluate the depressive mood of the rats under investigation. Rather than inserting the catheter through the external carotid artery (ECA), as stipulated for the original procedure, this MCAO technique has the monofilament passing directly through the ICA. This MCAO technique was developed a few years ago and leads to a reduction in mortality and variability. It is generally accepted that the criteria used are preferred in the selection of biological models. The data obtained with this protocol show that this model of MCAO could be a way of inducing PSD in rats and could potentially lead to the understanding of the pathophysiology and the future development of new drugs and other neuroprotective agents.

Background A common experimental rodent model for stroke includes induction by a technique in which middle cerebral artery is transiently (MCAO-t) or permanently (MCAO-p) occluded by catheterization. However, this model has prominent disadvantages which consist of the high variability of localization and size of the ischemic area, cases of intracranial hemorrhage and high mortality. Furthermore, the duration of a single MCAO operation takes about thirty minutes and requires highly trained staff. In this article, we propose an alternative method, which is based on laser-induced stroke in the motor cortex. In our research, we compared the original MCAO-p and MCAO-t models and a novel laser model. Results Compared with the impact of original MCAO-p and MCAO-t technique on brain tissue, the minimally invasive laser model demonstrated a decrease in: variability in body temperature, percent of infarcted volume, blood brain barrier breakdown and brain edema, as well as a prominent decrease of mortality and intracranial hemorrhage. Among other findings of this article, it can be noted that damage to the brain tissue in laser groups occurred only in the region of the motor cortex, without involving the striatal area. Conclusions The data presented in this paper show that the model of laser irradiation can serve as an effective method of inducible brain cortical infarction and may lead to a better understanding of the pathophysiology of ischemic stroke and the future development of new drugs and other neuro-protective agents.

Hypokalemia is common among critically ill patients. Parenteral correction of hyperkalemia depends on dosages and patient characteristics. Our aims were to assess changes in potassium levels following parenteral administration, and to derive a formula for predicting rises in serum potassium based on patient characteristics. We conducted a population-based retrospective cohort study of adults hospitalized in a general intensive care unit for 24 h or more between December 2006 and December 2017, with hypokalemia. The primary exposures were absolute cumulative intravenous doses of 20, 40, 60 or 80 mEq potassium supplement. Adjusted linear mixed models were used to estimate changes in serum potassium. Of 683 patients, 422 had mild and 261 moderate hypokalemia (serum potassium 3.0–3.5 mEq/L and 2.5–2.99 mEq, respectively). Following doses of 20–80 mEq potassium, serum potassium levels rose by a mean 0.27 (±0.4) mEq/L and 0.45 (±0.54) mEq/L in patients with mild and moderate hypokalemia, respectively. Changes were associated with creatinine level, and the use of mechanical ventilation and vasopressors. Among critically ill patients with mild to moderate hypokalemia, increases in serum potassium after intravenous potassium supplement are influenced by several clinical parameters. We generated a formula to predict the expected rise in serum potassium based on clinical parameters.

In recent years there has been a growing body of clinical and laboratory evidence demonstrating the neuroprotective effects of estrogen and progesterone after traumatic brain injury (TBI) and spinal cord injury (SCI). In humans, women have been shown to have a lower incidence of morbidity and mortality after TBI compared with age-matched men. Similarly, numerous laboratory studies have demonstrated that estrogen and progesterone administration is associated with a mortality reduction, improvement in neurological outcomes, and a reduction in neuronal apoptosis after TBI and SCI. Here, we review the evidence that supports hormone-related neuroprotection and discuss possible underlying mechanisms. Estrogen and progesterone-mediated neuroprotection are thought to be related to their effects on hormone receptors, signaling systems, direct antioxidant effects, effects on astrocytes and microglia, modulation of the inflammatory response, effects on cerebral blood flow and metabolism, and effects on mediating glutamate excitotoxicity. Future laboratory research is needed to better determine the mechanisms underlying the hormones' neuroprotective effects, which will allow for more clinical studies. Furthermore, large randomized clinical control trials are needed to better assess their role in human neurodegenerative conditions.

The usage of decision support tools in emergency departments, based on predictive models, capable of estimating the probability of admission for patients in the emergency department may give nursing staff the possibility of allocating resources in advance. We present a methodology for developing and building one such system for a large specialized care hospital using a logistic regression and an artificial neural network model using nine routinely collected variables available right at the end of the triage process.A database of 255.668 triaged nonobstetric emergency department presentations from the Ramon y Cajal University Hospital of Madrid, from January 2011 to December 2012, was used to develop and test the models, with 66% of the data used for derivation and 34% for validation, with an ordered nonrandom partition. On the validation dataset areas under the receiver operating characteristic curve were 0.8568 (95% confidence interval, 0.8508-0.8583) for the logistic regression model and 0.8575 (95% confidence interval, 0.8540-0. 8610) for the artificial neural network model. χ Values for Hosmer-Lemeshow fixed "deciles of risk" were 65.32 for the logistic regression model and 17.28 for the artificial neural network model. A nomogram was generated upon the logistic regression model and an automated software decision support system with a Web interface was built based on the artificial neural network model.

Background Depression is common and results in a significant morbidity and economic burden. Depression is associated with pervasive impairments in social functioning, and antidepressant treatments are highly variable in improving these impairments. The objectives of this study were to test the effects of depression on social organization and behavior in a rodent model of depression, and to study the effectiveness of antidepressant medication in improving both symptoms of depression and the social function of depressed animals. Methods One hundred-twenty male Sprague-Dawley rats were randomly and equally divided between the control group and depression group. After induction of depression by 5 weeks of chronic unpredictable stress, rats received either antidepressant treatment or placebo. In parallel with the initiation of drug therapy, 20 social groups of six rats were subjected to the complex diving-for-food situation to evaluate their social functioning. Four behavioral tests evaluated symptoms of depression and anxiety at 3 different time points. Results We found that 1) depressed rats were significantly more active and aggressive in all parameters of social organization test compared with the control and antidepressant treatment groups, 2) depressed rats that received antidepressant treatment exhibited social behaviors like the control group, and 3) depression in the experimental groups was not accompanied by symptoms of anxiety. Conclusions These results suggest that depression can significantly alter the social behavior and hierarchy in the social group in rats. Investigations of complex social group dynamics offer novel opportunities for translational studies of mood and psychiatric disorders.

Stroke plays a role in high morbidity and mortality. Deciphering its mechanisms and pathophysiology is critical for the creation of new drugs and therapies. Most of the previous animal models of stroke, aimed at identifying the extent and location of brain injury following stroke, require animal sacrifice, which, besides ethical considerations, also negates the ability for follow up studies with the same rats. Because of these failures, the use of clinical magnetic resonance scanners for evaluating small animal models has been increasing. Magnetic resonance imaging scanners used particularly for small-bore animals are eligible for use in high-resolution magnetic resonance imaging of rodent brains. However, high costs and scarcity factor heavily in the rare availability of these scanners. In our investigation, we sought to establish a unitary magnetic resonance imaging protocol for stroke assessment in rats. We made use of a 3-Tesla magnetic resonance imaging clinical scanner, as well as another clinical equipment, with the purpose of increasing its reproducibility. The results of inquest validated a new magnetic resonance imaging protocol, comparing a magnetic resonance imaging-measured infarcted zone to the “gold standard” of histological examination. We carried out the experimental procedure on a 3 Tesla magnetic resonance imaging clinical scanner using a conventional eight-channel receive-only coil. The two methods produced remarkable quantitative and qualitative correlations between them. Conclusively, we showed the clinical magnetic resonance imaging scanner to be a high-precision and sensitive image analysis instrument for evaluating both the infarct zone and the brain edema in a stroke experimental rat model.

Maternal-deprivation of rodent pups is a relevant model of extreme early-life stress that can be relevant to the understanding of long-term effects of war, migration, parental loss and displacement. Although even mild stress during infancy affects brain development and behavior, the current study focused on the effects of six hour daily maternal-separation, a model that reflects the severe distress often experienced in those circumstances. This study emphasizes the effect of maternal separation on social behavior in the context of a variety of factors that measure cognitive and emotional behavior which were subject to principle component analysis. Sprague-Dawley pups were separated from the dam for 6 h each day during the first 3-weeks of life and underwent a battery of behavioral tests at 3-months of age. We found that rodents exposed to postnatal maternal deprivation displayed submissive behavior in resident-intruder and dominant-submissive tests, as well as significantly more anxiety and anhedonia than control rats. The results of multivariate statistical analysis show that the dominant-submissive behavior correlates with depressive, anxiety and social behavior and can be predicted with an accuracy of 86.2%. The increased submissive behavior in male rats that had been subjected to severe postnatal stress suggests that exposure to stress during infancy and childhood could have long-term effects on social relationships. The mechanism of the long-term effects on depression, anxiety and submissive behavior requires further investigation.

Dynamic changes in urine output and neurological status are the recognized clinical signs of hemodynamically significant hemorrhage. In the present study, we analyzed the dynamic minute-to-minute changes in the UFR and also the changes in its minute-to-minute variability in a group of critically ill multiple trauma patients whose blood pressures were normal on admission to the ICU but who subsequently developed hypotension within the first few hours of their ICU admission. The study was retrospective and observational. Demographic and clinical data were extracted from the computerized register information systems initially; the clinical and laboratory data of 100 critically ill patients with multiple trauma who were admitted to the ICU during the study period were analyzed. Of this group, ten patients were eventually included in the study on the basis of the inclusion criteria. The minute-to-minute urine flow rate (UFR) and urine flow rate variability (UFRV) both decreased significantly during the periods of hypotension (p values 0.001 and 0.006, respectively). Notably, the decrease in UFRV preceded by at least 30 min a corresponding decline in the systolic and mean arterial blood pressures, which manifested as a flattening of UFRV amplitude which was observed prior to the occurrence of the lowest recorded systolic and mean arterial blood pressures. Statistical analysis by the Pearson method demonstrated a strong direct correlation between the decrease in UFRV and the decrease in the MAP (R = 0.9, p = 0.001), and SBP (R = 0.86, p = 0.001) and the decreasing urine output per hour (R = 0.88, p

Purpose: Acinetobacter baumannii is a multidrug resistant (MDR), gram-negative bacterium commonly implicated in ventilator-associated pneumonia (VAP) in critically ill patients. Patients in the intensive care unit (ICU) with VAP often subsequently develop A baumannii bacteremia, which may significantly worsen outcomes. Materials and Methods: In this study, we retrospectively reviewed the clinical and laboratory records of 129 ICU patients spanning 6 years with MDR A baumannii VAP; 46 (35%) of these patients had concomitant MDR A baumannii bacteremia. Results: The ICU mortality rate was higher in patients with VAP having A baumannii bacteremia compared to nonbacteremic patients (32.4% vs 9.6% respectively, P < .005). Age >65 years, an Acute Physiology and Chronic Health Evaluation II (APACHE-II) score higher than 20, a Sequential Organ Failure Assessment (SOFA) score higher than 7 on the day of bacteremia, and the presence of comorbid disease (chronic obstructive pulmonary disease [COPD] and chronic renal failure) were found to be independent risk factors for in-hospital mortality in this population. Multidrug resistant A baumannii was not an independent risk factor for mortality. Conclusion: Although the presence of comorbid diseases (COPD and chronic renal failure) and severity of disease (APACHE > 20 and SOFA >7) were found to be independent risk factors for ICU mortality, MDR A baumannii bacteremia was not an independent risk factor for mortality in our critically ill population.

Public healthcare providers in all Spanish Regions – Autonomous Communities (ACs) use All Patients Diagnosis-Related Groups (AP-DRGs) for billing non-insured patients, cost accounting and inpatient efficiency indicators. A national migration to All Patients Refined Diagnosis-Related Groups (APR-DRGs) has been scheduled for 2016. The analysis was performed on 202,912 inpatient care episodes ranging from 2005 to 2010. All episodes were grouped using AP-DRG v25.0 and APR-DRG v24.0. Normalised DRG weight variations for an AP-DRG to APR-DRG migration scenario were calculated and compared. Major differences exist between normalised weights for inpatient episodes depending on the DRGs family used. The usage of the APR-DRG system in Spain without any adjustments, as it was developed in the United States, should be approached with care. In order to avoid reverse incentives and provider financial risks, coding practices should be reviewed and structural differences between DRG families taken into account.

Contagious depression is a phenomenon that is yet to be fully recognized and this stems from insufficient material on the subject. At the moment, there is no existing format for studying the mechanism of action, prevention, containment, and treatment of contagious depression. The purpose of this study, therefore, was to establish the first animal model of contagious depression. Healthy rats can contract depressive behaviors if exposed to depressed rats. Depression is induced in rats by subjecting them to several manipulations of chronic unpredictable stress (CUS) over 5 weeks, as described in the protocol. A successful sucrose preference test confirmed the development of depression in the rats. The CUS-exposed rats were then caged with naive rats from the contagion group (1 naive rat/2 depressed rats in a cage) for an additional 5 weeks. 30 social groups were created from the combination of CUS-exposed rats and naive rats. This proposed depression-contagion protocol in animals consists mainly of cohabiting CUS-exposed and healthy rats for 5 weeks. To ensure that this method works, a series of tests are carried out - first, the sucrose preference test upon inducing depression to rats, then, the sucrose preference test, alongside the open field and forced-swim tests at the end of the cohabitation period. Throughout the experiment, rats are given tags and are always returned to their cages after each test. A few limitations to this method are the weak differences recorded between the experimental and control groups in the sucrose preference test and the irreversible traumatic outcome of the forced swim test. These may be worth considering for suitability before any future application of the protocol. Nonetheless, following the experiment, naive rats developed contagion depression after 5 weeks of sharing the same cage with the CUS-exposed rats.

BackgroundDepression is a common and important cause of morbidity, and results in a significant economic burden. Recent human studies have demonstrated that that depression is contagious, and depression in family and friends might cumulatively increase the likelihood that a person will exhibit depressive behaviors. The mechanisms underlying contagion depression are poorly understood, and there are currently no animal models for this condition.MethodsRats were divided into 3 groups: depression group, contagion group, and control group. After induction of depression by 5 weeks of chronic unpredictable stress, rats from the contagion group were housed with the depressed rats (1 naïve rat with 2 depressed rats) for 5 weeks. Rats were then subjected to sucrose preference, open field, and forced swim tests.ResultsThe sucrose preference was significantly reduced in the depressed rats (p

Stroke is a leading cause of mortality and morbidity worldwide. Few therapeutic options with proven efficacy are available for the treatment of this disabling disease. Lithium is the gold standard treatment for bipolar disorder. Moreover, lithium has been shown to exhibit neuroprotective effects and therapeutic efficacy as a treatment of other neurological disorders. This study was undertaken to examine the effects of lithium on brain inflammatory mediators levels, fever, and mortality in postischemic stroke rats. Ischemic stroke was induced by occlusion of the mid cerebral artery (MCAO). Pretreatment with a single dose of lithium at 2 hours before MCAO induction significantly reduced the elevation in interleukin- (IL-) 6 and prostaglandin E2levels in brain of post-MCAO rats, as compared to vehicle-treated animals. On the other hand, lithium did not affect the elevation in IL-1α, IL-10, IL-12, and tumor necrosis factor-αlevels in brain of post-MCAO rats. Moreover, pretreatment with lithium did not alter post-MCAO fever and mortality. These results suggest that acute pretreatment with a single dose of lithium did not markedly affect post-MCAO morbidity and mortality in rats.

Introduction: Intraoperative cardiovascular complications were previously demonstrated in relation to high sympathetic nervous system outflow or stimulation of the vagal nerve nucleus during theneurosurgical procedures on brain tumors. Main Symptoms and Important Clinical Findings: We are presenting clinical case of 13-year-old girl who suffered from midbrain glioma and developed life threatening cardiovascular events during neurosurgical procedure after surgicel hemostatic agent application. Therapeutic Interventions and Outcomes: Cardiovascular stability has been restored after immediate removal of surgicel from the operating field. We believe that it might be related to direct application of the surgicel hemostatic agent.

Background: If untreated, one third of patients who undergo surgery develop postoperative nausea and/or vomiting (PONV). The prevention of postoperative nausea and vomiting can improve satisfaction among vulnerable patients. We hypothesized that preoperative anxiety may increase the incidence of PONV. The objective was to assess whether administration of a benzodiazepine prior to surgery would reduce the incidence of PONV. Methods: 130 women (ASA I and II) scheduled to undergo dilatation and curettage comprised the study group. The women were allocated randomly to two study groups according to the type of anesthesia administered (with and without midazolam). Results: Sixty-eight women received midazolam and 62 did not. Patients treated with midazolam were feeling more comfortable (“friendliness”, p = 0.005 and “elation”, p = 0.01) and had less postoperative fatigue (p = 0.04) than non-midazolam-treated group. Patients treated with midazolam had significantly fewer emetic episodes during the first 4 hours after surgery than those without midazolam (0.1 ± 0.2 vs 0.3 ± 0.6, respectively, p = 0.003). Conclusions: Midazolam reduces the incidence of PONV and improves patient’s comfort. We suggest that midazolam has to be routinely included in the anesthesia protocol for short-term gynecological procedures (dilatation and curettage).

A low CD4/CD8 ratio during treated HIV infection reflects heightened immune activation and predicts death. The effects of different antiretroviral therapy regimens on CD4/CD8 ratio recovery remains unclear. We performed a post hoc analysis of the MERIT study, a randomized, double-blind trial of maraviroc versus efavirenz in combination with zidovudine-lamivudine in treatment-naive HIV-infected individuals. We found higher rates of CD4/CD8 ratio normalization with efavirenz, which was driven by a greater CD8 + T-cell decline.

Treatment of combined traumatic brain injury and hemorrhagic shock, poses a particular challenge due to the possible conflicting consequences. While restoring diminished volume is the treatment goal for hypovolemia, maintaining adequate cerebral perfusion pressure and avoidance of secondary damage remains a treatment goal for the injured brain. Various treatment modalities have been proposed, but the optimal resuscitation fluid and goals have not yet been clearly defined. A growing body of evidence suggests that in hypovolemic shock, resuscitation with fresh whole blood (FWB) may be superior to component therapy without platelets (which are likely to be unavailable in the pre-hospital setting). Nevertheless, the effects of this approach have not been studied in the combined injury. Previously, in a rat model of combined injury we have found that mild resuscitation to MABP of 80 mmHg with FWB is superior to fluid resuscitation or aggressive resuscitation with FWB. In this study, we investigate the physiological and neurological outcomes in a rat model of combined traumatic brain injury (TBI) and hypovolemic shock, submitted to treatment with varying amounts of FWB, compared to similar resuscitation goals with fractionated blood products—red blood cells (RBCs) and plasma in a 1:1 ratio regimen. 40 male Lewis rats were divided into control and treatment groups. TBI was inflicted by a free-falling rod on the exposed cranium. Hypovolemia was induced by controlled hemorrhage of 30% blood volume. Treatment groups were treated either with fresh whole blood or with RBC + plasma in a 1:1 ratio, achieving a resuscitation goal of a mean arterial blood pressure (MAP) of 80 mmHg at 15 min. MAP was assessed at 60 min, and neurological outcomes and mortality in the subsequent 24 h. At 60 min, hemodynamic parameters were improved compared to controls, but not significantly different between treatment groups. Survival rates at 48 h were 100% for both of the mildly resuscitated groups (MABP 80 mmHg) with FWB and RBC + plasma. The best neurological outcomes were found in the group mildly resuscitated with FWB and were better when compared to resuscitation with RBC + plasma to the same MABP goal (FWB: Neurological Severity Score (NSS) 6 ± 2, RBC + plasma: NSS 10 ± 2, p = 0.02). In this study, we find that mild resuscitation with goals of restoring MAP to 80 mmHg (which is lower than baseline) with FWB, provided better hemodynamic stability and survival. However, the best neurological outcomes were found in the group resuscitated with FWB. Thus, we suggest that resuscitation with FWB is a feasible modality in the combined TBI + hypovolemic shock scenario, and may result in improved outcomes compared to platelet-free component blood products.

Glutamate toxicity plays a well-established role in secondary brain damage following acute and chronic brain insults. Previous studies have demonstrated the efficacy of hemodialysis and peritoneal dialysis in reducing blood glutamate levels. However, these methods are not viable options for hemodynamically unstable patients. Given more favorable hemodynamics, longer treatment, and less needed anticoagulation, we investigated whether hemofiltration could be effective in lowering blood glutamate levels. Blood samples were taken from 10 critically ill patients immediately before initiation of hemofiltration and after 1, 2, 4, 6, and 12 h, for a total of 6 blood samples. Samples were sent for determination of glutamate, glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), hemoglobin, hematocrit, urea, creatinine, glucose, sodium, potassium, platelet, and white blood cell (WBC) levels. There was a statistically significant reduction in blood glutamate levels at all time points compared to baseline levels. There was no difference in levels of GOT or GPT. Hemofiltration can be a promising method of reducing blood glutamate levels, especially in critically ill patients where hemodialysis and peritoneal dialysis may be contraindicated.

Fat embolism syndrome (FES) is a life-threatening condition in which multiorgan dysfunction manifests 48–72 hours after long bone or pelvis fractures. Right ventricular (RV) failure, especially in the setting of pulmonary hypertension, is a frequent feature of FES. We report our experience treating 2 young, previously healthy trauma patients who developed severe hypoxemia in the setting of FES. Neither patient had evidence of RV dysfunction on echocardiogram. The patients were treated with inhaled nitric oxide (NO), and their oxygenation significantly improved over the subsequent few days. Neither patient developed any cardiovascular compromise. Patients with FES that have severe hypoxemia and evidence of adult respiratory distress syndrome (ARDS) are likely at risk for developing RV failure. We recommend that these patients with FES and severe refractory hypoxemia should be treated with inhaled NO therapy prior to the onset of RV dysfunction.

BACKGROUND Previous study has demonstrated the efficacy of hemodialysis in reducing blood glutamate levels. The purpose of the present study is to investigate whether peritoneal dialysis (PD) may be effective in lowering blood glutamate levels, which may serve as a potential tool for improving neurological function after brain injury. METHODS Two liters of dialysis solution were infused over 10 minutes into 18 patients with stage V chronic kidney disease. Blood samples were collected immediately before initiation of PD, and hourly for a total of 5 blood samples. Blood samples were sent for determination of glutamate, creatinine, urea, glucose, glutamate oxaloacetate transaminase, and glutamate pyruvate transaminase. PD samples were collected and analyzed for glutamate, creatinine, urea, and glucose at the same time points as the blood samples. RESULTS Blood glutamate concentrations were significantly reduced by 60 minutes after the infusion of dialysis solution (P

BACKGROUND The exact mechanism of hypothermia-induced neuroprotection has not been determined yet; however, we hypothesized that it may be mediated by a blood glutamate-scavenging effect. Here, we examine the effect of hypothermic conditions (mild, moderate, and deep) on blood glutamate levels in naive rats. To identify the mechanism of hypothermia-induced glutamate reduction, we also measured concentrations of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), the primary regulators of glutamate concentration in blood. METHODS Rats were anesthetized with isoflurane, and their rectal temperature was maintained for 6 hours at 36 to 37°C, 33 to 36°C, 30 to 32°C, 18 to 22°C, or was not maintained artificially. At 6 hours, active cooling was discontinued and rats were allowed to rewarm. There were 12 rats in each group for a total of 60 rats. Blood samples were drawn at 0, 3, 6, 12, 24, and 48 hours for the determination of blood glutamate, GOT, and GPT levels. RESULTS A strong correlation between body temperature and blood glutamate levels was observed (P

Objective. Hyperthyroidism has been described as elevated serum free T3 and/or free T4 levels with decreased thyrotropin (TSH) concentrations. The main causes are related to autoimmune and neoplastic pathology. However, it might be caused due to a long-term topical exposure (iodine solution dressing) or by intravenous administration of iodine-containing substances. Both clinical and laboratory features might be presented. The main management is based on interruption of all exposures with iodine solutions and also antithyroid medicine in case of severe laboratory and clinical disturbances.Data Sources. We present a case of iodine-induced hyperthyroidism in a critically ill ICU patient caused by excessive iodine containing antiseptic solution washes and contrast agent administration. The patient was successfully treated by discontinuing iodine exposure and beta-blocker administration.Conclusions. In patients with underlying thyroid gland pathology, thyroid-function tests and clinical observation in the ICU are of critical importance.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. The deleterious effects of secondary brain injury may be attenuated by early pharmacological therapy in the emergency room and intensive care unit (ICU). Current medical management of acute TBI is primarily supportive, aimed at reducing intracranial pressure (ICP) and optimizing cerebral perfusion. There are no pharmacological therapies to date that have been unequivocally demonstrated to improve neurological outcomes after TBI.The purpose of this systematic review was to evaluate the recent clinical studies from January 2013 through November 2015 that investigated neuroprotective functional outcomes of pharmacological agents after TBI.The following databases were searched for relevant studies: MEDLINE (OvidSP January Week 1, 2013-November Week 2 2015), Embase (OvidSP 2013 January 1-2015 November 24), and the unindexed material in PubMed (National Library of Medicine/National Institutes of Health [NLM/NIH]). This systematic review included only full-length clinical studies and case series that included at least five patients and were published in the English language. Only studies that examined functional clinical outcomes were included.Twenty-five of 527 studies met our inclusion criteria, which investigated 15 independent pharmacological therapies. Eight of these therapies demonstrated possible neuroprotective properties and improved functional outcomes, of which five were investigated with randomized clinical trials: statins, N-acetyl cysteine (NAC), Enzogenol, Cerebrolysin, and nitric oxide synthase inhibitor (VAS203). Three pharmacological agents did not demonstrate neuroprotective effects, and four agents had mixed results.While there is currently no single pharmacological therapy that will unequivocally improve clinical outcomes after TBI, several agents have demonstrated promising clinical benefits for specific TBI patients and should be investigated further.