Impact of Delusions and Hallucinations on Clinical Insight Dimensions in Schizophrenia Spectrum Disorders.

INTRODUCTION: Insight in psychosis has been conceptualized as a continuous, dynamic, and multidimensional phenomenon. This study aims to determine the impact of delusions and hallucinations in different dimensions of clinical insight in schizophrenia spectrum disorders. METHODS: Cross-sectional multicenter study including 516 patients (336 men) diagnosed with schizophrenia spectrum disorders. Based on dichotomized scores of Positive and Negative Syndrome Scale (PANSS) items P1 (delusions) and P3 (hallucinations), patients were assigned to four groups according to current clear presence of delusions (scores 4 or above 4 in PANSS item P1) and/or hallucinations (scores 4 or above 4 in PANNS item P3). Insight was assessed using the three main dimensions of the Scale of Unawareness of Mental Disorder (SUMD). RESULTS: Around 40% of patients showed unawareness of illness; 30% unawareness of the need for treatment; and 45% unawareness of the social consequences of the disorder. Patients with current clear presence of delusions had higher overall lack of awareness, regardless of current clear presence of hallucinations. Similarly, the clear presence of delusions showed a greater predictive value on insight than the presence of hallucinations, although the implication of both in the prediction was modest. CONCLUSIONS: Our results confirm that lack of insight is highly prevalent in schizophrenia spectrum disorders, particularly when patients experience delusions. This study adds insight-related data to the growing symptom-based research, where specific types of psychotic experiences such as hallucinations and delusions could form different psychopathological patterns, linking the phenomenology of delusions to a lack of clinical insight.

The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer.

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. MATERIALS AND METHODS: Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. RESULTS: The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). CONCLUSION: These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.

The Effects of Accompaniment on Maternal Anxiety During Elective Cesarean Delivery: A Quasi-experimental Study.

BACKGROUND: In Spain, allowing women to be accompanied by their partners during cesarean deliveries is a poorly consolidated practice. Going through this experience alone, not only deprives women from the opportunity of sharing the birth with their partners, but also, forces them to face, on their own, one of the most stressful experiences during pregnancy. OBJECTIVE: To analyze whether significant differences exist in levels of anxiety of women who receive an elective cesarean delivery, according to whether they are allowed to be accompanied by their partners. DESIGN: Quasi-experimental, longitudinal, prospective study, comparing a group of 31 women receiving elective cesarean deliveries, without the presence of their partners, with a group of 33 women with elective cesarean deliveries who were accompanied by their partners. Anxiety levels were assessed using the STAI-State/Trait scale. Participants were given a questionnaire to assess their level of satisfaction with the care received. RESULTS: Anxiety measured via total scores on the STAI-S scale was significantly lower (p < 0.004) among the women who were accompanied by their partners during the elective cesarean delivery (median = 25), compared to the group who were not (median = 50). The differences were also significant (p < 0.003) considering the impact of accompaniment upon the group with high scores in the STAI-S (> 31) and continue to be significant when using the cut-off point of very high scores on the STAI-S (> 45). CONCLUSIONS: Presence of partners during elective cesareans is a key factor for decreasing the anxiety caused by the surgery and for improving the overall experience of cesarean deliveries.

What is already known on this subject? Cesarean deliveries are one of the most stressful life experiences. Allowing women to be accompanied by their partners during cesarean deliveries is a poorly consolidated practice in some countries. Otherwise relevant international institutions recommend allowing an accompanying adult, present with the mother in the operating room during the entire process.What this study adds? Presence of partners during elective cesareans is a key factor for decreasing deliveries' anxiety, improving the overall experience, but it needs a mentality change in the obstetric and surgical team. These results could change the services organization in a more humane delivery, with overall positive impact in the patients' care.

Role of Extracellular Vesicles Produced by Stem Cells in Tissue Repair.

The purpose of this Special Issue is to emphasize the great potential of the translational applications of extracellular vesicles (EVs) produced by stem cells (mesenchymal stem cells, induced pluripotent stem cells, etc [...].

Tracking temporal response dynamics in the ventral striatum during social feedback in anorexia nervosa: A functional magnetic resonance imaging exploratory study.

OBJECTIVE: Research suggests abnormalities in reward-based processes in anorexia nervosa (AN). However, few studies have explored if such alterations might be associated with different temporal activation patterns. This study aims to characterize alterations in time-dependent processes in the ventral striatum (VS) during social feedback in AN using functional magnetic resonance imaging (fMRI). METHOD: Twenty women with restrictive-subtype AN and 20 age-matched healthy controls (HC) underwent a social judgment experimental fMRI task. Temporal VS hemodynamic responses were extracted in SPM for each participant and each social condition (acceptance/rejection). RESULTS: Compared with age-matched HC, patients with AN showed a significant time by group interaction of peak VS response throughout the task, with a progressive blunting of peak activation responses, accompanied by a progressive increase in baseline activity levels over time. DISCUSSION: The results suggest an attenuated response pattern to repetitive social rejection in the VS in patients with AN, together with a difficulty in returning to baseline. The information obtained from this study will guide future, design-specific studies to further explore alterations temporal dynamics.

Efficacy of Low-Dose versus High-Dose Continuous Cyclic Azithromycin Therapy for Preventing Acute Exacerbations of COPD.

BACKGROUND: Long-term azithromycin therapy significantly reduces the frequency of COPD exacerbations (ECOPD). However, previous studies have used different dosing regimens, and the efficacy of these regimens has not been compared. OBJECTIVE: Compare the efficacy of low-dose with high-dose continuous cyclic azithromycin (CC-A) in severe COPD. METHODS: Patients with severe COPD and repeated exacerbations (ECOPD ≥4 or ≥3 with at least 1 hospital admission in the previous year) were prospectively recruited (January 2017 to December 2019) as a multicenter cohort (from 3 university hospitals in the Barcelona area) and treated with low-dose CC-A: 250 mg 3 times per week (250-CC-A group). This cohort was compared with a historical (January 2007 to December 2013) single-center cohort of severe COPD with frequent ECOPD treated with high-dose CC-A: 500 mg 3 times per week (500-CC-A group). To assess differences in ECOPD prevention according to the administration of low-dose or high-dose CC-A, moderate-to-severe ECOPD was evaluated during the 12-month period before and after starting CC-A therapy. RESULTS: Fifty-eight patients with severe COPD were evaluated: 37 in the low-dose group and 21 in the high-dose group. The 250-CC-A therapy group achieved a mean reduction in moderate-to-severe ECOPD of 65.6% at 12 months after starting CC-A therapy (with a 61.5% reduction in hospitalizations), while the 500-CC-A group achieved a reduction of 60.5% (with a 44.8% reduction in hospitalizations). No significant differences between 250-CC-A and 500-CC-A dosages were observed in the mean annual reduction of moderate-to-severe ECOPD (p = 0.55) or hospitalizations (p = 0.07) with respect to the year prior to starting CC-A. CONCLUSIONS: Low-dose 250-CC-A therapy over a 1-year period is similar to high-dose 500-CC-A in reducing exacerbation frequency in severe COPD patients with frequent ECOPD despite maximal medical therapy.

Volume Infusion Markedly Increases Femoral dP/dtmax in Fluid-Responsive Patients Only.

OBJECTIVES: To evaluate the preload dependence of femoral maximal change in pressure over time (dP/dtmax) during volume expansion in preload dependent and independent critically ill patients. DESIGN: Retrospective database analysis. SETTING: Two adult polyvalent ICUs. PATIENTS: Twenty-five critically ill patients with acute circulatory failure. INTERVENTIONS: Thirty-five fluid infusions of 500 mL normal saline. MEASUREMENTS AND MAIN RESULTS: Changes in femoral dP/dtmax, systolic, diastolic, and pulse femoral arterial pressure were obtained from the pressure waveform analysis using the PiCCO2 system (Pulsion Medical Systems, Feldkirchen, Germany). Stroke volume index was obtained by transpulmonary thermodilution. Statistical analysis was performed comparing results before and after volume expansion and according to the presence or absence of preload dependence (increases in stroke volume index ≥ 15%). Femoral dP/dtmax increased by 46% after fluid infusion in preload-dependent cases (mean change = 510.6 mm Hg·s; p = 0.005) and remained stable in preload-independent ones (mean change = 49.2 mm Hg·s; p = 0.114). Fluid-induced changes in femoral dP/dtmax correlated with fluid-induced changes in stroke volume index in preload-dependent cases (r = 0.618; p = 0.032), but not in preload-independent ones. Femoral dP/dtmax strongly correlated with pulse and systolic arterial pressures and with total arterial stiffness, regardless of the preload dependence status (r > 0.9 and p < 0.001 in all cases). CONCLUSIONS: Femoral dP/dtmax increased with volume expansion in case of preload dependence but not in case of preload independence and was strongly related to pulse pressure and total arterial stiffness regardless of preload dependence status. Therefore, femoral dP/dtmax is not a load-independent marker of left ventricular contractility and should be not used to track contractility in critically ill patients.

Clinical Trials of Limbal Stem Cell Deficiency Treated with Oral Mucosal Epithelial Cells.

The corneal surface is an essential organ necessary for vision, and its clarity must be maintained. The corneal epithelium is renewed by limbal stem cells, located in the limbus and in palisades of Vogt. Palisades of Vogt maintain the clearness of the corneal epithelium by blocking the growth of conjunctival epithelium and the invasion of blood vessels over the cornea. The limbal region can be damaged by chemical burns, physical damage (e.g., by contact lenses), congenital disease, chronic inflammation, or limbal surgeries. The degree of limbus damage is associated with the degree of limbal stem cells deficiency (partial or total). For a long time, the only treatment to restore vision was grafting part of the healthy cornea from the other eye of the patient or by transplanting a cornea from cadavers. The regenerative medicine and stem cell therapies have been applied to restore normal vision using different methodologies. The source of stem cells varies from embryonic stem cells, mesenchymal stem cells, to induced pluripotent stem cells. This review focuses on the use of oral mucosa epithelial stem cells and their use in engineering cell sheets to treat limbal stem cell deficient patients.

Prediction of advanced colonic neoplasm in symptomatic patients: a scoring system to prioritize colonoscopy (COLONOFIT study).

BACKGROUND: Fast-track colonoscopy to detect patients with colorectal cancer based on high-risk symptoms is associated with low sensitivity and specificity. The aim was to derive a predictive score of advanced colonic neoplasia in symptomatic patients in fast-track programs. METHODS: All patients referred for fast-track colonoscopy were evaluated. Faecal immunological haemoglobin test (3 samples; positive> 4 µg Hb/g), and a survey to register clinical variables of interest were performed. Colorectal cancer and advanced adenoma were considered as advanced colonic neoplasia. A sample size of 600 and 500 individuals were calculated for each phase 1 and phase 2 of the study, respectively (Phase 1, derivation and Phase 2, validation cohort). A Bayesian logistic regression analysis was used to derive a predictive score. RESULTS: 1495 patients were included. Age (OR, 21), maximum faecal-Hb value (OR, 2.3), and number of positive samples (OR, 28) presented the highest ORs predictive of advanced colonic neoplasia. The additional significant predictive variables adjusted for age and faecal-Hb variables in Phase 1 were previous colonoscopy (last 5 years) and smoking (no, ex/active). With these variables a predictive score of advanced colonic neoplasia was derived. Applied to Phase 2, patients with a Score > 20 had an advanced colonic neoplasia probability of 66% (colorectal cancer, 32%), while those with a Score ≤ 10, a probability of 10% (colorectal cancer, 1%). Prioritizing patients with Score > 10, 49.4% of patients would be referred for fast-track colonoscopy, diagnosing 98.3% of colorectal cancers and 77% of advanced adenomas. CONCLUSIONS: A scoring system was derived and validated to prioritize fast-track colonoscopies according to risk, which was efficient, simple, and robust.

Parallel vessels as a predictor of benignity in solid breast masses.

To evaluate the presence of a parallel artery and vein on color Doppler ultrasound as a predictor of benignity in solid breast masses. This prospective study included all patients with solid breast masses identified by ultrasound at our center from January 2012 through December 2015. All masses were studied with B mode and color Doppler ultrasound. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value, and their respective 95% confidence intervals for the parallel vessel sign against the histologic findings or 2 years' follow-up without changes. A total of 526 solid masses were included in the 3-year period; the parallel vessel sign was observed in 377 (71.6%). We found 74.8% (95% CI: 70.9-78.7) sensitivity, 65% (95% CI: 50.2-79.7) specificity, 96.2% (95% CI: 94.3-98.1) positive predictive value, and 17.5% (95% CI: 11.4-23.6) negative predictive value. Of the 379 masses classified as breast imaging reporting and data system (BI-RADS) 3, the parallel vessel sign was observed in 275 (72.5%); all of these were definitively benign. Of the 109 masses classified as BI-RADS 4, the parallel vessel sign was observed in 89 (80.7%); 88 (98.8%) of these were definitively benign. Of the 38 masses classified as BI-RADS 5, the parallel vessel sign was observed in 13 (34.2%); all of these were definitively malignant. The parallel artery and vein sign is a good predictor of benignity, although it must be analyzed together with other morphologic descriptors.

Effects of bupivacaine or levobupivacaine on cerebral oxygenation during spinal anesthesia in elderly patients undergoing orthopedic surgery for hip fracture: a randomized controlled trial.

BACKGROUND: Bupivacaine and levobupivacaine have similar pharmacokinetic and pharmacodynamic characteristics, and are used regularly in spinal anesthesia. Whether potential differences in their hemodynamic and anesthetic profiles could determine a differential risk of complications in elderly subjects, is controversial. The main objective was to compare the effects of intrathecally administered levobupivacaine (LB) versus bupivacaine (B), on regional cerebral O2 saturation during spinal anesthesia, cognitive status and neurological complications in elderly patients undergoing surgery for hip fracture. METHODS: This was a randomized, controlled, single blind study. 58 patients aged 70 or older undergoing surgery for hip fracture with spinal anesthesia were allocated with a 1:1 ratio to receive LB or B, combined with fentanyl 15 µg, by intrathecal route. The primary outcome was the proportion of intraoperative time with regional cerebral desaturation (≥20% reduction in regional cerebral oxygen saturation from baseline), monitored by near -infrared spectroscopy. Secondary endpoints included hemodynamic parameters, level of sensory and motor block, changes in Short Portable Mental Status Questionnaire (SPMSQ), and neurological complications. RESULTS: The mean percentage of intraoperative time with desaturation in the B group was 6.1% (SD: 17.5) and 4.7% (SD: 11.9) in the left and right hemisphere respectively; in the LB group the mean was 4.8% (SD: 11.4) in the left hemisphere and 2.4% (SD: 8.3) in the right one. No statistically significant differences were found between treatment groups. The level of sensory block at the start of surgery was lower for LB than for B (Th10 vs Th8, p:0.047) and motor block at 15 min was lower for LB (2.5 vs 3, p:0.009). No differences in postoperative SPMSQ were observed. Neurological complications such as confusional state, agitation or disorientation were reported in 50% of patients in the B group and 21.4% of patients in the LB group, p = 0.05. CONCLUSIONS: No statistically significant differences in regional cerebral oxygen saturation or hemodynamic parameters were observed between both treatment groups. Bupivacaine and levobupivacaine differed in sensory and motor block achieved. While no differences were observed in cognitive impairment measured by the SPMSQ between treatment groups neurological complications reported by the physician were more frequent with bupivacaine. TRIAL REGISTRATION: European Union Clinical Trials Register ( EudraCT 2013-000846 -20 ) (April 9th, 2013). ClinicalTrials.gov ( NCT01960543 ) (September 23rd, 2013).

Therapeutic Properties of Mesenchymal Stem Cell on Organ Ischemia-Reperfusion Injury.

The shortage of donor organs is a major global concern. Organ failure requires the transplantation of functional organs. Donor's organs are preserved for variable periods of warm and cold ischemia time, which requires placing them into a preservation device. Ischemia and reperfusion damage the organs, due to the lack of oxygen during the ischemia step, as well as the oxidative stress during the reperfusion step. Different methodologies are developed to prevent or to diminish the level of injuries. Preservation solutions were first developed to maximize cold static preservation, which includes the addition of several chemical compounds. The next chapter of organ preservation comes with the perfusion machine, where mechanical devices provide continuous flow and oxygenation ex vivo to the organs being preserved. In the addition of inhibitors of mitogen-activated protein kinase and inhibitors of the proteasome, mesenchymal stem cells began being used 13 years ago to prevent or diminish the organ's injuries. Mesenchymal stem cells (e.g., bone marrow stem cells, adipose derived stem cells and umbilical cord stem cells) have proven to be powerful tools in repairing damaged organs. This review will focus upon the use of some bone marrow stem cells, adipose-derived stem cells and umbilical cord stem cells on preventing or decreasing the injuries due to ischemia-reperfusion.

Nursing workload and compliance with non-pharmacological measures to prevent ventilator-associated pneumonia: a multicentre study.

BACKGROUND: Ventilator-associated pneumonia is common and associated with high mortality. Nurses play a fundamental role in preventing ventilator-associated pneumonia. Evidence-based guidelines and training interventions about preventing ventilator-associated pneumonia do not ensure compliance with recommendations. AIMS AND OBJECTIVE: To evaluate the impact of nursing workload on compliance with non-pharmacological measures to prevent ventilator-associated pneumonia. DESIGN: A prospective observational study in two medical-surgical adult ICUs in Spain. METHODS: We measured nurses' knowledge about preventing ventilator-associated pneumonia through a questionnaire and workload, categorized with the Nine Equivalents of Nursing Manpower Use Score. We directly observed nurses to measure compliance with non-pharmacological measures to prevent ventilator-associated pneumonia. RESULTS: A total of 97 nurses were studied; 76 (79%) were observed. There were 327 observations (mean 4·30 observations per nurse). The questionnaire showed good baseline knowledge of preventive measures [mean score (92% ± 16%)]. Nurses complied with the preventive measures in 66% ± 15% of observations; compliance ranged from 11·9% for pre-aspiration hand washing to 99·7% for using sterile aspiration probes. Mean Nine Equivalents of Nursing Manpower Use Score for each nurse observed was 50 ± 13, without differences between centres (49 ± 14 versus 51 ± 11, p = 0·4). Overall compliance was lower in the light workload group (p = 0·02), but no significant differences in compliance between workload groups were found when each measure was analysed separately. Compliance was higher in nurses aged 31-40 years than in those aged >51 years, although workload was similar in both groups. CONCLUSIONS: Compliance with non-pharmacological measures to prevent ventilator-associated pneumonia varies widely; non-compliance is not because of increased workload. RELEVANCE TO CLINICAL PRACTICE: Most critical care nurses have good baseline knowledge of non-pharmacological measures to prevent ventilator-associated pneumonia. Failure to comply with these measures is probably more related with behavioural, structural and organizational aspects than with nursing workload. Interventions to improve compliance might be more effective if they focus on factors such as work climate and professionals' attitudes.

Proteasome and Organs Ischemia-Reperfusion Injury.

The treatment of organ failure on patients requires the transplantation of functional organs, from donors. Over time, the methodology of transplantation was improved by the development of organ preservation solutions. The storage of organs in preservation solutions is followed by the ischemia of the organ, resulting in a shortage of oxygen and nutrients, which damage the tissues. When the organ is ready for the transplantation, the reperfusion of the organ induces an increase of the oxidative stress, endoplasmic reticulum stress, and inflammation which causes tissue damage, resulting in a decrease of the transplantation success. However, the addition of proteasome inhibitor in the preservation solution alleviated the injuries due to the ischemia-reperfusion process. The proteasome is a protein structure involved in the regulation the inflammation and the clearance of damaged proteins. The goal of this review is to summarize the role of the proteasome and pharmacological compounds that regulate the proteasome in protecting the organs from the ischemia-reperfusion injury.

Effectivity and Cost-effectivity of the Maintenance Electroconvulsive Therapy: A mirror naturalistic analysis.

INTRODUCTION: Maintenance Electroconvulsive Therapy (mECT) is a biological long-term treatment in which patients receive ECT on periods from 2 to 4 weeks, during a variable period of time, usually for more than 6 months. Recent studies showed the efficacy of mECT in prevention of relapse and recurrences. Our study wants to demostrate the effectivity and cost-effectivity of this therapy in the naturalistic conditions of our area. DESIGN: Retrospective longitudinal study, with mirror analysis in naturalistic conditions. SUBJECTS: Patients attended at the Corporació Sanitària Parc Taulí (Sabadell, Catalonia), and included in the mECT program during more than six months. We performed diagnostic following DSM-IV criteria, subdividing the sample in three groups: patients affected of Recurrent Major Depression, Bipolar Disorder and Schizophrenia and Related Disorders. MEASURES: Number and duration of hospitalizations for the previous three years before the beginning of mECT, compared with the same data for the next three years following the beginning of mECT. Comparative analysis of direct hospitalization costs, costs of the mECT and pharmacologic costs. Statistic: Descriptive and non- parametric tests. RESULTS: Sample of 35 patients (1997-2008). There is a significative reduction the number of hospitalizations and days of hospitalization in the total sample and also in each of the three subgroups. The direct total cost decreased but it was only significant in the Bipolar Disorder subgroup, due to the increased pharmacological costs. CONCLUSIONS: mECT in our area is an effective and costeffective treatment with a great impact on the reduction of clinical decline and hospitalizations.

Outpatient multimodal intravenous analgesia in patients undergoing day-case surgery: description of a three year experience.

BACKGROUND: The use of elastomeric devices for ambulatory intravenous pain treatment in Major Ambulatory Surgery (MAS) has been described to improve postoperative pain management. The objective of the study was to describe the first 3 years experience of the use of elastomeric devices for ambulatory intravenous pain treatment in MAS implemented at our site since 2010. METHODS: Data were retrieved from the medical records for all patients who, between January 2010 and March 2014, underwent surgical procedures at the ambulatory surgical centre at our hospital and were prescribed a home-based continuous intravenous analgesia. RESULTS: Data were retrieved from the medical records of 1128 patients. The most frequent surgical interventions included orthopedic and proctology surgeries. 80 % of patients were discharged home without pain; during the first 48 h after discharge roughly 40 % of subjects were completely free of pain, 50 % reported mild pain (VAS 1 to 3) and 9 % reported higher pain scores (4 and above). Peripheral nerve block was associated to better pain control in the immediate postoperative period. Vomiting in the first 24 h was 4.6 % before introducing haloperidol into the drug schemes, and 2.6 % thereafter. Complications related with the intravenous route required treatment withdrawal in 1.1 % cases. Only 3.5 % of patients returned to the hospital in the first 72 h, mainly for non-pain related reasons. Overall, 99.5 % of patients were satisfied with the treatment received at home. CONCLUSION: Our initial experience suggest that outpatient multimodal intravenous analgesia in patients undergoing day-case surgery is a feasible alternative in our setting, that allows an effective management of postoperative pain with a small rate of adverse events and complications requiring readmission.

Relevance of Endoplasmic Reticulum Stress Cell Signaling in Liver Cold Ischemia Reperfusion Injury.

The endoplasmic reticulum (ER) is involved in calcium homeostasis, protein folding and lipid biosynthesis. Perturbations in its normal functions lead to a condition called endoplasmic reticulum stress (ERS). This can be triggered by many physiopathological conditions such as alcoholic steatohepatitis, insulin resistance or ischemia-reperfusion injury. The cell reacts to ERS by initiating a defensive process known as the unfolded protein response (UPR), which comprises cellular mechanisms for adaptation and the safeguarding of cell survival or, in cases of excessively severe stress, for the initiation of the cell death program. Recent experimental data suggest the involvement of ERS in ischemia/reperfusion injury (IRI) of the liver graft, which has been considered as one of major problems influencing outcome after liver transplantation. The purpose of this review is to summarize updated data on the molecular mechanisms of ERS/UPR and the consequences of this pathology, focusing specifically on solid organ preservation and liver transplantation models. We will also discuss the potential role of ERS, beyond the simple adaptive response and the regulation of cell death, in the modification of cell functional properties and phenotypic changes.

Mental Health Emergencies in Paediatric Services: Characteristics, Diagnostic Stability and Gender differences.

INTRODUCTION: Child and adolescent psychiatric emergencies have increased in recent years. The main objective of our study is to analyze sociodemographic and clinical characteristics of psychiatric emergencies under 18 years old that came to our hospital. Secondary objectives were to study diagnostic stability made in the emergency department and undertake a gender analysis. METHODS: Descriptive cross-sectional study of patients attending the pediatric emergency department who required consultation to psychiatry service during 2010 and 2011, comparing data with two previous cross-sectional cuts (2002-2003 and 2006-2007). Then we track the diagnoses assigned during a year. Statistical analysis was descriptive. We also include a gender analysis. RESULTS: We analyzed 328 episodes corresponding to 179 different patients (average age 14.48). We detected a progressive increase of prevalence of psychiatric emergencies from 2002 to 2011. Diagnostic distribution showed a significant association of Behavioral Disorders with males and an association of Self-injured Behaviors and Eating Disorders with females. The admission rate was 18.5%. One-year diagnostic outcomes showed differences comparing to emergency diagnosis. CONCLUSIONS: Increase and complexity of psychiatric consultations in Pediatric Emergency Department requires a greater coordination and training of these services to enhance patients care. Emergency visit could mean the entrance of complex and severe patients to a specialized care. Our results detect gender differences: more Behavioral Disorders, Psychosis and Substance Use Disorders in males and Self-Injury and Eating Behavior Disorders in females.

Relationship between volume and survival in closed intensive care units is weak and apparent only in mechanically ventilated patients.

BACKGROUND: Recent studies have found an association between increased volume and increased intensive care unit (ICU) survival; however, this association might not hold true in ICUs with permanent intensivist coverage. Our objective was to determine whether ICU volume correlates with survival in the Spanish healthcare system. METHODS: Post hoc analysis of a prospective study of all patients admitted to 29 ICUs during 3 months. At ICU discharge, the authors recorded demographic variables, severity score, and specific ICU treatments. Follow-up variables included ICU readmission and hospital mortality. Statistics include logistic multivariate analyses for hospital mortality according to quartiles of volume of patients. RESULTS: The authors studied 4,001 patients with a mean predicted risk of death of 23% (range at hospital level: 14-46%). Observed hospital mortality was 19% (range at hospital level: 11-35%), resulting in a standardized mortality ratio of 0.81 (range: 0.5-1.3). Among the 1,923 patients needing mechanical ventilation, the predicted risk of death was 32% (14-60%) and observed hospital mortality was 30% (12-61%), resulting in a standardized mortality ratio of 0.96 (0.5-1.7). The authors found no correlation between standardized mortality ratio and ICU volume in the entire population or in mechanically ventilated patients. Only mechanically ventilated patients in very low-volume ICUs had slightly worse outcome. CONCLUSION: In the currently studied healthcare system characterized by 24/7 intensivist coverage, the authors found wide variability in outcome among ICUs even after adjusting for severity of illness but no relationship between ICU volume and outcome. Only mechanically ventilated patients in very low-volume centers had slightly worse outcomes.

Proteasome inhibitors protect the steatotic and non-steatotic liver graft against cold ischemia reperfusion injury.

BACKGROUND: The dramatic shortage of organs leads to consider the steatotic livers for transplantation although their poor tolerance against ischemia reperfusion injury (IRI). Ubiquitin proteasome system (UPS) inhibition during hypothermia prolongs myocardial graft preservation. The role of UPS in the liver IRI is not fully understood. Bortezomib (BRZ) treatment at non-toxic doses of rats fed alcohol chronically has shown protective effects by increasing liver antioxidant enzymes. We evaluated and compared both proteasome inhibitors BRZ and MG132 in addition to University of Wisconsin preservation solution (UW) at low and non-toxic dose for fatty liver graft protection against cold IRI. EXPERIMENTAL: Steatotic and non-steatotic livers have been stored in UW enriched with BRZ (100 nM) or MG132 (25 µM), for 24h at 4°C and then subjected to 2-h normothermic reperfusion (37 °C). Liver injury (AST/ALT), hepatic function (bile output; vascular resistance), mitochondrial damage (GLDH), oxidative stress (MDA), nitric oxide (NO) (e-NOS activity; nitrates/nitrites), proteasome chymotrypsin-like activity (ChT), and UPS (19S and 20S5 beta) protein levels have been measured. RESULTS: ChT was inhibited when BRZ and MG132 were added to UW. Both inhibitors prevented liver injury (AST/ALT), when compared to UW alone. BRZ increased bile production more efficiently than MG132. Only BRZ decreased vascular resistance in fatty livers, which correlated with an increase in NO generation (through e-NOS activation) and AMPK phosphorylation. GLDH and MDA were also prevented by BRZ. In addition, BRZ inhibited adiponectin, IL-1, and TNF alpha, only in steatotic livers. CONCLUSION: MG132 and BRZ, administrated at low and non toxic doses, are very efficient to protect fatty liver grafts against cold IRI. The benefits of BRZ are more effective than those of MG132. This evidenced for the first time the potential use of UPS inhibitors for the preservation of marginal liver grafts and for future applications in the prevention of IRI.