Growing rods in meningomyelocele lead to increased risk for complications in comparison with fusion; a retrospective study of 30 patients treated for at the University Hospital of Uppsala.

PURPOSE: To compare the complication rates of two different types of posterior instrumentation in patients with MMC, namely, definitive fusion and fusionless surgery (growing rods). METHODS: Single-center retrospective study of 30 MMC patients that underwent posterior instrumentation for deformity (scoliosis and/or kyphosis) treatment from 2008 until 2020. The patients were grouped based on whether they received definitive fusion or a growth-accommodating system, whether they had a complication that led to early surgery, osteotomy or non-osteotomy. Number of major operations, Cobb angle correction and perioperative blood loss were the outcomes. RESULTS: 18 patients received a growing system and 12 were fused at index surgery. The growing system group underwent a mean of 2.38 (± 1.03) surgeries versus 1.91 (± 2.27) in the fusion group, p = 0.01. If an early revision was necessitated due to a complication, then the number of major surgeries per patient was 3.37 (± 2.44) versus 1.77 (± 0.97) in the group that did not undergo an early revision, p = 0.01. Four patients developed a superficial and six a deep wound infection, while loosening/breakage occurred in 10 patients. The Cobb angle was improved from a mean of 69 to 22 degrees postoperatively. Osteotomy did not lead to an increase in perioperative blood loss or number of major operations. CONCLUSION: Growing systems had more major operations in comparison with fusion surgery and early revision surgery led to higher numbers of major operations per patient; these differences were statistically significant. Definitive fusion at index surgery might be the better option in some MMC patients with a high-risk profile.

Nuclear upregulation of class I phosphoinositide 3-kinase p110ß correlates with high 47S rRNA levels in cancer cells.

The class I phosphoinositide 3-kinase (PI3K) catalytic subunits p110α and p110ß are ubiquitously expressed but differently targeted in tumours. In cancer, PIK3CB (encoding p110ß) is seldom mutated compared with PIK3CA (encoding p110α) but can contribute to tumorigenesis in certain PTEN-deficient tumours. The underlying molecular mechanisms are, however, unclear. We have previously reported that p110ß is highly expressed in endometrial cancer (EC) cell lines and at the mRNA level in primary patient tumours. Here, we show that p110ß protein levels are high in both the cytoplasmic and nuclear compartments in EC cells. Moreover, high nuclear:cytoplasmic staining ratios were detected in high-grade primary tumours. High levels of phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] were measured in the nucleus of EC cells, and pharmacological and genetic approaches showed that its production was partly dependent upon p110ß activity. Using immunofluorescence staining, p110ß and PtdIns(3,4,5)P3 were localised in the nucleolus, which correlated with high levels of 47S pre-rRNA. p110ß inhibition led to a decrease in both 47S rRNA levels and cell proliferation. In conclusion, these results present a nucleolar role for p110ß that may contribute to tumorigenesis in EC.This article has an associated First Person interview with Fatemeh Mazloumi Gavgani, joint first author of the paper.

Outcome prediction for patients assessed by the medical emergency team: a retrospective cohort study.

BACKGROUND: Medical emergency teams (METs) have been implemented to reduce hospital mortality by the early recognition and treatment of potentially life-threatening conditions. The objective of this study was to establish a clinically useful association between clinical variables and mortality risk, among patients assessed by the MET, and further to design an easy-to-use risk score for the prediction of death within 30 days. METHODS: Observational retrospective register study in a tertiary university hospital in Sweden, comprising 2,601 patients, assessed by the MET from 2010 to 2015. Patient registry data at the time of MET assessment was analysed from an epidemiological perspective, using univariable and multivariable analyses with death within 30 days as the outcome variable. Predictors of outcome were defined from age, gender, type of ward for admittance, previous medical history, acute medical condition, vital parameters and laboratory biomarkers. Identified factors independently associated with mortality were then used to develop a prognostic risk score for mortality. RESULTS: The overall 30-day mortality was high (29.0%). We identified thirteen factors independently associated with 30-day mortality concerning; age, type of ward for admittance, vital parameters, laboratory biomarkers, previous medical history and acute medical condition. A MET risk score for mortality based on the impact of these individual thirteen factors in the model yielded a median (range) AUC of 0.780 (0.774-0.785) with good calibration. When corrected for optimism by internal validation, the score yielded a median (range) AUC of 0.768 (0.762-0.773). CONCLUSIONS: Among clinical variables available at the time of MET assessment, thirteen factors were found to be independently associated with 30-day mortality. By applying a simple risk scoring system based on these individual factors, patients at higher risk of dying within 30 days after the MET assessment may be identified and treated earlier in the process.

Predictors of short- and long-term mortality in critically ill, older adults admitted to the emergency department: an observational study.

BACKGROUND: In the future, we can expect an increase in older patients in emergency departments (ED) and acute wards. The main purpose of this study was to identify predictors of short- and long-term mortality in the ED and at hospital discharge. METHODS: This is a retrospective, observational, single-center, cohort study, involving critically ill older adults, recruited consecutively in an ED. The primary outcome was mortality. All patients were followed for 6.5-7.5 years. The Cox proportional hazards model was used. RESULTS: Regarding all critically ill patients aged ≥ 70 years and identified in the ED (n = 402), there was a significant association between mortality at 30 days after ED admission and unconsciousness on admission (HR 3.14, 95% CI 2.09-4.74), hypoxia on admission (HR 2.51, 95% CI 1.69-3.74) and age (HR 1.06 per year, 95% CI 1.03-1.09), (all p < 0.001). Of 402 critically ill patients aged ≥ 70 years and identified in the ED, 303 were discharged alive from hospital. There was a significant association between long-term mortality and the Charlson Comorbidity Index (CCI) > 2 (HR 1.90, 95% CI 1.46-2.48), length of stay (LOS) > 7 days (HR 1.72, 95% CI 1.32-2.23), discharge diagnosis of pneumonia (HR 1.65, 95% CI 1.24-2.21) and age (HR 1.08 per year, 95% CI 1.05-1.10), (all p < 0.001). The only symptom or vital sign associated with long-term mortality was hypoxia on admission (HR 1.70, 05% CI 1.30-2.22). CONCLUSIONS: Among critically ill older adults admitted to an ED and discharged alive the following factors were predictive of long-term mortality: CCI > 2, LOS > 7 days, hypoxia on admission, discharge diagnosis of pneumonia and age. The following factors were predictive of mortality at 30 days after ED admission: unconsciousness on admission, hypoxia and age. These data might be clinically relevant when it comes to individualized care planning, which should take account of risk prediction and estimated prognosis.

Association between inflammatory response and outcome after subarachnoid haemorrhage.

OBJECTIVES: Recent reports suggest an association between the inflammatory response after aneurysmal subarachnoid haemorrhage (aSAH) and patients' outcome. The primary aim of this study was to identify a potential association between the inflammatory response after aSAH and 1-year outcome. The secondary aim was to investigate whether the inflammatory response after aSAH could predict the development of delayed cerebral ischaemia (DCI). MATERIALS AND METHODS: This prospective observational pilot study included patients with an aSAH admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, between May 2015 and October 2016. The patients were stratified according to the extended Glasgow Outcome Scale (GOSE) as having an unfavourable (score: 1-4) or favourable outcome (score: 5-8). Furthermore, patients were stratified depending on development of DCI or not. Patient data and blood samples were collected and analysed at admission and after 10 days. RESULTS: Elevated serum concentrations of inflammatory markers such as tumour necrosis factor-α and interleukin (IL)-6, IL-1Ra, C-reactive protein and intercellular adhesion molecule-1 were detected in patients with unfavourable outcome. When adjustments for Glasgow coma scale were made, only IL-1Ra remained significantly associated with poor outcome (p = 0.012). The inflammatory response after aSAH was not predictive of the development of DCI. CONCLUSION: Elevated serum concentrations of inflammatory markers were associated with poor neurological outcome 1-year after aSAH. However, inflammatory markers are affected by many clinical events, and when adjustments were made, only IL-1Ra remained significantly associated with poor outcome. The robustness of these results needs to be tested in a larger trial.

A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia.

Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined ß = 0.19, 95% confidence interval 0.13-0.24, P = 4.3 × 10-11). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P = 1.2 × 10-15). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age- and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.

Percutaneous coronary intervention in the very elderly with NSTE-ACS: the randomized 80+ study.

Objective: The treatment strategy in the very elderly with NSTE-ACS is debated, as they are often under-represented in clinical trials. The aim of this multicenter randomized controlled trial was to compare invasive and conservative strategies in the very elderly with NSTE-ACS.Methods: We randomly assigned patients ≥ 80 years of age with NSTE-ACS to an invasive strategy with coronary angiography and optimal medical treatment or a conservative strategy with only optimal medical treatment. The primary outcome was the combined endpoint of major adverse cardiac and cerebrovascular events (MACCE). Sample size was powered for a 50% reduction of event rate in MACCE with an invasive strategy. We used intention-to-treat analysis.Results: Altogether, 186 patients were included between 2009 and 2017. The study was terminated prematurely due to slow enrollment. At 12-month follow-up, the primary outcome occurred in 31 (33.3%) of the invasive treatment group and 34 (36.6%) of the conservative treatment group, with a hazard ratio (HR) of 0.90 (95% CI 0.55‒1.46; p = 0.66) for the invasive group relative to the conservative group. The corresponding HR value for urgent revascularization was 0.29 (95% CI 0.10‒0.85; p = 0.02), 0.56 (95% CI 0.27‒1.18; p = 0.13) for myocardial infarction, 0.70 (95% CI 0.31‒1.58; p = 0.40) for all-cause mortality, 1.35 (95% CI 0.23‒7.98; p = 0.74) for stroke, and 1.62 (95% CI 0.67‒3.90; p = 0.28) for recurrent hospitalization for cardiac reasons.Conclusion: In the very elderly with NSTE-ACS, we did not find any significant difference in MACCE between invasive and conservative treatment groups at 12-month follow-up, possibly due to small sample size. ClinicalTrials.gov: NCT02126202.

Unrecorded Alcohol Consumption in Seven European Union Countries.

INTRODUCTION: Unrecorded alcohol, that is, alcohol not reflected in official statistics of the country where it is consumed, contributes markedly to overall consumption of alcohol. However, empirical data on unrecorded alcohol consumption are scarce, especially in high-income countries. This study measures the contribution of unrecorded alcohol in 7 member states of the European Union. METHODS: Two categories of unrecorded consumption were assessed in general population surveys (reducing alcohol related harm Standardized European Alcohol Survey; n = 11,224): home-made alcohol and cross-border shopping. Country-specific logistic regressions were used to link respondent characteristics to odds of acquisition of unrecorded alcohol. Total per capita alcohol consumption was estimated under different assumptions of calculating unrecorded alcohol consumption. RESULTS: Individuals with higher drinking levels were more likely to acquire unrecorded alcohol in all 7 countries. In some countries, male sex and more affluent social class were also positively linked to acquisition of unrecorded alcohol. There was a substantial contribution of unrecorded alcohol to overall consumption in 5 out of 7 member states (Croatia, Finland, Greece, Hungary, Portugal), but not in Poland or Spain. In Greece, up to two-thirds of all alcohol consumed was estimated to be unrecorded. CONCLUSION: Unrecorded alcohol contributes to overall consumption even in high-income countries, and thus needs to be monitored. In monitoring, as many categories of unrecorded alcohol as possible should be clearly defined (e.g., surrogate alcohol) and included in future surveys.

Pre-hospital predictors of an adverse outcome among patients with dyspnoea as the main symptom assessed by pre-hospital emergency nurses - a retrospective observational study.

BACKGROUND: Dyspnoea is one of the most common reasons for patients contacting emergency medical services (EMS). Pre-hospital Emergency Nurses (PENs) are independently responsible for advanced care and to meet these patients individual needs. Patients with dyspnoea constitute a complex group, with multiple different final diagnoses and with a high risk of death. This study aimed to describe on-scene factors associated with an increased risk of a time-sensitive final diagnosis and the risk of death. METHODS: A retrospective observational study including patients aged ≥16 years, presenting mainly with dyspnoea was conducted. Patients were identified thorough an EMS database, and were assessed by PENs in the south-western part of Sweden during January to December 2017. Of 7260 missions (9% of all primary missions), 6354 were included. Among those, 4587 patients were randomly selected in conjunction with adjusting for unique patients with single occasions. Data were manually collected through both EMS- and hospital records and final diagnoses were determined through the final diagnoses verified in hospital records. Analysis was performed using multiple logistic regression and multiple imputations. RESULTS: Among all unique patients with dyspnoea as the main symptom, 13% had a time-sensitive final diagnosis. The three most frequent final time-sensitive diagnoses were cardiac diseases (4.1% of all diagnoses), infectious/inflammatory diseases (2.6%), and vascular diseases (2.4%). A history of hypertension, renal disease, symptoms of pain, abnormal respiratory rate, impaired consciousness, a pathologic ECG and a short delay until call for EMS were associated with an increased risk of a time-sensitive final diagnosis. Among patients with time-sensitive diagnoses, approximately 27% died within 30 days. Increasing age, a history of renal disease, cancer, low systolic blood pressures, impaired consciousness and abnormal body temperature were associated with an increased risk of death. CONCLUSIONS: Among patients with dyspnoea as the main symptom, age, previous medical history, deviating vital signs, ECG pattern, symptoms of pain, and a short delay until call for EMS are important factors to consider in the prehospital assessment of the combined risk of either having a time-sensitive diagnosis or death.

Seventeen-Year Mortality following the Acute Coronary Syndrome: Gender-Specific Baseline Variables and Impact on Outcome.

BACKGROUND: Gender differences in outcome and its predictors in patients with acute coronary syndrome (ACS) continue to be debated. OBJECTIVES: To assess long-term mortality and explore its association with the baseline variables in women and men. METHODS: We followed 2,176 consecutive patients (665 women and 1,511 men) with ACS admitted to a single hospital and still alive after 30 days for a median of 16 years 8 months. RESULTS: At the end of the follow-up, 415 (62.4%) women and 849 (56.2%) men had died (unadjusted hazard ratio [HR] for women/men 1.18 (95% confidence interval [CI], 1.05-1.33, p =0.005). After adjustment for age, the HR was reversed to 0.88 (95% CI, 0.78-1.00, p =0.04). Additional adjustment for potential confounders yielded a HR of 0.86 (95% CI, 0.76-0.98, p = 0.02). Using multivariable Cox regression, previous heart failure, previous or new-onset atrial fibrillation, and psychotropic drugs at discharge were significantly associated with increased long-term mortality in men only. Known hypertension, elevated creatinine, and inhospital Killip class >1/cardiogenic shock were significantly associated with mortality only in women. For late mortality, hypertension and inhospital Killip class >1/cardiogenic shock interacted significantly with gender. CONCLUSION: For patients with ACS surviving the first 30 days, late mortality was lower in women than in men after adjusting for age. The effects of several baseline characteristics on late outcome differed between women and men. Gender-specific strategies for long-term follow-up of ACS patients should be considered.

The performance of the EMS triage (RETTS-p) and the agreement between the field assessment and final hospital diagnosis: a prospective observational study among children < 16 years.

BACKGROUND: The rapid triage and treatment system for paediatrics (RETTS-p) has been used by the emergency medical services (EMS) in the west of Sweden since 2014. The performance of the RETTS-p in the pre-hospital setting and the agreement between the EMS nurse's field assessment and the hospital diagnosis is unknown. The aim of this study was to evaluate the performance of the RETTS-p in the EMS and the agreement between the EMS field assessment and the hospital diagnosis. METHODS: A prospective observational study was conducted among 454 patients < 16 years of age who were assessed and transported to the PED. Two instruments were used for comparison: 1) Classification of an emergent patient according to predefined criteria as compared to the RETTS-p and 2) Agreement between the EMS nurse's field assessment and the hospital diagnosis. RESULTS: Among all children, 11% were identified as having vital signs associated with an increased risk of death and 7% were diagnosed in hospital with a potentially life-threatening condition. Of the children triaged with RETTS-p (85.9%), 149 of 390 children (38.2%) were triaged to RETTS-p red or orange (life-threatening, potentially life-threatening), of which 40 (26.8%) children were classified as emergent. The hospitalised children were triaged with the highest frequency to level yellow (can wait; 41.5%). In children with RETTS-p red or orange, the sensitivity for a defined emergent patient was 66.7%, with a corresponding specificity of 67.0%. The EMS field assessment was in agreement with the final hospital diagnosis in 80% of the cases. CONCLUSIONS: The RETTS-p sensitivity in this study is considered moderate. Two thirds of the children triaged to life threatening or potentially life threatening were later identified as non-emergent. Of those, one in six was discharged from the PED without any intervention. Further, one third of the children were under triaged, the majority were found in the yellow triage level (can wait). The highest proportion of hospitalised patients was found in the yellow triage level. Our result is in agreement with previous studies using other triage instruments. A computerised decision support system might help the EMS triage to increase sensitivity and specificity.

Early cardiopulmonary resuscitation in out-of-hospital cardiac arrest.

BACKGROUND: Three million people in Sweden are trained in cardiopulmonary resuscitation (CPR). Whether this training increases the frequency of bystander CPR or the survival rate among persons who have out-of-hospital cardiac arrests has been questioned. METHODS: We analyzed a total of 30,381 out-of-hospital cardiac arrests witnessed in Sweden from January 1, 1990, through December 31, 2011, to determine whether CPR was performed before the arrival of emergency medical services (EMS) and whether early CPR was correlated with survival. RESULTS: CPR was performed before the arrival of EMS in 15,512 cases (51.1%) and was not performed before the arrival of EMS in 14,869 cases (48.9%). The 30-day survival rate was 10.5% when CPR was performed before EMS arrival versus 4.0% when CPR was not performed before EMS arrival (P<0.001). When adjustment was made for a propensity score (which included the variables of age, sex, location of cardiac arrest, cause of cardiac arrest, initial cardiac rhythm, EMS response time, time from collapse to call for EMS, and year of event), CPR before the arrival of EMS was associated with an increased 30-day survival rate (odds ratio, 2.15; 95% confidence interval, 1.88 to 2.45). When the time to defibrillation in patients who were found to be in ventricular fibrillation was included in the propensity score, the results were similar. The positive correlation between early CPR and survival rate remained stable over the course of the study period. An association was also observed between the time from collapse to the start of CPR and the 30-day survival rate. CONCLUSIONS: CPR performed before EMS arrival was associated with a 30-day survival rate after an out-of-hospital cardiac arrest that was more than twice as high as that associated with no CPR before EMS arrival. (Funded by the Laerdal Foundation for Acute Medicine and others.).

Association between the reported intensity of an acute symptom at first prehospital assessment and the subsequent outcome: a study on patients with acute chest pain and presumed acute coronary syndrome.

BACKGROUND: To decrease the morbidity burden of cardiovascular disease and to avoid the development of potentially preventable complications, early assessment and treatment of acute coronary syndrome (ACS) are important. The aim of this study has therefore been to explore the possible association between patients' estimated intensity of chest pain when first seen by the ambulance crew in suspected ACS, and the subsequent outcome before and after arrival in hospital. METHODS: Data was collected both prospectively and retrospectively. The inclusion criteria were chest pain raising suspicion of ACS and a reported intensity of pain ≥4 on the visual analogue scale. RESULTS: All in all, 1603 patients were included in the study. Increased intensity of chest pain was related to: 1) more heart-related complications before hospital admission; 2) a higher proportion of heart failure, anxiety and chest pain after hospital admission; 3) a higher proportion of acute myocardial infarction and 4) a prolonged hospitalisation. However, there was no significant association with mortality neither in 30 days nor in three years. Adjustment for possible confounders including age, a history of smoking and heart failure showed similar results. CONCLUSION: The estimated intensity of chest pain reported by the patients on admission by the ambulance team was associated with the risk of complications prior to hospital admission, heart failure, anxiety and chest pain after hospital admission, the final diagnosis and the number of days in hospital. TRIAL REGISTRATION: ClinicalTrials.gov 151:2008/4564 Identifier: NCT00792181. Registred 17 November 2008 'retrospectively registered'.

Early predictors of poor outcome after out-of-hospital cardiac arrest.

BACKGROUND: Early identification of predictors for a poor long-term outcome in patients who survive the initial phase of out-of-hospital cardiac arrest (OHCA) may facilitate future clinical research, the process of care and information provided to relatives. The aim of this study was to determine the association between variables available from the patient's history and status at intensive care admission with outcome in unconscious survivors of OHCA. METHODS: Using the cohort of the Target Temperature Management trial, we performed a post hoc analysis of 933 unconscious patients with OHCA of presumed cardiac cause who had a complete 6-month follow-up. Outcomes were survival and neurological function as defined by the Cerebral Performance Category (CPC) scale at 6 months after OHCA. After multiple imputations to compensate for missing data, backward stepwise multivariable logistic regression was applied to identify factors independently predictive of a poor outcome (CPC 3-5). On the basis of these factors, a risk score for poor outcome was constructed. RESULTS: We identified ten independent predictors of a poor outcome: older age, cardiac arrest occurring at home, initial rhythm other than ventricular fibrillation/tachycardia, longer duration of no flow, longer duration of low flow, administration of adrenaline, bilateral absence of corneal and pupillary reflexes, Glasgow Coma Scale motor response 1, lower pH and a partial pressure of carbon dioxide in arterial blood value lower than 4.5 kPa at hospital admission. A risk score based on the impact of each of these variables in the model yielded a median (range) AUC of 0.842 (0.840-0.845) and good calibration. Internal validation of the score using bootstrapping yielded a median (range) AUC corrected for optimism of 0.818 (0.816-0.821). CONCLUSIONS: Among variables available at admission to intensive care, we identified ten independent predictors of a poor outcome at 6 months for initial survivors of OHCA. They reflected pre-hospital circumstances (six variables) and patient status on hospital admission (four variables). By using a simple and easy-to-use risk scoring system based on these variables, patients at high risk for a poor outcome after OHCA may be identified early.

A polybasic motif in ErbB3-binding protein 1 (EBP1) has key functions in nucleolar localization and polyphosphoinositide interaction.

Polyphosphoinositides (PPIns) are present in the nucleus where they participate in crucial nuclear processes, such as chromatin remodelling, transcription and mRNA processing. In a previous interactomics study, aimed to gain further insight into nuclear PPIns functions, we identified ErbB3 binding protein 1 (EBP1) as a potential nuclear PPIn-binding protein in a lipid pull-down screen. EBP1 is a ubiquitous and conserved protein, located in both the cytoplasm and nucleolus, and associated with cell proliferation and survival. In the present study, we show that EBP1 binds directly to several PPIns via two distinct PPIn-binding sites consisting of clusters of lysine residues and positioned at the N- and C-termini of the protein. Using interaction mutants, we show that the C-terminal PPIn-binding motif contributes the most to the localization of EBP1 in the nucleolus. Importantly, a K372N point mutation, located within the C-terminal motif and found in endometrial tumours, is sufficient to alter the nucleolar targeting of EBP1. Our study reveals also the presence of the class I phosphoinositide 3-kinase (PI3K) catalytic subunit p110ß and its product PtdIns(3,4,5)P3 together with EBP1 in the nucleolus. Using NMR, we further demonstrate an association between EBP1 and PtdIns(3,4,5)P3 via both electrostatic and hydrophobic interactions. Taken together, these results show that EBP1 interacts directly with PPIns and associate with PtdIns(3,4,5)P3 in the nucleolus. The presence of p110ß and PtdIns(3,4,5)P3 in the nucleolus indicates their potential role in regulating nucleolar processes, at least via EBP1.

Mild induced hypothermia and survival after out-of-hospital cardiac arrest.

BACKGROUND: Mild induced hypothermia (MIH) was introduced for post cardiac arrest care in Sweden in 2003, based on two clinical trials. This retrospective study evaluated its association with 30-day survival after out-of-hospital cardiac arrest (OHCA) in a Swedish community from 2003 to 2015. METHODS: Out of 3680 patients with OHCA, 1100 were hospitalized after return of spontaneous circulation and 871 patients who remained unconscious were included in the analysis. Prehospital data were extracted from the Swedish Registry of Cardiopulmonary Resuscitation and in-hospital data were extracted from clinical records. Propensity score analysis on complete data sets and multivariable logistic regression with multiple imputations to compensate for missing data were performed. RESULTS: Unadjusted 30-day survival was 23.5%; 37% in 386/871 (44%) MIH treated and 13% in 485/871 (56%) non-MIH treated patients. Unadjusted odds ratio (OR) for 30-day survival in patients treated with MIH compared to non-MIH treated patients was 3.79 (95% CI 2.71-5.29; p<0.0001). Using stratified propensity score analysis and in addition adjusting for in-hospital factors, 30-day survival was not significantly different in patients treated with MIH compared to non-MIH treated patients; OR 1.33 (95% CI 0.83-2.15; p=0.24). Using multiple imputations to handle missing data yielded a similar adjusted OR of 1.40 (95% CI 0.88-2.22; p=0.15). Good neurologic outcome at hospital discharge was seen in 82% of patients discharged alive. CONCLUSION: Treatment with MIH was not significantly associated with increased 30-day survival in patients remaining unconscious after OHCA when adjusting for potential confounders.

Characteristics and outcome among 14,933 adult cases of in-hospital cardiac arrest: A nationwide study with the emphasis on gender and age.

AIM: To investigate characteristics and outcome among patients suffering in-hospital cardiac arrest (IHCA) with the emphasis on gender and age. METHODS: Using the Swedish Register of Cardiopulmonary Resuscitation, we analyzed associations between gender, age and co-morbidities, etiology, management, 30-day survival and cerebral function among survivors in 14,933 cases of IHCA. Age was divided into three ordered categories: young (18-49years), middle-aged (50-64years) and older (65years and above). Comparisons between men and women were age adjusted. RESULTS: The mean age was 72.7years and women were significantly older than men. Renal dysfunction was the most prevalent co-morbidity. Myocardial infarction/ischemia was the most common condition preceding IHCA, with men having 27% higher odds of having MI as the underlying etiology. A shockable rhythm was found in 31.8% of patients, with men having 52% higher odds of being found in VT/VF. After adjusting for various confounders, it was found that men had a 10% lower chance than women of surviving to 30days. Older individuals were managed less aggressively than younger patients. Increasing age was associated with lower 30-day survival but not with poorer cerebral function among survivors. CONCLUSION: When adjusting for various confounders, it was found that men had a 10% lower chance than women of surviving to 30days after in-hospital cardiac arrest. Older individuals were managed less aggressively than younger patients, despite a lower chance of survival. Higher age was, however, not associated with poorer cerebral function among survivors.

New hypothesis on pontine-frontal eye field connectivity in Kleine-Levin syndrome.

Previous studies have indicated involvement of the thalamus and the pons in Kleine-Levin syndrome. In the present study, functional connectivity of the thalamus and the pons was investigated in asymptomatic patients with Kleine-Levin syndrome and healthy controls. Twelve patients and 14 healthy controls were investigated by functional magnetic resonance imaging during rest. Resting state images were analysed using seed regions of interest in the thalamus and the pons. The results showed significantly lower functional connectivity between the pons and the frontal eye field in persons with Kleine-Levin syndrome compared with healthy controls. There were no connectivity differences involving the thalamus. Based on these findings, a relation is proposed between the sleep disorder Kleine-Levin syndrome and cerebral control of eye movements, which in turn is related to visual attention and working memory. This hypothesis has to be tested in future studies of oculomotor control in Kleine-Levin syndrome.

Possible effects of a course in cardiovascular nursing on prehospital care of patients experiencing suspected acute coronary syndrome: a cluster randomised controlled trial.

BACKGROUND: Current research suggests that nurses can influence the outcome for patients with acute coronary syndrome (ACS). The aim of this study has been to evaluate whether a course in cardiovascular nursing (CVN) can improve ambulance nurses' (ANs') prehospital care of patients experiencing suspected ACS, related to pain intensity. METHODS: This is a cluster randomised controlled trial that was conducted in the ambulance services. Patients were allocated to one of two groups: in the first group, patients were treated by ANs who had attended the CVN course and in the second group patients were treated by ANs without this qualification. Inclusion criteria were: 1/pain raising suspicion of ACS, and 2/pain score ≥4 on a visual analogue scale (VAS). The primary outcome was the estimated intensity of pain or discomfort according to VAS 15 min after randomisation. Secondary outcomes were estimated intensity of pain or discomfort on admission to hospital and further requirement of pain treatment, as well as symptoms such as paleness and/or cold sweat; nausea and/or vomiting; anxiety, dyspnea, degree of alertness, respiratory depression and aggressiveness. A further secondary outcome measured was survival to 30 days. Lastly, a final diagnosis was made. A total of 38 ANs attended the CVN course. There were 1,747 patients who fulfilled the inclusion criteria. RESULTS: The pain score did not differ significantly between the two groups fifteen minutes after randomisation (median value of VAS was 4.0 in both groups). On admission to hospital the pain score was significantly lower for patients treated by an AN who had attended the CVN course (n = 332) compared with those treated by an AN who had not attended the course (n = 1,415) (median 2.5 and 3.0 respectively, p = 0.001). The ANs who had attended the course used higher doses of morphine. CONCLUSIONS: An educational intervention with a CVN course did not relate significantly to more efficient pain relief in suspected ACS during the first 15 min. However, this intervention was associated with more effective pain relief later on in the prehospital setting. Thus, a CVN course for ANs appears to be associated with reduced pain intensity among patients experiencing suspected ACS. This result needs however to be confirmed in further trials. TRIAL REGISTRATION: The ClinicalTrials.gov Protocol Registration System (registration number NCT00792181).