Transcriptomic clustering of critically ill COVID-19 patients.

BACKGROUND: Infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause a severe disease, termed coronavirus disease 2019 (COVID-19), with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms and their modulation has shown a mortality benefit. METHODS: In a cohort of 56 critically ill COVID-19 patients, peripheral blood transcriptomes were obtained at admission to an intensive care unit (ICU) and clustered using an unsupervised algorithm. Differences in gene expression, circulating microRNAs (c-miRNAs) and clinical data between clusters were assessed, and circulating cell populations estimated from sequencing data. A transcriptomic signature was defined and applied to an external cohort to validate the findings. RESULTS: We identified two transcriptomic clusters characterised by expression of either interferon-related or immune checkpoint genes, respectively. Steroids have cluster-specific effects, decreasing lymphocyte activation in the former but promoting B-cell activation in the latter. These profiles have different ICU outcomes, despite no major clinical differences at ICU admission. A transcriptomic signature was used to identify these clusters in two external validation cohorts (with 50 and 60 patients), yielding similar results. CONCLUSIONS: These results reveal different underlying pathogenetic mechanisms and illustrate the potential of transcriptomics to identify patient endotypes in severe COVID-19 with the aim to ultimately personalise their therapies.

Results in clinical practice in the treatment of severe eosinophilic asthma with mepolizumab: a real-life study.

OBJECTIVE: Add-on therapy with monoclonal antibodies is the recommended therapy for severe asthmatic patients refractory to maintenance treatment. In randomized control trials, mepolizumab reduced the number of exacerbations, the need of oral corticosteroids (OCS), increased asthma control, and lung function in a population of uncontrolled severe eosinophilic asthmatic patients. In this piece of work, we aimed to assess mepolizumab efficacy and safety in a cohort of patients with severe eosinophilic asthma in real-life conditions. METHODS: A retrospective study was carried out at eight hospitals from Asturias (Spain). The sample included patients treated with mepolizumab from 1 January 2016 to 31 March 2019. Demographic and clinical variables were collected, including OCS use, asthma control, lung function, and exacerbation rate. RESULTS: Sixty-nine patients (72% women) with mean age 56 ± 13 years were included. Annual exacerbation rate decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) (p < 0.001). The number of patients requiring OCS treatment decreased from 25 patients (36%, mean prednisone dose = 18 mg/day) to 13 patients (19%, mean prednisone dose = 9 mg/day) (p < 0.001). Twelve patients (48%) stopped OCS treatment. Forced expired volume in one second (FEV1) as percentage increased from 68% (SD 20) to 76% (SD 21) (p < 0.001). Fifty-six patients (81%) were considered responders to mepolizumab. No serious adverse events were detected during the study period. CONCLUSIONS: Overall, this study demonstrates mepolizumab efficacy and safety in a cohort of patients with uncontrolled severe eosinophilic asthma in routine clinical practice.

Compulsive buying behavior of Smartphones by university students.

BACKGROUND: Few studies have analyzed compulsive buying behavior in relation to a specific product. Smartphones are hugely popular products today, especially among young people. These two aspects have motivated this research into the compulsive buying behavior of Smartphones by university students. METHODS: To study this behavior, the main features that differentiate compulsive buyers from those that are not are analyzed, and their risk profiles are obtained through a discrete choice model. RESULTS: Sociodemographic features that define buyers with the greatest propensity to compulsiveness are younger age, longer time spent daily using social networks, higher spending on the acquisition of Smartphones and having owned a greater number of these devices. These buyers also show shopping addiction and greater feelings of guilt after the purchase as well as more positive and negative affective states when purchasing Smartphones. CONCLUSIONS: This analysis not only determines the characteristics that define young individuals with a tendency toward compulsiveness in Smartphone purchases, but also contributes to quantifying the probability of having this tendency.

Structural connectivity alterations in chronic and episodic migraine: A diffusion magnetic resonance imaging connectomics study.

OBJECTIVE: To identify possible structural connectivity alterations in patients with episodic and chronic migraine using magnetic resonance imaging data. METHODS: Fifty-four episodic migraine, 56 chronic migraine patients and 50 controls underwent T1-weighted and diffusion-weighted magnetic resonance imaging acquisitions. Number of streamlines (trajectories of estimated fiber-tracts), mean fractional anisotropy, axial diffusivity and radial diffusivity were the connectome measures. Correlation analysis between connectome measures and duration and frequency of migraine was performed. RESULTS: Higher and lower number of streamlines were found in connections involving regions like the superior frontal gyrus when comparing episodic and chronic migraineurs with controls (p < .05 false discovery rate). Between the left caudal anterior cingulate and right superior frontal gyri, more streamlines were found in chronic compared to episodic migraine. Higher and lower fractional anisotropy, axial diffusivity, and radial diffusivity were found between migraine groups and controls in connections involving regions like the hippocampus. Lower radial diffusivity and axial diffusivity were found in chronic compared to episodic migraine in connections involving regions like the putamen. In chronic migraine, duration of migraine was positively correlated with fractional anisotropy and axial diffusivity. CONCLUSIONS: Structural strengthening of connections involving subcortical regions associated with pain processing and weakening in connections involving cortical regions associated with hyperexcitability may coexist in migraine.

Drug susceptibility patterns of rapidly growing mycobacteria isolated from skin and soft tissue infections in Venezuela.

To our knowledge, this is the first work on drug susceptibility patterns of rapid growing mycobacteria from Latin America. The susceptibility patterns for 14 antimicrobial agents of the three most important species that cause skin infections in Venezuela were determined as follows: 63 strains belonging to Mycobacterium abscessus group, 66 strains of the Mycobacterium fortuitum group, and 13 Mycobacterium chelonae strains. The M. abscessus group strains were resistant to most antibiotics tested while M. fortuitum strains were relatively susceptible to a large number of antibiotics. We demonstrate the presence of an inducible and truncated erm(41) gene in M. abscessus group, namely M. abscessus subsp. massiliense. We show the variations in susceptibility to antimicrobial agents within and between the mycobacterial species and compare our susceptibility patterns with those reported from other countries. We conclude that the identification of mycobacteria to the species level can guide the antibiotic treatment, but that it is always important to consider drug susceptibility testing when rapidly mycobacteria are isolated.

RNA-Seq analysis reveals that spring viraemia of carp virus induces a broad spectrum of PIM kinases in zebrafish kidney that promote viral entry.

PIM kinases are a family of serine/threonine protein kinases that potentiate the progression of the cell cycle and inhibit apoptosis. Because of this, they are considered to be proto-oncogenes, and they represent an interesting target for the development of anticancer drugs. In mammals, three PIM kinases exist (PIM-1, PIM-2 and PIM-3), and different inhibitors have been developed to block their activity. In addition to their involvement in cancer, some publications have reported that the PIM kinases have pro-viral activity, and different mechanisms where PIM kinases favour viral infections have been proposed. Zebrafish possess more than 300 Pim kinase members in their genome, and by using RNA-Seq analysis, we found a high number of Pim kinase genes that were significantly induced after infection with spring viraemia of carp virus (SVCV). Moreover, analysis of the miRNAs modulated by this infection revealed that some of them could be involved in the post-transcriptional regulation of Pim kinase abundance. To elucidate the potential role of the 16 overexpressed Pim kinases in the infectivity of SVCV, we used three different pan-PIM kinase inhibitors (SGI-1776, INCB053914 and AZD1208), and different experiments were conducted both in vitro and in vivo. We observed that the PIM kinase inhibitors had a protective effect against SVCV, indicating that, similar to what is observed in mammals, PIM kinases are beneficial for the virus in zebrafish. Moreover, zebrafish Pim kinases seem to facilitate viral entry into the host cells because when ZF4 cells were pre-incubated with the virus and then were treated with the inhibitors, the protective effect of the inhibitors was abrogated. Although more investigation is necessary, these results show that pan-PIM kinase inhibitors could serve as a useful treatment for preventing the spread of viral diseases.

Gray Matter Structural Alterations in Chronic and Episodic Migraine: A Morphometric Magnetic Resonance Imaging Study.

OBJECTIVE: This study evaluates different parameters describing the gray matter structure to analyze differences between healthy controls, patients with episodic migraine, and patients with chronic migraine. DESIGN: Cohort study. SETTING: Spanish community. SUBJECTS: Fifty-two healthy controls, 57 episodic migraine patients, and 57 chronic migraine patients were included in the study and underwent T1-weighted magnetic resonance imaging acquisition. METHODS: Eighty-four cortical and subcortical gray matter regions were extracted, and gray matter volume, cortical curvature, thickness, and surface area values were computed (where applicable). Correlation analysis between clinical features and structural parameters was performed. RESULTS: Statistically significant differences were found between all three groups, generally consisting of increases in cortical curvature and decreases in gray matter volume, cortical thickness, and surface area in migraineurs with respect to healthy controls. Furthermore, differences were also found between chronic and episodic migraine. Significant correlations were found between duration of migraine history and several structural parameters. CONCLUSIONS: Migraine is associated with structural alterations in widespread gray matter regions of the brain. Moreover, the results suggest that the pattern of differences between healthy controls and episodic migraine patients is qualitatively different from that occurring between episodic and chronic migraine patients.

[Influence of the labor quality of life on the employeeperformance of public hospitals from Mexico: a vision based on the team management]. / Influencia de la calidad de vida laboral sobre el desempeño de trabajadores de hospitales públicos de México: una visión desde la gestión directiva.

OBJECTIVE: To assess the relationship between labor quality of life (LQL) and organizational workers performance (OWP) from seven public hospitals, analyzing the influence of the personnel management (PM) as mediator of this relationship. MATERIALS AND METHODS: A cross-sectional study was conducted in 866 professionals and managers of public hospitals from Tlaxcala and Mexico City. The LQL was assessed with a validated questionnaire, OWP with 34 indicators, and PM with an instrument designed for this study. RESULTS: Mean scores of LQL, were significantly lower among workers from Tlaxcala. Participants who perceived an adequate PM, they increased at 2.7 times their likelihood of having highest LQL, and participants categorized in the high LQL presented 69% higher likelihood of having an adequate OWP. CONCLUSIONS: The appropriate PM was associated with greater LQL, showing to be a mediator variable between the positive relationship of CVL and the OWP.

OBJETIVO: Evaluar la relación entre calidad de vida laboral (CVL) y el desempeño organizacional (DO) de trabajadores de siete hospitales públicos, a partir del análisis de la influencia de la gestión directiva (GD) como mediadora de esta relación. MATERIAL Y MÉTODOS: Se realizó un estudio transversal en 866 profesionales y directivos de hospitales públicos de Tlaxcala y de la Ciudad de México. La CVL fue medida con un instrumento validado, el DO con 34 indicadores y la GD con un instrumento diseñado para este estudio. RESULTADOS: Los puntajes de gestión directiva, CVL, DO y GD fueron sig- nificativamente menores en los trabajadores de Tlaxcala. Los participantes que percibieron adecuada GD incrementaron 2.7 veces más la probabilidad de percibir elevada CVL y los participantes categorizados en elevada CVL presentaron 69% mayor probabilidad de tener adecuado DO. CONCLUSIONES: La adecuada GD se asoció con una mejor CVL, lo que mostró ser una variable mediadora de la relación positiva entre CVL y DO.

White matter changes in chronic and episodic migraine: a diffusion tensor imaging study.

BACKGROUND: White matter alterations have been observed in patients with migraine. However, no microstructural white matter alterations have been found particularly in episodic or chronic migraine patients, and there is limited research focused on the comparison between these two groups of migraine patients. METHODS: Fifty-one healthy controls, 55 episodic migraine patients and 57 chronic migraine patients were recruited and underwent brain T1-weighted and diffusion-weighted MRI acquisition. Using Tract-Based Spatial Statistics (TBSS), fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity were compared between the different groups. On the one hand, all migraine patients were compared against healthy controls. On the other hand, patients from each migraine group were compared between them and also against healthy controls. Correlation analysis between clinical features (duration of migraine in years, time from onset of chronic migraine in months, where applicable, and headache and migraine frequency, where applicable) and Diffusion Tensor Imaging measures was performed. RESULTS: Fifty healthy controls, 54 episodic migraine and 56 chronic migraine patients were finally included in the analysis. Significant decreased axial diffusivity (p < .05 false discovery rate and by number of contrasts corrected) was found in chronic migraine compared to episodic migraine in 38 white matter regions from the Johns Hopkins University ICBM-DTI-81 White-Matter Atlas. Significant positive correlation was found between time from onset of chronic migraine and mean fractional anisotropy in the bilateral external capsule, and negative correlation between time from onset of chronic migraine and mean radial diffusivity in the bilateral external capsule. CONCLUSIONS: These findings suggest global white matter structural differences between episodic migraine and chronic migraine. Patients with chronic migraine could present axonal integrity impairment in the first months of chronic migraine with respect to episodic migraine patients. White matter changes after the onset of chronic migraine might reflect a set of maladaptive plastic changes.

Diagnostic validity of the STRATIFY and Downton instruments for evaluating the risk of falls by hospitalised acute-care patients: a multicentre longitudinal study.

BACKGROUND: Falls are major adverse events in hospitals. The appropriateness of using risk assessment instruments for falls in hospitals has recently been questioned, although the research performed in this respect presents some methodological shortcomings. The purpose of the present study is to evaluate the accuracy of the Downton and STRATIFY instruments to determine the risk of falls and to predict their incidence in acute care hospitals in the public health system in Andalusia (Spain). METHODS: A longitudinal, multicentre prospective study was made of a cohort of patients recruited between May 2014 and March 2016. The risk of falls was assessed using each of the above instruments during the first 24 h after hospital admittance, with later re-evaluations every 72 h until discharge. Descriptive statistics were obtained, bivariate and multivariate analysis were performed. The diagnostic validity of the process was assessed by calculations of sensitivity, specificity, positive and negative predictive values and ratios of positive and negative likelihood. ROC curve analysis was performed for both instruments. RESULTS: For this study, 1247 patients were recruited, of whom 977 completed all the follow-up assessments. Twenty-three of these patients (2.35%) suffered 24 falls. ROC curve analysis showed that the optimal cut-off point for each assessment instrument was below that described by the authors: AUC STRATIFY = 0.69 (95% CI: 0.57-0.8); AUC Downton = 0.6 (95% CI: 0.48-0.72). With a cut-off point of 1, the sensitivity of STRATIFY was 47.6% and its specificity, 85%. With a cut-off point of 2, Downton presented a sensitivity of 66.7% and a specificity of 55.3%. CONCLUSIONS: The Downton and STRATIFY falls risk assessment instruments presented little utility as means of detecting the risk of falls among a sample of adult patients admitted to acute care hospitals. Fall prevention in hospitals should be based on the study of individual risk factors.

[Validation of a scale to assess the labour quality of life in public hospitals from Tlaxcala]. / Validación de una escala para medir la calidad de vida laboral en hospitales públicos de Tlaxcala.

OBJECTIVE:: To validate a scale for assessing the labour quality of life in public hospitals (LQL-PH) from Tlaxcala, Mexico. MATERIALS AND METHODS:: The instrument was validated among 669 health workers from six hospitals from the Ministry of Health of Tlaxcala, Mexico. Content validity was by inquiry to experts, construct validity by factor analysis, criterion validity by comparing with other scales, and reliability with Cronbach's Alpha. RESULTS:: The factor analysis uncovered four dimensions: "individual welfare", "conditions and labour environment", "organization", and "well-being accomplished by the work"; reliability was 0.921. Workers who perceibed better LQL-PH were: under 50 years old, with temporary contract, with less seniority in job, with work schedule at daytime of weekends, and those with academic degree. CONCLUSIONS:: LQL-PH showed to be an instrument phsycometrically valid and reliable. It's recommendable to prove this scale in other public and private health institutions, as well as its relationship with key health care indicators of labour performance and management.

Development and psychometric validation of a questionnaire to evaluate nurses' adherence to recommendations for preventing pressure ulcers (QARPPU).

AIM OF THE STUDY: The main objective of this work is the development and psychometric validation of an instrument to evaluate nurses' adherence to the main recommendations issued for preventing pressure ulcers. MATERIAL AND METHODS: An instrument was designed based on the main recommendations for the prevention of pressure ulcers published in various clinical practice guides. Subsequently, it was proceeded to evaluate the face and content validity of the instrument by an expert group. It has been applied to 249 Spanish nurses took part in a cross-sectional study to obtain a psychometric evaluation (reliability and construct validity) of the instrument. The study data were compiled from June 2015 to July 2016. RESULTS: From the results of the psychometric analysis, a final 18-item, 4-factor questionnaire was derived, which explained 60.5% of the variance and presented the following optimal indices of fit (CMIN/DF: 1.40 p < 0.001; GFI: 0.93; NFI: 0.92; CFI: 0.98; TLI: 0.97; RMSEA: 0.04 (90% CI 0.025-0.054). CONCLUSIONS: The results obtained show that the instrument presents suitable psychometric properties for evaluating nurses' adherence to recommendations for the prevention of pressure ulcers.

Aspheric lens to increase the depth of focus.

For high-resolution optical systems, a long depth of focus is desirable. Unfortunately, resolution and depth of focus are inversely related. In this work, a novel lens is presented to produce long depth of focus beams, keeping the same resolution. The equations to perform the optical design of this kind of lenses and results are shown for a simple lens that can produce beams with a spot size of 2.9 µm over a range of 1.5 mm and for an achromatic doublet with a focus depth of 10 mm.

Validation of the STRATIFY falls risk-assessment tool for acute-care hospital patients and nursing home residents: study protocol.

AIM: To evaluate the accuracy of the STRATIFY tool in detecting and predicting fall risk in acute-care hospitals and nursing homes for the older people. BACKGROUND: Falls are the predominant cause of injury in people aged over 65 years. Testing the falls risk-assessment tools in settings other than those for which they were originally developed obtained conflicting results and has highlighted difficulties in their adoption for widespread use. Current guidelines for practice call into question the appropriateness of using these instruments. DESIGN: Two-stage study: a cross-cultural adaptation and psychometric validation; and a longitudinal, prospective follow-up of the cohort of patients recruited. METHODS: A cross-cultural adaptation of STRATIFY, followed by its empirical validation will be performed, on a total sample of 2097 patients. The diagnostic validity will be assessed by calculating the sensitivity, specificity, positive and negative predictive values and the ratios of positive and negative probability. Data for statistical reliability and the internal consistency of the instrument will be calculated; construct validity will be assessed by factor analysis and criterion validity determined according to the Downton index. The incidence and the hazard ratio of falls will be analysed for the study factors included. Funding of the review was confirmed in December 2013. DISCUSSION: The rigorous assessment of STRATIFY using large samples, in populations with different levels of risk and implementing a longitudinal follow-up to determine the effect of revaluation on the incidence of falls, will give stronger evidence for the establishment of future recommendations in Clinical Practice Guidelines.

Sweetened beverage consumption and the risk of hyperuricemia in Mexican adults: a cross-sectional study.

BACKGROUND: The prevalence of hyperuricemia has doubled worldwide during the last few decades. The substantial increase in sweetened beverage (SB) consumption has also coincided with the secular trend of hyperuricemia. Recent studies do show that the consumption of SB can induce hyperuricemia. However, the association between SB and hyperuricemia remains unclear. The aim of this study was to evaluate the association between SB consumption and levels of uric acid in Mexican adults. METHODS: We performed a cross-sectional analysis of data from selected adults participating in the baseline assessment of the Health Workers Cohort Study. A total of 6,705 participants of both sexes between ages 18 and 70 years were included. SB intake was estimated using a validated semi-quantitative food frequency questionnaire. Biochemical and anthropometric information was collected using standard procedures. Hyperuricemia was defined as uric acid levels ≥ 7.0 mg/dL in men and ≥ 5.8 mg/dL in women. The association of interest was assessed by multiple logistic regression models. RESULTS: The odds ratios (OR) for hyperuricemia in men who consume 0.5-1 SB/day was 1.59 (95% CI; 1.05-2.40) and 2.29 (95% CI; 1.55-3.38) for those who consume ≥3 SB/day when compared to men who consume less than half a SB/day. In women, the OR for hyperuricemia for those who consume >1.0- < 3.0 SB/day was 1.33 (95% CI; 1.04-1.70) and 1.35 (95% CI; 1.04-1.75) for those who consume ≥3 SB/day when compared to women who consume less than half a SB/day, independent of other covariables. Men and women with high SB consumption and a body mass index (BMI) ≥ 25 Kg/m2 had greater risk for hyperuricemia than men and women with low SB consumption and normal BMI < 25 Kg/m2. CONCLUSIONS: Our findings suggest that the consumption of SB is associated with an increased risk of hyperuricemia in Mexican adults. However, longitudinal research is needed to confirm the association between SB intake and hyperuricemia.

Detection of minimal residual disease in acute myeloid leukemia: evaluating utility and challenges.

This study discusses the importance of minimal residual disease (MRD) detection in acute myeloid leukemia (AML) patients using liquid biopsy and next-generation sequencing (NGS). AML prognosis is based on various factors, including genetic alterations. NGS has revealed the molecular complexity of AML and helped refine risk stratification and personalized therapies. The long-term survival rates for AML patients are low, and MRD assessment is crucial in predicting prognosis. Currently, the most common methods for MRD detection are flow cytometry and quantitative PCR, but NGS is being incorporated into clinical practice due to its ability to detect genomic aberrations in the majority of AML patients. Typically, bone marrow samples are used for MRD assessment, but using peripheral blood samples or liquid biopsies would be less invasive. Leukemia originates in the bone marrow, along with the cfDNA obtained from peripheral blood. This study aimed to assess the utility of cell-free DNA (cfDNA) from peripheral blood samples for MRD detection in AML patients. A cohort of 20 AML patients was analyzed using NGS, and a correlation between MRD assessment by cfDNA and circulating tumor cells (CTCs) in paired samples was observed. Furthermore, a higher tumor signal was detected in cfDNA compared to CTCs, indicating greater sensitivity. Challenges for the application of liquid biopsy in MRD assessment were discussed, including the selection of appropriate markers and the sensitivity of certain markers. This study emphasizes the potential of liquid biopsy using cfDNA for MRD detection in AML patients and highlights the need for further research in this area.

Identification of host endotypes using peripheral blood transcriptomics in a prospective cohort of patients with endocarditis.

OBJECTIVES: Host responses to infection are a major determinant of outcome. However, the existence of different response profiles in patients with endocarditis has not been addressed. Our objective was to apply transcriptomics to identify endotypes in patients with infective endocarditis. METHODS: A total of 32 patients with infective endocarditis were studied. Clinical data and blood samples were collected at diagnosis and RNA sequenced. Gene expression was used to identify two clusters (endocarditis endotype 1 [EE1] and endocarditis endotype 2 [EE2]). RNA sequencing was repeated after surgery. Transcriptionally active cell populations were identified by deconvolution. Differences between endotypes in clinical data, survival, gene expression, and molecular pathways involved were assessed. The identified endotypes were recapitulated in a cohort of COVID-19 patients. RESULTS: A total of 18 and 14 patients were assigned to EE1 and EE2, respectively, with no differences in clinical data. Patients assigned to EE2 showed an enrichment in genes related to T-cell maturation and a decrease in the activation of the signal transducer and activator of transcription protein family pathway, with higher counts of active T cells and lower counts of neutrophils. A total of 14 patients (nine in EE1 and five in EE2) were submitted to surgery. Surgery in EE2 patients shifted gene expression toward a EE1-like profile. In-hospital mortality was higher in EE1 (56% vs 14%, P = 0.027), with an adjusted hazard ratio of 12.987 (95% confidence interval 3.356-50). Translation of these endotypes to COVID-19 and non-COVID-19 septic patients yielded similar results in cell populations and outcome. CONCLUSIONS: Gene expression reveals two endotypes in patients with acute endocarditis, with different underlying pathogenetic mechanisms, responses to surgery, and outcomes.

Septic serum induces glucocorticoid resistance and modifies the expression of glucocorticoid isoforms receptors: a prospective cohort study and in vitro experimental assay.

BACKGROUND: A protective role for glucocorticoid therapy in animal models of sepsis was shown many decades ago. In human sepsis, there is new interest in glucocorticoid therapy at a physiological dose after reports of improved response to vasopressor drugs and decreased mortality in a selected group of patients. However, other reports have not confirmed these results. Cellular glucocorticoid resistance could explain a possible cause of that. To evaluate this hypothesis, we evaluated the expression of glucocorticoid receptor beta, the dominant negative isoform of glucocorticoid receptor, in peripheral mononuclear cells of septic patients and the effect of serum septic patients over glucocorticoid receptor expression and glucocorticoid sensitivity in immune cells culture. METHODS: A prospective cohort study and an in vitro experimental study with matched controls were developed. Nine patients with septic shock and nine healthy controls were prospectively enrolled. Mononuclear cells and serum samples were obtained from the patients with sepsis on admission to the Intensive Care Unit and on the day of discharge from hospital, and from healthy volunteers matched by age and sex with the patients. Glucocorticoid receptor alpha and beta expression from patients and from immune cell lines cultured in the presence of serum from septic patients were studied by western blot. Glucocorticoid sensitivity was studied in control mononuclear cells cultured in the presence of serum from normal or septic patients. A statistical analysis was performed using a Mann-Whitney test for non-parametric data and analysis of variance for multiple comparison; P<0.05 was considered significant. RESULTS: The patients' glucocorticoid receptor beta expression was significantly higher on admission than on discharge, whereas the alpha receptor was not significantly different. In vitro, septic serum induced increased expression of both receptors in T and B cells in culture, with a greater effect on receptor beta than the control serum. Septic serum induced glucocorticoid resistance in control mononuclear cells. CONCLUSION: There is a transient increased expression of glucocorticoid receptor beta in mononuclear cells from septic patients. Serum from septic patients induces cell glucocorticoid resistance in vitro. Our findings support a possible cell glucocorticoid resistance in sepsis.

Instruments for assessing the risk of falls in acute hospitalized patients: a systematic review and meta-analysis.

BACKGROUND: Falls are a serious problem for hospitalized patients, reducing the duration and quality of life. It is estimated that over 84% of all adverse events in hospitalized patients are related to falls. Some fall risk assessment tools have been developed and tested in environments other than those for which they were developed with serious validity discrepancies. The aim of this review is to determine the accuracy of instruments for detecting fall risk and predicting falls in acute hospitalized patients. METHODS: Systematic review and meta-analysis. Main databases, related websites and grey literature were searched. Two blinded reviewers evaluated title and abstracts of the selected articles and, if they met inclusion criteria, methodological quality was assessed in a new blinded process. Meta-analyses of diagnostic ORs (DOR) and likelihood (LH) coefficients were performed with the random effects method. Forest plots were calculated for sensitivity and specificity, DOR and LH. Additionally, summary ROC (SROC) curves were calculated for every analysis. RESULTS: Fourteen studies were selected for the review. The meta-analysis was performed with the Morse (MFS), STRATIFY and Hendrich II Fall Risk Model scales. The STRATIFY tool provided greater diagnostic validity, with a DOR value of 7.64 (4.86 - 12.00). A meta-regression was performed to assess the effect of average patient age over 65 years and the performance or otherwise of risk reassessments during the patient's stay. The reassessment showed a significant reduction in the DOR on the MFS (rDOR 0.75, 95% CI: 0.64 - 0.89, p = 0.017). CONCLUSIONS: The STRATIFY scale was found to be the best tool for assessing the risk of falls by hospitalized acutely-ill adults. However, the behaviour of these instruments varies considerably depending on the population and the environment, and so their operation should be tested prior to implementation. Further studies are needed to investigate the effect of the reassessment of these instruments with respect to hospitalized adult patients, and to consider the real compliance by healthcare personnel with procedures related to patient safety, and in particular concerning the prevention of falls.