Ceratophyllum demersum alleviates microplastics uptake and physiological stress responses in aquatic organisms, an overlooked ability.

It has been demonstrated that microplastics (MPs) may be inadvertently ingested by aquatic animals, causing harm to their physiological functions and potentially entering the food chain, thereby posing risks to human food safety. To achieve an environmentally friendly and efficient reduction of MPs in freshwater environments, this experiment investigates the depuration effect of C. demersum on MPs using three common aquatic animals: Macrobrachium nipponense, Corbicula fluminea, and Bellamya aeruginosa as research subjects. The amounts of MPs, digestive enzyme activity, oxidative stress index, and energy metabolism enzyme activity in the digestive and non-digestive systems of three aquatic animals were measured on exposure days 1, 3, and 7 and on depuration days 1 and 3. The results indicated that the depuration effect of C. demersum and the species interaction were significant for the whole individual. Concerning digestive tissue, C. demersum was the most effective in purifying B. aeruginosa. When subjected to short-term exposure to MPs, C. demersum displayed a superior depuration effect. Among non-digestive tissues, C. demersum exhibited the earliest purifying effect on C. fluminea. Additionally, C. demersum alleviated physiological responses caused by MPs. In conclusion, this study underscores C. demersum as a promising new method for removing MPs from aquatic organisms.

Accuracy of acute hyperglycemia as a biomarker of severe brain damage in children with traumatic brain injury.

PURPOSE: Biomarkers are substances measured at the systemic level to evaluate organic responses in certain situations, establishing diagnoses, disease staging, and prognosis. Blood glucose is a biomarker recognized as a predictor of prognosis in children victims of traumatic brain injury (TBI). The scope of this study was to identify the accuracy of blood glucose as a biomarker of severe brain injury. METHODS: A retrospective analytical study was conducted through the consecutive review of medical records of children and teenage victims of TBI who underwent neurological surgery between 2016 and 2023 in a level 1 trauma center. Two groups were compared: children with Glasgow Coma Scale (GCS) score ≤ 8 and children with GCS > 8. We calculated the predictive values to define the accuracy of blood glucose as a biomarker of brain injury. RESULTS: Ninety-two medical records were included for analysis. Hyperglycemia predominated in cases with GCS ≤ 8 (48% vs 3%; p < 0.0001; OR, 30; 95% CI, 5.9902-150.2448). The glycemic measurement considering the cutoff point of 200 mg/dL or 11.1 mmol/L showed a specificity of 97%, a positive predictive value of 86%, an accuracy of 84%, and a likelihood ratio for a positive test of 16. CONCLUSION: Victims with GCS ≤ 8 are 16 times more likely to develop acute hyperglycemia after TBI when compared to those with GCS > 8. Blood glucose is a biomarker with an accuracy of 84% to predict severe brain injury, considering the cutoff point of 200 mg/dL or 11.1 mmol/L.

Unveiling ecological/evolutionary insights in HIV viral load dynamics: Allowing random slopes to observe correlational changes to CpG-contents and other molecular and clinical predictors.

In the context of infectious diseases, the dynamic interplay between ever-changing host populations and viral biology demands a more flexible modeling approach than common fixed correlations. Embracing random-effects regression models allows for a nuanced understanding of the intricate ecological and evolutionary dynamics underlying complex phenomena, offering valuable insights into disease progression and transmission patterns. In this article, we employed a random-effects regression to model an observed decreasing median plasma viral load (pVL) among individuals with HIV in Mexico City during 2019-2021. We identified how these functional slope changes (i.e. random slopes by year) improved predictions of the observed pVL median changes between 2019 and 2021, leading us to hypothesize underlying ecological and evolutionary factors. Our analysis involved a dataset of pVL values from 7325 ART-naïve individuals living with HIV, accompanied by their associated clinical and viral molecular predictors. A conventional fixed-effects linear model revealed significant correlations between pVL and predictors that evolved over time. However, this fixed-effects model could not fully explain the reduction in median pVL; thus, prompting us to adopt random-effects models. After applying a random effects regression model-with random slopes and intercepts by year-, we observed potential "functional changes" within the local HIV viral population, highlighting the importance of ecological and evolutionary considerations in HIV dynamics: A notably stronger negative correlation emerged between HIV pVL and the CpG content in the pol gene, suggesting a changing immune landscape influenced by CpG-induced innate immune responses that could impact viral load dynamics. Our study underscores the significance of random effects models in capturing dynamic correlations and the crucial role of molecular characteristics like CpG content. By enriching our understanding of changing host-virus interactions and HIV progression, our findings contribute to the broader relevance of such models in infectious disease research. They shed light on the changing interplay between host and pathogen, driving us closer to more effective strategies for managing infectious diseases. SIGNIFICANCE OF THE STUDY: This study highlights a decreasing trend in median plasma viral loads among ART-naïve individuals living with HIV in Mexico City between 2019 and 2021. It uncovers various predictors significantly correlated with pVL, shedding light on the complex interplay between host-virus interactions and disease progression. By employing a random-slopes model, the researchers move beyond traditional fixed-effects models to better capture dynamic correlations and evolutionary changes in HIV dynamics. The discovery of a stronger negative correlation between pVL and CpG content in HIV-pol sequences suggests potential changes in the immune landscape and innate immune responses, opening avenues for further research into adaptive changes and responses to environmental shifts in the context of HIV infection. The study's emphasis on molecular characteristics as predictors of pVL adds valuable insights to epidemiological and evolutionary studies of viruses, providing new avenues for understanding and managing HIV infection at the population level.

Evaluation of biological markers for the risk assessment of carbon black in epidemiological studies.

Background/objectives: Engineered nanomaterials (ENMs) have been suggested as being capable of promoting inflammation, a key component in the pathways associated with carcinogenesis, cardiovascular disease, and other conditions. As a result, the risk assessment of biological markers as early-stage indicators has the potential to improve translation from experimental toxicologic findings to identifying evidence in human studies. The study aims to review the possible early biological changes in workers exposed to carbon black (CB), followed by an evidentiary quality evaluation to determine the predictive value of the biological markers. Methods: We conducted a literature search to identify epidemiological studies that assessed biological markers that were involved in the inflammatory process at early stages among workers with exposure to CB. We reviewed the studies with specific reference to the study design, statistical analyses, findings, and limitations. Results: We identified five Chinese studies that investigated the potential impact of exposure to CB on inflammatory markers, bronchial wall thickening, genomic instability, and lung function impairment in CB production workers. Of the five Chinese studies, four were cross-sectional; another study reported results at two-time points over six years of follow-up. The authors of all five studies concluded positive relationships between exposure and the inflammatory cytokine profiles. The weak to very weak correlations between biomarkers and early-stage endpoints were reported. Conclusion: Most inflammatory markers failed to satisfy the proposed evidentiary quality criteria. The significance of the results of the reviewed studies is limited by the cross-sectional study design, inconsistency in results, uncertain clinical relevance, and high occupational exposures. Based on this review, the risk assessment relying on inflammatory markers does not seem appropriate at this time. Nevertheless, the novel research warrants further exploration in assessing exposure to ENMs and corresponding potential health risks in occupational settings.

Building diagnostic neuroimaging biomarkers for psychiatric disorders using reverse inference approaches: A viable route?

The advent of structural magnetic resonance imaging (sMRI) at the end of the 20th century opened the way toward a deeper understanding of the neurophysiology of psychiatric disorders, substantiating regional structural abnormalities underlying this group of clinical conditions. However, despite abundant and flourishing scientific research, sMRI methodologies are not currently integrated into daily diagnostic practice. One reason behind this failed translation may be the prevailing approach to logical reasoning in neuroimaging: The forward inference via frequentist-based statistics. This reasoning prevents clinicians from obtaining information about the selectivity of results, which are therefore of limited use regarding the definition of biomarkers and refinement of diagnostic processes. Recently, another type of inferential approach has started to emerge in the neuroimaging field: The reverse inference via Bayesian statistics. Here, we introduce the key concepts of this approach, with a particular emphasis on the clinical sMRI environment. We survey recent findings showing significant potential for clinical translation. Clinical opportunities and challenges for developing reverse inference-based neural markers for psychiatry are also discussed. We propose that a systematic sharing of imaging data across the human brain mapping community is an essential first step toward a paradigmatic clinical shift. We conclude that a defined synergy between forward-based and reverse-based sMRI research can illuminate current discussions on diagnostic brain markers, offering clarity on key issues and fostering new tailored diagnostic avenues.

Obsessive-Compulsive Disorder as an Epiphenomenon of Comorbid Bipolar Disorder? An Updated Systematic Review.

BACKGROUND: Bipolar disorder (BD) and obsessive-compulsive disorder (OCD) comorbidity is an emerging condition in psychiatry, with relevant nosological, clinical, and therapeutic implications. METHODS: We updated our previous systematic review on epidemiology and standard diagnostic validators (including phenomenology, course of illness, heredity, biological markers, and treatment response) of BD-OCD. Relevant papers published until (and including) 15 October 2023 were identified by searching the electronic databases MEDLINE, Embase, PsychINFO, and Cochrane Library, according to the PRISMA statement (PROSPERO registration number, CRD42021267685). RESULTS: We identified 38 new articles, which added to the previous 64 and raised the total to 102. The lifetime comorbidity prevalence ranged from 0.26 to 27.8% for BD and from 0.3 to 53.3% for OCD. The onset of the two disorders appears to be often overlapping, although the appearance of the primary disorder may influence the outcome. Compared to a single diagnosis, BD-OCD exhibited a distinct pattern of OC symptoms typically following an episodic course, occurring in up to 75% of cases (vs. 3%). Notably, these OC symptoms tended to worsen during depressive episodes (78%) and improve during manic or hypomanic episodes (64%). Similarly, a BD course appears to be chronic in individuals with BD-OCD in comparison to patients without. Additionally, individuals with BD-OCD comorbidity experienced more depressive episodes (mean of 8.9 ± 4.2) compared to those without comorbidity (mean of 4.1 ± 2.7). CONCLUSIONS: We found a greater likelihood of antidepressant-induced manic/hypomanic episodes (60% vs. 4.1%), and mood stabilizers with antipsychotic add-ons emerging as a preferred treatment. In line with our previous work, BD-OCD comorbidity encompasses a condition of greater nosological and clinical complexity than individual disorders.

Biological markers of adipose tissue: Adipokines.

We currently have a large sum of clinical and experimental data documenting the involvement of numerous adipokines in the maintenance of energy homeostasis in healthy individuals and their dysregulation in diseases such as obesity, metabolic syndrome or type 2 diabetes. Despite the impressive discoveries made in this field over many years, much remains to be done before understanding all the physiological and pathological implications, and hoping for the development of other effective and safe therapeutic strategies. Two original adipokines will be taken as examples to illustrate these remarks, chemerin and neuregulin 4.

Diagnostic value of procalcitonin in patients with periprosthetic joint infection: a diagnostic meta-analysis.

Background: The success rate of periprosthetic joint infection (PJI) treatment is still low. Early diagnosis is the key to successful treatment. Therefore, it is necessary to find a biomarker with high sensitivity and specificity. The diagnostic value of serum procalcitonin (PCT) for PJI was systematically evaluated to provide the theoretical basis for clinical diagnosis and treatment in this study. Methods: We searched the Web of Science, Embase, Cochrane Library, and PubMed for studies that evaluated the diagnostic value of serum PCT for PJI (from the inception of each database until September 2020). Two authors independently screened the literature according to the inclusion and exclusion criteria. The quality of each selected literature was evaluated by using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) tool. RevMan 5.3 software was used for the quality evaluation. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were merged by using Meta-DiSc 1.4 software. The area under the curve (AUC) and Q index were calculated after the summary receiver operating characteristic (SROC) was generated. We also performed subgroup analysis. Results: A total of 621 patients were enrolled in the nine studies. The pooled sensitivity of serum PCT for PJI diagnosis was 0.441 [95% confidence interval (CI), 0.384-0.500], the pooled specificity was 0.852 (95% CI, 0.811-0.888), the pooled PLR was 2.271 (95% CI, 1.808-2.853), the pooled NLR was 0.713 (95% CI, 0.646-0.786), and the pooled DOR was 5.756 (95% CI, 3.673-9.026). The area under SROC (the pooled AUC) was 0.76 (0.72-0.79). Q index was 0.6948. Conclusion: This study showed that PCT detection of PJI had poor diagnostic accuracy. Hence, the serum PCT is not suitable as a serum marker for PJI diagnosis.

Pharmacogenomic Clinical Support Tools for the Treatment of Depression.

OBJECTIVE: In this review, the authors update the 2018 position statement of the American Psychiatric Association Council of Research Workgroup on Biomarkers and Novel Treatments on pharmacogenomic (PGx) tools for treatment selection in depression. METHODS: The literature was reviewed for new clinical trials and meta-analyses, published from 2017 to 2022, of studies using PGx tools for treatment selection in depression. The blinding and control conditions, as well as primary and secondary outcomes and post hoc analyses, were summarized. RESULTS: Eleven new clinical trials and five meta-analyses were identified; all studies had primary outcome measures related to speed or efficacy of treatment response. Three trials (27%) demonstrated efficacy on the primary outcome measure with statistical significance; the three studies used different PGx tools; one study was open-label and the other two were small single-blind trials. Five trials (45%) did not detect efficacy with statistical significance on either primary or secondary outcome measures. Only one trial (9%) used adverse events as a primary outcome measure. All studies had significant limitations; for example, none adopted a fully blinded study design, only two studies attempted to blind the treating clinician, and none incorporated measures to estimate the effectiveness of the blinds or the influence of lack of blinding on the study results. CONCLUSIONS: The addition of these new data do not alter the recommendations of the 2018 report, or the advice of the U.S. Food and Drug Administration, that the evidence does not support the use of currently available combinatorial PGx tools for treatment selection in major depressive disorder. Priority efforts for future studies and the development and testing of effective tools include fully blinded study designs, inclusion of promising genetic variants not currently included in any commercially available tests, and investigation of other uses of pharmacogenomics, such as estimating the likelihood of rare adverse drug effects, rather than increasing the speed or magnitude of drug response.

Narrative Review of Biological Markers in Chronic Limb-Threatening Ischemia.

BACKGROUND: Chronic limb-threatening ischemia (CLTI), the advanced stage of peripheral arterial disease, is diagnosed in the presence of ischemic rest pain, non-healing ulcers, or gangrene. Several studies have demonstrated that inflammation and endothelial dysfunction are some of the main substrates of CLTI. METHODS: A narrative review was conducted and reported according to PRISMA guidelines. Three databases were searched-Web of Science, Medline, and EMBASE-for the studies assessing CLTI and the biological markers related to it. RESULTS: We included 22 studies, and all the markers identified (C-reactive protein, D-dimers, fibrinogen, cytokines, IL-6, TNF-α, ICAM-1 (Intracellular Adhesion Molecule-1), VCAM-1 (Vascular Cell Adhesion Molecule-1), neutrophile-to-lymphocytes ratio (NLR), IL-8, Pentraxin-3, neutrophil gelatinase-associated lipocalin (NGAL), calprotectin, E-selectin, P-selectin, neopterin, High-Mobility Group Box-1 protein (HGMB-1), Osteoprotegerin (OPG) and Sortilin) were positively associated with advanced CLTI, with major limb or major cardiovascular events in these patients. CONCLUSIONS: All the studied markers had increased values in patients with CLTI, especially when associated with diabetes mellitus, proving a very important association between diabetes and major limb or cardiovascular events in these patients. There is a need for more studies to validate these markers in terms of diagnosis or prognosis in CLTI patients and in trying to find new medical strategies that target inflammation or endothelial dysfunction in these patients.

Capacidad del biomarcador suPAR para estratificar el pronóstico en pacientes atendidos en servicios de urgencias hospitalarios / Value of the soluble urokinase-type plasminogen activator receptor as a predictor of prognosis in patients attended in hospital emergency departments

Objetivos. Determinar la capacidad del receptor soluble del activador del plasminógeno tipo uroquinasa (suPAR) para la estratificación pronóstica en pacientes atendidos en servicios de urgencias hospitalarios (SUH). Los objetivos secundarios son: 1)medir la capacidad de los puntos de decisión habituales, 2)identificar una población de bajo riesgo de mortalidad que puede darse de alta de forma segura desde el SUH, y 3)medir la correlación entre suPAR y otros biomarcadores. Métodos. Estudio observacional de cohortes prospectivo de pacientes atendidos en SUH. Se registraron variables sociodemográficas, de comorbilidad, datos del episodio agudo, biomarcadores de uso común en urgencias y suPAR. Las variables de resultado fueron la necesidad de ingreso en el episodio índice, reconsulta al SUH y mortalidad a los 90 días. Resultados. Se incluyeron 990 pacientes, la edad fue de 68 (53-81) años, 50,8% eran hombres, la mediana de suPAR fue de 3,8 (2,8-6,0) ng/ml, 112 pacientes (11,31%) requirieron ingreso. En el seguimiento a 90 días hubo 276 reconsultas (27,9%) y 47 pacientes (4,74%) fallecieron. Los pacientes con suPAR<4 ng/ml (52,5%) tenían menor mortalidad (1%), menor reconsulta (24,4%) y menor necesidad de ingreso hospitalario (20,6%), que pacientes con suPAR>6 ng/ml (mortalidad 13,5%, reconsulta 39,6% e ingreso 56,3%). Un suPAR>6 ng/ml mostró una hazard ratio (IC 95%) ajustada de 4,61 (1,68-12,67) para predecir mortalidad a 90 días y de 1,59 (1,13-2,10) para la reconsulta, y una odds ratio de 1,62 (0,99-2,62) para la necesidad de ingreso hospitalario. Conclusiones. Un valor de suPAR < 4 ng/ml identifica pacientes con riesgo bajo de mortalidad a 90 días, de reconsulta y de necesidad de ingreso, mientras que los pacientes con suPAR>6 ng/ml tienen mayor mortalidad, reconsulta y necesidad de ingreso. (AU)

Objectives. To determine the value of the soluble urokinase-type plasminogen activator receptor (suPAR) for predicting outcomes in emergency department (ED) patients. Secondary objectives were 1)to measure the predictive value of the usual decision points, 2)to identify patients at low risk for mortality who could be safely discharged from the ED, and 3)to measure the correlation between suPAR and other biomarkers. Methods. Prospective observational cohort study of patients attended in the EDs of participating hospitals. We recorded sociodemographic variables, comorbidity, variables related to the acute episode, prognostic markers commonly used in EDs, and suPAR concentration. Outcome variables were the need for hospital admission during the index episode, ED revisits within 90 days, and 90-day mortality. Results. A total of 990 patients with a median (interquartile range) age of 68 (53-81 years) were studied; 50.8% were men. The median suPAR concentration was 3.8 (2.8-6.0) ng/mL, and 112 patients (11.31%) required admission. At 90 days there were 276 revisits (27.9% of the cohort), and 47 patients (4.74%) had died. Mortality was lower (1%) in patients with suPAR concentrations less than 4 ng/mL (52.5%), and fewer of these patients revisited (24.4%) or required hospitalization (20.6%) than patients with suPAR concentrations higher than 6 ng/mL (mortality, 13.5%; revisits, 39.6%; admissions, 56.3%). A suPAR concentration over 6 ng/mL was associated with 90-day mortality and revisits (adjusted hazard ratios and 95% CIs of 4.61 [1.68-12.67] and 1.59 [1.13-2.10]), respectively. The high suPAR concentration was also associated with hospital admission (odds ratio, 1.62 [0.99-2.62]). Conclusions. A suPAR concentration of less than 4 ng/mL identifies patients at low risk of 90-day mortality and revisits or need for hospitalization, whereas a suPAR concentration higher than 6 ng/mL is associated with higher risk for these outcomes. (AU)

Modelos predictivos de bacteriemia en el servicio de urgencias: revisión sistemática / Models to predict bacteremia in the emergency department: a systematic review

Objetivo. La obtención de hemocultivos (HC) se realiza en el 15% de los pacientes atendidos con sospecha de infección en los servicios de urgencias (SU) con una rentabilidad diagnóstica variable (2-20%). La mortalidad a 30 días de estos pacientes con bacteriemia es elevada, doble o triple que el resto con el mismo proceso. Así, encontrar un modelo predictivo de bacteriemia eficaz y aplicable en los SU sería muy importante. Clásicamente, el modelo de Shapiro ha sido la referencia en todo el mundo. El objetivo de esta revisión sistemática (RS) es comparar la capacidad para predecir bacteriemia en los SU de los distintos modelos predictivos publicados desde el año 2008 (fecha de publicación del modelo de Shapiro). Métodos. Se realiza una RS siguiendo la normativa PRISMA en las bases de datos de PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase y ClinicalTrials.gov desde enero de 2008 hasta 31 mayo 2023 sin restricción de idiomas y utilizando una combinación de términos MESH: “Bacteremia/Bacteraemia/Blood Stream Infection”, “Prediction Model/Clinical Prediction Rule/Risk Prediction Model”, “Emergencies/Emergency/Emergency Department” y “Adults”. Se incluyeron estudios de cohortes observacionales (analíticos de rendimiento diagnóstico). Para valorar la calidad del método empleado y el riesgo de sesgos de los artículos incluidos se utilizó la NewcastleOttawa Scale (NOS). No se incluyeron estudios de casos y controles, revisiones narrativas y en otros tipos de artículos. No se realizaron técnicas de metanálisis, pero los resultados se compararon narrativamente. El protocolo de la RS se registró en PROSPERO (CRD42023426327). Resultados. Se identificaron 917 artículos y se analizaron finalmente 20 que cumplían los criterios de inclusión. Los estudios incluidos contienen 33.182 HC procesados con 5.074 bacteriemias (15,3%). Once estudios fueron calificados de calidad alta, 7 moderada y 2 baja... (AU)

Objective. Blood cultures are ordered in emergency departments for 15% of patients with suspected infection. The diagnostic yield varies from 2% to 20%. Thirty-day mortality in patients with bacteremia is high, doubling or tripling the rate in patients with the same infection but without bacteremia. Thus, finding an effective model to predict bacteremia that is applicable in emergency departments is an important goal. Shapiro’s model is the one traditionally used as a reference internationally. The aim of this systematic review was to compare the predictive power of bacteremia risk models published since 2008, when Shapiro’s model first appeared. Methods. We followed the recommendations of the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) statement, searching in the following databases for articles published between January 2008 and May 31, 2023: PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Trip Medical Database, and ClinicalTrials.gov. No language restrictions were specified. The search terms were the following Medical Subject Headings: bacteremia/bacteraemia/blood stream infection, prediction model/clinical prediction rule/risk prediction model, emergencies/emergency/emergency department, and adults. Observational cohort studies analyzing diagnostic yield were included; case-control studies, narrative reviews, and other types of articles were excluded. The Newcastle-Ottawa Scale was used to score quality and risk of bias in the included studies. The results were compared descriptively, without meta-analysis. The protocol was included in the PROSPERO register (CRD42023426327). Results. Twenty studies out of a total of 917 were found to meet the inclusion criteria. The included studies together analyzed 33 182 blood cultures, which detected 5074 cases of bacteremia (15.3%). Eleven studies were of high quality, 7 of moderate quality, and 2 of low quality... (AU)

Capacidad del biomarcador suPAR para estratificar el pronóstico en pacientes atendidos en servicios de urgencias hospitalarios / Value of the soluble urokinase-type plasminogen activator receptor as a predictor of prognosis in patients attended in hospital emergency departments

Objetivos. Determinar la capacidad del receptor soluble del activador del plasminógeno tipo uroquinasa (suPAR) para la estratificación pronóstica en pacientes atendidos en servicios de urgencias hospitalarios (SUH). Los objetivos secundarios son: 1)medir la capacidad de los puntos de decisión habituales, 2)identificar una población de bajo riesgo de mortalidad que puede darse de alta de forma segura desde el SUH, y 3)medir la correlación entre suPAR y otros biomarcadores. Métodos. Estudio observacional de cohortes prospectivo de pacientes atendidos en SUH. Se registraron variables sociodemográficas, de comorbilidad, datos del episodio agudo, biomarcadores de uso común en urgencias y suPAR. Las variables de resultado fueron la necesidad de ingreso en el episodio índice, reconsulta al SUH y mortalidad a los 90 días. Resultados. Se incluyeron 990 pacientes, la edad fue de 68 (53-81) años, 50,8% eran hombres, la mediana de suPAR fue de 3,8 (2,8-6,0) ng/ml, 112 pacientes (11,31%) requirieron ingreso. En el seguimiento a 90 días hubo 276 reconsultas (27,9%) y 47 pacientes (4,74%) fallecieron. Los pacientes con suPAR<4 ng/ml (52,5%) tenían menor mortalidad (1%), menor reconsulta (24,4%) y menor necesidad de ingreso hospitalario (20,6%), que pacientes con suPAR>6 ng/ml (mortalidad 13,5%, reconsulta 39,6% e ingreso 56,3%). Un suPAR>6 ng/ml mostró una hazard ratio (IC 95%) ajustada de 4,61 (1,68-12,67) para predecir mortalidad a 90 días y de 1,59 (1,13-2,10) para la reconsulta, y una odds ratio de 1,62 (0,99-2,62) para la necesidad de ingreso hospitalario. Conclusiones. Un valor de suPAR < 4 ng/ml identifica pacientes con riesgo bajo de mortalidad a 90 días, de reconsulta y de necesidad de ingreso, mientras que los pacientes con suPAR>6 ng/ml tienen mayor mortalidad, reconsulta y necesidad de ingreso. (AU)

Objectives. To determine the value of the soluble urokinase-type plasminogen activator receptor (suPAR) for predicting outcomes in emergency department (ED) patients. Secondary objectives were 1)to measure the predictive value of the usual decision points, 2)to identify patients at low risk for mortality who could be safely discharged from the ED, and 3)to measure the correlation between suPAR and other biomarkers. Methods. Prospective observational cohort study of patients attended in the EDs of participating hospitals. We recorded sociodemographic variables, comorbidity, variables related to the acute episode, prognostic markers commonly used in EDs, and suPAR concentration. Outcome variables were the need for hospital admission during the index episode, ED revisits within 90 days, and 90-day mortality. Results. A total of 990 patients with a median (interquartile range) age of 68 (53-81 years) were studied; 50.8% were men. The median suPAR concentration was 3.8 (2.8-6.0) ng/mL, and 112 patients (11.31%) required admission. At 90 days there were 276 revisits (27.9% of the cohort), and 47 patients (4.74%) had died. Mortality was lower (1%) in patients with suPAR concentrations less than 4 ng/mL (52.5%), and fewer of these patients revisited (24.4%) or required hospitalization (20.6%) than patients with suPAR concentrations higher than 6 ng/mL (mortality, 13.5%; revisits, 39.6%; admissions, 56.3%). A suPAR concentration over 6 ng/mL was associated with 90-day mortality and revisits (adjusted hazard ratios and 95% CIs of 4.61 [1.68-12.67] and 1.59 [1.13-2.10]), respectively. The high suPAR concentration was also associated with hospital admission (odds ratio, 1.62 [0.99-2.62]). Conclusions. A suPAR concentration of less than 4 ng/mL identifies patients at low risk of 90-day mortality and revisits or need for hospitalization, whereas a suPAR concentration higher than 6 ng/mL is associated with higher risk for these outcomes. (AU)

Modelos predictivos de bacteriemia en el servicio de urgencias: revisión sistemática / Models to predict bacteremia in the emergency department: a systematic review

Objetivo. La obtención de hemocultivos (HC) se realiza en el 15% de los pacientes atendidos con sospecha de infección en los servicios de urgencias (SU) con una rentabilidad diagnóstica variable (2-20%). La mortalidad a 30 días de estos pacientes con bacteriemia es elevada, doble o triple que el resto con el mismo proceso. Así, encontrar un modelo predictivo de bacteriemia eficaz y aplicable en los SU sería muy importante. Clásicamente, el modelo de Shapiro ha sido la referencia en todo el mundo. El objetivo de esta revisión sistemática (RS) es comparar la capacidad para predecir bacteriemia en los SU de los distintos modelos predictivos publicados desde el año 2008 (fecha de publicación del modelo de Shapiro). Métodos. Se realiza una RS siguiendo la normativa PRISMA en las bases de datos de PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase y ClinicalTrials.gov desde enero de 2008 hasta 31 mayo 2023 sin restricción de idiomas y utilizando una combinación de términos MESH: “Bacteremia/Bacteraemia/Blood Stream Infection”, “Prediction Model/Clinical Prediction Rule/Risk Prediction Model”, “Emergencies/Emergency/Emergency Department” y “Adults”. Se incluyeron estudios de cohortes observacionales (analíticos de rendimiento diagnóstico). Para valorar la calidad del método empleado y el riesgo de sesgos de los artículos incluidos se utilizó la NewcastleOttawa Scale (NOS). No se incluyeron estudios de casos y controles, revisiones narrativas y en otros tipos de artículos. No se realizaron técnicas de metanálisis, pero los resultados se compararon narrativamente. El protocolo de la RS se registró en PROSPERO (CRD42023426327). Resultados. Se identificaron 917 artículos y se analizaron finalmente 20 que cumplían los criterios de inclusión. Los estudios incluidos contienen 33.182 HC procesados con 5.074 bacteriemias (15,3%). Once estudios fueron calificados de calidad alta, 7 moderada y 2 baja... (AU)

Objective. Blood cultures are ordered in emergency departments for 15% of patients with suspected infection. The diagnostic yield varies from 2% to 20%. Thirty-day mortality in patients with bacteremia is high, doubling or tripling the rate in patients with the same infection but without bacteremia. Thus, finding an effective model to predict bacteremia that is applicable in emergency departments is an important goal. Shapiro’s model is the one traditionally used as a reference internationally. The aim of this systematic review was to compare the predictive power of bacteremia risk models published since 2008, when Shapiro’s model first appeared. Methods. We followed the recommendations of the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) statement, searching in the following databases for articles published between January 2008 and May 31, 2023: PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Trip Medical Database, and ClinicalTrials.gov. No language restrictions were specified. The search terms were the following Medical Subject Headings: bacteremia/bacteraemia/blood stream infection, prediction model/clinical prediction rule/risk prediction model, emergencies/emergency/emergency department, and adults. Observational cohort studies analyzing diagnostic yield were included; case-control studies, narrative reviews, and other types of articles were excluded. The Newcastle-Ottawa Scale was used to score quality and risk of bias in the included studies. The results were compared descriptively, without meta-analysis. The protocol was included in the PROSPERO register (CRD42023426327). Results. Twenty studies out of a total of 917 were found to meet the inclusion criteria. The included studies together analyzed 33 182 blood cultures, which detected 5074 cases of bacteremia (15.3%). Eleven studies were of high quality, 7 of moderate quality, and 2 of low quality... (AU)

Diagnostic Accuracy of Point-of-Care Testing of C-Reactive Protein, Interleukin-6, and Procalcitonin in Neonates with Clinically Suspected Sepsis: A Prospective Observational Study.

OBJECTIVE: Sepsis often prompts clinicians to start empirical antibiotics in suspected neonates while awaiting diagnosis. The next-generation testing with point-of-care (POC) techniques offers a lead-time advantage that could bridge the gap by providing a timely diagnosis. MATERIALS AND METHODS: We conducted a prospective diagnostic study in 82 neonates enrolled between May and October 2022 in a level III neonatal intensive care unit. All neonates with a new episode of clinically suspected sepsis were included. Diagnostic accuracy of POC testing of C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) with standard laboratory methods was performed. RESULTS: The mean gestation age and birth weight of the neonates were 33.17 ± 4.25 weeks and 1,695.4 ± 700.74 grams, respectively. Most neonates were preterm (75%) with nearly equal proportions of early (51.22%) and late-onset (48.78%) sepsis. The POC CRP correlated well with standard CRP (r = 0.8001, 95% CI: 0.706-0.867, p < 0.0001). Among the three biomarkers, CRP had the maximum diagnostic accuracy (area under the curve [AUC] - 0.73) followed by PCT (AUC - 0.65) and IL-6 (0.55). There was no significant difference in the diagnostic accuracy of CRP (p = 0.46), PCT (p = 0.29), and IL-6 (p = 0.60) in early- and late-onset sepsis. The mean time for POC estimation of IL-6, PCT, and CRP was 12 ± 3 min which was significantly less compared to 366 ± 61 min for standard techniques (p < 0.001). CONCLUSION: POC CRP correlates well with standard techniques of estimation, and CRP alone and in combination with PCT has good diagnostic accuracy in neonatal sepsis.

N2 Responses in Youths With Psychosis Risk Syndrome and Their Association With Clinical Outcomes: A Cohort Follow-Up Study Based on the Three-Stimulus Visual Oddball Paradigm.

OBJECTIVE: Schizophrenia often occurs during youth, and psychosis risk syndrome occurs before the onset of psychosis. The aim of this study was to determine whether the visual event-related potential responses in youths with psychosis risk syndrome were defective in the presence of interference stimuli and associated with their clinical outcomes. METHODS: A total of 223 participants, including 122 patients with psychosis risk syndrome, 50 patients with emotional disorders, and 51 healthy control subjects, were assessed. Baseline EEG was recorded during the three-stimulus visual oddball task. The event-related potentials induced by square pictures with different colors were measured. Almost all patients with psychosis risk syndrome were followed up for 12 months and were reclassified into three subgroups: conversion, symptomatic, and remission. The differences in baseline event-related potential responses were compared among the clinical outcome subgroups. RESULTS: The average N2 amplitude of the psychosis risk syndrome group was significantly less negative than that in the healthy control group (d=0.53). The baseline average N2 amplitude in the conversion subgroup was significantly less negative than that in the symptomatic (d=0.58) and remission (d=0.50) subgroups and in the healthy control group (d=0.97). The average N2 amplitude did not differ significantly between the symptomatic and remission subgroups (d=0.02). However, it was significantly less negative in the symptomatic and remission subgroups than in the healthy control group (d=0.46 and d=0.38). No statistically significant results were found in the P3 response. CONCLUSIONS: Youths with psychosis risk syndrome had significant N2 amplitude defects in attention processing with interference stimuli. N2 amplitude shows potential as a prognostic biomarker of clinical outcome in the psychosis risk syndrome.

Laboratory Diagnostics Accuracy for COVID-19 versus Post-COVID-19 Syndrome in Lung Disease Patients with Multimorbidity.

The laboratory tests and identification of risk factors such as comorbidities are essential in the management, treatment and prognosis of patients with chronic respiratory diseases. Performing rigorous monitoring among patients with post-COVID-19 syndrome and early identification of risk factors associated with poor prognosis are crucial in improving patient outcomes. In the present study, 182 patients diagnosed with COVID-19 and PCI during 2020-2022 were included. A clinical and epidemiological evaluation was performed for each patient. Laboratory tests at admission included complete blood count, Erythrocyte Sedimentation Rate (ESR) and biochemical tests. Receiver operating curve (ROC) and area under the curve (AUC) were calculated to compare the diagnostic performance of each parameter. Regarding comorbidities, arterial hypertension, diabetes mellitus and obesity were the most frequent ones. In the case of chronic lung diseases, asthma and Chronic Obstructive Pulmonary Disease (COPD) were the most frequent. Pleurisy was found especially in patients with PCI Variations in serum LDH values were observed, especially in severe forms of COVID-19 in 2020, with a mean value of 481.44 U/L, compared to patients with PCI, whose mean values (122 U/L) were within the biological range of reference. High neutrophil/lymphocyte ratio (NLR) values quantified in this study were especially associated with moderate and severe forms of COVID-19 and also PCI. The Spearman correlation coefficient was determined to measure the correlations between the clinical parameters of all investigated subjects. A value of p < 0.05 was considered statistically significant. The statistical results indicated that serum lactate dehydrogenase (LDH), glucose and C-reactive protein (CRP) are sensitive markers with a diagnostic role in COVID-19, and lymphocyte (Ly) count, CRP, ESR and glucose were evidenced to be target markers in PCI. LDH values were observed to be statistically significant (p < 0.005) in patients with COVID-19 and obesity evaluated in 2021, while Ly count was statistically significant (p = 0.05) in patients with PCI and arterial hypertension. Regarding comorbidities, it has been observed that obesity, arterial hypertension and cardiovascular diseases represent risk factors in COVID-19/PCI, associated especially with the severe forms of the disease.

Value of the soluble urokinase-type plasminogen activator receptor as a predictor of prognosis in patients attended in hospital emergency departments. / Capacidad del biomarcador suPAR para estratificar el pronóstico en pacientes atendidos en servicios de urgencias hospitalarios.

OBJECTIVES: To determine the value of the soluble urokinase-type plasminogen activator receptor (suPAR) for predicting outcomes in emergency department (ED) patients. Secondary objectives were 1) to measure the predictive value of the usual decision points, 2) to identify patients at low risk for mortality who could be safely discharged from the ED, and 3) to measure the correlation between suPAR and other biomarkers. MATERIAL AND METHODS: Prospective observational cohort study of patients attended in the EDs of participating hospitals. We recorded sociodemographic variables, comorbidity, variables related to the acute episode, prognostic markers commonly used in EDs, and suPAR concentration. Outcome variables were the need for hospital admission during the index episode, ED revisits within 90 days, and 90-day mortality. RESULTS: A total of 990 patients with a median (interquartile range) age of 68 (53-81 years) were studied; 50.8% were men. The median suPAR concentration was 3.8 (2.8-6.0) ng/mL, and 112 patients (11.31%) required admission. At 90 days there were 276 revisits (27.9% of the cohort), and 47 patients (4.74%) had died. Mortality was lower (1%) in patients with suPAR concentrations less than 4 ng/mL (52.5%), and fewer of these patients revisited (24.4%) or required hospitalization (20.6%) than patients with suPAR concentrations higher than 6 ng/mL (mortality, 13.5%; revisits, 39.6%; admissions, 56.3%). A suPAR concentration over 6 ng/mL was associated with 90-day mortality and revisits (adjusted hazard ratios and 95% CIs of 4.61 [1.68-12.67] and 1.59 [1.13-2.10]), respectively. The high suPAR concentration was also associated with hospital admission (odds ratio, 1.62 [0.99-2.62]). CONCLUSION: A suPAR concentration of less than 4 ng/mL identifies patients at low risk of 90-day mortality and revisits or need for hospitalization, whereas a suPAR concentration higher than 6 ng/mL is associated with higher risk for these outcomes.

OBJETIVO: Determinar la capacidad del receptor soluble del activador del plasminógeno tipo uroquinasa (suPAR) para la estratificación pronóstica en pacientes atendidos en servicios de urgencias hospitalarios (SUH). Los objetivos secundarios son: 1) medir la capacidad de los `puntos de decisión habituales, 2) identificar una población de bajo riesgo de mortalidad que puede darse de alta de forma segura desde el SUH, y 3) medir la correlación entre suPAR y otros biomarcadores. METODO: Estudio observacional de cohortes prospectivo de pacientes atendidos en SUH. Se registraron variables sociodemográficas, de comorbilidad, datos del episodio agudo, biomarcadores de uso común en urgencias y suPAR. Las variables de resultado fueron la necesidad de ingreso en el episodio índice, reconsulta al SUH y mortalidad a los 90 días. RESULTADOS: Se incluyeron 990 pacientes, la edad fue de 68 (53-81) años, 50,8% eran hombres, la mediana de suPAR fue de 3,8 (2,8-6,0) ng/ml, 112 pacientes (11,31%) requirieron ingreso. En el seguimiento a 90 días hubo 276 reconsultas (27,9%) y 47 pacientes (4,74%) fallecieron. Los pacientes con suPAR 4 ng/ml (52,5%) tenían menor mortalidad (1%), menor reconsulta (24,4%) y menor necesidad de ingreso hospitalario (20,6%), que pacientes con suPAR 6 ng/ml (mortalidad 13,5%, reconsulta 39,6% e ingreso 56,3%). Un suPAR 6 ng/ml mostró una hazard ratio (IC 95%) ajustada de 4,61 (1,68-12,67) para predecir mortalidad a 90 días y de 1,59 (1,13-2,10) para la reconsulta, y una odds ratio de 1,62 (0,99-2,62) para la necesidad de ingreso hospitalario. CONCLUSIONES: Un valor de suPAR 4 ng/ml identifica pacientes con riesgo bajo de mortalidad a 90 días, de reconsulta y de necesidad de ingreso, mientras que los pacientes con suPAR 6 ng/ml tienen mayor mortalidad, reconsulta y necesidad de ingreso.

Models to predict bacteremia in the emergency department: a systematic review. / Modelos predictivos de bacteriemia en el servicio de urgencias: revisión sistemática.

OBJECTIVES: Blood cultures are ordered in emergency departments for 15% of patients with suspected infection. The diagnostic yield varies from 2% to 20%. Thirty-day mortality in patients with bacteremia is high, doubling or tripling the rate in patients with the same infection but without bacteremia. Thus, finding an effective model to predict bacteremia that is applicable in emergency departments is an important goal. Shapiro's model is the one traditionally used as a reference internationally. The aim of this systematic review was to compare the predictive power of bacteremia risk models published since 2008, when Shapiro's model first appeared. MATERIAL AND METHODS: We followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, searching in the following databases for articles published between January 2008 and May 31, 2023: PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Trip Medical Database, and ClinicalTrials.gov. No language restrictions were specified. The search terms were the following Medical Subject Headings: bacteremia/bacteraemia/blood stream infection, prediction model/clinical prediction rule/risk prediction model, emergencies/emergency/emergency department, and adults. Observational cohort studies analyzing diagnostic yield were included; case-control studies, narrative reviews, and other types of articles were excluded. The Newcastle-Ottawa Scale was used to score quality and risk of bias in the included studies. The results were compared descriptively, without meta-analysis. The protocol was included in the PROSPERO register (CRD42023426327). RESULTS: Twenty studies out of a total of 917 were found to meet the inclusion criteria. The included studies together analyzed 33 182 blood cultures, which detected 5074 cases of bacteremia (15.3%). Eleven studies were of high quality, 7 of moderate quality, and 2 of low quality. The area under the receiver operating characteristic curve (AUC) of Shapiro's model varied from 0.71 to 0.83. Sensitivity was as high as 98%, and specificity ranged from 26% to 69%. Three models with high scores for quality were also supported by both internal and external validation studies: Lee's model (AUC, 0.81; sensitivity 68%; specificity, 81%), the 5MPB-Toledo model (AUC, 0.906 to 0.946), and the MPB-INFURG-SEMES model (AUC, 0.924; sensitivity, 97%; specificity, 76%. CONCLUSION: The 5MPB-Toledo and MPB-INFURG-SEMES are useful for assessing the true risk of bacteremia in patients attended in emergency departments.

OBJETIVO: La obtención de hemocultivos (HC) se realiza en el 15% de los pacientes atendidos con sospecha de infección en los servicios de urgencias (SU) con una rentabilidad diagnóstica variable (2-20%). La mortalidad a 30 días de estos pacientes con bacteriemia es elevada, doble o triple que el resto con el mismo proceso. Así, encontrar un modelo predictivo de bacteriemia eficaz y aplicable en los SU sería muy importante. Clásicamente, el modelo de Shapiro ha sido la referencia en todo el mundo. El objetivo de esta revisión sistemática (RS) es comparar la capacidad para predecir bacteriemia en los SU de los distintos modelos predictivos publicados desde el año 2008 (fecha de publicación del modelo de Shapiro). METODO: Se realiza una RS siguiendo la normativa PRISMA en las bases de datos de PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase y ClinicalTrials.gov desde enero de 2008 hasta 31 mayo 2023 sin restricción de idiomas y utilizando una combinación de términos MESH: "Bacteremia/Bacteraemia/Blood Stream Infection", "Prediction Model/Clinical Prediction Rule/Risk Prediction Model", "Emergencies/Emergency/Emergency Department" y "Adults". Se incluyeron estudios de cohortes observacionales (analíticos de rendimiento diagnóstico). Para valorar la calidad del método empleado y el riesgo de sesgos de los artículos incluidos se utilizó la Newcastle-Ottawa Scale (NOS). No se incluyeron estudios de casos y controles, revisiones narrativas y en otros tipos de artículos. No se realizaron técnicas de metanálisis, pero los resultados se compararon narrativamente. El protocolo de la RS se registró en PROSPERO (CRD42023426327). RESULTADOS: Se identificaron 917 artículos y se analizaron finalmente 20 que cumplían los criterios de inclusión. Los estudios incluidos contienen 33.182 HC procesados con 5.074 bacteriemias (15,3%). Once estudios fueron calificados de calidad alta, 7 moderada y 2 baja. El ABC-COR conseguida por el modelo de Shapiro varía de 0,71 a 0,83, con sensibilidad (Se) hasta del 98%, con especificidad (Es) (26% a 69%). Para los tres modelos que tienen validación interna y externa y una buena calidad metodológica, el modelo de Lee consigue un ABC-COR de 0,81 con Se: 68% y Es: 81%, el modelo 5MPB-Toledo consigue un ABC-COR entre 0,91 y 0,95, y el MPB-INFURG-SEMES obtiene una ABC-COR de 0,92 con una Se: 97% y Es: 76%. CONCLUSIONES: Los modelos 5MPB-Toledo y MPB-INFURG-SEMES representan herramientas útiles para la estratificación del riesgo real de bacteriemia en los pacientes atendidos en los SU.