We aimed to explore the role of interleukin (IL)‐6, interferon‐gamma (IFNγ), IL‐10, and tumor necrosis factor (TNF) as predictors of systemic lupus erythematosus (SLE) clinical and serological ...activity, and their correlation with the treatment received. We performed a retrospective analysis of 77 patients with SLE according to the 2012 Systemic Lupus International Collaborative Clinics (SLICC) criteria. The outcomes were serological activity (SA), active disease (AD), complete remission (CR), the low‐disease activity state (LDAS), and immunosuppressive treatment. SA was present in 17.1%, AD in 17.3%, CR in 13%, and LDAS in 64.9% of patients. IL‐6 values were higher in patients in SA, in AD, in those receiving steroids alone, and in patients without CR or LDAS (p < 0.05). IFNγ was associated with anti‐double stranded DNA (dsDNA) antibodies positivity and immunosuppression, whereas IL‐10 values were higher in patients with CR (p < 0.05). The IL6‐IFN product was able to predict anti‐double stranded DNA (anti‐dsDNA) antibodies positivity (area under the receiver operating characteristic curve AUC‐ROC = 0.705, 95% confidence interval CI 0.563–0.847), SA (AUC‐ROC = 0.720, 95% CI 0.542–0.899), AD (AUC‐ROC = 0.701, 95% CI 0.520–0.882), steroid treatment (AUC‐ROC = 0.751, 95% CI 0.622–0.879), and the absence of LDAS (AUC‐ROC = 0.700, 95% CI 0.558–0.834). The IL6‐IFN/IL10 ratio predicted AD (AUC‐ROC = 0.742, 955 CI 0.540–0.944), steroid treatment (AUC‐ROC = 0.721, 95% CI 0.572–0.870), and the absence of LDAS (AUC‐ROC = 0.694, 95% CI 0.536–0.853). In conclusion, IL‐6, IL‐10, and IFNγ might help to assess SLE serological and clinical activity. Their combination in the IL‐6‐IFN product and the IL‐6xIFN to IL‐10 ratio results in novel tools to determine and predict SA, AD, and LDAS. Prompt detection of SLE activity might allow a rapid intervention to avoid established or chronic damage.
Abstract
Background
Advanced age is a well-known risk factor for poor prognosis in COVID-19. However, few studies have specifically focused on very old inpatients with COVID-19. This study aims to ...describe the clinical characteristics of very old inpatients with COVID-19 and identify risk factors for in-hospital mortality at admission.
Methods
We conducted a nationwide, multicenter, retrospective, observational study in patients ≥ 80 years hospitalized with COVID-19 in 150 Spanish hospitals (SEMI-COVID-19) Registry (March 1–May 29, 2020). The primary outcome was in-hospital mortality. A uni- and multivariate logistic regression was performed to assess predictors of mortality at admission.
Results
A total of 2772 consecutive patients (49.4% men, median age 86.3 years) were analyzed. Rates of atherosclerotic cardiovascular disease, diabetes mellitus, dementia, and Barthel Index < 60 were 30.8%, 25.6%, 30.5%, and 21.0%, respectively. The overall case-fatality rate was 46.9% (n: 1301) and increased with age (80–84 years: 41.6%; 85–90 years: 47.3%; 90–94 years: 52.7%; ≥95 years: 54.2%). After analysis, male sex and moderate-to-severe dependence were independently associated with in-hospital mortality; comorbidities were not predictive. At admission, independent risk factors for death were: oxygen saturation < 90%; temperature ≥ 37.8°C; quick sequential organ failure assessment (qSOFA) score ≥ 2; and unilateral–bilateral infiltrates on chest x-rays. Some analytical findings were independent risk factors for death, including estimated glomerular filtration rate < 45 mL/min/1.73 m2; lactate dehydrogenase ≥ 500 U/L; C-reactive protein ≥ 80 mg/L; neutrophils ≥ 7.5 × 103/μL; lymphocytes < 0.8 × 103/μL; and monocytes < 0.5 × 103/μL.
Conclusions
This first large, multicenter cohort of very old inpatients with COVID-19 shows that age, male sex, and poor preadmission functional status—not comorbidities—are independently associated with in-hospital mortality. Severe COVID-19 at admission is related to poor prognosis.
Neuronal loss is the best neuropathological substrate that correlates with cortical atrophy and dementia in Alzheimer's disease (AD). Defective GABAergic neuronal functions may lead to cortical ...network hyperactivity and aberrant neuronal oscillations and in consequence, generate a detrimental alteration in memory processes. In this study, using immunohistochemical and stereological approaches, we report that the two major and non‐overlapping groups of inhibitory interneurons (SOM‐cells and PV‐cells) displayed distinct vulnerability in the perirhinal cortex of APP/PS1 mice and AD patients. SOM‐positive neurons were notably sensitive and exhibited a dramatic decrease in the perirhinal cortex of 6‐month‐old transgenic mice (57% and 61% in areas 36 and 35, respectively) and, most importantly, in AD patients (91% in Braak V–VI cases). In addition, this interneuron degenerative process seems to occur in parallel, and closely related, with the progression of the amyloid pathology. However, the population expressing PV was unaffected in APP/PS1 mice while in AD brains suffered a pronounced and significant loss (69%). As a key component of cortico‐hippocampal networks, the perirhinal cortex plays an important role in memory processes, especially in familiarity‐based memory recognition. Therefore, disrupted functional connectivity of this cortical region, as a result of the early SOM and PV neurodegeneration, might contribute to the altered brain rhythms and cognitive failures observed in the initial clinical phase of AD patients. Finally, these findings highlight the failure of amyloidogenic AD models to fully recapitulate the selective neuronal degeneration occurring in humans.
Abstract
Background
Mechanical ventilation increases the risk of lung injury (VILI). Some authors propose that the way to reduce VILI is to find the threshold of driving pressure below which VILI is ...minimized. In this study, we propose a method to titrate the driving pressure to pulmonary elastance in an acute respiratory distress syndrome model using Young’s modulus and its consequences on ventilatory-induced lung injury.
Material and methods
20 Wistar Han male rats were used. After generating an acute respiratory distress syndrome, two groups were studied: (a) standard protective mechanical ventilation: 10 rats received 150 min of mechanical ventilation with driving pressure = 14 cm H
2
O, tidal volume < 6 mL/kg) and (b) individualized mechanical ventilation: 10 rats received 150 min of mechanical ventilation with an individualized driving pressure according to their Young’s modulus. In both groups, an individualized PEEP was programmed in the same manner. We analyzed the concentration of IL-6, TNF-α, and IL-1ß in BAL and the acute lung injury score in lung tissue postmortem.
Results
Global driving pressure was different between the groups (14 vs 11 cm H2O,
p
= 0.03). The individualized mechanical ventilation group had lower concentrations in bronchoalveolar lavage of IL-6 (270 pg/mL vs 155 pg/mL,
p
= 0.02), TNF-α (292 pg/mL vs 139 pg/mL,
p
< 0.01) and IL-1ß (563 pg/mL vs 131 pg/mL,
p
= 0.05). They presented lower proportion of lymphocytes (96% vs 79%,
p
= 0.05) as well as lower lung injury score (6.0 points vs 2.0 points,
p
= 0.02).
Conclusion
In our model, individualization of DP to pulmonary elastance through Young’s modulus decreases lung inflammation and structural lung injury without a significant impact on oxygenation.
We aimed to evaluate the clinical outcome of Systemic Autoimmune Diseases (SADs) patients hospitalized with COVID-19 in Spain, before the introduction of SARS-CoV-2 vaccines. A nationwide, ...retrospective and observational analysis of the patients admitted during 2020, based on the ICD10 codes in the National Registry of Hospital Discharges, was performed. Among 117,694 patients, only 892 (0.8%) presented any type of SAD before COVID-19-related admission: Sjogren’s Syndrome constituted 25%, Systemic Vasculitides 21%, Systemic Lupus Erythematosus 19%, Sarcoidosis 17%, Systemic Sclerosis 11%, Mixed and Undifferentiated Connective Tissue Disease 4%, Behçet’s Disease 4% and Inflammatory Myopathies 2%. The in-hospital mortality rate was higher in SAD individuals (20% vs. 16%, p < 0.001). After adjustment by baseline conditions, SADs were not associated with a higher mortality risk (OR = 0.93, 95% CI 0.78−1.11). Mortality in the SADs patients was determined by age (OR = 1.05, 95% CI 1.04−1.07), heart failure (OR = 1.67, 95% CI 1.10−2.49), chronic kidney disease (OR = 1.29, 95% CI 1.05−1.59) and liver disease (OR = 1.97, 95% CI 1.13−3.44). In conclusion, the higher COVID-19 mortality rate seen in SADs patients hospitalized in Spain in 2020 was related to the higher burden of comorbidities, secondary to direct organ damage and sequelae of their condition. Whilst further studies should evaluate the impact of baseline immunosuppression on COVID-19 outcomes in this population, efforts should be focused on the optimal management of SAD to minimize the impact of the organ damage that has been shown to determine COVID-19 prognosis.
SARS-CoV-2 is a highly contagious virus, and despite professionals' best efforts, nosocomial COVID-19 (NC) infections have been reported. This work aimed to describe differences in symptoms and ...outcomes between patients with NC and community-acquired COVID-19 (CAC) and to identify risk factors for severe outcomes among NC patients.
This is a nationwide, retrospective, multicenter, observational study that analyzed patients hospitalized with confirmed COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry) from March 1, 2020, to April 30, 2021. NC was defined as patients admitted for non-COVID-19 diseases with a positive SARS-CoV-2 test on the fifth day of hospitalization or later. The primary outcome was 30-day in-hospital mortality (IHM). The secondary outcome was other COVID-19-related complications. A multivariable logistic regression analysis was performed.
Of the 23,219 patients hospitalized with COVID-19, 1,104 (4.8%) were NC. Compared to CAC patients, NC patients were older (median 76 vs. 69 years; p < 0.001), had more comorbidities (median Charlson Comorbidity Index 5 vs. 3; p < 0.001), were less symptomatic (p < 0.001), and had normal chest X-rays more frequently (30.8% vs. 12.5%, p < 0.001). After adjusting for sex, age, dependence, COVID-19 wave, and comorbidities, NC was associated with lower risk of moderate/severe acute respiratory distress syndrome (ARDS) (adjusted odds ratio aOR: 0.72; 95% confidence interval CI: 0.59-0.87; p < 0.001) and higher risk of acute heart failure (aOR: 1.40; 1.12-1.72; p = 0.003), sepsis (aOR: 1.73; 1.33-2.54; p < 0.001), and readmission (aOR: 1.35; 1.03-1.83; p = 0.028). NC was associated with a higher case fatality rate (39.1% vs. 19.2%) in all age groups. IHM was significantly higher among NC patients (aOR: 2.07; 1.81-2.68; p < 0.001). Risk factors for increased IHM in NC patients were age, moderate/severe dependence, malignancy, dyspnea, moderate/severe ARDS, multiple organ dysfunction syndrome, and shock; odynophagia was associated with lower IHM.
NC is associated with greater mortality and complications compared to CAC. Hospital strategies to prevent NC must be strengthened.
Alzheimer's disease (AD) constitutes the most prominent form of dementia among elderly individuals worldwide. Disease modeling using murine transgenic mice was first initiated thanks to the discovery ...of heritable mutations in amyloid precursor protein (APP) and presenilins (PS) genes. However, due to the repeated failure of translational applications from animal models to human patients, along with the recent advances in genetic susceptibility and our current understanding on disease biology, these models have evolved over time in an attempt to better reproduce the complexity of this devastating disease and improve their applicability. In this review, we provide a comprehensive overview about the major pathological elements of human AD (plaques, tauopathy, synaptic damage, neuronal death, neuroinflammation and glial dysfunction), discussing the knowledge that available mouse models have provided about the mechanisms underlying human disease. Moreover, we highlight the pros and cons of current models, and the revolution offered by the concomitant use of transgenic mice and omics technologies that may lead to a more rapid improvement of the present modeling battery.
Resumen Introducción: la enfermedad por coronavirus 2019 (COVID-19) engloba un amplio espectro de síntomas entre los que destacan los trastornos respiratorios, digestivos, hematológicos y ...dermatológicos. La interacción del virus con las células ubicadas en el tracto respiratorio provoca la liberación de mediadores inflamatorios cuya producción podría estar relacionada con la obesidad, la diabetes y los eventos cardiovasculares. Objetivos: el objetivo de esta investigación ha sido analizar el estado metabólico al ingreso de los pacientes infectados por SARS-CoV-2 y su capacidad para predecir el desenlace clínico. Métodos: este trabajo consiste en un estudio retrospectivo basado en una cohorte de 165 pacientes ingresados consecutivamente en el Hospital Universitario Puerta de Hierro Majadahonda entre marzo y abril de 2020 con criterios de neumonía COVID-19 según las pautas de la OMS. Las variables registradas incluyeron datos socio-demográficos y epidemiológicos, herramientas diagnósticas y complicaciones durante el ingreso hospitalario. El Servicio de Bioquímica del centro realizó los análisis de laboratorio empleando procedimientos validados. El estudio estadístico incluye modelos univariantes y multivariados, ajustados por las características basales clínicamente relevantes de la población. Resultados: la comorbilidad más frecuente en nuestra población fue la hipertensión arterial (44,0 %), seguida por la dislipemia (32,1 %), la obesidad (30,9 %) y la diabetes mellitus (20,0 %). En el análisis multivariante, la asociación del ingreso en la Unidad de Cuidados Intensivos (UCI) con el índice de masa corporal (IMC) resultó estadísticamente significativa, con un 19 % más de riesgo en aquellos pacientes con IMC ≥ 30 kg/m2. El modelo univariante reveló la asociación estadísticamente significativa de la obesidad y el ingreso en la UCI con la duración de la estancia hospitalaria (p < 0,05). La relación entre glucemia basal y mortalidad intrahospitalaria también resultó estadísticamente significativa (p = 0,03). Los niveles bajos de colesterol total se asociaron a una tasa mayor de ingresos en la UCI (p = 0,007). Conclusiones: la obesidad se asocia a una mayor estancia hospitalaria y necesidad de ingreso en la UCI en los pacientes infectados por el SARS-CoV-2. El descenso en las cifras de colesterol total y una glucemia basal alterada son factores de riesgo del ingreso en la UCI y la mortalidad intrahospitalaria. La categorización en función del grado de obesidad de los pacientes podría ser de utilidad en el desarrollo de un modelo de medicina de precisión en el contexto de la COVID-19.
To describe the impact of different doses of corticosteroids on the evolution of patients with COVID-19 pneumonia, based on the potential benefit of the non-genomic mechanism of these drugs at higher ...doses.
Observational study using data collected from the SEMI-COVID-19 Registry. We evaluated the epidemiological, radiological and analytical scenario between patients treated with megadoses therapy of corticosteroids vs low-dose of corticosteroids and the development of complications. The primary endpoint was all-cause in-hospital mortality according to use of corticosteroids megadoses.
Of a total of 14,921 patients, corticosteroids were used in 5,262 (35.3%). Of them, 2,216 (46%) specifically received megadoses. Age was a factor that differed between those who received megadoses therapy versus those who did not in a significant manner (69 years IQR 59-79 vs 73 years IQR 61-83; p < .001). Radiological and analytical findings showed a higher use of megadoses therapy among patients with an interstitial infiltrate and elevated inflammatory markers associated with COVID-19. In the univariate study it appears that steroid use is associated with increased mortality (OR 2.07 95% CI 1.91-2.24 p < .001) and megadose use with increased survival (OR 0.84 95% CI 0.75-0.96, p 0.011), but when adjusting for possible confounding factors, it is observed that the use of megadoses is also associated with higher mortality (OR 1.54, 95% CI 1.32-1.80; p < .001). There is no difference between megadoses and low-dose (p .298). Although, there are differences in the use of megadoses versus low-dose in terms of complications, mainly infectious, with fewer pneumonias and sepsis in the megadoses group (OR 0.82 95% CI 0.71-0.95; p < .001 and OR 0.80 95% CI 0.65-0.97; p < .001) respectively.
There is no difference in mortality with megadoses versus low-dose, but there is a lower incidence of infectious complications with glucocorticoid megadoses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•This is the largest study assessing the efficacy of LPV/r against SARS-CoV-2.•The overall use of LPV/r was not associated with lower mortality in CoVID19 patients.•The early use of LPV/r (median 5 ...days) showed no benefit either.
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