Acute and sustained increase in endothelial biomarkers in COVID-19.

Endothelial injury is related to poor outcomes in respiratory infections yet little is known in relation to COVID-19. Performing a longitudinal analysis (on emergency department admission and post-hospitalisation follow-up), we evaluated endothelial damage via surrogate systemic endothelial biomarkers, that is, proadrenomedullin (proADM) and proendothelin, in patients with COVID-19. Higher proADM and/or proendothelin levels at baseline were associated with the most severe episodes and intensive care unit admission when compared with ward-admitted individuals and outpatients. Elevated levels of proADM or proendothelin at day 1 were associated with in-hospital mortality. High levels maintained after discharge were associated with reduced diffusing capacity.

Incidence, risk factors, and thrombotic load of pulmonary embolism in patients hospitalized for COVID-19 infection.

OBJECTIVE: To determine the incidence, characteristics, and risk factors of pulmonary embolism (PE) among patients hospitalized for COVID-19. PATIENTS AND METHODS: We performed a prospective observational study of a randomly selected cohort of consecutive patients hospitalized for COVID-19 infection between March 8, 2020 through April 25, 2020. All eligible patients underwent a computed tomography pulmonary angiography independently of their PE clinical suspicion and were pre-screened for a baseline elevated D-dimer level. RESULTS: 119 patients were randomly selected from the 372 admitted to one tertiary hospital in Valencia (Spain) for COVID-19 infection during the period of study. Seventy-three patients fulfilled both the inclusion criteria and none of the exclusion criteria and were finally included in the study. Despite a high level of pharmacological thromboprophylaxis (89%), the incidence of PE was 35.6% (95% confidence interval [CI], 29.6 to 41.6%), mostly with a peripheral location and low thrombotic load (Qanadli score 18.5%). Multivariate analysis showed that heart rate (Hazard Ratio [HR], 1.04), room-air oxygen saturation (spO2) (HR, 0.87), D-dimer (HR, 1.02), and C-reactive protein (CRP) levels (HR, 1.01) at the time of admission were independent predictors of incident PE during hospitalization. A risk score was constructed with these four variables showing a high predictive value of incident PE (AUC-ROC: 0.86; 95% CI: 0.80 to 0.93). CONCLUSIONS: Our findings confirmed a high incidence of PE in hospitalized COVID-19 patients. Heart rate, spO2, D-dimer, and CRP levels at admission were associated with higher rates of PE during hospitalization.

Adenoma paratiroideo como causa de hipercalcemia / Parathyroid adenoma as a cause of hypercalcemia

Existen numerosas causas de hipercalcemia que exigen un amplio diagnóstico diferencial, entre las que se encuentra el adenoma paratiroideo, una etiología rara en la edad pediátrica. El adenoma paratiroideo produce un incremento de hormona paratiroidea (PTH) que desencadena hipercalcemia mediante aumento de la absorción gastrointestinal y tubular renal de calcio, y mayor resorción ósea. El tratamiento inicial tiene como objetivo reducir la calcemia y el tratamiento definitivo consiste en la exéresis quirúrgica del adenoma, ayudada de monitorización de niveles intraoperatorios de PTH. Se presenta el caso de una paciente de diez años, con hallazgo de hipercalcemia en un estudio de dolor abdominal de larga evolución, que en los últimos días asociaba vómitos, anorexia, poliuria y polidipsia. Se trata de un hiperparatiroidismo debido a un adenoma paratiroideo en el que fue necesario utilizar todos los escalones terapéuticos de la hipercalcemia, concluyendo finalmente con la exéresis quirúrgica del adenoma

There are numerous causes of hypercalcemia, which require a wide differential diagnosis, including parathyroid adenoma, a rare etiology in the pediatric age. Parathyroid adenoma produces an increase in parathyroid hormone (PTH) that triggers hypercalcemia by increasing gastrointestinal and tubular calcium absorption and increased bone resorption. The initial treatment aims to reduce the calcemia and the definitive treatment consists in the surgical excision of the adenoma, aided of monitoring of intraoperative levels of PTH. We present the case of a 10-year-old patient with a finding of hypercalcemia in the study of abdominal pain of long evolution, which associated vomiting, anorexia, polyuria and polydipsia. It is a hyperparathyroidism due to a parathyroid adenoma in which it was necessary to use all the therapeutic steps of hypercalcemia finally concluding with surgical excision of the adenoma

Simultaneous Depression of Immunological Synapse and Endothelial Injury is Associated with Organ Dysfunction in Community-Acquired Pneumonia.

RATIONALE: A depressed expression of antigen presentation is, along with endothelial dysfunction, a recognized signature of severe community-acquired pneumonia (CAP). We aimed to evaluate the expression of a number of genes involved in the immunological synapse in non-critically ill CAP patients with or without organ dysfunction and to profile endothelial biomarkers such as proendothelin-1 (proET1) and proadrenomedullin (proADM). METHODS: A nested study in a prospective cohort in CAP patients was performed. Expression levels of major histocompatibility complex class II DR alpha (HLA-DRA), CD40 ligand (CD40LG), CD3E, CD28, and inducible T-cell costimulator (ICOS) were quantified by using droplet digital polymerase chain reaction and endothelial biomarkers by immunofluorescence. RESULTS: Ninety-four patients were included, 44.7% of whom had organ failure in one or more organs. A significant decrease in the expression of the five genes with increased levels of proadrenomedullin (proADM) and proendothelin-1 (proET1) was found in CAP with organ failure. The depressed expression of HLA-DRA (odds ratio (OR), 2.94), CD40LG (OR, 3.90), and CD28 (OR, 3.48) was independently associated with organ failure after adjustment for age, Charlson score, and severity. CONCLUSIONS: CAP with organ failure showed depressed expression of immunological synapse genes with increased levels of biomarkers denoting endothelial damage. Simultaneous profiling of immunological and endothelial signatures could help in the early identification of organ failure in CAP and in the implementation of personalized treatment.

Unstable control of breathing can lead to ineffective noninvasive ventilation in amyotrophic lateral sclerosis.

Upper airway obstruction with decreased central drive (ODCD) is one of the causes of ineffective noninvasive ventilation (NIV) in amyotrophic lateral sclerosis (ALS). The aim of this study is to determine the mechanism responsible for ODCD in ALS patients using NIV. This is a prospective study that included ALS patients with home NIV. Severity of bulbar dysfunction was assessed with the Norris scale bulbar subscore; data on upper or lower bulbar motor neuron predominant dysfunction on physical examination were collected. Polysomnography was performed on every patient while using NIV and the ODCD index (ODCDI: number of ODCD events/total sleep time) was calculated. To determine the possible central origin of ODCD, controller gain was measured by inducing a hypocapnic hyperventilation apnoea. Sonography of the upper airway during NIV was performed to determine the location of the ODCD. 30 patients were enrolled; three (10%) had ODCDI >5 h-1. The vast majority of ODCD events were produced during non-rapid eye movement sleep stages and were a consequence of an adduction of the vocal folds. Patients with ODCDI >5 h-1 had upper motor neuron predominant dysfunction at the bulbar level, and had greater controller gain (1.97±0.33 versus 0.91±0.36 L·min-1·mmHg-1; p<0.001) and lower carbon dioxide (CO2) reserve (4.00±0.00 versus 10.37±5.13 mmHg; p=0.043). ODCDI was correlated with the severity of bulbar dysfunction (r= -0.37; p=0.044), controller gain (r=0.59; p=0.001) and CO2 reserve (r= -0.35; p=0.037). ODCD events in ALS patients using NIV have a central origin, and are associated with instability in the control of breathing and an upper motor neuron predominant dysfunction at the bulbar level.

Ultrasound measures of tendon thickness: Intra-rater, Inter-rater and Inter-machine reliability.

BACKGROUND: Ultrasound imaging is often used by physiotherapists and other healthcare professionals but the reliability of image acquisition with different ultrasound machines is unknown. The objective was to compare the intra-rater, inter-rater and intermachine reliability of thickness measurements of the plantar fascia (PF), Achilles tendon (AT), patellar tendon (PT) and elbow common extensor tendon (ECET) with musculoskeletal ultrasound imaging (MSUS). METHODS: Tendon thickness was measured in four anatomical structures (14 participants, 28 images per tendon) by two sonographers and with two different ultrasound machines. Intraclass Correlation Coefficients (ICCs) and Bland-Altman plots were calculated. The standard error of measurement (SEM) and minimum detectable difference (MDD) were calculated. RESULTS: Inter-rater reliability was excellent for AT (ICC=0.98; 95% CI= 0.96-0.99) and very good for PT (ICC=0.85; 95% CI = 0.67-0.93) and ECET (ICC=0.81; 95% CI= 0.72-0.94). Reliability for PF was moderate, with an ICC of 0.63 (CI 95%= 0.20-0.83). Bland-Altman plot for inter-machine reliability showed a mean difference of 1 m for PF measurements and a mean difference of 4 m and 20 m for AT and PT. The relative SEMs were below 7% and the MDCs were below 0.7 mm. CONCLUSION: The MSUS reliability in measuring thickness of the four tendons is confirmed by the homogeneous readings intra sonographers, between operators and between different machines. Level of evidence: Tendon thickness can be measured reliably on different ultrasound devices, which is an important step forward in the use of this technique in daily clinical practice and research. LEVEL OF EVIDENCE: III.

Sonoelastography of Plantar Fascia: Reproducibility and Pattern Description in Healthy Subjects and Symptomatic Subjects.

The purpose of the work reported here was to describe the sonoelastographic appearance of the plantar fascia of healthy volunteers and patients with fasciitis. Twenty-three healthy subjects and 21 patients with plantar fasciitis were examined using B-mode and real-time sonoelastography (RTSR) scanning. B-Mode examination included fascia thickness and echotexture. Echogenicity and echovariation of the color histogram were analyzed. Fasciae were classified into type 1, blue (more elastic); type 2, blue/green (intermediate); or type 3, green (less elastic). RTSE revealed 72.7% of fasciae as type 2, with no significant association with fasciitis (χ(2) = 3.6, df = 2, p = 0.17). Quantitative analysis of the color histogram revealed a significantly greater intensity of green (mean = 77.8, 95% confidence interval [CI] = 71.9-83.6) and blue (mean = 74.2, 95% CI = 69.7-78.8) in healthy subjects. Echovariation of the color red was 33.4% higher in the fasciitis group than in the healthy group (95% CI = 16.7-50.1). Sonoelastography with quantitative analysis of echovariation can be a useful tool for evaluation of plantar fascia pathology.

Biomechanics of the Median Nerve During Stretching as Assessed by Ultrasonography.

The objective of this observational cross-sectional study was to investigate the normal motion of the median nerve when stretched during a neurodynamic exercise. In recent years, ultrasonography has been increasingly accepted as an imaging technique for examining peripheral nerves in vivo, offering a reliable and noninvasive method for a precise evaluation of nerve movement. Transverse motion of the median nerve in the arm during a neurodynamic test was measured. A volunteer sample of 22 healthy subjects (11 women) participated in the study. Nerve displacement and deformation were assessed by dynamic ultrasonography. Excellent interobserver agreement was obtained, with kappa coefficient of .7-.8. Ultrasonography showed no lateral motion during wrist extension in 68% of nerves, while 73% moved dorsally, with statistically significant differences between sexes (ORlat = 6.3; 95% CI = 1.4-27.7 and ORdor = 8.3; 95% CI = 1.6-44.6). The cross-sectional area was significantly greater in men (3.6 mm2). Quantitative analysis revealed no other statistically significant differences. Our results provide evidence of substantial individual differences in median nerve transverse displacement in response to a neurodynamic exercise.

Fiabilidad y reproducibilidad de un nuevo método de análisis morfotextural de imágenes ecográficas del tendón rotuliano / Reliability and reproducibility of a morpho-textural image analysis method over a patellar ligament ultrasonography

Objetivos. La aplicación de ecografía cuantitativa sobre el tejido tendinoso puede resultar de utilidad pero es necesario conocer la fiabilidad tanto del proceso de la toma ecográfica como de la selección de las regiones para el análisis. Los objetivos del trabajo fueron calcular la fiabilidad y reproducibilidad del método de análisis morfotextural intra-ecografía e interecografía del tendón rotuliano. Material y métodos. Estudio de concordancia del tipo testretest sobre 120 ecografías transversales del tendón rotuliano a 1cm del pico de la rótula, con un ecógrafo Sonosite Titan y sonda L-38 (5–10MHz) y el software de análisis Image J v1.40. Se calcularon variables morfométricas: perímetro, área, anchura, grosor y ecogenicidad media; y texturales: uniformidad, homogeneidad y entropía. Se calculó el coeficiente de correlación intraclase (CCI) junto con las representaciones gráficas de Bland con un IC del 95%. Resultados. Se encontraron coeficientes de correlación intraclase con valores superiores a 0,70, con fuerza de la concordancia entre buena y muy buena en todas las variables y tanto en el estudio intraecografía como en el estudio interecografía. Conclusión. La fiabilidad del método fue buena por lo que la variabilidad introducida por los exploradores no es significativa y el método es potencialmente válido para el estudio y cuantificación ecográfica del tejido tendinoso (AU)

Objective. Image analysis techniques over ultrasonograms may be useful to extract quantitative information. Because ecography and the selection of the area of interest are technician-dependent, the objective of this work was to calculate the reliability and the reproducibility of the analysis method. Material and methods. Test-retest reliability study on 60 cross-sectional patellar ligament ultrasonograms on 1cm of patella were carried out. Sonosite Titan L-38 (5–10MHz) and the Image analysis software J v1.40 were used. Morphometric variables were: perimeter, area, width, thickness, and mean echogenity; textural variables were: uniformity, homogeneity and entropy. The intraclass correlation coefficient (ICC) was calculated with a confidence interval of 95%. Results. Intraclass correlation coefficients over 0,70 were found, with an agreement ranging from good to very good in all of the variables both for the intra ecography and inter ecography studies. Conclusion. Very good levels of reliability and internal consistency were seen, demonstrating that from the statistical point of view, the variability introduced by the technician is not significant. This method can be taken as a reference to analyze the reliability between several ultrasonographers (AU)

[Reliability and reproducibility of a morpho-textural image analysis method over a patellar ligament ultrasonography]. / Fiabilidad y reproducibilidad de un nuevo método de análisis morfotextural de imágenes ecográficas del tendón rotuliano.

OBJECTIVE: Image analysis techniques over ultrasonograms may be useful to extract quantitative information. Because ecography and the selection of the area of interest are technician-dependent, the objective of this work was to calculate the reliability and the reproducibility of the analysis method. MATERIAL AND METHODS: Test-retest reliability study on 60 cross-sectional patellar ligament ultrasonograms on 1cm of patella were carried out. Sonosite Titan L-38 (5-10 MHz) and the Image analysis software J v1.40 were used. Morphometric variables were: perimeter, area, width, thickness, and mean echogenity; textural variables were: uniformity, homogeneity and entropy. The intraclass correlation coefficient (ICC) was calculated with a confidence interval of 95%. RESULTS: Intraclass correlation coefficients over 0.70 were found, with an agreement ranging from good to very good in all of the variables both for the intra ecography and inter ecography studies. CONCLUSION: Very good levels of reliability and internal consistency were seen, demonstrating that from the statistical point of view, the variability introduced by the technician is not significant. This method can be taken as a reference to analyze the reliability between several ultrasonographers.

Quantitative assessment of nitric oxide in rat skeletal muscle and plasma after exercise.

Nitric oxide (NO), a short-lived vasoactive substance that has multiple physiological functions, is also involved in skeletal muscle physiology. This work examines the levels of nitrate (the metabolic end-product of NO) in muscle and plasma after different exercise protocols: namely acute, eccentric, cardiac stress and training. Plasma nitrate levels were augmented after strenuous exercise and did not change after training. The vastus intermedius and the gastrocnemius, both oxidative muscles, showed the highest concentrations of cytosolic nitrate after strenuous exercise. NO levels varied, depending on the fibre type, and this may correlate well with the specific contractile function performed.