Thyroid hormone alterations in critically and non-critically ill patients with SARS-CoV-2 infection

Objective: Following the evolution of COVID-19 pandemic, reports pointed on a high prevalence of thyroiditis-related thyrotoxicosis. Interpretation of thyroid tests during illness, however, is hampered by changes occurring in the context of non-thyroidal illness syndrome (NTIS). In order to elucidate these findings, w e studied thyroid function in carefully selected cohorts of COVID-19 positive and negative patients. Design: Cohort observational study. Methods: We measured TSH, FT4, T3 within 24 h of admission in 196 patients without thyroid disease and/or confounding medications. In this study, 102 patients were SARS-CoV-2 positive; 41 admitted in the ICU, 46 in the ward and 15 outpatients. Controls consisted of 94 SARS-CoV-2 negative patients; 39 in the ICU and 55 in the ward. We designated the thyroid hormone patterns as consistent with NTIS, thyrotoxicosis and hypothyroidism. Results: A NTIS pattern was encountered in 60% of ICU and 36% of ward patients, with similar frequencies between SARS-CoV-2 positive and negative patients (46.0% vs 46.8%, P = NS). A thyrotoxicosis pattern was observed in 14.6% SARS-CoV-2 ICU patients vs 7.7% in ICU negative (P = NS) and, overall in 8.8% of SARS-CoV-2 positive vs 7.4% of neg ative patients. In these patients, thyroglobulin levels were similar to those with normal thyroid function or NTIS. The hypothyroidism pattern was rare. Conclusions: NTIS pattern is common and relates to the severity of disease rather than SARS-CoV-2 infection. A thyrotoxicosis pattern is less frequently observed with similar frequency between patients with and without COVID-19. It is suggested that thyroid hormone monitoring in COVID-19 should not differ from other crit ically ill patients

Dynamic identification of the Augusta hybrid base isolated building using data from full scale push and sudden release tests

A three-story reinforced concrete building in Augusta (IT), isolated at the base and designed according to the provisions of the latest Italian seismic regulations, was subjected to a series of push and sudden release tests in March 2013. The Augusta isolation system is hybrid, consisting of 16 High Damping Rubber Bearings (HDRB) and 20 Low Friction Sliding Bearings (LFSB). The tests were characterized by a long quasi-static phase, where the building was pushed slowly to the desired displacement amplitude (sliding velocity $\approx 0.1mm/sec$, strain bearing demand $\gamma=0.39-0.78$), and a dynamic phase where the building was left free to oscillate. The duration of the dynamic phase was utmost $1 \%$ the duration of the static phase. The recordings included the displacements at the isolation level and the floor accelerations. A baseline fitting scheme was developed for the removal of the low frequency noise in the records. Application of the adjustment scheme provided reliable estimates of the floor velocities and displacements. The advantage of the proposed signal processing method other than its simplicity, is its ability to account for boundary conditions, for instance initial and residual displacements. Once the signals obtained from all eight tests performed were adjusted, they were used in the identification of the non-linear isolation system and the flexible superstructure (linear in the range of interest). The identification was performed in the time domain using the Covariance Matrix Adaptation Evolution Strategy, a stochastic algorithm for difficult, non linear black-box optimization. The identification of the isolation system provided the mass of the rigid block, the bi-linear properties used in the mechanical representation of the rubber bearings and the sliding coefficient of friction for the Coulomb model used in the modelling of the sliders. The obtained parameters, showed that rubber bearing properties were closer to the corresponding static laboratory properties, therefore implying that after the long quasi-static phase the HDRBs did not have time to recover their dynamic properties. The identified sliding coefficient of friction was in average $1\%$, leading to significant energy dissipation. The identified superstructure properties were the distribution of the floor masses, the modal frequencies, damping ratios and mode shapes. The identified data for the isolation system and the superstructure were input in a synthesized model of the isolated Augusta building, for the dynamic response simulation of the structure. A constrained optimization algorithm was developed ad hoc for the time-step solution of the coupled equations of motion. The obtained simulated response of the Augusta building matched the experimental response, in terms of displacements, velocities and accelerations

Baseline correction of digital accelerograms from field testing of a seismically isolated building

A three-story reinforced concrete building in Augusta (Sicily, Italy), isolated at the base and designed according to the provisions of the latest Italian seismic regulations, was subjected to a series of push and sudden release tests in March 2013. During the tests, the displacements at the isolation level were measured along with the accelerations at each floor of the building. The obtained records were then treated for the removal of low frequency noise using a simple baseline fitting scheme. The developed signal processing scheme consists of defining the duration of the main event, removing the background noise, and using polynomial curves for the adjustment of the distorted baseline. The method does not require significant computational effort and accounts for initial and end conditions, provided that these are known. Implementation of the method provides the adjusted response in terms of absolute and relative floor accelerations, velocities and displacements and inter-story drifts

An explainable XGBoost-based approach towards assessing the risk of cardiovascular disease in patients with Type 2 Diabetes Mellitus

Cardiovascular Disease ( CVD) is an important cause of disability and death among individuals with Diabetes Mellitus (DM). International clinical guidelines for the management of Type 2 DM (T2DM) are founded on primary and secondary prevention and favor the evaluation of CVD-related risk factors towards appropriate treatment initiation. CVD risk prediction models can provide valuable tools for optimizing the frequency of medical visits and performing timely preventive and therapeutic interventions against CVD events. The integration of explainability modalities in these models can enhance human understanding on the reasoning process, maximize transparency and embellish trust towards the models’ adoption in clinical practice. The aim of the present study is to develop and evaluate an explainable personalized risk prediction model for the fatal or non-fatal CVD incidence in T2DM individuals. An explainable approach based on the eXtreme Gradient Boosting (XGBoost) and the Tree SHAP (SHapley Additive exPlanations) method is deployed for the calculation of the 5-year CVD risk and the generation of individual explanations on the model’s decisions. Data from the 5- year follow up of 560 patients with T2DM are used for development and evaluation purposes. The obtained results (AUC=71.13%) indicate the potential of the proposed approach to handle the unbalanced nature of the used dataset, while providing clinically meaningful insights about the model’s decision process

Investigation of Serum Endocan Levels and Age in Critical Inflammatory Conditions

Aging negatively affects the endothelium. Endocan (ESM-1), an endothelium-derived soluble proteoglycan, participates in fundamental biological processes of endothelial cells. We aimed to examine the role of endothelial dysfunction and age in poor outcomes in critical illness. ESM-1 levels were measured in the sera of mechanically ventilated critically ill patients, including COVID-19, non-septic, and septic patients. The 3 patient cohorts were divided based on age (≥65 and <65). Critically ill COVID-19 patients had statistically higher ESM-1 levels compared to critically ill septic and non-septic patients. Only in critically ill septic patients were ESM-1 levels higher in older compared to younger patients. Finally, the age-subgrouped patients were further subdivided based on intensive care unit (ICU) outcome. ESM-1 levels were similar in COVID-19 survivors and non-survivors, irrespective of age. Interestingly, only for the younger critically ill septic patients, non-survivors had higher ESM-1 levels compared to survivors. In the non-septic survivors and non-survivors, ESM-1 levels remained unaltered in the younger patients and tended to be higher in the elderly. Even though endocan has been recognized as an important prognostic biomarker in critically ill patients with sepsis, in our patient cohort, increased age, as well as the extent of endothelial dysfunction, seemed to affect its prognostic ability

Glucocorticoid and mineralocorticoid receptor expression in critical illness: A narrative review.

The glucocorticoid receptor (GCR) and the mineralocorticoid receptor (MR) are members of the steroid receptor superfamily of hormone-dependent transcription factors. The receptors are structurally and functionally related. They are localized in the cytosol and translocate into the nucleus after ligand binding. GCRs and MRs can be co-expressed within the same cell, and it is believed that the balance in GCR and MR expression is crucial for homeostasis and plays a key role in normal adaptation. In critical illness, the hypothalamic-pituitary-adrenal axis is activated, and as a consequence, serum cortisol concentrations are high. However, a number of patients exhibit relatively low cortisol levels for the degree of illness severity. Glucocorticoid (GC) actions are facilitated by GCR, whose dysfunction leads to GC tissue resistance. The MR is unique in this family in that it binds to both aldosterone and cortisol. Endogenous GCs play a critical role in controlling inflammatory responses in critical illness. Intracellular GC concentrations can differ greatly from blood levels due to the action of the two 11β-hydroxysteroid dehydrogenase isozymes, type 1 and type 2. 11β-hydroxysteroid dehydrogenases interconvert endogenous active cortisol and intrinsically inert cortisone. The degree of expression of the two isozymes has the potential to dramatically influence local GC availability within cells and tissues. In this review, we will explore the clinical studies that aimed to elucidate the role of MR and GCR expression in the inflammatory response seen in critical illness

Orofacial Muscle Weakening in Facioscapulohumeral Muscular Dystrophy (FSHD) Patients

Background: Facioscapulohumeral muscular dystrophy is the third most commonly found type of muscular dystrophy. The aim of this study was to correlate the D4Z4 repeat array fragment size to the orofacial muscle weakening exhibited in a group of patients with a genetically supported diagnosis of FSHD. Methods: Molecular genetic analysis was performed for 52 patients (27 female and 25 male) from a group that consisted of 36 patients with autosomal dominant pedigrees and 16 patients with either sporadic or unknown family status. The patients were tested with the southern blotting technique, using EcoRI/Avrll double digestion, and fragments were detected by a p13E-11 telomeric probe. Spearman’s correlation was used to compare the fragment size with the degree of muscle weakening found in the forehead, periocular and perioral muscles. Results: A positive non-significant correlation between the DNA fragment size and severity of muscle weakness was found for the forehead (r = 0.27; p = 0187), the periocular (r = 0.24; p = 0.232) and the left and right perioral (r = 0.29; p = 0.122), (r = 0.32; p = 0.085) muscles. Conclusions: Although FSHD patients exhibited a decrease in muscular activity related to the forehead, perioral, and periocular muscles the genotype–phenotype associations confirmed a weak to moderate non-significant correlation between repeat size and the severity of muscle weakness. Orofacial muscle weakening and its association with a D4Z4 contraction alone may not have the significance to serve as a prognostic biomarker, due to the weak to moderate association. Further studies with larger sample sizes are needed to determine the degree of genetic involvement in the facial growth in FSHD patients

Orofacial Muscle Weakening in Facioscapulohumeral Muscular Dystrophy (FSHD) Patients

Background: Facioscapulohumeral muscular dystrophy is the third most commonly found type of muscular dystrophy. The aim of this study was to correlate the D4Z4 repeat array fragment size to the orofacial muscle weakening exhibited in a group of patients with a genetically supported diagnosis of FSHD. Methods: Molecular genetic analysis was performed for 52 patients (27 female and 25 male) from a group that consisted of 36 patients with autosomal dominant pedigrees and 16 patients with either sporadic or unknown family status. The patients were tested with the southern blotting technique, using EcoRI/Avrll double digestion, and fragments were detected by a p13E-11 telomeric probe. Spearman&apos;s correlation was used to compare the fragment size with the degree of muscle weakening found in the forehead, periocular and perioral muscles. Results: A positive non-significant correlation between the DNA fragment size and severity of muscle weakness was found for the forehead (r = 0.27; p = 0187), the periocular (r = 0.24; p = 0.232) and the left and right perioral (r = 0.29; p = 0.122), (r = 0.32; p = 0.085) muscles. Conclusions: Although FSHD patients exhibited a decrease in muscular activity related to the forehead, perioral, and periocular muscles the genotype-phenotype associations confirmed a weak to moderate non-significant correlation between repeat size and the severity of muscle weakness. Orofacial muscle weakening and its association with a D4Z4 contraction alone may not have the significance to serve as a prognostic biomarker, due to the weak to moderate association. Further studies with larger sample sizes are needed to determine the degree of genetic involvement in the facial growth in FSHD patients