The AIFELL Score as a Predictor of Coronavirus Disease 2019 (COVID-19) Severity and Progression in Hospitalized Patients.

Since the beginning of the COVID-19 pandemic, SARS-CoV-2 has caused a global burden for health care systems due to high morbidity and mortality rates, leading to caseloads that episodically surpass hospital resources. Due to different disease manifestations, the triage of patients at high risk for a poor outcome continues to be a major challenge for clinicians. The AIFELL score was developed as a simple decision instrument for emergency rooms to distinguish COVID-19 patients in severe disease stages from less severe COVID-19 and non-COVID-19 cases. In the present study, we aimed to evaluate the AIFELL score as a prediction tool for clinical deterioration and disease severity in hospitalized COVID-19 patients. During the second wave of the COVID-19 pandemic in Switzerland, we analyzed consecutively hospitalized patients at the Triemli Hospital Zurich from the end of November 2020 until mid-February 2021. Statistical analyses were performed for group comparisons and to evaluate significance. AIFELL scores of patients developing severe COVID-19 stages IIb and III during hospitalization were significantly higher upon admission compared to those patients not surpassing stages I and IIa. Group comparisons indicated significantly different AIFELL scores between each stage. In conclusion, the AIFELL score at admission was useful to predict the disease severity and progression in hospitalized COVID-19 patients.

A Rat Model of Post-Traumatic Stress Syndrome Causes Phenotype-Associated Morphological Changes and Hypofunction of the Adrenal Gland.

BACKGROUND: Rats exposed to chronic predator scent stress mimic the phenotype of complex post-traumatic stress disorder (PTSD) in humans, including altered adrenal morphology and function. High- and low-anxiety phenotypes have been described in rats exposed to predator scent stress (PSS). This study aimed to determine whether these high- and low-anxiety phenotypes correlate with changes in adrenal histomorphology and corticosteroid production. METHODS: Rats were exposed to PSS for ten days. Thirty days later, the rats' anxiety index (AI) was assessed with an elevated plus-maze test. Based on differences in AI, the rats were segregated into low- (AI ≤ 0.8, n = 9) and high- (AI > 0.8, n = 10) anxiety phenotypes. Plasma corticosterone (CORT) concentrations were measured by ELISA. Adrenal CORT, desoxyCORT, and 11-dehydroCORT were measured by high-performance liquid chromatography. After staining with hematoxylin and eosin, adrenal histomorphometric changes were evaluated by measuring the thickness of the functional zones of the adrenal cortex. RESULTS: Decreased plasma CORT concentrations, as well as decreased adrenal CORT, desoxyCORT and 11-dehydroCORT concentrations, were observed in high- but not in low-anxiety phenotypes. These decreases were associated with increases in AI. PSS led to a significant decrease in the thickness of the zona fasciculata and an increase in the thickness of the zona intermedia. The increase in the thickness of the zona intermedia was more pronounced in low-anxiety than in high-anxiety rats. A decrease in the adrenal capsule thickness was observed only in low-anxiety rats. The nucleus diameter of cells in the zona fasciculata of high-anxiety rats was significantly smaller than that of control or low-anxiety rats. CONCLUSION: Phenotype-associated changes in adrenal function and histomorphology were observed in a rat model of complex post-traumatic stress disorder.

Lamotrigine Reduces Stress Symptoms of Chronic Anxiety in the Times of the Covid-19 Natural Catastrophe-A Case Report.

The SARS-CoV-2 pandemic has been a worldwide chronic, stress-inducing natural catastrophe associated with increased emotional challenging. Patients with Post-traumatic stress disorder (PTSD), self-injury behavior, and obesity are predisposed to aggravation of their symptoms at this time, requiring new therapeutic approaches to balance their disrupted neuro-hormonal stress axis. Here we present our observations of an off-label treatment with lamotrigine in an adolescent girl with PTSD, self-injury behavior, and obesity. Lamotrigine was an efficacious pharmaceutical intervention that helped the patient deal with chronic stress and associated anxiety. The results are discussed based on our previous basic research outcomes in animals and humans that focused on the glutamate-cortisol circuits within the limbic brain.

Offensive Behavior, Striatal Glutamate Metabolites, and Limbic-Hypothalamic-Pituitary-Adrenal Responses to Stress in Chronic Anxiety.

Variations in anxiety-related behavior are associated with individual allostatic set-points in chronically stressed rats. Actively offensive rats with the externalizing indicators of sniffling and climbing the stimulus and material tearing during 10 days of predator scent stress had reduced plasma corticosterone, increased striatal glutamate metabolites, and increased adrenal 11-dehydrocorticosterone content compared to passively defensive rats with the internalizing indicators of freezing and grooming, as well as to controls without any behavioral changes. These findings suggest that rats that display active offensive activity in response to stress develop anxiety associated with decreased allostatic set-points and increased resistance to stress.

Triage tool for suspected COVID-19 patients in the emergency room: AIFELL score

Abstract Clinical prediction scores support the assessment of patients in the emergency setting to determine the need for further diagnostic and therapeutic steps. During the current COVID-19 pandemic, physicians in emergency rooms (ER) of many hospitals have a considerably higher patient load and need to decide within a short time frame whom to hospitalize. Based on our clinical experiences in dealing with COVID-19 patients at the University Hospital in Zurich, we created a triage score with the acronym "AIFELL" consisting of clinical, radiological and laboratory findings.The score was then evaluated in a retrospective analysis of 122 consecutive patients with suspected COVID-19 from March until mid-April 2020. Descriptive statistics, Student's t-test, ANOVA and Scheffe's post-hoc analysis confirmed the diagnostic power of the score. The results suggest that the AIFELL score has potential as a triage tool in the ER setting intended to select probable COVID-19 cases for hospitalization in spontaneously presenting or referred patients with acute respiratory symptoms.

Triage tool for suspected COVID-19 patients in the emergency room: AIFELL score.

Clinical prediction scores support the assessment of patients in the emergency setting to determine the need for further diagnostic and therapeutic steps. During the current COVID-19 pandemic, physicians in emergency rooms (ER) of many hospitals have a considerably higher patient load and need to decide within a short time frame whom to hospitalize. Based on our clinical experiences in dealing with COVID-19 patients at the University Hospital in Zurich, we created a triage score with the acronym "AIFELL" consisting of clinical, radiological and laboratory findings. The score was then evaluated in a retrospective analysis of 122 consecutive patients with suspected COVID-19 from March until mid-April 2020. Descriptive statistics, Student's t-test, ANOVA and Scheffe's post-hoc analysis confirmed the diagnostic power of the score. The results suggest that the AIFELL score has potential as a triage tool in the ER setting intended to select probable COVID-19 cases for hospitalization in spontaneously presenting or referred patients with acute respiratory symptoms.

High/low cortisol reactivity and food intake in people with obesity and healthy weight.

Increased food intake, termed "comfort eating", is a pathologic coping mechanism in chronic stress. Cortisol reactivity under stress is a potent predictor of stress-induced eating behavior affecting the body mass index (BMI). However, cortisol reactivity and food intake under stress in people with obesity has not been evaluated. The aim of this study was to investigate the effect of high/low cortisol reactivity on food intake in people with obesity and healthy weight test controls, following standardized stress induction and a resting condition. Thirty-six men and women with obesity (BMI: 33.00 ± 3.23 kg/m²), as well as 36 age- and gender-matched healthy weight controls (BMI: 21.98 ± 1.81 kg/m²) were categorized into high cortisol reactors (HCR) and low cortisol reactors (LCR) in the Trier Social Stress Test (TSST). Following the TSST and a resting condition, the food intake of all participants was recorded in a standardized laboratory meal. Obese HCR demonstrated a significantly higher food intake than LCR (t (34) = -2.046, p ≤ 0.05). However, there were no significant differences between HCR and LCR in the healthy weight controls (p = 0.26). In addition, HCR of the people with obesity showed lower values in the emotion coping strategy of cognitive reappraisal than obese LCR (t (32) = 2.087, p ≤ 0.05). In conclusion, the magnitude of the cortisol reactivity to stress predicts stress-induced food intake in people with obesity, but not in the healthy weight controls. Limited use of cognitive reappraisal in emotion regulation in the obese HCR may be a marker of vulnerability to stress-induced eating.

From Allostatic Load to Allostatic State-An Endogenous Sympathetic Strategy to Deal With Chronic Anxiety and Stress?

The concepts of allostatic load and overload, i. e., a dramatic increase in the allostatic load that predisposes to disease, have been extensively described in the literature. Here, we show that rats engaging in active offensive response (AOR) behavioral strategies to chronic predator scent stress (PSS) display less anxiety behavior and lower plasma cortisol levels vs. rats engaging in passive defensive response (PDR) behavioral strategies to chronic PSS. In the same chronic PSS paradigm, AOR rats also have higher lactate and lower glutamate levels in amygdala but not in control-region hippocampus vs. PDR rats. The implications of these findings for regulation of allostatic and stress responses, and post-traumatic stress disorder (PTSD) are discussed.

PreImplantation Factor (PIF*) Regulates Stress-Induced Adrenal Steroidogenesis and Anti-Inflammatory Cytokines: Potential Application for Bioartificial Adrenal Transplant.

The main treatment algorithm for adrenal insufficiency is hormonal replacement, however, inadequate hormone substitution often leads to severe side effects. Adrenal cell transplantation could be a more effective alternative but would require life-long immune suppressive therapy. PreImplantation Factor (PIF) is an endogenous peptide secreted by viable human embryos that leads to maternal tolerance without immunosuppression. PIF could be effective for xenogeneic cell transplantation such as of bovine adrenocortical cells (BAC), which are used for bioartificial adrenal gland development that may more effectively restore complex adrenal functions. We report here that PIF exerts a dual regulatory effect on BAC by targeting mostly hyper-activated cells to specifically reduce adrenocorticotropic hormone (ACTH)-stimulated cortisol secretion. Reverse transcription real time PCR analysis revealed that PIF modulates the expression of two genes in the cortisol synthesis pathway, Steroidogenic Factor 1 (SF1), an activator of steroidogenesis, and the downstream steroidogenic enzyme Cytochrome P450 17A1 (CYP17A1). PIF increased basal expression of SF1 and CYP17A1 regardless of the activation level of the adrenocortical cells. In contrast, following ACTH stimulation, PIF reduced SF1 expression and induced expression of the immune suppressing anti-inflammatory cytokine IL10 only in the hyper-activated cells, suggesting both a protective and immune tolerant function. In conclusion, PIF regulates stress-induced adrenal steroidogenesis and immune tolerance in BAC, supporting a potential clinical application to reduce rejection by the host's immune response following xenotransplantation.