The increased cortisol levels with preserved rhythmicity in aging and its relationship with dementia and metabolic syndrome.

BACKGROUND: In the aging process, the cumulative exposure to stress with increased cortisol levels is considered to be associated to the senescence itself and its related disorders. AIMS: To evaluate the role of cortisol in elderly subjects, with or without dementia, by the means of the AGICO study. METHODS: The AGICO study enrolled patients from ten Geriatric Units in Italy in 2012-2017 (Study Director Prof Paolo Falaschi, S. Andrea Hospital of Rome). Every subject received a comprehensive geriatric assessment (including the Mini-Mental State Examination, MMSE), the neurological examination (with a computed tomography scan or magnetic resonance imaging of the brain), the assessment of the metabolic syndrome (MetS), the evaluation of the cortisol activity by two consecutive urine collections (diurnal and nocturnal). RESULTS: The MMSE was inversely related to the standardized diurnal and nocturnal urinary cortisol levels (p < 0.025 and p < 0.01, respectively) and the age was positively related (p < 0.01 and p < 0.001, respectively). The ratio between the standardized diurnal and nocturnal urinary cortisol levels was 1.50 ± 1.2 (mean ± standard deviation) and it was not modified by the age or dementia. The standardized diurnal and nocturnal urinary cortisol levels were significantly higher in patients with dementia (MMSE < 24) (p < 0.01). In the analysis of the subgroups with MetS, the highest concentrations of diurnal and nocturnal cortisol were found in patients with both dementia and MetS (p < 0.025 and p < 0.01, respectively). DISCUSSION: The AGICO study showed that the stress response significantly and progressively increases with age. CONCLUSION: The cortisol increase in aging is related to the presence of both dementia and metabolic syndrome.

[Mobbing: ten-year evaluation experience in a University Hospital]. / Mobbing: esperienza decennale di valutazione in un Policlinico Universitario.

OBJECTIVES: Bullying is a manifestation of occupational stress and can therefore be considered as a real "organizational pathology." Include the activities of the surgery dedicated to Mobbing, Unit of Occupational Medicine Sant'Andrea Hospital, which began operations in June 2001. METHODS: In over ten years of operation (July 2012), the sample, consisting of 50.7% for men and 49.3% women, is heterogeneous in age. The schooling of the sample is medium-high as more than 82% have higher education level. The business sector is the service sector accounted for most (84%) than in industry (9%) and agriculture (2%). RESULTS: Of the 1545 patients seen, 1320 completed the diagnostic path, while 225 have stopped. 814 users have been certified for compatibility bullying (63% of cases) with a net reduction of the awards from 2007 onwards. CONCLUSIONS: Considerations are expressed about the possible intervention strategies: the presence of dedicated experts at the counters of listening and professionals as the trusted advisor, to which workers in distress can call on for advice and guidance on how to defend itself from, in accordance with the implemented for years at the Ministry of Health, the establishment of such figures as the manager rehability that in other European countries, are scheduled for some time in work organization.

Recent advances in the role of cortisol and metabolic syndrome in age-related degenerative diseases.

The metabolic syndrome (MetS) presents an increasing prevalence in elderly people. A significant role in MetS is played by the stress response and cortisol. The hypothalamic-pituitary-adrenal (HPA) axis activity is increased by central (loss of hippocampal glucocorticoid receptors) and peripheral (11ß-hydroxysteroid dehydrogenase type 1, 11ß-HSD1, hyperactivity) mechanisms. The HPA hyperactivity has been found in chronic diseases affecting the endocrine (abdominal obesity with MetS, type 2 diabetes), cardiovascular (atherosclerosis, essential hypertension), and nervous systems (dementia, depression), in aging. A novel therapeutic approach (11ß-HSD1 inhibition) is promising in treating the HPA axis hyperactivity in chronic diseases with MetS. A large-scale national clinical trial (AGICO, AGIng, and COrtisol study) has been proposed by our group to evaluate the role of cortisol and MetS in the main pathologies of aging (vascular and degenerative dementia, cardiovascular diseases, type 2 diabetes, abdominal obesity).

Effects of escitalopram on serum BDNF levels in elderly patients with depression: a preliminary report.

BACKGROUND AND AIMS: Increasing evidence in the literature suggests a link between the brain-derived neurotrophic factor (BDNF) system and adult depression, supporting a role in the pathophysiology of the disease and response to therapy. Few studies have reported BDNF serum levels in elderly depressed subjects and their relationship with antidepressant therapy. The aim of the study was to evaluate BDNF serum levels in naive elderly depressed patients, before and after antidepressant treatment. METHODS: We enrolled n = 5 elderly naive patients affected by depression, according to the Diagnostic and Statistical Manual of Mental Disorders-IV Text Revision criteria for major depressive episode. BDNF serum levels were evaluated through ELISA method. Cognitive functions were examined by Mini Mental State Examination (MMSE) and severity of depression was assessed by Geriatric Depression Scale (GDS). BDNF levels were measured at baseline (T0) and after 2 months (T2) of escitalopram. Ten healthy elderly subjects were enrolled as a control group. RESULTS: The serum BDNF levels in patients (T0) and controls were 11.5 ± 0.6 and 13.6 ± 3.4 ng/ml (m ± SD), respectively. At T2, the patients showed a significant improvement of depressive symptoms (p < 0.05), with a not significant increase of MMSE. The serum BDNF concentrations increased to 16.0 ± 2.7 ng/ml at T2 (p < 0.05), beyond the levels of BDNF in controls. The increase in BDNF levels was significantly related to the improvement in GDS scores of the patients (r = 0.9, p < 0.05). CONCLUSIONS: Serum BDNF levels may be considered as a marker of response to antidepressant treatment for depression in the elderly.

A bedside ultrasound protocol to the measurement of the systemic vascular resistances: Preliminary results in the patients with sepsis.

BACKGROUND: The use of the ultrasound (US) bedside examination is increasing for the detailed evaluation of the hemodynamic parameters, allowing the physicians to set the appropriate therapeutic strategies with greater precision. OBJECTIVE: The aim of this study is to evaluate the hemodynamic parameters (the cardiac output or CO, the central venous pressure or CVP and the systemic vascular resistance or SVR) in the patients with sepsis, by using a bedside US approach. METHODS: We consecutively enrolled n.82 patients of S.Andrea Hospital (n.47 with sepsis and n.35 without sepsis), examining the hemodynamic parameters by a bedside US evaluation. RESULTS: The incidence of sepsis was more than 50% of cases. The patients with sepsis presented higher comorbidity and polypharmacy (p < 0.01, p < 0.001), with increased creatinine (p < 0.001) and consequent esteemed glomerular filtration rate (p < 0.01), C-reactive protein (p < 0.01), SOFA (Sepsis-related Organ Failure Assessment) score (p < 1.58×10-7) and reduced SVR (p < 0.05). The SOFA score was inversely related to the SVR (p < 0.05). CONCLUSIONS: To our best knowledge, this is the first study with a bedside US protocol to measure SVR, beyond the abdominal and cardiac qualitative evaluation.

The Point-of-Care Ultrasound (POCUS) by the Handheld Ultrasound Devices (HUDs) in the COVID-19 Scenario: a Review of the Literature.

The use of portable ultrasound (US) devices is increasing, due to its accessibility, versatility, non-invasiveness, and its significant support in the patient management, extending the traditional physical examination through the POCUS (point-of-care ultrasound). The pocket-size or handheld ultrasound devices (HUDs) can easily perform focused exams, not aiming to substitute for the high-end US systems (gold standard), since the HUDs usually have more limited functions. The HUDs are promising tools for the diagnosis, prognosis, and monitoring of the COVID-19 infection and its related disorders. In conclusion, the routine use of HUDs may ameliorate the management of COVID-19 pandemic, according to the guidelines for the POCUS approach and the procedures for the protection of the patients and the professionals.

The measurement of the left ventricle ejection fraction by a bedside FoCUS examination.

The use of point-of-care ultrasound is rapidly increasing in medical practice. This study aims to evaluate the left ventricle systolic function by the bedside focus cardiac ultrasound (FoCUS). We consecutively enrolled n.59 patients of the Emergency Medicine Unit of S. Andrea Hospital. Every patient received a bedside FoCUS examination to estimate the left ventricle (LV) ejection fraction (EF); the LV EF measurements were compared with those obtained by standard echocardiography (as gold standard). The LV EF obtained by the bedside FoCUS examination and the standard echocardiography, resulted, respectively: 50.2 ± 15.1% (by the Quinones equation), 39.5 + 12.0% (by the Lvivo app) and 53.7 + 11.1% (by the standard echocardiography). The correlations between the bedside FoCUS EF measurements versus standard echocardiography were statistically significant: r = + 0.694 p < 1.9 × 10-6 (Quinones equation, Bland-Altman analysis mean = - 2.3%) and r = + 0.571 p < 0.01 (Lvivo app, Bland-Altman analysis mean = - 13.3%). In conclusion, the present study showed a high accuracy of the bedside FoCUS EF evaluations, which may support the diagnosis of the heart failure in an emergency setting without delaying. The EF measurements by the operational method are more precise than those obtained by the unselected images of the software application.

Comparison of Computerized Prescription Support Systems in COVID-19 Patients: INTERCheck and Drug-PIN.

The coronavirus disease 19 (COVID-19) infection requires major efforts in healthcare systems, due to the high risk of mortality, particularly in subjects with significant comorbidity (≥ 2 pathologies) and polypharmacy (≥ 5 drugs). The treatment of COVID-19 needs a careful evaluation, to reduce the risk of potentially adverse drug reactions. The aim of the study was to examine the use of computerized prescription support in the management and treatment of the COVID-19 infection. We evaluated n.33 patients (51% females) admitted to the west COVID Low-Medium Intensity of Care of Sant'Andrea Hospital during the period March-April 2020 and n.42 subjects (50% females) admitted to the Internal Medicine ward (as control group), by INTERCheck® and Drug-PIN®. The comorbidity (n. pathologies), polypharmacy (n. drugs), and total INTERCheck score in COVID-19 patients and controls were, respectively (mean ± standard deviation): 5.8 ± 3.8, 7.9 ± 4.5, and 9.2 ± 7.1 and 6.8 ± 2.6, 8.0 ± 2.6, and 4.9 ± 3.8 (statistically significant for comorbidity p < 0.01 and INTERCheck score p < 0.01). The correlation between the scores obtained by the INTERCheck and Drug-PIN software was statistically significant, either at admission (p < 0.0000001) or during hospitalization (p < 0.00000001). Both the computerized prescription support systems, INTERCheck® and Drug-PIN®, are useful to better characterize the patients and to ameliorate the drugs prescriptions in COVID-19 infection, with particular attention to the elderly population.

The effects of the glycaemic control on the severity of the delirium in the advanced phase of Alzheimer's disease.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) and delirium are common in advanced phases of Alzheimer's disease (AD). METHODS: Thirty-eight moderate-severe AD patients were enrolled (n=16 affected by type 2 diabetes). Each patient received a comprehensive geriatric assessment (CGA) (including evaluation of BPSD and frailty), and a complete metabolic evaluation (including the measurement of the glycated hemoglobin, HbA1c). RESULTS: Both the hyper- and hypo-glycemic extremes of the glycemic spectrum worsened BPSD, but delirium was more susceptible to hypoglycemic events. The severity of delirium was significantly related to cognitive function (r = -0.585, p<0.001) and frailty (r = +0.440, p<0.05). CONCLUSIONS: The measurement of HbA1c was useful for evaluating the risk of delirium in relationship to glycemic control and nutritional status.

Clinical Management of Adult Coronavirus Infection Disease 2019 (COVID-19) Positive in the Setting of Low and Medium Intensity of Care: a Short Practical Review.

Coronavirus disease 2019 (COVID-2019) is a viral infection which is rapidly spreading on a global scale and causing a severe acute respiratory syndrome that affects today about four and a half million registered cases of people around the world. The aim of this narrative review is to provide an urgent guidance for the doctors who take care of these patients. Recommendations contained in this protocol are based on limited, non-definitive, evidence and experience-based opinions about patients with low and medium intensity of care. A short guidance on the management of COVID-19 is provided for an extensive use in different hospital settings. The evidence-based knowledge of COVID-19 is rapidly evolving, and we hope that, in the near future, a definitive and most efficacious treatment will be available including a specific vaccine for SARS-CoV-2.

Using INTERCheck® to Evaluate the Incidence of Adverse Events and Drug-Drug Interactions in Out- and Inpatients Exposed to Polypharmacy.

BACKGROUND: Polypharmacy exposes patients with comorbidities (particularly elderly patients) to an increased risk of drug-specific adverse events and drug-drug interactions. These adverse events could be avoided with the use of a computerized prescription support system in the primary care setting. The INTERCheck® software is a prescription support system developed with the aim of balancing the risks and benefits of polytherapy and examining drug-drug interactions. OBJECTIVES: This observational study used the INTERCheck® software to evaluate the incidence of adverse events and of drug-drug interactions in outpatients and inpatients receiving multiple medications. METHODS: Patients were randomly enrolled from the outpatient department (n = 98) and internal medicine ward (n = 46) of S. Andrea Hospital of Rome. Polypharmacological treatment was analyzed using INTERCheck® software, and the prevalence of risk indicators and adverse events was compared between the two groups. RESULTS: Polypharmacy (use of five or more drugs) applied to all except three cases among outpatients and one case among inpatients. A significant positive correlation was found between the number of medications and the INTERCheck® score (ρ = 0.67; p < 0.000001), and a significant negative correlation was found between the drug-related anticholinergic burden and cognitive impairment (r = - 0.30 p = 0.01). Based on the INTERCheck® analysis, inpatients had a higher score for class D (contraindicated drug combination should be avoided) than did outpatients (p = 0.01). The potential class D drug-drug interactions were associated with adverse events that caused hospitalization (χ2 = 7.428, p = 0.01). CONCLUSIONS: INTERCheck® analysis indicated that inpatients had a high risk of drug-drug interactions and a high percentage of related adverse drug events. Further prospective studies are necessary to evaluate whether the INTERCheck® software may help reduce polypharmacy-related adverse events when used in a primary care setting and thus potentially avoid related hospitalization and severe complications such as physical and cognitive decline.

Inverse correlation between morning plasma cortisol levels and MMPI psychasthenia and depression scale scores in victims of mobbing with adjustment disorders.

OBJECTIVES: Evidence in the literature suggests stress-related changes of hypothalamus-pituitary-adrenal (HPA) axis in mobbing. We investigated the association between HPA activity and psychological profiles in mobbing, using a multidisciplinary approach. DESIGN: Forty-eight victims of mobbing were evaluated by a working group of the Departments of Occupational Medicine, Psychiatry and Internal Medicine. After an informed consent, a detailed occupational history, a psychiatric interview with Minnesota Multiphasic Personality Inventory 2 (MMPI-2) administration and a blood sample (8:00 AM) for the determination of basal adrenocorticotropin (ACTH), cortisol and dehydroepiandrosterone sulphate (DHEAS) plasma levels were collected. Twenty-six patients received an overnight dexamethasone (dex) test. RESULTS: Mean ACTH, cortisol and DHEAS levels were within normal ranges. The dex-test response was normal, with a significant hormone suppression (ACTH p<0.001, cortisol p<0.001, DHEAS p<0.001). The correlations between basal hormones and the psychometric scales of MMPI-2 revealed that cortisol was significantly and negatively related to Psychasthenia (Pt, p=0.003) and Depression (D, p=0.006), while DHEAS showed a significant negative correlation to Hysteria (Hy, p=0.008). Basal ACTH levels were not significantly related to psychometric scales. CONCLUSION: A significant inverse correlation between morning plasma cortisol levels and psychometric parameters in victims of mobbing with adjustment disorders was observed. A larger group of patients is necessary to identify and validate a cut-off cortisol level that may become an innovative biological parameter for the diagnosis and follow-up in victims of mobbing.

Hepatitis C virus infection and thyroid autoimmune disorders: A model of interactions between the host and the environment.

The hepatitis C virus (HCV) infection is an important public health problem and it is associated with hepatic and extrahepatic manifestations. Autoimmune thyroid diseases are common in HCV infected patients and the standard interferon-based treatment is associated with an increase of the immune-mediated thyroid damage. Recent evidence in the literature analyzed critical points of the mechanisms of thyroid damage, focusing on the balance between the two sides of the interaction: The environment (virus infection with potential cross-reaction) and the host (susceptibility genes with consistent immune response). The spectrum of antiviral treatment for chronic HCV infection is rapidly expanding for the development of dual o triple therapy. The availability of interferon-free combined treatment with direct antiviral agents for HCV is very promising, in order to ameliorate the patient compliance and to reduce the development of thyroid autoimmunity.

Association between human leukocyte antigen (HLA) and interferon- induced thyroid diseases in four patients with HCV-related chronic hepatitis.

OBJECTIVES: The interferon-alpha (IFN-alpha) therapy for HCV hepatitis may exacerbate or induce underlying thyroid disorders. Besides viral factors, the human leukocyte antigen (HLA) may be an independent risk factor. METHODS: We evaluated fifteen patients with HCV chronic hepatitis during a period of 40 months. At the enrollment, all the patients were negative for thyroid disorders, excluding one patient with subclinical hypothyroidism. Eleven patients received IFN-alpha therapy. The HLA system was examined in every patient, evaluating antigens (n=40) of locus A, B and Cw and alleles (n=19) of locus DRB1* and DQB1*. The HLA system was also examined in healthy subjects (n=107) as a control group. RESULTS: The HCV genotype distribution in patients was: 1b=20%, 2a=60%, 3a=20%. Four IFN-treated patients presented clinical thyroid disorders, including autoimmune hypothyroidism (n=2), transient thyrotoxicosis (n=1) and subacute thyroiditis (n=1). The HLA susceptibility to thyroid disorders (antigen/allele frequency) in the whole group of patients was not different in respect to controls and normal Italian population. The patients with HCV chronic hepatitis that developed thyroid diseases after IFN- treatment had a double and specific association with the HLA system (Mantel-Haenszel X(c)(2)=4.706, p<0.05). CONCLUSIONS: This case report suggests that HLA system examination is an important and promising diagnostic aspect that may be considered in order to evaluate the appearance of thyroid disorders during the IFN-alpha treatment for HCV-related chronic hepatitis.

The Prevention and Treatment of Delirium in Elderly Patients Following Hip Fracture Surgery.

Osteoporotic hip fracture needs a specific approach and treatment, since elderly patients are at high risk for adverse outcomes after surgery. In particular, delirium often occurs in the peri-operative period, and it is associated with death, hospital-acquired complications, persistent cognitive impairments, poor functional recovery after surgery and increased healthcare costs. The pre-operative assessment of the risk factors for delirium improves the preventive measures. The delirium diagnostic tools should be included in the standard of orthogeriatric cure for hip fracture. Given the increasing complexity of the clinical pictures, we present a review of the available treatment options for delirium in patients with hip fracture. The metabolic pre-operative disorders and the management of co-morbid diseases are specific targets of treatment in order to optimize the outcomes after surgery. In particular, elderly patients with Alzheimer's disease are highly vulnerable to hip fracture and delirium, and they are severely frail with reduced physiologic reserves. An integrated approach combining environmental and pharmacological strategies is useful in the delirium treatment, with a close collaboration between the orthopedic and geriatric team.

Increased serum concentration of nerve growth factor in patients with microprolactinoma.

Nerve growth factor (NGF) is known to play a role as a circulating neurokine, integrating signals from the neuro-immuno-endocrine system. The ability of NGF to activate the pituitary-adrenocortical axis, together with the increase of its serum concentration in pregnancy and lactation, supports the hypothesis that NGF is secreted by the pituitary gland and plays a role as modulator of endocrine functions. Evidence obtained both in vitro and in vivo in experimental animal models suggests that lactotroph cells secrete both prolactin (PRL) and NGF. Furthermore, in previous studies we demonstrate that cell lines derived from dopamine (DA)-sensitive human prolactinomas express high levels of NGF messenger RNA and protein. On these basis, we studied serum NGF concentrations in female patients with microprolactinoma (n = 4) and in control women (n = 5). PRL and NGF were measured at the diagnosis, during the thyrotropin releasing hormone (TRH) test and after the therapy with DA D2 receptor agonist cabergoline (0.25 mg, twice a week). Results obtained suggested that hyperprolactinemia (70.3+/-8.4 ng/ml) paralleled markedly higher NGF levels (58.4+/-18.7 pg/ml) compared to controls (PRL 8.7+/-3.2 ng/ml, NGF 8.4+/-1.3 pg/ml). Serum concentrations of NGF and PRL during the TRH test were closely associated (r = 0.943, p < 0.01). Cabergoline therapy normalized PRL (7.9+/-3.6 ng/ml) and induced a significant decrease of NGF levels (12.5+/-4.9 pg/ml). In conclusions, data reported here indicated that, in human microprolactinomas, NGF is released in the bloodstream paralleling PRL-secretion and it is modulated by a neurotransmitter-regulated mechanism, since the normalization of PRL elicited by the DA D2 receptor agonist cabergoline induced a significant decrease of serum NGF as well.

The hypothalamic-pituitary-thyroid axis in subjects with subclinical thyroid diseases: the impact of the negative feedback mechanism.

OBJECTIVE: To evaluate the hypothalamus-pituitary-thyroid (HPT) axis in patients with subclinical thyroid dysfunction recently reported to have either symptoms or organ involvements with potential morbidity, in order to better differentiate these patients with respect to controls. PATIENTS: Sixtythree patients with subclinical hyperthyroidism (HyperT), 178 normal subjects (EuT) and 106 patients with subclinical hypothyroidism (HypoT) were enrolled; the groups presented normal thyroid hormone (FT4, FT3) levels and, respectively, reduced (HyperT), normal (EuT) and increased (HypoT) TSH levels. The negative feedback was simultaneously evaluated by multiple linear regression. RESULTS: The mean TSH, FT4 and FT3 levels were significantly different in the three groups. The negative correlation between thyroid hormones (FT4 and FT3) and TSH secretion was significant (p<0.001 in HyperT; p<0.01 in EuT; p<0.000001 in HypoT group). FT4 mostly contributed to the negative correlation with TSH. The normal ranges of TSH values was accurately defined on the basis of the regression equation in the EuT group, due to the combining influence of both thyroid hormones (FT3 and FT4). No patient of the HyperT or HypoT group fell inside the range of estimated values of the normal group. CONCLUSIONS: The HPT axis in patients with subclinical hyper- and hypo-thyroidism is significantly modified with respect to normal subjects. The status of the axis, as evaluated by the relationship between the three hormones (FT4, FT3, TSH) together considered, is characteristic of the normal or pathologic condition. A reliable method based on the regression analysis is proposed to correctly evaluate the status of the HPT axis.

Effects of mental stress on cardiovascular and endocrine response in Air Force Academy cadets.

OBJECTIVES: Pilots are exposed to the "stress of flight" and the chronically activated stress response may play an important role in circulatory system disease progression. We studied the effect of an experimental mental stress on cardiovascular and neuroendocrine activity, in Air Force Academy cadets, before and after one month intensive course. DESIGN: Nine cadets were submitted to a psychometric evaluation before Stroop test (ST), including Minnesota Multiphasic Personality Inventory, State and Trait Anxiety Inventory (STAI X1 and X2 form) and Reaction Scheme Test. After ST, subjects completed a STAI X1 form. Heart rate (HR), systolic and diastolic blood pressure (SBP and DBP) were monitored and serum prolactin (PRL), growth hormone (GH), adrenocorticotropin (ACTH) and cortisol levels were determined, during ST. The protocol was repeated at the end of the course. RESULTS: No significant differences were evident in PRL, GH and ACTH levels. Cortisol concentrations were significantly higher before the course. ST did not modify hormone secretion. ST induced a significant and reproducible elevation of HR and SBP. Basal HR, SBP and DBP values were significantly elevated after the course. Two subjects presented a particular psychometric profile, a different cardiovascular response to ST and did not pass the course. CONCLUSIONS: acute mental stress significantly activated cardiovascular response without modifying endocrine responses, in relation to the psychological profiles. A significant increase of cardiovascular parameters was present after the course, with enhanced dichotomy between the endocrine and sympathetic system, suggesting a careful evaluation and follow-up for circulatory system diseases in cadets.