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.

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 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.

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.

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.

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.

[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.

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.

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).

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.

Diagnosis of hepatic glycogenosis in poorly controlled type 1 diabetes mellitus.

Hepatic glycogenosis (HG) in type 1 diabetes is a underrecognized complication. Mauriac firstly described the syndrome characterized by hepatomegaly with altered liver enzymes, growth impairment, delay puberty and Cushingoid features, during childhood. HG in adulthood is characterized by the liver disorder (with circulating aminotransferase increase) in the presence of poor glycemic control (elevation of glycated hemoglobin, HbA1c levels). The advances in the comprehension of the metabolic pathways driving to the hepatic glycogen deposition point out the role of glucose transporters and insulin mediated activations of glucokinase and glycogen synthase, with inhibition of glucose-6-phosphatase. The differential diagnosis of HG consists in the exclusion of causes of liver damage (infectious, metabolic, obstructive and autoimmune disease). The imaging study (ultrasonography and/or radiological examinations) gives information about the liver alterations (hepatomegaly), but the diagnosis needs to be confirmed by the liver biopsy. The main treatment of HG is the amelioration of glycemic control that is usually accompanied by the reversal of the liver disorder. In selected cases, more aggressive treatment options (transplantation) have been successfully reported.

Treatment of insulin resistance in the neurodegeneration.

The association between diabetes and neurodegenerative diseases is increasing with aging. Several common mechanisms are involved in both these diseases. The endothelial cells of the blood brain barrier, neurons and glia express typical and different receptors of the glucose metabolism (glucose transporters, insulin receptors and glucagon-like peptide-1 receptors). The impairment in insulin signaling leads to an impairment of neuronal function and increases neurodegeneration, and, conversely, neurodegeneration causes a reduction of insulin signaling on neurons. Increased detailed knowledge of common physiological processes opens up the opportunities for developing new treatments that may prevent or reduce the onset of neurodegenerative diseases. The aim of the review is to discuss the potential neuroprotective effects of the antidiabetic drugs. The article presents some promising patents on the treatment of insulin resistance in the neurodegeneration.

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.

Targets of anti-glucocorticoid therapy for stress-related diseases.

The stress response during chronic conditions increases vulnerability to diseases through the activation of adaptive systems, in particular, the hypothalamus-pituitary-adrenal (HPA) axis. Dysregulation in HPA activity (central and peripheral) has been reported in chronic diseases, like metabolic syndrome, type-2 diabetes mellitus, atherosclerosis-related disease, essential hypertension, dementia, depression, particularly during comorbid conditions. Different targets of anti-glucocorticoid treatment have been proposed, acting at supra-hypothalamic, HPA axis, glucocorticoid receptor and post-receptor levels. The recent promising patents on the therapy against glucocorticoid-mediated damage will be presented and discussed.

Pharmacological strategies against glucocorticoid-mediated brain damage during chronic disorders.

The brain controls coping with aversive situations, modulating the activity of the adaptive systems (the nervous, endocrine and immune systems). In this review, we focus the involvement of the hypothalamus-pituitary-adrenal (HPA) axis in the stress response. In the physiological response, the hypothalamic paraventricular nucleus secretes CRH (corticotrophin releasing hormone) that stimulates pituitary ACTH (adrenocorticotropic hormone), through CRH-receptor type 1 (CRH-R1). In turn, ACTH activates adrenal glands to produce cortisol, acting on type-2 melanocortin receptors (MC2-R). The glucocorticoid negative feedback inhibits the HPA axis activity through the glucocorticoid receptor (GR). The hippocampus plays a central role as an important connection between cortex and hypothalamus, and, together with the suprachiasmatic nucleus (SCN), regulates cortisol rhythm. Peripherally, an important regulator of cortisol metabolism in local tissues is 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), that produces cortisol within the splanchnic bed. The stress response during chronic conditions increases vulnerability to diseases through the activation of adaptive systems, in particular, the HPA axis. Increased levels of allostatic load (a measure of stress with multisystem dysregulation) are associated with the development of functional and cognitive decline, frailty and with mortality in high-functioning older adults. Moreover, HPA axis hyperactivity is a feature that can be present in chronic diseases, affecting endocrine (abdominal obesity, type-2 diabetes mellitus), cardiovascular (atherosclerosis, essential hypertension) and nervous system (dementia, depression), particularly during comorbid conditions. In conclusion, the spectrum of molecules interacting at the different levels of HPA axis is exponentially increasing, ranging from supra-hypothalamic targets to post-receptor mechanisms and it includes agents acting on SCN, CRH-R1 receptor, adrenal steroidogenesis, GR and peripheral/central 11ß-HSD1 enzyme. This area of research is rapidly advancing in order to develop therapeutic strategies to counteract HPA axis hyperactivity and to reduce the burden of stress-related disorders. The article presented some promising patents on the strategies against glucocorticoid-mediated brain damage.

The burden of comorbidity and the C-reactive protein levels in nonthyroidal illness syndrome with metabolic syndrome and atherosclerosis-related cardiovascular complications.

Thyroid hormones undergo significant modifications during severe illnesses, and the low T3 levels are the hallmark of nonthyoidal illness syndrome (NTIS), due to a reduced extrathyroidal conversion from T4. We examined 41 patients with NTIS by a modified cumulative illness rating scale (CIRS) and the measurement of FT3, FT4, TSH, and C-reactive protein (CRP) levels. Fifty-seven control subjects were enrolled. We observed reduced FT3 and increased FT4 levels in NTIS patients (P < 0.05). The CIRS scores (severity and comordity index) were inversely related to FT3 and positively related to FT4 levels (P < 0.05). The CRP and the FT4 concentrations were positively associated (P < 0.01). Our study showed that the reduced FT3 and increased FT4 levels were significantly related to the comorbidity and severity of systemic illnesses, probably as a result of impairment in the peripheral hormonal conversion. The CIRS scale and the CRP are useful tools for a better evaluation of these patients.