The cortisol burden in elderly subjects with metabolic syndrome and its association with low-grade inflammation.

BACKGROUND: Elderly people are exposed to an increased load of stressful events and neuro-hormonal stimulation is a key finding in metabolic syndrome and its related disorders. AIMS: To determine the role of cortisol in elderly subjects, with or without metabolic syndrome (MetS), by means of a national multicentre observational study, AGICO (AGIng and Cortisol). METHODS: From 2012 to 2017, the AGICO study enrolled n.339 subjects (aged > 65), after obtaining their informed consent. The investigators assessed a cardio-metabolic panel (including electrocardiogram, carotid ultrasonography and echocardiography), the presence of MetS (on Adult Treatment Panel III criteria), a neurological examination (including brain imaging), and cortisol activity (using a consecutive collection of diurnal and nocturnal urine). RESULTS: In the patients presenting with MetS, the standardized diurnal and nocturnal cortisol excretion rates were 210.7 ± 145.5 and 173.7 ± 118.1 (mean ± standard deviation) µg/g creatinine/12 h; in those without MetS, the standardized diurnal and nocturnal cortisol excretion rates were 188.7 ± 92.7 and 144.1 ± 82.3 µg/g creatinine/12 h, respectively (nocturnal urinary cortisol in patients with MetS versus those without MetS p = 0.05, female patients with MetS vs female patients without MetS, p < 0.025). A significant positive correlation was found between the CRP levels and both the diurnal and nocturnal urinary cortisol levels with r = 0.187 (p < 0.025) and r = 0.411 (p < 0.00000001), respectively. DISCUSSION: The elderly patients with MetS showed a trend towards increased standardized nocturnal cortisol excretions, with particular regard to the female subjects. CONCLUSION: The positive correlation between cortisol excretion and low-grade inflammation suggests a common mechanism driving both hormonal and inflammatory changes.

A global call to action to improve the care of people with fragility fractures.

The ageing of society is driving an enormous increase in fragility fracture incidence and imposing a massive burden on patients, their families, health systems and societies globally. Disrupting the status quo has therefore become an obligation and a necessity. Initiated by the Fragility Fracture Network (FFN) at a "Presidents' Roundtable" during the 5th FFN Global Congress in 2016 several leading organisations agreed that a global multidisciplinary and multiprofessional collaboration, resulting in a Global Call to Action (CtA), would be the right step forward to improve the care of people presenting with fragility fractures. So far global and regional organisations in geriatrics/internal medicine, orthopaedics, osteoporosis/metabolic bone disease, rehabilitation and rheumatology were contacted as well as national organisations in five highly populated countries (Brazil, China, India, Japan and the United States), resulting in 81societies endorsing the CtA. We call for implementation of a systematic approach to fragility fracture care with the goal of restoring function and preventing subsequent fractures without further delay. There is an urgent need to improve: To address this fragility fracture crisis, the undersigned organisations pledge to intensify their efforts to improve the current management of all fragility fractures, prevent subsequent fractures, and strive to restore functional abilities and quality of life.

Hypovitaminosis D: comparison between patients with hip fracture and patients with vertebral fractures.

This study analyses the difference in 25OH-vitamin D values between two groups of patients both affected by severe osteoporosis with fragility fractures, but one group has vertebral fractures and the other one has hip fractures. Patients with hip fractures have vitamin D values lower than patients with vertebral fractures. INTRODUCTION: The purpose of this study was to evaluate 25OHD levels in patients with fragility vertebral fractures (VF) and hip fractures (HF) and make a comparison between the groups. METHODS: In the first group were enrolled ambulatory patients with 3 or more moderate to severe VF; in the second group were enrolled patients hospitalized in the Department of Orthogeriatrics undergoing surgery for HF. For all patients, we collected values of 25OHD and PTH. The group of patients with VF was further subdivided into pre-existing VF or recent VF treated within 30 days with vertebroplasty. RESULTS: The sample consists of 180 subjects divided into two groups: 90 with VF and 90 with HF. The average value of 25OHD in the total sample was 13.2 ± 9.6 ng/ml, Vitamin D was significantly lower in the HF group than the VF group (p < 0.001)(VF 18.6 ± 9.7 ng/ml, HF 7.9 ± 5.7 ng/ml). The mean PTH value in the total sample was 67.5 ± 54.9 pg/ml and PTH was significantly higher in the HF group compared to the group with VF (p < 0.001) (VF 55.6 ± 27.2 pg/ml, HF 78.7 ± 70.2 pg/ml). The mean 25OHD value in the recent VF group is 16.0 ± 6.6 ng/ml while in the pre-existing VF group is 19.5 ± 10.4 ng/ml with a statistically significant difference (p < 0.001). CONCLUSIONS: Patients of the same age with severe osteoporosis have a lower 25OHD value when the fracture occur at the hip and is recent, probably this is due to the inflammation caused by fracture and/or surgical intervention.

The management of hip fracture in the older population. Joint position statement by Gruppo Italiano Ortogeriatria (GIOG).

This document is a Joint Position Statement by Gruppo Italiano di OrtoGeriatria (GIOG) supported by Società Italiana di Gerontologia e Geriatria (SIGG), and Associazione Italiana Psicogeriatria (AIP) on management of hip fracture older patients. Orthogeriatric care is at present the best model of care to improve results in older patients after hip fracture. The implementation of orthogeriatric model of care, based on the collaboration between orthopaedic surgeons and geriatricians, must take into account the local availability of resources and facilities and should be integrated into the local context. At the same time the programme must be based on the best available evidences and planned following accepted quality standards that ensure the efficacy of the intervention. The position paper focused on eight quality standards for the management of hip fracture older patients in orthogeriatric model of care. The GIOG promotes the development of a clinic database with the aim of obtaining a qualitative improvement in the management of hip fracture.

Adherence to anti-osteoporotic therapies: role and determinants of "spot therapy".

UNLABELLED: A successful therapy needs high level of adherence consisting in right drug intake in terms of persistence and compliance. Our study suggests adherence is higher if spot (less than 30 days) therapies are excluded; the analysis of spot therapy causes underlines the importance of the interpersonal aspects of medical practice. INTRODUCTION: A successful therapy needs a high level of adherence consisting in right drug intake in terms of persistence and compliance. The aim of this study was to evaluate anti-osteoporotic therapies recorded in general practitioner databases in the area of Rome, which used the same computerized medical record management. The study focused on evaluating therapy adherence, any adherence changes excluding spot therapies (less than 30 days), and any cause of early therapy discontinuation in a subgroup of patients randomly selected. METHODS: Thirty-one databases were evaluated, including a total of 6,390 anti-osteoporotic therapies: 5,853 were prescribed to women and 537 to men. The prescribed drugs were: vitamin D (13 %), calcium (8.7 %), vitamin D + calcium (40.1 %), raloxifene (3.3 %), alendronate (16.4 %), risedronate (7.7 %), clodronate (10.4 %), or other drugs (0.4 %). Spot therapies represented 53.7 % of the total prescriptions. The difference between adherence in the total group (24.64 %) and the group excluding spot therapies (43.38 %) is significant. The main factors influencing low adherence were side effects (27 %), misinformation given by the physician (17 %), insufficient motivation (9 %), difficult intake (9 %), and no perceived benefits (9 %). RESULTS: Our study suggests adherence is high and similar to other chronic diseases if spot therapies are excluded. The analysis of spot therapy causes suggests that an important role is played by the physician and the interpersonal aspects of medical practice, especially at the first prescriptions. CONCLUSIONS: The physician should collaborate with patients in choosing a personalized medical treatment. Reducing spot therapy could be the real goal in order to improve anti-osteoporotic therapy adherence.

Approach in glucocorticoid-induced osteoporosis prevention: results from the Italian multicenter observational EGEO study.

Glucocorticoid-induced osteoporosis (GIO) is the most frequent cause of secondary osteoporosis. GIO is linked to glucocorticoids (GC) daily assumption with maximum effect within first months of treatment and decreasing to basal levels as the therapy is discontinued. In Italy, primary prevention of GIO is suggested when GC therapy (prednisone >5 mg/day or equivalent) is taken for longer than 3 months. Lazio GISMO (Italian Group for Study and Diagnosis of Bone Metabolism Diseases) group organized the GC and Osteoporosis Epidemiology study (EGEO) to evaluate physician's approach in preventing GIO. The study involved 19 osteoporosis centers. Patients taking long-term GC therapy were recruited and information collected: medical history and anthropometric data, GC therapy, primary disease, physician's specialty, osteopororosis screening, and pharmacological intervention. The study included 1334 patients. Mean age was 63 ± 13 yr; 243 (18%) patients had a history of falls from standing position in the previous 12 months, 78 (35%) vertebral fractures, 91 (41%) fractures other than vertebral, 27 (12%) femoral fractures, and 27 (12%) multiple sites fractures. The molecules of GC more often prescribed were prednisone and 6-metil prednisolone. One thousand and forty patients (78%) were taking GC for more than 6 months. GC therapy was prescribed more frequently by rheumatologists (62%). Antiosteoporotic drugs for GIO prevention were prescribed in 431 patients (32%). Among the patients, only 27% (360) received calcium and vitamin D supplements, and 39% (319) treated by rheumatologists received anti-resorptive drugs. In conclusion, our data show that in Italy, as already described elsewhere, only a small subpopulation of GC-treated patients was supported by an anti-osteoporotic therapy, indicating the need to further stimulate awareness of both patients and specialists, prescribing GC therapy, to an appropriate and prompt GIO prevention.

Screening of frailty in elderly patients with disability by the means of Marigliano-Cacciafesta polypathology scale (MCPS) and Canadian Study of Health and Aging (CSHA) scales.

Frailty is an age-related condition, characterized by a decreased homeostatic reserve and increased vulnerability to stressful events, with high risk of adverse outcomes. The aim of this study was to compare the evaluation of the frailty by the means of the MCPS and the Rockwood criteria. We enrolled 98 patients (mean age ± standard deviation, m ± SD, 80.7 ± 7.0 years) and 20 controls (82.7 ± 3.4 ys), who attended our outpatient clinic for the evaluation of disability and the renewal of driving license, respectively. The multidisciplinary geriatric assessment (MGA) was performed including the administration of the following scales for frailty: MCPS scale (range 0-245), CSHA-Rules-Based Definition of Frailty (CSHA-RBDF) (range 0-3) and CSHA-Clinical Frailty Scale (CSHA-CFS) (range 0-7). The patients and controls showed MCPS=52.39 ± 11.36 and 4.6 ± 3.28, CSHA-RBDF=2.27 ± 0.62 and 0.10 ± 0.44, CSHA-CFS=6.22 ± 0.75 and 2.95 ± 0.51, respectively (p<0.000001). Frailty scores were higher in female than in male (p=0.065 for CSHA-RDBF and p<0.05 for CSHA-CFS). The MCPS scores were significantly related to both CSHA-RDBF (r=0.753, p<0.001) and CSHA-CFS scores (r=0.793, p<0.001). The frailty scales were significantly related to disability, cognitive impairment and polypathology. In conclusion, the frail patient may be a carrier of multiple chronic pathologies and/or of physical/cognitive decline. The frail patient has to be considered the elective geriatric patient, characterized by a continuous multidimensional care requirement. MCPS is an useful tool for the frailty screening and to set up a tailored program of geriatric rehabilitation, in order to prevent or reduce the development of frailty-related complications.

Sex steroids in autoimmune diseases.

A sexual dysmorphism in the immune response has been described and females display an increased incidence of autoimmune diseases. Experimental data show that sex steroids influence immune cell development and have immunomodulatory effects. The distribution, the action (genomic and nongenomic), the sex and tissue-depending expression pattern of estrogen, progesterone and androgen receptors and their functional disruptions in corresponding receptor knockout animals will be discussed, pointing out the difference among sex steroid hormones. Recent advances indicate an immunomodulatory role of sex steroids in the pathogenesis of systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis. The outcomes of the clinical trials will help to find the best use of sex steroids in combination with current therapeutic drugs in autoimmune diseases. Sex steroid receptor modulating drugs will provide new therapeutic approaches in these pathologies.

The evaluation of the presence of comorbidity by the Marigliano-Cacciafesta polypathology scale (MCPS) and the cumulative illness rating scale (CIRS) in elderly subjects with disability.

Multiple factors associated with the frailty syndrome may be involved in the appearance of disability, including the presence of comorbidity. The CIRS is commonly used for the evaluation of comorbidity, consisting of two parts: the comorbidity index (CI) and the severity index (SI). A multidimensional scale, the MCPS, has been recently developed, predicting the risk to develop disability. Fifty-nine subjects were examined by a structured multidimensional geriatric assessment. The MCPS and CIRS was significantly correlated (r=0.410; p<0.01 with the CI; and r=0.443, p<0.001 with the SI). The patients were divided in two groups, according to the MCPS score. The mean activities of daily living (ADL) and instrumental activities of daily living (IADL), as well as the corrected mini-mental state examination (MMSE) score (+/-S.E.M.) were: 3.19+/-0.26; 0.28+/-0.04 and 24.00+/-1.14 in moderate-severe polypathology (n=21); 2.16+/-0.22; 0.13+/-0.02 and 21.23+/-0.72 in severe polypathology (n=38) (p<0.001, p<0.01 and p<0.05), respectively. The MCPS score was correlated with the main indices of disability. In conclusion, we found that the MCPS is a useful tool in order to quantify and classify the presence of comorbidity, with results significantly related to that obtained with the CIRS. The MCPS offers an important stratification of the patients on the base of a well-established classification, not supplied by the CIRS.

Arbuscular mycorrhizae increase the arsenic translocation factor in the As hyperaccumulating fern Pteris vittata L.

Phytoremediation techniques are receiving more attention as decontaminating strategies. Phytoextraction makes use of plants to transfer contaminants from soil to the aboveground biomass. This research is devoted to study the effects of arbuscular mycorrhizae (AM) on growth and As hyperaccumulation in the Chinese brake fern Pteris vittata. We grew for 45 days P. vittata sporophytes, infected or not infected with the AM fungi Glomus mosseae or Gigaspora margarita, in a hydroponic system on quartz sand. As-treated plants were weekly fed with 25 ppm As. The As treatment produced a dramatic increase of As concentration in pinnae and a much lower increase in roots of both mycorrhizal and control plants. Mycorrhization increased pinnae dry weight (DW) (G. margarita = G. mosseae) and leaf area (G. margarita > G. mosseae), strongly reduced root As concentration (G. mosseae > G. margarita), and increased the As translocation factor (G. mosseae > G. margarita). The concentration of phosphorus in pinnae and roots was enhanced by both fungi (G. margarita > G. mosseae). The quantitatively different effects of the two AM fungi on plant growth as well as on As and P distribution in the fern suggest that the As hyperaccumulation in P. vittata can be optimized by a careful choice of the symbiont.

Sex-related variations in serum nerve growth factor concentration in humans.

A role of nerve growth factor (NGF) in the neuro-endocrine-immune interactions has been recently suggested by the presence of NGF and its receptors in cells of the immune and endocrine systems. The improvement in the comprehension of the role played by NGF in humans is linked to the availability of a sensitive and reliable method to quantify NGF concentrations in body fluids and tissues. As a consequence of different methods used, normal levels of human serum NGF reported in the literature show wide differences. The present results indicate that ELISA appears very sensitive (detection limit 1.4pg/ml) and allows the discrimination of subtle variations of serum NGF concentrations. ELISA performed in serum obtained from men indicated that NGF concentration was 40.8+/-10.8pg/ml, whereas women showed significantly lower levels that were influenced by the menstrual cycle. In particular, the mean value of this neurotrophin during the follicular phase was 8.2+/-1.4pg/ml; the luteal phase, in turn, showed levels up to 14.4+/-2.9pg/ml. The difference of serum NGF concentrations between the follicular and luteal phase in each woman was statistically significant. Differences in NGF concentrations between men and women (in both phases of the menstrual cycles) were also statistically significant. In conclusion, a possible role of sex steroids as modulators of NGF secretion in humans is strongly supported by the present paper. However, mechanisms underlying this phenomenon are still unknown. The evidence indicating physiological sex hormone-related variations in NGF levels would be of interest in view of the possible use of circulating NGF modifications as a laboratory biomarker in different diseases.

High incidence of hyperandrogenism-related clinical signs in patients with multiple sclerosis.

A mild prevalence of multiple sclerosis (MS) is present in females (2:1). To elucidate the pathogenetic role of sex steroids on the disease, we studied 76 women affected by MS, compared to 50 healthy women (mean age +/- SD, 34.9 +/- 0.9 vs. 33.4 +/- 1.7 years). The menarche was at mean age of 12.3 +/- 0.2 vs. 12.4 +/- 0.2. Interval between menses was 28.0 +/- 0.3 vs 27.8 +/- 0.3 days, with duration of menstrual flow of 5.0 +/- 0.2 vs. 5.0 +/- 0.2 days. Oligo- or amenorrhea was present in 20% of patients and in 16% of controls. Oral contraceptives were assumed by 21% of patients and 34% of controls (n.s.). Premenstrual symptoms were found in 43% of patients and in 46% of controls (n.s.). The incidence of hyperandrogenism (greasy skin, acne and hirsutism), evaluated by a specific questionnaire, was higher and statistically significant in MS patients than in controls (28% vs. 10%, p<0.05). Further studies, including a complete clinical and laboratory evaluation of gonadal function, are necessary in order to clarify whether hyperandrogenism may influence MS disease activity.

Hashimoto's disease during interferon-alpha therapy in a patient with pre-treatment negative anti-thyroid autoantibodies and with the specific genetic susceptibility to the thyroid disease.

OBJECTIVES: The authors described a case of Hashimoto's disease during interferon-alpha (IFN-alpha) treatment for chronic viral C hepatitis in a patient with the specific genetic susceptibility associated with the thyroid disease. RESULTS: A 60-year-old woman with chronic active viral C hepatitis (HCV genotype = 3a) started IFN-alpha therapy in November '96. Before treatment thyroid function tests were normal and anti-thyroid (anti-thyroglobulin and anti-thyroid peroxidase) Abs were negative. During IFN therapy, serum aminotransferases fell within the normal range and viremia (serum HCV-RNA) became negative after one year. After 20 months, the patient presented clinical features of primary hypothyroidism. Anti-thyroid Abs were found positive. Hormonal, ultrasonographic, radioiodine scanning and fine needle aspiration findings were consistent with the diagnosis of Hashimoto's thyroiditis. The tissutal typing of the patient showed the presence of Human Leukocyte Antigen (HLA) DRB1*11 gene (corresponding to DR5 antigen). IFN-alpha therapy was suspended and a treatment with l-T4 started. Chronic viral infection relapsed after the suspension of the IFN-alpha therapy. CONCLUSIONS: This case report showed that the clinical appearance of Hashimoto's disease after IFN-alpha therapy for chronic C hepatitis in our patient was associated with a specific genetic predisposition (DR5) for this pathology. Further studies are necessary to evaluate whether the study of HLA antigens may be a very useful tool to detect the patients with a predisposition to develop autoimmune thyroiditis, in order to make a early diagnosis of thyroid disorders during the IFN-alpha treatment.

Thyrotoxicosis, unstable angina and normal coronary angiogram.

It is well known that thyrotoxicosis may elicit acute myocardial ischemia even in patients with angiographically normal coronary vessels. The involved mechanisms are not clearly defined although some hypothesis have been suggested. We report a case of a 54-year-old woman affected by Graves' disease with thyrotoxicosis which was referred to our Institute because of unstable angina. During hospitalization a two dimensional echocardiogram, performed during chest discomfort, showed left ventricular apical akinesis and impaired global systolic function. A subsequent coronary angiography revealed normal epicardial vessels. She was successfully treated with high-dose methimazole and propranolol and a repeat echocardiogram evaluation showed normalization of left ventricular systolic function. Six months later, because of the appearance of paroxysmal atrial fibrillation, the patient underwent total thyroidectomy and a substitutive therapy with L-T4 (100 micrograms/die) was started. The authors review the possible mechanisms involved in the pathogenesis of myocardial ischemia during thyrotoxicosis.

MRI in multiple sclerosis during the menstrual cycle: relationship with sex hormone patterns.

We investigated MRI activity in MS during the menstrual cycle in relation to physiologic sex hormone fluctuations. Eight women with relapsing-remitting MS were submitted to serial brain gadolinium-enhanced MRI examinations over a 3-month period in two alternate follicular and luteal phases of the menstrual cycle. The ratio of progesterone/17-beta-estradiol during the luteal phase was significantly associated with both number (r = 0.6, p = 0.03) and volume (r = 0.7, p = 0.009) of enhancing lesions, providing support for a role of these hormones as immunomodulatory factors in MS.

Total compared with subtotal thyroidectomy in benign nodular disease: personal series and review of published reports.

OBJECTIVE: To evaluate the outcome after total and subtotal thyroidectomy for the treatment of single and multinodular goitres in two comparable groups of patients. DESIGN: Prospective randomised study. SETTING: University hospital, Italy. SUBJECTS: 141 Patients operated on for benign goitre from 1975-85. INTERVENTIONS: 69 Patients were randomised to have total thyroidectomy and 72 subtotal thyroidectomy by standard techniques. MAIN OUTCOME MEASURES: Temporary or permanent palsy of the recurrent laryngeal nerve, temporary or permanent hypoparathyroidism, recurrence of the goitre, and the incidence of iatrogenic injuries after completion thyroidectomy. RESULTS: Patients were followed up for a median of 14.5 years (range 10-21). After total thyroidectomy 2 patients (3%) developed temporary palsy of the recurrent laryngeal nerve but there were no permanent lesions; and 24 (35%) developed temporary and 2 (3%) permanent hypoparathyroidism. After subtotal thyroidectomy 2 (3%) developed temporary and 1 (1%) permanent palsy of the recurrent laryngeal nerve; and 13 (18%) developed temporary and 1 (1%) permanent hypoparathyroidism. In addition, there were 10 recurrent goitres (14%). After completion thyroidectomy (n = 9) there were 2 cases of temporary and 1 of permanent palsy of the recurrent laryngeal nerve, and 2 cases of temporary and 2 of permanent hypoparathyroidism. CONCLUSION: Total thyroidectomy is the procedure of choice for the treatment of benign nodular goitre.

Effect of r-interferon alpha administration on hypothalamus-pituitary-thyroid axis in chronic hepatitis.

Recent studies pointed out the development of autoimmune thyroid diseases during interferon (IFN) therapy, mainly in patients with positive thyroid autoantibodies (MsAb and TgAb) before treatment. The effects of recombinant human IFN alpha (rhIFNalpha) on thyroid function and thyroid autoantibodies were studied in 12 patients with chronic active hepatitis associated with virus B or C, selected on the basis of negative results for MsAb and TgAb. No significant variation in T3, T4 and TSH levels was observed either after the first administration of rhIFN alpha (3 million IU i.m.) or after three months of therapy (3 million IU i.m. 3 times a week). TSH response to TRH was in the normal range either before or after the therapy. The absence of MsAb and TgAb was confirmed in all the patients at the end of the treatment. These results indicate that no patient developed thyroid disorder during IFN therapy. Nevertheless, since positive MsAb and TgAb have been considered as a risk factor for thyroid diseases, in patients selected for IFN therapy they should be carefully assessed for autoantibodies before undergoing IFN treatment.