Background: L’abuso degli anziani è un problema diffuso ma sottostimato. L’entità di tale problema non è del tutto nota sia per la mancanza di segnalazioni e/o denunce sia per la difficoltà di individuare precocemente gli indicatori di un buso. Esistono molte forme di abuso sugli anziani, tra cui quelle di natura psicologica, economica, sessuale, fisica, sociale, istituzionale, ma l’abuso include anche l’incuria e l’abbandono. È chiaro, quindi, che il maltrattamento può concretizzarsi non solo con una condotta attiva, ma anche con un atteggiamento omissivo attraverso il silenzio, la sottovalutazione o l’omessa segnalazione. Saper individuare i segni caratteristici di un maltrattamento dell’anziano rappresenta un dovere da parte di ogni operatore sanitario, cruciale per l’adozione di idonee misure di difesa a tutela della vittima e di contrasto all’autore del reato. Obiettivo: Verificare il grado di percezione del fenomeno da parte degli operatori sanitari, e se essi stessi siano in grado di identificare tempestivamente i segni precoci di abuso ed adottare le azioni necessarie per la segnalazione. Materiali e metodi: Dal 1 al 30 aprile 2015, a tutti gli operatori (Medici, Medici in formazione specialistica, Infermieri, OSS e Portantini) delle Unità Operative di Medicina Interna e di Geriatria dell’Ospedale Cardarelli di Campobasso (Molise) e del Policlinico dell’Università degli Studi di Bari “Aldo Moro” (Puglia) è stato sottoposto un questionario formulato sulla scorta di altri già debitamente utilizzati e validati in altre realtà internazionali, che va ad esplorare: 1. la conoscenza da parte degli operatori del fenomeno, 2. la loro capacità di riconoscere gli eventuali segni di abuso, 3. la prevalenza del fenomeno (nel senso se abbiano mai avuto esperienza di abuso sugli anziani) 4. la conoscenza degli stessi operatori riguardo le azioni da adottare nel momento in cui si trovino di fronte ad un abuso. Risultati: La raccolta dei dati ha permesso di ottenere un totale di 98 questionari compilati su 142 somministrati (69.0%). La maggioranza dei questionari è stata compilata da soggetti di sesso femminile (75.5%), di età compresa tra 41 e 50 anni (27.6%) e con qualifica di infermiere (46.9%). La Tabella 1 descrive i dati preliminari ottenuti e la divisione per Unità Operative e per qualifica dei compilatori. La tabella 2 mostra la distribuzione per sesso e classi di età dei compilatori in base alla sede ed all’Unità Operativa di appartenenzaConclusioni: Da questi dati preliminari si evince come l’interesse per l’abuso sugli anziani, sebbene presente, non rappresenti per tutti gli operatori sanitari una priorità né un problema sentito, probabilmente in relazione alla scarsa conoscenza del fenomeno, ma soprattutto degli indicatori di abuso e delle procedure da attuare nel qual caso si venga a conoscenza di tale fenomeno. Quindi emerge forte l’esigenza di una formazione continua ed aggiornata sugli indicatori di abuso al fine di una loro più precisa individuazione nonché sulle procedure di segnalazione obbligatori alle Direzioni Sanitarie ed all’Autorità Giudiziaria.

The aim of this retrospective observational study was to evaluate whether adding liraglutide to lifestyle changes, metformin (Met) and testosterone replacement therapy (TRT), by means of improving weight and glycaemic control, could boost erectile function in type 2 diabetic obese men with overt hypogonadism and erectile dysfunction (ED) in a 'real-life setting'. Forty-three obese, diabetic and hypogonadal men (aged 45-59 years) were evaluated because of complaining about the recent onset of ED. They were subdivided into two groups according to whether hypogonadism occurred after puberty (G1; n = 30: 25 with dysfunctional hypogonadism and 5 with acquired hypogonadotropic hypogonadism) or before puberty (G2; n = 13: 10 with Klinefelter's syndrome and 3 with idiopathic hypogonadotropic hypogonadism). Both G1 and G2 patients were given a combination of testosterone (T) [testosterone undecanoate (TU) 1000 mg/every 12 weeks] and Met (2000-3000 mg/day) for 1 year. In the poor responders (N) to this therapy in terms of glycaemic target (G1N: n = 16; G2N: n = 10), liraglutide (L) (1.2 μg/day) was added for a second year, while the good responders (Y) to T + Met (G1Y: 14/30 and G2Y: 3/13) continued this two drugs regimen therapy for another year. All patients were asked to fill in the International Index of Erectile Function (IIEF 15) questionnaire before starting TU plus Met (T1) and after 12 months (T2) and 24 months (T3) of treatment. Patients underwent a clinical examination and a determination of serum sex hormone binding globulin (SHBG), total testosterone (T) and glycosylated haemoglobin (HbA1c) at T1, T2 and T3. At T2, each patient obtained an improvement of ED (p < 0.01) and of the metabolic parameters without reaching, however, the glycaemic goals [HbA1c = >7.5% (>58 mmol/mol)], while T turned out to be within the range of young men. L added to TU and Met regimen in G1N and G2N allowed these patients to reach not only the glycaemic target [HbA1c = <7.5% (<58 nmol/mol)] and a significant reduction in body weight (p < 0.01), but also a further increase in SHBG (p < 0.05) and T (p < 0.01) plasma levels as well as a significant increment of IIEF score (T3). Conversely, at T3 G1Y and G2Y, who received the combined therapy with TRT and Met for the second year, showed a partial failure of that treatment given that there was no improvement of the IIEF score and they showed a significant rise in serum HbA1c (p < 0.05) and weight (p < 0.04) compared with the assessments at T2. These results suggest that TRT could improve clinical and metabolic parameters in obese, type 2 diabetic men with ED and overt hypogonadism (independently of when T deficit occurred). Furthermore, in case of insufficient metabolic control the addition of L to TRT and Met regimen allows to achieve serum T levels in the range of healthy men, as well as to reach glycaemic target and to lower weight, leading to a considerable improvement of ED.

Cognitive frailty is a condition recently defined by operationalized criteria describing the simultaneous presence of physical frailty and mild cognitive impairment (MCI). Two subtypes for this clinical construct have been proposed: "potentially reversible" cognitive frailty (physical frailty plus MCI) and "reversible" cognitive frailty (physical frailty plus pre-MCI subjective cognitive decline). Here the prevalence of a potentially reversible cognitive frailty model was estimated. It was also evaluated if introducing a diagnosis of MCI in older subjects with physical frailty could have an additive role on the risk of dementia, disability, and all-cause mortality in comparison with frailty state or MCI condition alone, with analyses separately performed for inflammatory state.

The enzyme stearoyl-coenzyme A desaturase 1 (SCD or SCD1) produces mono-unsaturated fatty acids by introducing double bonds into saturated bonds between carbons 9 and 10, with oleic acid as the main product. SCD1 is present in the intestinal epithelium and fatty acids regulate cell proliferation, so we investigated the effects of SCD1-induced production of oleic acid in enterocytes in mice.

We evaluated the incidence of myocardial infarction (MI) in a population of Southern Italy and the relationship of dietary macronutrients with incident MI. The ONCONUT cohort included 5632 subjects followed-up, over 50 years, recruited in 1992. At baseline, they completed a validated semi-quantitative food frequency questionnaire and gave details of their medical history. After 5years they were traced by their family physician, who found 108 incident MI. Ninety-seven of them and 194 controls, sampled from the noncases at baseline and paired for diabetes to the cases, entered this nested case-control study. MI rate per 1000 person-years was 9.6 in males and 3.7 in females. In non-diabetics, saturated fat were associated with MI directly (odds ratio (OR): tertile 2 vs. 1 Z 2.32, tertile 3 vs. 1 Z 2.82; chi-square for trend, p Z 0.03) and polyunsaturated fats inversely (OR: tertile 2 vs. 1Z0.80, tertile 3 vs. 1Z0.37; chi-square for trend, pZ0.05), while in diabetics, starchy carbohydrates (OR: tertile 2 vs. 1 Z 1.51, tertile 3 vs. 1 Z 6.73; chi-square for trend, p Z 0.01) and glycaemic index (OR: tertile 2 vs. 1 Z 2.74, tertile 3 vs. 1 Z 5.34; chi-square for trend, p Z 0.01) were associated directly with MI. MI incidence in this population was lower than that found in northern countries. In non-diabetics, saturated fats were associated directly and polyunsaturated fat inversely with MI; in diabetics, starchy carbohydrates and high-glycaemic-index foods were associated directly with MI.

The somatotroph axis function shows a decline in the elderly (somatopause). In particular growth hormone (GH) response to GH-releasing hormone (GHRH) is reduced in aged man but less than that observed in GH-deficient adults (GHDAs). Plasma GH response to GHRH (1 mu g/kg BW) was significantly lower in four GHDAs than in seven healthy aged men 30, 60, and 90 min after acute GHRH administration. To verify whether a priming regimen might be able to increase the reduced GH response to GHRH, both healthy aged men and GHDA patients underwent repetitive administration of GHRH (100 mu g GHRH intravenously as a single morning dose, every 2 days for 12 days). After the GHRH-priming regimen, plasma GH values 30, 60, and 90 min after the acute GHRH test were significantly higher than values at the corresponding time points before priming regimen in healthy aged men but not in GHDA patients. These findings confirmed that somatotroph cells become less sensitive to GHRH with normal aging and demonstrate that repetitive administration of GHRH restores the attenuated response only in healthy aged men but not in GHDA patients. This could support the possible use of GHRH or its analogs instead of recombinant human GH in elderly patients with the advantage of preserving the endogenous pulses of GH with the secretion of the different isoforms of GH. However, concerns arise about the possible role of these molecules in tumorigenesis and tumor growth promotion.

Hereditary haemorrhagic telangiectasia (HHT) is rare, and characterised by vascular dysplasia that leads to various symptoms including visceral arteriovenous malformations and mucocutaneous telangiectatic lesions. Our aim was to describe the clinical features and options for the treatment of multiple oral lesions, and to illustrate the efficacy of the diode laser in the treatment of early (<2mm) and advanced lesions (2mm or more). We report 24 patients with 1200 oral telangiectatic lesions, which were often associated with regular bleeding (from monthly to daily), superinfection, pain, and swelling, and treated with multiple sessions of laser according to the number and size of the lesions. Early lesions were treated with a single laser impulse in ultrapulsed mode, and advanced lesions with repeated laser impulses in pulsed mode (t-on 200ms/t-off 500ms), at a power of 8W. Early lesions healed completely after laser photocoagulation with no operative or postoperative complications, while advanced lesions improved with a remarkable reduction in size but more discomfort. Protective occlusal plates were sometimes used to reduce the incidence of new lesions caused by dental trauma. The treatment of oral telangiectatic lesions is still being debated, and it is important to improve quality of life for patients. Diode laser surgery could be an effective treatment for oral lesions in those with hereditary haemorrhagic telangiectasia.

Purpose. Hereditary haemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber disease, is a rare autosomal dominant disorder characterised by mucocutaneous or visceral vascular abnormalities that may be widely distributed throughout the cardiovascular system. The purpose of this study was to compare multislice computed tomography angiography (MSCTA) and 4D dynamic contrast-enhanced magnetic resonance angiography (D-MRA) for evaluating vascular hepatic involvement in patients with HHT. Materials and methods. Fifty-two consecutive HHT patients underwent MSCTA and D-MRA examinations for systematic analysis of vascular visceral involvement. The images from the two techniques were reviewed independently by two expert radiologists to identify the following vascular abnormalities: telangiectases or large vascular masses; perfusion disorders [transient hepatic attenuation differences (THADs)]; hepatic arteriovenous malformations (HAVMs). Data, as well as diameters of the common hepatic artery and portal vein, were compared with Cohen's kappa statistic, Student's t test and receiver operating characteristic (ROC) curve analysis, as appropriate. Results. Both MSCTA and D-MRA detected one or more of the following hepatic vascular abnormalities in 36/52 cases (telangiectases in 29/52, THADs in 23/52 and HAVMs in 25/52[CE1]). A good concordance was found between the two techniques when determining the type of hepatic shunt (kappa=0.9). No statistically significant differences were found when comparing mean common hepatic artery and portal vein diameters (p=0.09 and 0.22, respectively) and their accuracy in predicting HAVMs. Conclusions. D-MRA has the same diagnostic accuracy as MSCTA and has the advantage of being less invasive due to the absence of ionising radiation.

The clinical occurrence of ectopic thyroid gland is an infrequently encountered condition, resulting from a developmental abnormality during the migration of the thyroid anlage from the floor of the primitive foregut to its final position in the neck. It can be found along the way of thyroid descent, in the midline, or laterally in the neck or even in the mediastinum or under the diaphragm. This condition is often asymptomatic, whereas symptoms could be related to ectopic thyroid size, to its relationships with surrounding organs or to diseases affecting the ectopic thyroid in the same way they involve orthotopic glands. Sometimes, a growing mass can lead to the clinical suspicion of a tumor disease. On the other hand, thyroid ectopy must be distinguished from metastasis of thyroid cancer. Scintigraphy and ultrasonography are the main diagnostic means for evaluating ectopic thyroid tissue, whereas fine needle aspiration could be useful in the presence of a nodular ectopic gland or when the coexistence of an orthotopic thyroid can arise the suspicion of a metastasis from a thyroid cancer. Surgical removal is indicated in symptomatic cases, whereas radioiodine ablation is reserved to recurrent disease. In this paper we report an emblematic case of ectopic thyroid gland and a review of the literature dealing with this condition.

After attending this presentation, attendees will more fully appreciate the importance of knowing how to recognize the various signs of elder abuse and the need to take the necessary steps both in prevention and in response. This presentation will impact the forensic science community by demonstrating that elder abuse comes in many forms, some obvious and others not so obvious. New ways to address this phenomenon must be formulated and put into practice. Background: Elder abuse is a widespread but underestimated problem. The full extent of this difficult situation is not known due to a lack of reports and/or complaints, as well as the difficulty in identifying the early warning signs of abuse. Many forms of elder abuse exist and are psychological, economic, sexual, physical, social, and institutional in nature; however, abuse also includes neglect and abandonment. It is clear that maltreatment may arise not only through active behavior, but also through omissive behavior such as silence, underestimation, and failure to report. Knowing how to identify the characteristic signs of elder abuse is the duty of every healthcare worker and is crucial in the adoption of suitable defense measures to protect the victim as well as in dealing with the offender.1,2 Objective: To establish the level of awareness of this issue by healthcare workers and to understand if they are able to promptly identify the early signs of abuse and take the necessary actions to report them. Materials and Methods: From April 1 - 30, 2015, all employees (i.e., physicians, specializing physicians in training, nurses, office support staff, social-healthcare workers, and orderlies) from the Internal Medicine Operating Unit and the Geriatrics Department at Cardelli Hospital in Campobasso (Molise) and from the Policlinico of the University of Bari “Aldo Moro” (Puglia) answered a questionnaire that was formulated by utilizing the provisions of other duly used and validated questionnaires from other international situations that are used to explore: (1) employees’ awareness of the phenomenon; (2) employees’ ability to recognize possible signs of abuse; (3) the prevalence of the phenomenon; and, (4) employees’ awareness regarding the proper actions to take when they encounter a case of abuse. Results: Data collection resulted in a total of 98 questionnaires administered to 142 respondents (69.0%). The majority of questionnaires were completed by females (75.5%) between the ages of 41 and 50 years of age (26.7%) and by qualified nurses (46.9%). Table 1 describes the preliminary data obtained and is broken down by unit and title of those who filled out the questionnaire. Table 2 shows distribution by sex and the age range of compilers according to the operating unit to which they belong. Table 1 BARI (Puglia) CAMPOBASSO (Molise) Internal Medicine Geriatrics Internal Medicine Geriatrics Title Enrolled Collected Enrolled Collected Enrolled Collected Enrolled Collected Physician 7 4 7 1 9 4 4 3 Physician in training 15 11 15 14 0 0 0 0 Nurses 12 11 12 10 20 16 15 9 OSS 4 3 4 1 3 1 3 1 Orderlies 2 2 2 2 2 1 2 1 Aides 2 1 2 2 0 0 0 0 Total 42 32 42 30 34 22 24 14 Table 2 BARI (Puglia) CAMPOBASSO (Molise) Total Internal Medicine Geriatrics Internal Medicine Geriatrics Sex (M/F) 10/22 6/24 5/17 3/11 98 Age 21-30 10 10 4 0 24 31-40 8 5 6 2 21 41-50 7 8 4 8 27 >50 7 4 8 4 23 No response 0 3 0 0 3 877 *Presenting Author Conclusions: These preliminary data show that interest in elder abuse, even when present, is neither a priority for all healthcare workers nor is it perceived as a problem by them. This is probably due to a lack of knowledge about the phenomenon, indicators of abuse, and the procedures to follow when one becomes aware of such an issue. As a result, a great need has been identified for ongoing and updated training regarding more precise indicators of abuse and the p

Until the 2000s Testosterone (T) Replacement Therapy (TRT) was not very satisfactory for male hypogonadic patients because the available T formulations were not able to reproduce the physiological pattern of T secretion in man. In fact, oral formulations (oral undecanoate T) showed very short half-life (<24 hours), requiring the administration of several daily doses, whereas the old injection products (T esters) were characterized by very long half-life (>7 days) because of their adipose tissue storage, requiring to be administered every 2-3 weeks but determining remarkable and quick fluctuations (in 2-3 weeks) of the testosteronemia with variations in a few days from over-physiological levels (> 2000 ng/dl) to very low levels (< 200 ng/dl). Nowadays, several compounds can attain the standards of suitability and effectiveness of TRT in hypogonadal men. Both transcutaneous (gel) T and long-acting injectable formulations are the most modern preparations that can satisfy the criteria of an ideal chronic replacement therapy. In fact, they keep the serum T levels in the physiological range imitating its circadian rhythm, leading to the development and/or the preservation of male sexual characteristics and, finally, positively influencing bone mass, skeletal muscle and adipose tissue distribution. In particular, the availability and use of long-acting injectable undecanoate T can really improve the patients' compliance as requested for a life-long treatment. However, definitive and conclusive evidence regarding the main end-points, such as the diminished recurrence of falls in elderly men, the decrease in fractures in osteoporotic subjects, the reduction in disabling conditions and the extension of life, have not been reached so far. Therefore, the aim of this review is to sum up the most important evidence that has been collected regarding TRT, highlighting in particular those concerning both transcutaneous and long-acting injectable T compounds.

BACKGROUND AND PURPOSE: Women live longer and outnumber men. On the other hand, older women develop more chronic diseases and conditions such as arthritis, osteoporosis and depression, leading to a greater number of years of living with disabilities. The aim of this study was to describe whether or not there are gender differences in the demographic profile, disease distribution and outcome in a population of hospitalized elderly people. METHODS: Retrospective observational study including all patients recruited for the REPOSI study in the year 2010. Analyses are referred to the whole group and gender categorization was applied. RESULTS: A total of 1380 hospitalized elderly subjects, 50.5% women and 49.5% men, were considered. Women were older than men, more often widow and living alone or in nursing homes. Disease distribution showed that malignancy, diabetes, coronary artery disease, chronic kidney disease and chronic obstructive pulmonary disease were more frequent in men, but hypertension, osteoarthritis, anemia and depression were more frequent in women. Severity and comorbidity indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were higher in men, while cognitive impairment evaluated by the Short Blessed Test (SBT), mood disorders by the Geriatric Depression Scale (GDS) and disability in daily life measured by Barthel Index (BI) were worse in women. In-hospital and 3-month mortality rates were higher in men. CONCLUSIONS: Our study showed a gender dimorphism in the demographic and morbidity profiles of hospitalized elderly people, emphasizing once more the need for a personalized process of healthcare

ABUSI E VIOLENZE SUGLI ANZIANI: COSA NE PENSANO GLI OPERATORI? PRIMI RISULTATI DI UNA INDAGINE Corbi G1, Grattagliano I2, Scarabaggio L1, Catanesi R2, Sabbà C3, Fiore G3, Ferrara N4, Campobasso CP1 1 Dip. di Medicina e Scienze della Salute “V. Tiberio” , Università degli Studi del Molise 2 Sezione di Psichiatria Forense (DIMIMP), Università degli studi di Bari Aldo Moro 3 Dip. Interdisciplinare di Medicina, Università degli studi di Bari Aldo Moro 4 Dip. di Scienze Mediche e Traslazionali, Università “Federico II” di Napoli Background. L’abuso degli anziani è un problema diffuso ma sottostimato. L'entità di tale problema non è del tutto nota sia per la mancanza di segnalazioni e/o denunce sia per la difficoltà di individuare precocemente gli indicatori di un buso. Esistono molte forme di abuso sugli anziani, tra cui quelle di natura psicologica, economica, sessuale, fisica, sociale, istituzionale, ma l’abuso include anche l’incuria e l’abbandono. È chiaro, quindi, che il maltrattamento può concretizzarsi non solo con una condotta attiva, ma anche con un atteggiamento omissivo attraverso il silenzio, la sottovalutazione o l’omessa segnalazione. Saper individuare i segni caratteristici di un maltrattamento dell’anziano rappresenta un dovere da parte di ogni operatore sanitario, cruciale per l’adozione di idonee misure di difesa a tutela della vittima e di contrasto all’autore del reato. Obiettivo. Verificare il grado di percezione del fenomeno da parte degli operatori sanitari, e se essi stessi siano in grado di identificare tempestivamente i segni precoci di abuso ed adottare le azioni necessarie per la segnalazione. Materiali e metodi: Dal 1 al 30 aprile 2015, a tutti gli operatori (Medici, Medici in formazione specialistica, Infermieri, OSS e Portantini) delle Unità Operative di Medicina Interna e di Geriatria dell’Ospedale Cardarelli di Campobasso (Molise) e del Policlinico dell’Università degli Studi di Bari “Aldo Moro” (Puglia) è stato sottoposto un questionario formulato sulla scorta di altri già debitamente utilizzati e validati in altre realtà internazionali, che va ad esplorare: 1. la conoscenza da parte degli operatori del fenomeno, 2. la loro capacità di riconoscere gli eventuali segni di abuso, 3. la prevalenza del fenomeno (nel senso se abbiano mai avuto esperienza di abuso sugli anziani) 4. la conoscenza degli stessi operatori riguardo le azioni da adottare nel momento in cui si trovino di fronte ad un abuso. Risultati: La raccolta dei dati ha permesso di ottenere un totale di 98 questionari compilati su 142 somministrati (69.0%). La maggioranza dei questionari è stata compilata da soggetti di sesso femminile (75.5%), di età compresa tra 41 e 50 anni (27.6%) e con qualifica di infermiere (46.9%). La Tabella 1 descrive i dati preliminari ottenuti e la divisione per Unità Operative e per qualifica dei compilatori. La tabella 2 mostra la distribuzione per sesso e classi di età dei compilatori in base alla sede ed all’Unità Operativa di appartenenza. Tab. 1. BARI (PUGLIA) CAMPOBASSO (MOLISE) Medicina Interna Geriatria Medicina Interna Geriatria Qualifica Arruolati Raccolti Arruolati Raccolti Arruolati Raccolti Arruolati Raccolti Medici 7 4 7 1 9 4 4 3 Med. in form. 15 11 15 14 0 0 0 0 Infermieri 12 11 12 10 20 16 15 9 OSS 4 3 4 1 3 1 3 1 Portantini 2 2 2 2 2 1 2 1 Ausiliari 2 1 2 2 0 0 0 0 Totale 42 32 42 30 34 22 24 14 Tab. 2 BARI (PUGLIA) CAMPOBASSO (MOLISE) Totale Medicina Interna Geriatria Medicina Interna Geriatria Sesso (M/F) 10/22 6/24 5/17 3/11 98 Età 21-30 10 10 4 0 24 31-40 8 5 6 2 21 41-50 7 8 4 8 27 >50 7 4 8 4 23 Non risposto 0 3 0 0 3 Conclusioni. Da questi dati preliminari si evince come l’interesse per l’abuso sugli anziani, sebbene presente, non rappresenti per tutti gli operatori sanitari una priori

Lynch syndrome (LS), or hereditary non-polyposis colorectal cancer (HNPCC), is an autosomal dominant condition responsible for early onset cancer mostly in the colonrectum and endometrium as well as in other organ sites. Lynch syndrome is caused by germline mutations in mismatch repair genes, prevalently in hMSH2, hMLH1, and less frequently in hMSH6 and hPMS2. Twenty-nine non-related index cases with colorectal cancer (CRC) were collected from a region in southeast Italy (Apulia). Among this set of patients, fifteen fulfilled the Amsterdam criteria II. The presence of tumor microsatellite instability (MSI) was assessed in all index cases and 19 (15 AC+/4 AC-) were classified as MSI-H. Mutation analysis performed on all patients, identified 15 pathogenic mutations in hMLH1 and 4 in hMSH2. 4/15 mutations in hMLH1 and 2/4 hMSH2 mutations have not been previously reported. Three previously reported mutations were further investigated for the possibility of a common founder effect. Genetic counseling was offered to all probands and extended to 183 relatives after molecular testing and 85 (46%) mutation carriers were identified. Eighty mutation carriers underwent an accurate clinical and instrumental surveillance protocol. Our results confirm that the identification of LS patients based exclusively on family history may miss patients carrying germline mutations in the MMR genes. Moreover, our results demonstrated that molecular screening and subsequent instrumental surveillance are very effective in identifying CRCs at earlier stages and reducing the number of deaths from secondary cancers in HNPCC patients.

metabolic syndrome is a cluster of cardio-metabolic risk factors associated to atherosclerosis and low-grade inflammation. Using unbiased expression screenings in peripheral blood mononuclear cells, we depict here a novel expression chart of 678 genes and 84 miRNAs controlling inflammatory, immune and metabolic responses. In order to further elucidate the link between inflammation and the HDL cholesterol pathway in metabolic syndrome (MS), we focused on the regulation of the ATP-binding cassette transporter A1 (ABCA1), a key player in cholesterol efflux.

Epicardial adipose tissue (EAT) is an atypical fat depot surrounding the heart with a putative role in the development of atherosclerosis.

OBJECTIVE: To assess the relationship between chronic endometritis (CE) and proinflammatory cytokine levels in menstrual effluents and to develop a simple noninvasive test for screening CE. DESIGN: Case-control study. SETTING: Academic center. PATIENT(S): Sixty-four women referred to our center for infertility. INTERVENTION(S): Office hysteroscopy; endometrial biopsy; collection of menstrual blood at subsequent cycle. MAIN OUTCOME MEASURE(S): Interleukin (IL) 6, IL-1β, and tumor necrosis factor (TNF) α concentrations in menstrual effluents. RESULT(S): Thirty-six out of 64 infertile women had histologically proven CE. The remaining 28 women were included as controls. IL-6, IL-1β, and TNF-α levels were markedly higher in menstrual effluents of women with CE compared with control subjects. Receiver operating characteristic curve analysis revealed a good CE screening capacity for all of the cytokines. The combined evaluation of either IL-6/TNF-α or IL-6/IL-1β increased the diagnostic capacity of the test, which reached a 100% sensitivity and a negative predictive value of 100 when at least one cytokine was found to exceed its cutoff value; it also reached a 100% specificity and a positive predictive value of 100 in cases of positivity of both cytokines. Logistic regression analysis confirmed the IL-6/TNF-α-based model as a significant predictor of CE. CONCLUSION(S): Proinflammatory cytokine levels are increased in menstrual effluents of women with CE. A test dosing IL-6 and TNF-α seems to have a high screening capacity for CE.

BACKGROUND: Scores for cardio-embolic and bleeding risk in patients with atrial fibrillation are described in the literature. However, it is not clear how they co-classify elderly patients with multimorbidity, nor whether and how they affect the physician's decision on thromboprophylaxis. METHODS: Four scores for cardio-embolic and bleeding risks were retrospectively calculated for ≥ 65 year old patients with atrial fibrillation enrolled in the REPOSI registry. The co-classification of patients according to risk categories based on different score combinations was described and the relationship between risk categories tested. The association between the antithrombotic therapy received and the scores was investigated by logistic regressions and CART analyses. RESULTS: At admission, among 543 patients the median scores (range) were: CHADS2 2 (0-6), CHA2DS2-VASc 4 (1-9), HEMORR2HAGES 3 (0-7), HAS-BLED 2 (1-6). Most of the patients were at high cardio-embolic/high-intermediate bleeding risk (70.5% combining CHADS2 and HEMORR2HAGES, 98.3% combining CHA2DS2-VASc and HAS-BLED). 50-60% of patients were classified in a cardio-embolic risk category higher than the bleeding risk category. In univariate and multivariable analyses, a higher bleeding score was negatively associated with warfarin prescription, and positively associated with aspirin prescription. The cardio-embolic scores were associated with the therapeutic choice only after adjusting for bleeding score or age. CONCLUSION: REPOSI patients represented a population at high cardio-embolic and bleeding risks, but most of them were classified by the scores as having a higher cardio-embolic than bleeding risk. Yet, prescription and type of antithrombotic therapy appeared to be primarily dictated by the bleeding risk

The dramatic demographic changes that are occurring in the third millennium are modifying the mission of generalist professionals such as primary care physicians and internists. Multiple chronic diseases and the related prescription of multiple medications are becoming typical problems and present many challenges. Unfortunately, the available evidence regarding the efficacy of medications has been generated by clinical trials involving patients completely different from those currently admitted to internal medicine: much younger, affected by a single disease and managed in a highly controlled research environment. Because only registries can provide information on drug effectiveness in real-life conditions, REPOSI started in 2008 with the goal of acquiring data on elderly people acutely admitted to medical or geriatric hospital wards in Italy. The main goals of the registry were to evaluate drug prescription appropriateness, the relationship between multimorbidity/polypharmacy and such cogent outcomes as hospital mortality and re-hospitalization, and the identification of disease clusters that most often concomitantly occur in the elderly. The findings of 3-yearly REPOSI runs (2008, 2010, 2012) suggest the following pertinent tasks for the internist in order to optimally handle their elderly patients: the management of multiple medications, the need to become acquainted with geriatric multidimensional tools, the promotion and implementation of a multidisciplinary team approach to patient health and care and the corresponding involvement of patients and their relatives and caregivers. There is also a need for more research, tailored to the peculiar features of the multimorbid elderly patient

Cardiac hypertrophy/remodeling is a critical condition that if not efficiently contrasted may predispose to fatal heart failure and multiple organ dysfunction as a result of irreversible neuroendocrine, autonomic and immune system imbalances. Indeed, in chronic heart failure (CHF) the over-excitation of sympathetic and/or the breakdown of central parasympathetic tone are believed to be the basis of the persistent immune activation that in part is primed by inflammatory reactions in the Central Nervous System. Moreover, the clinical management of CHF still today requires the identification of molecularly targeted drugs alternative to those considered so far. In this review are focused the possible neuroimmune-mediated pathways involved in CHF and set out the current therapeutic strategies.

The nuclear receptor farnesoid X receptor (FXR) is the master regulator of bile acids (BAs) homeostasis since it transcriptionally drives modulation of BA synthesis, influx, efflux, and detoxification along the enterohepatic axis. Due to its crucial role, FXR alterations are involved in the progression of a plethora of BAs associated inflammatory disorders in the liver and in the gut. The involvement of the FXR pathway in cholestasis development and management has been elucidated so far with a direct role of FXR activating therapy in this condition. However, the recent identification of a new type of genetic progressive familial intrahepatic cholestasis (PFIC) linked to FXR mutations has strengthen also the bona fide beneficial effects of target therapies that by-pass FXR activation, directly promoting the action of its target, namely the enterokine FGF19, in the repression of hepatic BAs synthesis with reduction of total BA levels in the liver and serum, accomplishing one of the major goals in cholestasis. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni and Peter Jansen.

There have been a large number of observational studies on the impact of nutrition on neuroprotection, however, there was a lack of evidence from randomized clinical trials (RCTs). In the present systematic review, from the 32 included RCTs published in the last four years (2014-2017) in patients aged 60 years and older with different late-life cognitive disorders, nutritional intervention through medical food/nutraceutical supplementation and multidomain approach improved magnetic resonance imaging findings and other cognitive-related biomarkers, but without clear effect on cognition in mild Alzheimer's disease (AD) and mild cognitive impairment (MCI). Antioxidant-rich foods (nuts, grapes, cherries) and fatty acid supplementation, mainly n-3 polyunsaturated fatty acids (PUFA), improved specific cognitive domains and cognitive-related outcomes in MCI, mild-to-moderate dementia, and AD. Antioxidant vitamin and trace element supplementations improved only cognitive-related outcomes and biomarkers, high-dose B vitamin supplementation in AD and MCI patients improved cognitive outcomes in the subjects with a high baseline plasma n-3 PUFA, while folic acid supplementation had positive impact on specific cognitive domains in those with high homocysteine.

Background: Peutz-Jeghers syndrome (PJS) is a rare dominantly inherited disease characterized by the association of gastrointestinal hamartomatous polyposis, mucocutaneous hyperpigmentation, and increased risk of cancer at different target organs. Its occurrence with differentiated thyroid cancer, particularly papillary thyroid carcinoma (PTC), even if rare, has been described. Summary: We here present a case of PTC observed in a PJS patient and a review of the literature aiming at discussing the utility of thyroid surveillance in the management of these patients. A 22-year-old woman presenting with hyperpigmented lesions of the lips and hamartomatous polyps in the stomach, duodenum, jejunum, and ileum, leading to the suspicion of PJS, was submitted to genetic analysis. Mutation scanning of the Liver Kinase B1 (LKB1) gene identified the presence of the truncating mutation E265X, thus confirming the clinical diagnosis. Beside the endoscopic, radiologic, and echographic evaluations required by the standard surveillance guidelines, the patient had a neck ultrasound (US), which showed a 5 x 4 x 6 mm hypoechoic nodule in the right thyroid lobe. The nodule contained microcalcifications and a perinodular vascular pattern. The cytological preparations derived from US-guided fine-needle aspiration biopsy of the nodule demonstrated the presence of PTC. The patient underwent a video-assisted total thyroidectomy and the histological examination revealed a follicular variant of papillary microcarcinoma. Radioactive iodine therapy was not performed because of the small size of the lesion. The patient was started on levothyroxine therapy to keep the serum thyrotropin levels suppressed. Both the sequencing and the multiplex ligation-dependent probe amplification analysis could not identify any LKB1 mutation in the tumor specimen, and the methylation-specific polymerase chain reaction assay excluded hypermethylation of the LKB1 promoter as the mechanism of inactivation for the remaining normal allele in the tumor. Conclusions: Although other mechanisms of LKB1 silencing may be responsible for its inactivation in the thyroid cancer, we cannot rule out that the occurrence of thyroid carcinoma could be a coincidental finding in this patient. However, the case here presented suggests that US of the thyroid could possibly become an integral part of the evaluation and the follow-up program adopted for PJS patients.

To the Editor: Nonvalvular atrial fibrillation (NVAF) is the most common sustained arrhythmia encountered in clinical practice and is associated with a 5-fold increased risk for stroke (1). Moreover, patients with NVAF often suffer from atherosclerotic complications such as acute myocardial infarction (AMI) (2). Peripheral artery disease (PAD) is an established marker of systemic atherosclerosis but its prevalence in NVAF is still unclear. We reasoned that inclusion of ankle-brachial index (ABI), which is an established tool for diagnosis of PAD (3), in the CHA2DS2-VASc (4) score would better define the prevalence of vascular disease. Toaddress this issue, the ItalianSociety of InternalMedicine (SIMI) established an Italian registry documenting ABI inNVAF patients. The Atrial Fibrillation Registry for the ARAPACIS (Ankle- brachial Index Prevalence Assessment: Collaborative Italian Study) study is an independent research project involving all Regional Councils of SIMI. The first objective of the study was to estimate the prevalence of ABI 0.90 in NVAF patients. Consecutive patients with NVAF referred to internal medicine wards were eligible for the enrollment. Enrollment started in October 2010 and continued until October 30, 2012. Patients were enrolled if they were 18 years or older and had a diagnosis of NVAF, recording during the qualifying admission/consultation or in the preceding 12 months, and if it was possible to obtain the ABI measurement. Exclusion criteria included the following: acquired or congenital valvular AF, active cancer, disease with life expectancy <3 years, hyperthyroidism and pregnancy. We initially planned to include 3,000 patients. The Data and Safety Monitoring Board (Online Appendix) decided to perform an interim analysis to assess the prevalence of ABI in the enrolled populationsdas a higher than expected prevalence of low ABI was detecteddand decided to interrupt the patients’ enrollment. The sample size was amended as follows: a sample of 2,027 patients leads to the expected prevalence of 21% with a 95% confidence interval width of 3.5% (StataCorp LP, College Station, Texas). Among the 2,027 NVAF patients included in the study, hyper- tension was detected in 83%, diabetes mellitus in 23%, dyslipidemia in 39%, metabolic syndrome in 29%, and smoking in 15%. At least 1 atherosclerotic risk factor was detected in 90% of patients. The NVAF population was at high risk for stroke, with only 18% having a CHA2DS2-VASc score of 0 to 1, while 82% had a risk 2. Despite this, 16% were untreated with any antith- rombotic drug, 19% were treated with antiplatelet drugs (APs), and 61% with oral anticoagulants (OAC); 4% of patients were treated with both APs and OAC. Among the AF population, 428 patients (21%) had ABI 0.90 (69%); 204 patients (10%) had ABI 1.40 (Fig. 1). ABI recorded only in 1 leg was excluded from the analysis (n ¼ 14). ABI 0.90 progressively increased from paroxysmal to permanent NVAF (18%, tensive (88% vs. 82%; p ¼ 0.032), diabetic (34% vs. 20%; p < 0.0001), or smokers (20% vs. 14%; p ¼ 0.0008), or to have experi- enced transient ischemic attack or stroke (17% vs. 10%; p < 0.001). 21%, 24%; p ¼ 0.0315). NVAF patients with ABI 0.90 were more likely to be hyper- NVAF patients with ABI 0.90 had a higher percentage of CHA2DS2-VASc score 2 compared with those with ABI >0.90 (93% vs. 82%; p < 0.0001). significantly associated with a smoking habit (odds ratio [OR]: 1.99; 95% confidence interval [CI]: 1.48 to 2.66; p < 0.0001), diabetes (OR: 1.93; 95% CI: 1.51 to 2.46; p < 0.0001), age class 65 to 74 years (OR: 2.05; 95% CI: 1.40 to 3.07; p < 0.0001), age Logistic regression analysis demonstrated that ABI 0.90 was class 75 years (OR: 3.12; 95% CI: 2.16 to 4.61; p < 0.0001), and history of previous transient ischemic attack/stroke (OR: 1.64; 95% CI: 1.20 to 2.24; p ¼ 0.002). Vascul

Pharmacological thromboprophylaxis (TP) is known to reduce venous thromboembolism (VTE) in medical inpatients, but the criteria for risk-driven prescription, safety and impact on mortality are still debated. We analyze data on elderly patients with multimorbidities admitted in the year 2010 to the Italian internal medicine wards participating in the REPOSI registry to investigate the rate of TP during the hospital stay, and analyze the factors that are related to its prescription. Multivariate logistic regression, area under the ROC curve and CART analysis were performed to look for independent predictors of TP prescription. Association between TP and VTE, bleeding and death in hospital and during the 3-month post-discharge follow-up were explored by logistic regression and propensity score analysis. Among the 1,380 patients enrolled, 171 (15.2 %) were on TP during the hospital stay (162 on low molecular weight heparins, 9 on fondaparinux). The disability Barthel index was the main independent predictor of TP prescription. Rate of fatal and non-fatal VTE and bleeding during and after hospitalization did not differ between TP and non-TP patients. In-hospital and post-discharge mortality was significantly higher in patients on TP, that however was not an independent predictor of mortality. Among elderly medical patients there was a relatively low rate of TP, that was more frequently prescribed to patients with a higher degree of disability and who had an overall higher mortality

BACKGROUND: A 17-year-old boy was referred to our center with a history of brain abscess (BA) recurring after 9 years. The patient reported 2 previous treatments for pulmonary arteriovenous malformations, sporadic nosebleeds, and familial history for epistaxis. Clinical investigations revealed arteriovenous malformations in lung, brain, and liver, as well as mucocutaneous telangiectases.A definite diagnosis of hereditary hemorrhagic telangiectasia was made based on clinical criteria and confirmed by genetic analysis. This is the first report of BA recurrence at the end of pediatric age. CONCLUSIONS:: The present case and the literature review of all cases of BA thus far reported highlight the need to raise the suspicion of a pulmonary arteriovenous malformations, both isolated and in the context of a possible hereditary hemorrhagic telangiectasia, for any case of BA of unexplained etiology, in children as well as in adults.

In the last decade, the association between diet and cognitive function or dementia has been largely investigated. In the present article, we systematically reviewed observational studies published in the last three years (2014-2016) on the relationship among dietary factors and late-life cognitive disorders at different levels of investigation (i.e., dietary patterns, foods and food-groups, and dietary micro- and macronutrients), and possible underlying mechanisms of the proposed associations. From the reviewed evidence, the National Institute on Aging-Alzheimer's Association guidelines for Alzheimer's disease (AD) and cognitive decline due to AD pathology introduced some evidence suggesting a direct relation between diet and changes in the brain structure and activity. There was also accumulating evidence that combinations of foods and nutrients into certain patterns may act synergistically to provide stronger health effects than those conferred by their individual dietary components. In particular, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline. Moreover, also other emerging healthy dietary patterns such as the Dietary Approach to Stop Hypertension (DASH) and the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) diets were associated with slower rates of cognitive decline and significant reduction of AD rate. Furthermore, some foods or food groups traditionally considered harmful such as eggs and red meat have been partially rehabilitated, while there is still a negative correlation of cognitive functions with saturated fatty acids and a protective effect against cognitive decline of elevated fish consumption, high intake of monounsaturated fatty acids and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA.

Cognitive frailty, a condition describing the simultaneous presence of physical frailty and mild cognitive impairment, has been recently defined by an international consensus group. We estimated the predictive role of a "reversible" cognitive frailty model on incident dementia, its subtypes, and all-cause mortality in nondemented older individuals. We verified if vascular risk factors or depressive symptoms could modify this predictive role.

The endocrine fibroblast growth factors (FGFs), FGF19, FGF21 and FGF23, are critical for maintaining whole-body homeostasis, with roles in bile acid, glucose and lipid metabolism, modulation of vitamin D and phosphate homeostasis and metabolic adaptation during fasting. Given these functions, the endocrine FGFs have therapeutic potential in a wide array of chronic human diseases, including obesity, type 2 diabetes, cancer, and kidney and cardiovascular disease. However, the safety and feasibility of chronic endocrine FGF administration has been challenged, and FGF analogues and mimetics are now being investigated. Here, we discuss current knowledge of the complex biology of the endocrine FGFs and assess how this may be harnessed therapeutically.

This review summarizes the document elaborated by the Italian Association for the Study of the Liver (AISF) ad hoc committee "Vascular disorders of the liver" on the primary circulatory liver diseases, which include Budd-Chiari syndrome, obstruction of the hepatic portion of the inferior vena cava, portal vein thrombosis, sinusoidal obstruction syndrome (veno-occlusive disease) and hereditary hemorrhagic telangiectasia. A characteristic of the primary circulatory liver diseases is that portal hypertension usually precedes liver dysfunction. Significant overlap exists amongst the diseases and risk factors that predispose patients to the primary circulatory liver diseases, though the pathogenesis of individual diseases varies. Management of the different vascular disorders is very peculiar and often multidisciplinary and patients should be referred to a tertiary referral centre for optimal care. (C) 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The response of arginin-vasopressin (AVP) to baroreceptor activation (tilt testing) was investigated in patients with diabetic autonomic neuropathy (DAN). The present data show that hypothension induced by upright position showed a slight increase of AVP in patients with DAN in comparison with normal subjects and diabetic patients without DAN. These findings suggest that the blunted AVP response to hypothension may be due to lesions of afferent autonomic pathways present in DAN and plays a role in the pathogenesis of postural hypothension.</.