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Coffee is one of the most widely consumed beverages in the world due to its unique aroma and psychostimulant effects, mainly due to the presence of caffeine. In recent years, experimental evidence has shown that the moderate consumption of coffee (3/4 cups per day) is safe and beneficial to human health, revealing protective effects against numerous chronic metabolic diseases such as diabetes, cardiovascular, neurodegenerative, and hepatic diseases. This review focuses on two of coffee's main bioactive compounds, i.e., caffeine and chlorogenic acids, and their effects on the progression of chronic liver diseases, demonstrating that regular coffee consumption correlates with a lower risk of the development and progression of non-alcoholic steatohepatitis, viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. In particular, this review analyzes caffeine and chlorogenic acid from a pharmacological point of view and explores the molecular mechanism through which these compounds are responsible for the protective role of coffee. Both bioactive compounds, therefore, have antifibrotic effects on hepatic stellate cells and hepatocytes, induce a decrease in connective tissue growth factor, stimulate increased apoptosis with anti-cancer effects, and promote a major inhibition of focal adhesion kinase, actin, and protocollagen synthesis. In conclusion, coffee shows many beneficial effects, and experimental data in favor of coffee consumption in patients with liver diseases are encouraging, but further prospective studies are needed to demonstrate its preventive and therapeutic role in chronic liver diseases.

Background and aims: Management of severe thrombocytopenia poses significant challenges in patients with chronic liver disease. Here, we aimed to evaluate the first real-world European post-marketing cohort of cirrhotic patients treated with lusutrombopag, a thrombopoietin receptor agonist, verifying the efficacy and safety of the drug. Methods: In the REAl-world Lusutrombopag treatment in ITalY (REALITY) study, we collected data from consecutive cirrhotic patients treated with lusutrombopag in 19 Italian hepatology centers, mostly joined to the "Club Epatologi Ospedalieri" (CLEO). Primary and secondary efficacy endpoints were the ability of lusutrombopag to avoid platelet transfusions and to raise the platelet count to ≥50,000/μL, respectively. Treatment-associated adverse events were also collected. Results: A total of 66 patients and 73 cycles of treatment were included in the study, since 5 patients received multiple doses of lusutrombopag over time for different invasive procedures. Fourteen patients (19%) had a history of portal vein thrombosis (PVT). Lusutrombopag determined a significant increase in platelet count [from 37,000 (33,000-44,000/μL) to 58,000 (49,000-82,000), p < 0.001]. The primary endpoint was met in 84% of patients and the secondary endpoint in 74% of patients. Baseline platelet count was the only independent factor associated with response in multivariate logistic regression analysis (OR for any 1000 uL of 1.13, CI95% 1.04-1.26, p 0.01), with a good discrimination power (AUROC: 0.78). Notably, a baseline platelet count ≤ 29,000/μL was identified as the threshold for identifying patients unlikely to respond to the drug (sensitivity of 91%). Finally, de novo PVT was observed in four patients (5%), none of whom had undergone repeated treatment, and no other safety or hemorrhagic events were recorded in the entire population analyzed. Conclusions: In this first European real-world series, lusutrombopag demonstrated efficacy and safety consistent with the results of registrational studies. According to our results, patients with baseline platelet counts ≤29,000/μL are unlikely to respond to the drug.

Background & Aims: Obeticholic acid (OCA) is the only licensed second-line therapy for primary biliary cholangitis (PBC). With novel therapeutics in advanced development, clinical tools are needed to tailor the treatment algorithm. We aimed to derive and externally validate the OCA response score (ORS) for predicting the response probability of individuals with PBC to OCA., Methods: We used data from the Italian RECAPITULATE (N = 441) and the IBER-PBC (N = 244) OCA real-world prospective cohorts to derive/validate a score including widely available variables obtained either pre-treatment (ORS) or also after 6 months of treatment (ORS+). Multivariable Cox regressions with backward selection were applied to obtain parsimonious predictive models. The predicted outcomes were biochemical response according to POISE (alkaline phosphatase [ALP]/upper limit of normal [ULN]<1.67 with a reduction of at least 15%, and normal bilirubin), or ALP/ULN<1.67, or normal range criteria (NR: normal ALP, alanine aminotransferase [ALT], and bilirubin) up to 24 months., Results: Depending on the response criteria, ORS included age, pruritus, cirrhosis, ALP/ULN, ALT/ULN, GGT/ULN, and bilirubin. ORS+ also included ALP/ULN and bilirubin after 6 months of OCA therapy. Internally validated c-statistics for ORS were 0.75, 0.78, and 0.72 for POISE, ALP/ULN<1.67, and NR response, which raised to 0.83, 0.88, and 0.81 with ORS+, respectively. The respective performances in validation were 0.70, 0.72, and 0.71 for ORS and 0.80, 0.84, and 0.78 for ORS+. Results were consistent across groups with mild/severe disease., Conclusions: We developed and externally validated a scoring system capable to predict OCA response according to different criteria. This tool will enhance a stratified second-line therapy model to streamline standard care and trial delivery in PBC., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: We assessed the performance of direct-acting antivirals (DAAs) in hepatitis C virus (HCV)-infected people who use drugs (PWUDs) in terms of sustained virological response (SVR) and adherence rates in comparison to a location-matched cohort of non-PWUD HCV patients., Methods: All consecutive HCV RNA-positive PWUDs were enrolled between 2015 and 2019. All subjects underwent DAA treatment according to international guidelines and then followed, at least, up to 12 weeks after the end of treatment (SVR12). The SVR and adherence to treatment was compared with that of non-PWUD HCV patients observed at hepatological units of the CLEO platform. Intention-to-treat analysis was performed., Results: A total of 1,786 PWUDs who were followed up were available for assessment. Most PWUDs (85.4%) were managed inside the specialized outpatient addiction clinics (SerDs). The overall SVR rate was 95.4%. The SerDs group achieved an SVR rate of 96.2% compared with 91.6% of the non-SerDs group (P < 0.001). Comparison with the non-SerDs group and the control HCV group showed a significant difference in the dropout rate (0.6% in the SerDs group versus 2.8% in the non-SerDs group and 1.2% in the control group; P < 0.001). At multivariate analysis, factors independently associated with SVR were use of the most recent regimens (elbasvir/grazoprevir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir; odds ratio: 3.126; P = 0.000) and belonging to the SerDs group (odds ratio: 2.356; P = 0.002)., Discussion: The performance of DAAs in PWUD is excellent, if 2 conditions are met: (i) that the latest generation drugs are used and (ii) that the patients are managed within the SerDs., (Copyright © 2021 by The American College of Gastroenterology.)

Background and aim: Response to ursodeoxycholic acid (UDCA) is crucial for the prediction of primary biliary cholangitis (PBC) prognosis, and different response criteria were validated and proposed by reference centers for PBC. To date, rates of non-response to UDCA from real-world series are lacking. Methods: Hepatology/Gastroenterology centers belonging to 'Club Epatologi Ospedalieri' (CLEO) and 'Associazione Italiana Gastroenterologi Ospedalieri' (AIGO) were invited to participate in the study, and asked to extract all patients followed for PBC, without any selection or exclusion, and fill in the database provided. Results: Thirty-four centers were enrolled throughout Italy, for a total of 713 patients. None of these centers, except one, had a hepatology outpatient clinic devoted to the care of patients with autoimmune liver diseases. After excluding 79 cases of PBC/autoimmune hepatitis overlaps, 634 patients were analyzed: mean age, 64.4 ± 12.0 years; 91.2% females; F/M 10.3/1. For patients with at least 1 year of UDCA treatment (583), rates of non-response to UDCA were evaluated according to the Paris-I/-II, Toronto and GLOBE criteria, and compared with those in the original cohorts: 27% vs 39% in Paris-I cohort; 39.6% vs 52% in Paris-II; 20.1% vs 43.5% in Toronto; 15.7% vs 30% in GLOBE (age-specific cutoffs). Mean alkaline phosphatase levels on UDCA treatment, and the age-adjusted prevalence of F3/F4 fibrosis, appeared lower in this PBC population than in reference cohorts. Conclusions: A mean ∼15% better response to UDCA is observed in a real-world PBC population, probably due to migration of some of most severe/advanced cases to PBC referral centers.

Background: Pretreatment evaluation of HCV-infected patients is a complex interplay between multiple clinical and viral parameters, leading to a tailored approach that may bring real-life sustained virological response (SVR) rates close to 98%-99%., Objectives: As proof-of-concept, we evaluated the efficacy of all-oral direct-acting antiviral (DAA) regimens in patients whose personalization included pre-therapy evaluation of natural resistance-associated substitutions (RASs), in addition to international guideline recommendations., Methods: One hundred and thirty-one patients who started a first-line all-oral DAA regimen between April 2015 and December 2016 were tested for baseline NS3 and NS5A RASs by Sanger sequencing. SVR12 was defined as HCV-RNA undetectability 12 weeks after treatment discontinuation., Results: Compatibly with a real-life context, 74.0% (97 of 131) of patients presented ≥2 pretreatment risk factors for failure to achieve SVR12 (infection by GT-1a/GT-3a; cirrhosis; previous treatment experience; HCV-RNA ≥800 000 IU/mL) and 33.6% had ≥3 risk factors. Natural RASs were frequently detected (32.1% prevalence), with substantial prevalence of NS5A RASs (15.3%), mostly represented by Y93H in GT-1b (3 of 36, 8.3%) and GT-3a (3 of 25, 12.0%) and F28C in GT-2c (2 of 11, 18.2%). Overall, personalized treatment led to 100% SVR12, even in those patients for whom treatment strategy was either strengthened (by ribavirin inclusion and/or duration increase) or simplified (by ribavirin exclusion and/or duration reduction), thanks to baseline RAS evaluation., Conclusions: Even with newer DAA regimens, an integrated interpretation of clinical and virological pretreatment parameters, including natural RASs, may play a relevant role in bringing SVR rates close to the highest achievable. Treatment tailoring can be foreseen in 'hard-to-treat' patients, but also in 'easy' patients with favourable indicators, whereby a simplification/shortening of recommended regimens can be indicated., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background & Aims: The proportion of HCV-infected patients over age 65 years in Western countries is increasing. This growth and the advent of new antiviral therapy bring into the question the real-world efficacy and safety of the combination of sofosbuvir (SOF) and simeprevir (SMV) plus a flat dose of 800 mg/d ribavirin (RBV) in elderly patients with cirrhosis compared to younger patients., Methods: Retrospective observational multicentre real-life investigation study of SOF/SMV/RBV for a duration of 12 weeks in HCV genotype 1-infected patients with cirrhosis., Results: Of the 270 patients enrolled in this study, with compensated cirrhosis, 133 (49.2%) were ≥65 years of age. Sustained virological response at 12 weeks (SVR12) was achieved by 94.2% (129/137) of those aged <65 years and 97.7% (130/133) of those ≥65 years. Diabetes was the most common comorbidity in patients ≥65 years compared to younger patients (26.3% vs 12.4% P<.003). The most common adverse event (AE) in elderly patients was a grade 2 anaemia (35.3% vs 19.9% P<.004)., Conclusions: Sofosbuvir/simeprevir plus a daily flat dose of RBV 800 mg for 12 weeks was highly effective and safe in genotype 1 elderly patients with compensated cirrhosis., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures., Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N=200) and whenever possible at baseline (N=70)., Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P<.001). Interestingly, 57.1% of DAA IFN-free non-responders had a misclassified genotype, and 3/4 sofosbuvir breakthroughs showed the major-RAS-S282T, while RAS-L159F was frequently found in sofosbuvir relapsers (18.2%). Notably, 9.0% of patients showed also extra target RASs, and 47.4% of patients treated with ≥2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure., Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We describe the cases of two patients with clinical and radiological findings of the reflex sympathetic dystrophy syndrome (RSDS) in whom the history of a previous genito-urinary inflammation and high levels of ESR lead us to suspect a hidden reactive arthritis. However, instrumental examinations showed a characteristic picture of RSDS without evident signs of arthritis. In both patients we decided a treatment with quinolones because of detection of an ureaplasma urealyticum genito-urinary infection. This brought to complete remission of the joint symptoms in a few days. Our findings suggest that ureaplasma urealyticum can cause and sustain a RSDS picture, maybe with a reactive arthritis-like mechanism, and that an antibiogram-driven antimicrobial treatment can be rapidly effective against this disorder.

Purpose: To evaluate a new method, used for the first time in Italy, of administering the Medical Licensing Examination (MLE)., Method: Eighty medical school graduates taking the MLE were studied. The MLE was based on the Multimedia Integrated Pilot Project (MIPP), a single two-step examination that combines computer-based case simulations (step 1) and clinical encounters using standardized patients (step 2). Step 1 assessed mainly clinical knowledge and decision-making skills. Step 2 measured the ability to obtain a focused history, perform a relevant physical examination, prioritize a differential diagnosis and management plan, and provide patient education or counseling. The correlations between the total MIPP scores and the exam scores students obtained during the six-year medical school curriculum were evaluated., Results: The step 1, step 2, and total MIPP scores were moderately correlated with the curriculum scores. A moderate correlation also existed between the scores reported in step 1 and those of step 2., Conclusions: The MIPP is a good tool for assessing clinical competence. Internationally, computer-based and standardized patient assessments are being used more often in licensing examinations. Continuous use of this method could improve medical graduates' performances.

Asthma is one of the most common chronic diseases in children and adults. Recent studies have shown that in asthmatic patients treated with inhaled corticosteroids there is a better disease’s control when adding a second drug, than increasing the corticosteroid’s dose. The aim of this study has been to evaluate the effectiveness and tolerance of zafirlukast, a leukotriene receptor antagonist, versus budesonide in clinically steady patients with mild persistent bronchial asthma. We have enrolled 36 subjects non smokers, with mild persistent bronchial asthma and 12 healthy subjects as control group. At the beginning of this study and at the end of the treatment (8 weeks), all patients underwent complete clinical work-up, pulmonary function testing (FEV1, PEF and FVC) and methacholine challenge test. The patients were divided into 3 groups: group A) 20 mg of zafirlukast twice a day; group B) 400 mg of budesonide twice a day; group C) 20 mg of zafirlukast twice a day and 400 mg of budesonide twice a day. Basal FEV1 and PEF presented no significant statistical differences between control subjects and patients of group A, B and C. After eight weeks there were no significant changes for FEV1 and PEF among the three groups. After therapy a strong significant increase of PD20 was documented in group A (p&#x003C;0.005), group B (p&#x003C;0.001) and group C (p&#x003C;0.005), respect to baseline values. The antileukotriene drugs could be taken as an alternative drug, or in association with low-dose inhaled corticosteroids, in patients with mild persistent asthma, both for their clinical effectiveness and their easy ingestion, which is confirmed in compliance studies on inhaled steroids.

The Medical Licensing Examination (MLE) is governed, in Italy, by a law enacted in 1956. An ideal clinical competence assessment tool should effectively, reliably and objectively measure all the components of clinical competence: basic knowledge and clinical skills as history-taking, performing a physical examination, formulating the most likely diagnosis, establishing a management plan, communication and interpersonal relations. Since 1998 first session of the MLE, Chieti University implemented computer-based case simulations and standardized patients in the Multimedia Integrated Pilot Project (MIPP) administration. At the present time, we have examined 370 subjects during five sessions of MLE. This preliminary work shows results regarding the examinees in the first examination session of 1998 and 1999. The two groups of examinees are relatively homogeneous for number, age, gender, length of curriculum and country of University degree. In both groups the curriculum scores (preclinical, clinical and total) and the MIPP final score are reported for all subjects, first ten and last ten examinees. The MIPP final score is moderately correlated with the preclinical, clinical and total curriculum scores. Recently, the Federation of State Medical Boards and the National Board of Medical Examiners, sponsoring organisations of the United States Medical Licensing Examination (USMLE), have been planning the implementation of computer-based testing for the USMLE. It is important to point out that our MIPP-based MLE is not a mere didactic experiment, but a legal certifying examination valid for licensure.

Background and Aim: The teaching of Clinical Nutrition (CN) is frequently neglected in Medical Schools, though many official institutions strongly recommend its incorporation in their curricula. This work aimed to assess CN knowledge among final-year medical students and final-year dietology diploma students., Methods and Results: We compared the performances of final-year Medical School students who did and who did not take the CN course and final-year dietology students in a computer-based multiple choice question examination related to core CN competencies that primary-care physicians and dieticians should know and be able to put into practice. The medical students who did not take the CN course correctly answered significantly fewer questions compared with those who did and the dietology students (both p < 0.001). There was also a difference in the percentages of who passed the test: students who did not take the course: those 18%; those who did: 77%; dietology students: 76% (p < 0.001)., Conclusions: There are numerous barriers to the incorporation of nutrition in Medical School curricula. The medical school students may have achieved poorer results because dietology students followed nutrition education programs later in their curriculum. Our Medical School has therefore included CN education as part of its internal medicine course since 1998.

The goal of sulphonylurea (S) treatment in Non-Insulin-Dependent Diabetes Mellitus (NIDDM - type 2 diabetes) subjects should be to obtain a satisfactory glycemic control (fasting glycemic levels &#x003C; 140 mg&#x0025;). The loss of an adequate blood glucose control after an initial variable period of S is known as secondary failure (SF). The number of SF are extremely variable among different trials for many reasons, some of which are patient-related: increased food intake, weight gain, non-compliance, poor physical activity, stress, diseases and&#x00F7;or impaired pancreatic beta cell function, desensitization after S chronic therapy, reduced absorption, concomitant therapies. Many therapeutic strategies have been proposed to achieve an adequate metabolic control in type 2 diabetes patients: switch to intensive insulin therapy and subsequent return to S therapy; association with insulin; association with sulphonylureas plus biguanides. The association biguanides and S, in particular glibenclamide plus metformin, is now widely used by diabetologists in SF since glibenclamide improves insulin secretion while metformin exerts its antidiabetic.

Objective: To study significant factors associated with the risk of hypertension among obese women, with and without a history of weight cycling (WC)., Design: Case-control study., Setting: Obesity Clinic of Chieti University, Italy., Subjects: A group of 258 obese women aged 25-64 y (103 cases with hypertension and 155 controls) were recruited. All obese subjects had the same clinical characteristics, were without a family history for hypertension, were non-smokers, had normal lipidemic profiles and normal glucose tolerance, were not taking any medication and were otherwise healthy., Intervention: In the weight cycling women, the history of WC was established on the basis of at least five weight losses in the previous 5 y due to dieting, with a weight loss of at least 4.5 kg per cycle. A logistic regression model adjusted for confounding variables such as waist-to-hip ratio (WHR) and weight cycling history parameters was used and the odds ratio (OR) with 95% confidence intervals was calculated., Results: The risk of hypertension increases in subjects with larger WHR (OR 7.8; 95% CI 3.4-17.9) and with a positive history for WC (OR 4.1; 95% CI 2.4-6.9). Further, in obese patients with WC, the weight cycling index and the sum of the weight regained are also important risk factors for hypertension., Conclusions: These findings could support the hypothesis that it is the combined exposure of central-type obesity and WC that strongly raises the risk of hypertension., Sponsorship: This work has been financially supported by a grant of Ministero dell'Università e della Ricerca Scientifica e Tecnologica.

Background: To determine whether an excessive, prolonged and, above all, unusual physical exertion could be associated with episodes of mild hypoglycaemia in non-insulin-dependent diabetes mellitus (NIDDM) patients treated with glibenclamide., Experimental Design: 11 months of observation with retrospective analysis of patient personal diaries to determine the hypoglycaemic risk., Setting: Diabetic Unit-Department of Medicine and Aging-Chieti University School of Medicine., Patients: We enrolled 340 NIDDM outpatients adjusted for sex, age, body mass index, alcohol intake and oral treatment regimen with glibenclamide. PATIENTS were tested monthly for circadian blood glucose profiles and glycosylated hemoglobin. Mild hypoglycaemia was defined on the basis of blood glucose values < 2.8 mmol/l associated with mild autonomic symptoms, without requiring external assistance. Each diabetic patient filled personal diary indicating the therapy regimen and the characteristics of eventual hypoglycaemic episodes occurring during the observation period., Results: 21.8% of NIDDM patients experienced one or two episodes of mild hypoglycaemia during the observation period. The analysis of the patients' diaries showed that 60% of the hypoglycaemic episodes was associated with excessive, prolonged and unexpected physical exertions. Within this group, about 70% of the episodes occurred during a holiday ("holiday hypoglycaemia"). After analyzing the socio-demographic and clinical characteristics of the diabetic patients reporting hypoglycaemic events, we found a higher risk for "holiday hypoglycaemia" in patients with a lower educational level, with a sedentary occupation or among the ex-farmers., Conclusions: As resulted in the present study, unexpected physical exertions may represent a relevant cause of mild hypoglycaemia in diabetic patients receiving oral antidiabetic therapy. However, this hypoglycaemic cause may have been underestimated in the literature. Educational programs conducted by general practitioners or diabetologists could be useful for the patients in reducing the number of mild hypoglycaemic episodes.

The aim of this study was to determine how different scoring methods could influence the results achieved in clinical competence assessment examinations at the end of the medical school curriculum. Fifty-six final-year medical school students were examined using a programme of multimedia computer-based simulated cases (Procuste programme). For generating results, the following scoring methods were applied: (1) the method used for the Internal Medicine official certification examination which includes both weighted and unweighted items; (2) a method with only unweighted items;(3) a method which includes single-item analysis. Each time an absolute pass/fail cut-off standard ( &#83 60/100) and a relative pass/fail cut-off (mean minus 1 standard deviation) were applied.Taking as a reference the first method, the effect of using different scoring methods on the percentage of student failure was evaluated. Furthermore, correlation studies between the results obtained with these scoring methods and the grades reported by the examinees during the medical school curriculum were performed. It was found that the first method generated a more realistic pass/fail rate compared with the two other methods. Furthermore this method, which has been used for the last 10 years for administering internal medicine examinations, showed better correlation coefficients with the curriculum scores.

Recent studies have documented a relationship between increased morbidity and mortality from cardiovascular diseases and a history of weight cycling (WC) in obese subjects. We performed a cross-sectional analysis in 96 weight-cycling android obese women, matched with 96 non-weight-cycling android obese women by age, body mass index (BMI) and waist-to-hip ratio (WHR), to evaluate any increase in blood pressure (BP) levels in association with WC. The patients were all between 20 and 45 years old, were non-menopausal, did not smoke, did not take any medication, had normal glucose tolerance and were otherwise healthy. A history of WC was established on the basis of at least five weight losses in the previous 5 years due to dieting, with a weight loss of at least 4.5 kg per cycle. We documented higher levels of casual BP in the weight-cycling obese compared with the non-weight-cycling subjects: 147+/-12/90+/-8 mmHg versus 125+/-14/79+/-8 mmHg (P<0.001). The women with WC showed a statistically significant positive correlation between BP and age, weight, BMI, waist circumference, WHR, total weight regained and weight cycling index (WCI). However, in a multiple regression model only the WHR and WCI contributed significantly to the BP variability. These findings could support the hypothesis that it is the combined exposure of central-type obesity and WC that strongly raises the prediction of hypertension.

An international collaborative project for the evaluation of clinical competence at the end of the Medical School curriculum using the ECFMG-CSA (Educational Commission for Foreign Medical Graduates--Clinical Skills Assessment) prototype was started in Italy in April 1996. Faculty representatives from Italian Medical Schools and experts from the ECFMG in Philadelphia participated in the Project. The CSA consists of integrated clinical encounters with 10 standardized patients during which the examinee is asked to obtain a focused history, perform a relevant physical examination and communicate initial diagnoses and management plan to the Standardized Patient (SP). The SP then completes checklists that are scored by Faculty members. The project was concluded in Spring 1998 and a total of 173 new graduates were examined. The data elaborated by the primary site in Chieti University will be available in the Fall 1998 by the ECFMG in Philadelphia. This preliminary communication reports the opinions of the examinees on the ECFMG-CSA, contained in the questionnaires administered after the test. Most of the examinees considered this new methodology as a valid tool for the assessment of clinical competence, especially history-taking and interpersonal skills and stated that the SP simulations were realistic. The 72% of examinees indicated that the Medical School curriculum does not adequately prepare for the CSA examination. Lastly, 68% was in favour of including the SP in the Medical Licensing Examination.

Objective: An association between body fat distribution indices and the amount of visceral adipose tissue (AT) with blood pressure (BP) has been documented. However, most studies used casual morning BP values as the dependent variable. The aim of our study was to identify which of the obesity indices (the body mass index (BMI), waist-to-hip ratio (WHR), sagittal diameter or visceral (AT) measured by ultrasonography (US)) better correlated with BP determined by 24 h ambulatory monitoring., Design: Retrospective study on obese women, outpatients at the Obesity Clinic, Internal Medicine Institute, Chieti University, Italy., Subjects and Measurements: In fifty-one obese outpatient women, BP was determined with a single morning measurement (casual BP) and with 24 h ambulatory monitoring (ABPM). The obesity parameters were the BMI, WHR, sagittal diameter and the amount of intra-abdominal and subcutaneous fat determined by US., Results: Except for the BMI, all obesity indices as WHR, sagittal diameter and visceral AT measured by US were strongly correlated with both casual and 24 h ambulatory BP values. When such parameters were evaluated in a multivariate analysis, only the WHR remained significantly related to 24 h ABPM parameters and not to casual values., Conclusions: These results suggest that a simple measure of fat distribution as the WHR could represent a good predictor of hypertension in obesity, providing that BP is measured in a more reproducible manner, such as by 24 h ambulatory BP monitoring.

Unlabelled: Treatment of mild hypertension with an antihypertensive drug administered by means of a transdermal therapeutic system (TTS) could produce favorable results, when compared with a traditional oral regimen., Purpose: Using 24-h ambulatory blood pressure (BP) monitoring (ABPM) in mild hypertensive male subjects, to analyze three aspects which have not been completely clarified: a) whether a latency in the antihypertensive effect may be present, recording BP already from the first day of application of the patch, b) the eventual hazardous enhancement of circadian nocturnal fall in BP values in treated mild hypertensive patients and, c) the possible overlapping of antihypertensive effect between the administration of two consecutive patches., Subjects and Methods: In 12 caucasian male outpatients (yrs 55 +/- 3 SEM) with uncomplicated essential mild hypertension, a patch containing placebo was applied for the first week (T 0 period). At the end of the T 0 period, a 5 mg TTS-2 clonidine patch was applied for one week, and, subsequently, a new patch of 5 mg TTS-2 clonidine was kept for another week. ABPM was performed on the last day of the placebo period (T 0) and on the 1st day (T1), the 7th day (T2) and the 14th day (T3) of transdermal clonidine therapy., Results: Both systolic and diastolic BP (24 h mean, day-night-time) decreased on the 1st, 7th and 14th day, when compared with T0. However, no significant differences were documented between the BP levels on the 1st and the 7th day of treatment. The incidence of nocturnal fall in systolic and diastolic BP was evaluated and no significant differences were found, when compared with night-time reference values., Conclusions: When compared with the placebo period, TTS-2 clonidine lowers SBP and DBP within the first 24 hours of application. The antihypertensive effect persists at the end of the first week, as well as after 14 days. The lowest values of systolic-diastolic BP documented were not below the levels reported in normotensive men. Therefore, TTS-2 clonidine seems to act as an antihypertensive agent rather than a hypotensive drug since it normalizes BP without lowering it below physiological levels.

Until now the different epidemiological studies performed have yielded widely different results in terms of the prevalence of hypertension in obese patients. This is mainly due to methodological errors in blood pressure (BP) measurements, including such false positives as white-coat or cuff hypertension, and more recently, to the different distribution in the study population of obese subjects at risk of hypertension (android obesity type). In 803 obese outpatient women (body mass index range: 28-45) randomly selected and subdivided into younger and older groups, and into android and gynaecoid, the casual BP was measured in the morning with a large size cuff. In addition, in 82 obese outpatients casual BP was measured simultaneously with the large and a standard size cuff. Another group of 94 patients was submitted to 24-h ambulatory blood pressure monitoring (ABPM). The aim was to observed if the use of inappropriate cuffs, or the incidence of white-coat hypertension and the prevalence of obese subjects at risk of hypertension, may contribute considerably to overestimating the prevalence of hypertension in obesity. The hypertension prevalence rate was 37.6% for the entire study group. The prevalence rate was 26.2% in women with gynaecoid type of obesity and 47.1% in android obese subjects. We could conclude that the use of inappropriate cuffs, office or white-coat hypertension and the prevalence of obese subjects at risk of hypertension, may contribute considerably to overestimating the prevalence of hypertension in obesity. The number of hypertensive subjects in younger obese subjects with gynaecoid fat distribution is similar to non-obese subjects who are age-adjusted, but our data confirm that the prevalence of hypertension in android type of obesity is significantly higher than in non-obese subjects.

Percutaneous transluminal coronary angioplasty (PTCA) is an established technique in the management of patients with angina pectoris or acute myocardial infarction. One of the major problems related to PTCA is myocardial ischemia following balloon catheter occlusion of the coronary artery. A new device utilized in an attempt to counteract myocardial ischemia is the perfusion balloon catheter which allows passive transmission of pulsatile blood flow to the distal myocardial bed. Our purpose was to compare immediate results following traditional PTCA and autoperfusion balloon PTCA in two groups randomly assigned to receive one of the two treatments (total patients n. = 158). The results show that coronary angioplasty was successfully performed in 98.87% of patients treated with autoperfusion PTCA and in 97.10% of those treated with conventional PTCA. In the autoperfusion PTCA group we observed a lower incidence (statistically significant) of ST elevation and of minor complications. We conclude that autoperfusion balloon catheter angioplasty may be recommended for its immediate success rate with good patient tolerance and lower incidence of in-hospital complications.

It is well known that extracorporeal circulation (ECC) may determine an impaired renal function. The aim of our study was to identify those patients who, on the basis of the presence of cardiovascular risk factors such as diabetes mellitus, hypertension and hyperlipidemia, show more evident signs of such dysfunction. The study was conducted on 333 male patients, aged > 49 years, with normal renal function, who underwent coronary artery by-pass surgery in extracorporeal circulation. The results show that, among the cardiovascular risk factors, hypertension has a major influence on renal function after performing extracorporeal circulation, particularly on glomerular filtration rate and, when associated to diabetes mellitus, renal dysfunction may persist until the 9th post-operative day.

Temporal endocrine structure (TES). It can be defined as a combination of predictable hormonal changes that are time-related. Regarding their frequency, endocrine rhythms may be circadian, ultradian and infradian. In this context, the endocrine circadian time structure (ECTS), that is closely dependent of some areas of the hypothalamus, is of particular interest. Long and short loop feedback link together the various components: central nervous system (CNS), hypothalamus and anterior pituitary with target glands and tissues. The hypothalamic neuropeptides (releasing hormones or factors - RH or RF - or inhibiting hormones or factors IH or IF) presently known are: thyrotropin releasing hormone (TRH); luteinizing releasing hormone (LH RH); prolactin releasing factor (PRF); Prolactin Inhibiting Factor (PIF); Corticotropin Releasing Factor (CRF); Growth Releasing hormone (GH RH). Some general remarks on endocrine rhythms should be noted: the circadian changes in hormones may depend on each other; even an apparently subordinate rhythm should be considered a true independent rhythm; accurate studies have shown that hormonal secretion occurs in all cases according to a rhythmic organization at many levels; these rhythms may not be evident at a first analysis. The hormone secretion is basically pulsating which makes it difficult to draw standard reference values. Although an ECTS is present at the cell level, in organs etc., it is evident that a rhythm hierarchy exists. Hormonal secretion and sleep-wake cycle. Although several reports state that no rhythm is totally dependent on the sleep-wake cycle, from a general point of view the hormone secretion rhythms can be divided in: sleep-dependent rhythms and sleep-independent rhythms. Meal-timing and hormonal secretion. In animals, meal-timing is a powerful synchronizer; however, there are no definitive and conclusive data to prove that meal-timing is a true synchronizer also in humans, although there have been some reports suggesting it. Endocrine rhythms. Data regarding the endocrine rhythms (circadian-ultradian-infradian) of the numerous hormones as GH; prolactin; aspects of temporal pattern of CRF-ACTH-corticosteroid and of hypothalamic - pituitary - thyroids axis; hypothalamic - pituitary - ovaric steroid and testosterone axis are reported. The study of a possible rhythmic pattern of insulin has been approached from many points of view as the basal rhythmicity of insulin; the diurnal variation of efficacy of injected insulin and of insulin responsiveness to insulinogenic stimuli.