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Background: A few studies have suggested that the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) was present in Northern Italy several weeks before its official detection on February 21, 2020. On the other hand, no clinical data have been provided so far to support such hypothesis. We investigated clinical-epidemiological evidence of SARS-CoV-2 infection among children and adults referring to emergency department (ED) in the main hospital of the center of Milan (Italy) before February 21, 2020. Methods: A retrospective analysis of medical records of ED visits at the Fondazione Ca′ Granda Policlinico, Milan between January 11 and February 15 in 2017, 2018, 2019 and in 2020 was performed. The number of subjects referring with fever, cough or dyspnea was compared between the studied period of 2020 and the previous 3 years, by calculating a standardized referral ratio (SRR, number of observed cases in 2020 divided by the number of expected cases according to 2017–2019) and the corresponding 95% confidence interval (CI). Results: In the pediatric ED, 7709 (average 2570/year) and 2736 patients were visited during the period 2017–2019 and in the 2020, respectively. Among adults, 13,465 (average 4488/year) and 4787 were visited during the period 2017–2019 and in the 2020, respectively. The SRR was 1.16 (95% CI 1.10–1.23) in children and 1.25 (95% CI 1.16–1.35) in adults. The ratio for the two (children and adults) SRRs was 0.93 (0.84–1.02), suggesting a trend towards a higher frequency in adults compared to children. Conclusions: This study suggests that SARS-CoV-2 might have spread in Milan before February 21, 2020 with a minor trend among children. [ABSTRACT FROM AUTHOR]

Appropriateness is one of the critical aspects of medicine. For this reason, the Italian Society of Internal Medicine (SIMI) decided to adhere to the Choosing Wisely Campaign. A bottom-up approach was chosen. All the recommendations published in the US and Canadian Choosing Wisely campaign have been screened, and an e-mail was sent to all the SIMI members for new suggestions. The thirty interventions that were judged as the highest priority by a committee were sent to all the SIMI members for voting. The first procedures selected were then revised, and constituted the five points of the SIMI choosing wisely campaign. The identified procedures were: (1) avoid prescribing bed rest unless an acceptable indication exists. Promote early mobilization; (2) Do not perform a D-dimer test without a precise indication; (3) Do not prescribe long term intravenous antibiotic therapy in the absence of symptoms; (4) Do not indefinitely prescribe proton pump inhibitors in the absence of specific indications; (5) Do not place, or leave in place, peripherally inserted central catheters for patient's or provider's convenience. Four of these points were not present in any other campaign, while one, the fifth, was already present. The bottom-up approach of the SIMI "Choosing Wisely" campaign favored the identification of different priorities compared to other campaigns. Future studies should now evaluate if the application of these "not-to-do" recommendations will be associated with an improvement of clinical outcome and a subsequent direct and indirect health care cost reduction. [ABSTRACT FROM AUTHOR]

The increasing global trend of obesity is a fundamental contributor to the growing prevalence of metabolic syndrome, a cluster of medical abnormalities including impaired glucose and lipid metabolism, obesity and hypertension. Results from animal and human investigations have shown that early life stress can result in weight gain and metabolic changes. Our aim is to investigate whether a particular type of an early adverse event, i.e. parental loss during childhood, is associated with the development of metabolic syndrome in severely obese subjects. One hundred thirty-five consecutive obese patients who were seeking bariatric surgery were assessed for metabolic syndrome according to the Adult Treatment Panel (ATP) III criteria. Information regarding the experience of parental separation or bereavement before the age of 17 was collected with the use of a semi-structured interview. In our population, 31.1% of the subjects met the criteria for metabolic syndrome. No significant differences in demographic factors, health habits or psychiatric diagnosis were found between patients with and without coexisting metabolic syndrome. After adjusting for age and gender, multivariate logistic regression analysis revealed that both childhood loss of a parent and a body mass index (BMI) value greater than 50 were significant predictors of metabolic syndrome. This study provides preliminary evidence linking childhood parental loss to risk factors for the development of metabolic syndrome. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Breastfeeding has effects on health throughout the lives of mothers and babies. In 2014 in Italy, 10,976 babies were born through ART (assisted reproductive technology), accounting for 2.2% of annual births. The study aims to assess how both social and biological variables and the mode of conception influence breastfeeding. Methods: This observational study involves 161 pregnancies from three different modes of conception: homologous in vitro fertilization, ovum donation, and spontaneous pregnancies. Neonatal and maternal characteristics were collected from the hospital database, while breastfeeding outcomes were obtained through telephone interviews. Results: The mode of conception did not influence any of the breastfeeding outcomes. Breastfeeding duration was negatively affected by smoking. Vaginal delivery, birth weight > 2500 g, delivery > 37 gestational weeks, breastfeeding intention, and rooming-in are positively associated with the initiation of breastfeeding, while skin-to-skin contact and receiving information concerning breastfeeding are the most significant variables associated with its exclusivity and duration. Conclusions: The duration and exclusivity of breastfeeding are mainly related with information thereon, promotion, and breastfeeding support, but not with the mode of conception. It is essential to adequately support women from the outset in breastfeeding, as recommended by the World Health Organization (WHO) guidelines. [ABSTRACT FROM AUTHOR]

• During Covid-19 epidemics Emergency Department (ED) presentations decreased. • This reduction was similar in different areas irrespective of Covid-19 prevalence. • Population mortality increased only in high Covid-19 prevalence zones. • This suggests that the reduction in ED presentations does not influence mortality. • Our results question the appropriateness of ED access. : In the spring of 2020, Italy experienced a significant reduction in the number of emergency department (ED) presentations during the first wave of the COVID-19 pandemic. If ED access has an impact on patients' prognosis, such a reduction in ED presentations would be expected to correlate with a parallel increase in the mortality rate of the corresponding population. The aim of the present study was to evaluate the impact of reduced ED presentations on the all-cause mortality of the general population. Absolute and relative variation in ED accesses from March 1 to April 30 of both 2019 and 2020 in three hub hospitals in areas with different COVID-19 prevalence and age-standardized mortality data from January 1 to June 30 in 2019 and 2020 of the same areas were evaluated. : During March and April 2020, ED consults were decreased of approximately 50% in all three hospitals, as compared with the same months in 2019. There was a marked increase in cumulative mortality in Milan (high SARS-CoV2 infection spread zone) compared with the same period in 2019. In the other two municipalities (Ferrara and Perugia), which had intermediate and low levels of infection spread, the mortality in 2020 was not substantially changed from that of 2019. : Taking into account the increase in mortality due to SARS-CoV-2, reductions in ED access did not seem to affect death rates. If this finding will be confirmed, ED organization and access would need to be reconsidered. [ABSTRACT FROM AUTHOR]

• Less is More and Choosing Wisely (CW) campaigns have raised awareness about inappropriate diagnostic procedures and therapeutic approaches among both physicians and patients. • Little is currently known about the effects of Choosing Wisely recommendation-driven educational programs on clinical practice. • The CW-SIMI study evaluated the impact of a simple educational program, based on the Italian Society of Internal Medicine (SIMI) Choosing Wisely recommendations, on clinical practice in internal medicine units. • The proposed online educational intervention effectively reduced the proton pump inhibitor (PPI) prescription rate and the mean duration of central venous catheter (CVC) usage. To evaluate the impact of an educational intervention based on the Italian Society of Internal Medicine Choosing Wisely (CW-SIMI) recommendations. Multicenter, interventional, controlled study. Twenty-three acute-care hospital wards in Italy. 303 Physicians working in internal medicine wards. An online educational course. The rate of proton pump inhibitor (PPI) prescriptions, the number of days of central venous catheter (CVC) usage, and the duration of intravenous (IV) antibiotic prescriptions evaluated at one month (T1) and at six months (T2) after course completion. Patients admitted and discharged during a 30-day period before the educational intervention (T0, one year before T2) were considered the comparison group. A total of 232 physicians completed the course, while 71 did not attend the course. Data from 608, 662, and 555 patients were analyzed at T0, T1, and T2, respectively. The rate of PPI prescriptions declined at one month (RR: 0.67, 95% CI: 0.52–0.87, p = 0.0005) and at six months (RR: 0.62, 95% CI: 0.46–0.84, p = 0.003), and the number of days of CVC usage was reduced at six months (9.13 days at T0 vs. 5.52 days at T2, p = 0.007). The duration of IV antibiotic prescriptions displayed a decreasing trend (7.94 days at T0 vs. 7.42 days at T2, p = 0.081). A simple online educational intervention based on the CW-SIMI recommendations was associated with a clinically relevant reduction in the usage of PPIs and CVCs. Further studies are needed to confirm these findings and a possible benefit on patients' outcomes. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long-term treatment outcomes is currently available to inform clinical decisions., Objectives: To describe the long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD., Methods: A multicentre, retrospective, dynamic cohort study was conducted to assess long-term effectiveness and safety of dupilumab in patients with moderate-to-severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria [defined as the simultaneous achievement of a 90% reduction in Eczema Area and Severity Index score, itch-numeric rating scale (NRS) score ≤ 1, sleep-NRS score ≤ 1 and Dermatology Life Quality Index ≤ 1] were investigated., Results: In total, 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506/2309 (21.9%), 769/1959 (39.3%), 628/1247 (50.4%), 330/596 (55.4%) and 58/106 (54.7%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AEs) were mild and were observed in 373/2364 (15.8%), 166/2066 (8.0%), 83/1291 (6.4%), 27/601 (4.5%) and 5/110 (4.5%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AEs led to treatment discontinuation in < 1% of patients during the evaluated time periods., Conclusions: The high long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate-to-severe AD, regardless of clinical phenotype and course (persisting or relapsing) at baseline. Further research will be needed to investigate the effect of T helper cell 2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Family history of Parkinson's disease (PD) is a common finding in PD patients. However, a few studies have systematically examined this aspect., Objectives: We investigated the family history of PD patients, comparing demographic and clinical features between familial PD (fPD) and sporadic PD (sPD)., Methods: A cross-sectional study enrolling 2035 PD patients was conducted in 28 Italian centers. Clinical data and family history up to the third degree of kinship were collected., Results: Family history of PD was determined in 21.9% of patients. fPD patients had earlier age at onset than sporadic patients. No relevant differences in the prevalence of motor and nonmotor symptoms were detected. Family history of mood disorders resulted more prevalently in the fPD group., Conclusions: fPD was found to recur more frequently than previously reported. Family history collection beyond the core family is essential to discover disease clusters and identify novel risk factors for PD., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Chemsex is a heterogeneous phenomenon with differences in distribution, setting, motivations and type of substances consumed between countries. The lack of data at national level of the Italian situation creates a perception of reduced need for intervention., Methods: Anonymous paper questionnaires were distributed to patients who had registered themselves at the STI Department IRCCS Ca' Granda Policlinico in Milan., Results: A significant association was demonstrated between use of sexualised drugs, chemsex and the following variables: (1). Number of partners: in the group of clients with more than five partners, sexualised drug users were more than twice compared with those in the group with less than five partners (35.2% vs 16.2%) p <0.0001. (2). Use of dating apps: more than one out of two persons who used drugs during sex affirmed looking for partners on internet, p = 0.0059. (3). Low condom uses with occasional partners: percentage of individuals who declared not to use condoms or devices during their sexual encounters with occasional partners is more than twice as high in the sexualised drug users group with respect to controls (44.6% vs 21.4%); p = 0.0006). (4). Use of post exposure prophylaxis (PEP): among the PEP users, more than half participants belonged to the sexualised drug users' group; p = 0.0021., Conclusions: Sexualised drug use and chemsex are frequently practiced in Milan. This survey identified a specific population with higher-risk sexual behaviours and increased incidence of acute bacterial STIs., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: COVID-19 is associated with a wide range of skin manifestations., Objective: To describe the clinical characteristics of COVID-19-associated skin manifestations and explore the relationships among the 6 main cutaneous phenotypes and systemic findings., Methods: Twenty-one Italian Dermatology Units were asked to collect the demographic, clinical, and histopathologic data of 200 patients with COVID-19-associated skin manifestations. The severity of COVID-19 was classified as asymptomatic, mild, moderate, or severe., Results: A chilblain-like acral pattern was significantly associated with a younger age (P < .0001) and, after adjusting for age, significantly associated with less severe COVID-19 (P = .0009). However, the median duration of chilblain-like lesions was significantly longer than that of the other cutaneous manifestations taken together (P < .0001). Patients with moderate/severe COVID-19 were more represented than those with asymptomatic/mild COVID-19 among the patients with cutaneous manifestations other than chilblain-like lesions, but only the confluent erythematous/maculo-papular/morbilliform phenotype was significantly associated with more severe COVID-19 (P = .015), and this significance disappeared after adjustment for age., Limitations: Laboratory confirmation of COVID-19 was not possible in all cases., Conclusions: After adjustment for age, there was no clear-cut spectrum of COVID-19 severity in patients with COVID-19-related skin manifestations, although chilblain-like acral lesions were more frequent in younger patients with asymptomatic/pauci-symptomatic COVID-19., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, controversial data were reported concerning angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) that induced a number of physicians to stop using them in patients with COVID-19. Although large-scale studies have ruled out this concern, it is common experience that patients with COVID-19 taking ACE inhibitors or ARBs are at increased risk of death. The aim of this study was to investigate the reasons for this apparently high mortality rate., Methods: During the first wave of the pandemic, we conducted a field study of 427 consecutive patients with COVID-19 upon their admission to the emergency department of a hospital in one of the most severely hit cities in northern Italy, and 30 days later. The disease was defined as being mild, moderate or severe on the basis of clinical, laboratory and imaging data, and a multivariate model was used to analyse the determinants of mortality., Results: Within 30 days of admission, 31.6% of the patients treated with ACE inhibitors or ARBs and 15.2% of those not treated with these drugs had died. Multivariate analysis showed that the determinants of mortality were age (p = 0.0001), hypertension (p = 0.0120) and diabetes (p = 0.0129), whereas ACE inhibitors or ARBs had no effect on mortality. There was no significant difference between the patients treated with ACE inhibitors and those treated with ARBs., Conclusion: The apparently increased mortality of patients with COVID-19 receiving long-term treatment with ACE inhibitors or ARBs is not due to the drugs themselves, but to the conditions associated with their use.

Background: During the COVID-19 pandemic, the number of individuals needing hospital admission has sometimes exceeded the availability of hospital beds. Since hospitalization can have detrimental effects on older individuals, preference has been given to younger patients. The aim of this study was to assess the utility of hospitalization for elderly affected by COVID-19. We hypothesized that their mortality decreases when there is greater access to hospitals., Methods: This study examined 1902 COVID-19 patients consecutively admitted to three large hospitals in Milan, Italy. Overall mortality data for Milan from the same period was retrieved. Based on emergency department (ED) data, both peak and off-peak phases were identified. The percentage of elderly patients admitted to EDs during these two phases were compared by calculating the standardized mortality ratio (SMR) of the individuals younger than, versus older than, 80 years., Results: The median age of the patients hospitalized during the peak phase was lower than the median age during the off-peak phase (64 vs. 75 years, respectively; p <0.001). However, while the SMR for the younger patients was lower during the off-peak phase (1.98, 95% CI: 1.72-2.29 versus 1.40, 95% CI: 1.25-1.58, respectively), the SMR was similar between both phases for the elderly patients (2.28, 95% CI: 2.07-2.52 versus 2.48, 95% CI: 2.32-2.65, respectively)., Conclusions: Greater access to hospitals during an off-peak phase did not affect the mortality rate of COVID-19-positive elderly patients in Milan. This finding, if confirmed in other settings, should influence future decisions regarding resource management of health care organizations., Competing Interests: The authors have declared that no competing interests exist.

Background: To date no studies evaluated liver stiffness and pancreatic stiffness by shear-wave elastography, in alcoholic liver disease setting., Aims: To assess feasibility and reproducibility of Shear-wave elastrography in measuring liver and pancreatic stiffness in alcoholic liver disease and investigate the correlation among liver and pancreatic stiffness and clinical data., Methods: Liver and pancreatic stiffness were measured by elastography (2 examiners) in patients with alcoholic liver disease and in healthy volunteers, for reference values. Effect of clinical data was evaluated on log-transformed pancreatic or liver stiffness, using univariate and multivariate linear regression model., Results: 87 patients and 46 healthy volunteers enrolled. Both the stiffness values were higher in patients than healthy volunteers (p < 0.001). For liver stiffness: no failure measurements found, the Intraclass correlation coefficient (between 2 examiners) was 0.72 and the variables significantly correlated at multivariate analysis were cirrhosis (p < 0.0001) and steatosis (p = .007). For pancreatic stiffness: 2 failures found, with ICC 0.40 and the only variable significantly correlated at multivariate analysis was liver cirrhosis (p = .005)., Conclusions: Shear-wave elastography feasibility was good for liver and pancreatic stiffness. Reproducibility was good for liver stiffness, whereas fair for pancreatic one. Both the stiffness correlated with alcoholic liver disease severity. Elastography could be a useful tool to detect and monitor alcohol-related liver and pancreatic damage., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Hepatocellular carcinoma (HCC) is a frequent complication of liver disease. When feasible, hepatic resection is the first-choice therapy. However, tumor recurrence complicates at least 2/3 hepatic resections at 5 years. Early recurrences are mainly tumor or treatment-related, but predictors of late recurrences are undefined. We aimed to evaluate the factors related to HCC recurrence after curative resection, with liver and spleen stiffness measurement (LSM and SSM) as markers of severity and duration of the underlying liver disease., Methods: We enrolled patients with chronic liver disease and primary HCC suitable for hepatic resection. We followed up patients for at least 30 months or until HCC recurrence. We performed uni- and multivariate analyses to evaluate the predictive role of tumor characteristics, laboratory data, LSM and SSM for both early and late recurrence of HCC., Results: We prospectively enrolled 175 patients. Early HCC recurrence at multivariate analysis was associated with viral etiology, HCC grading (3 or 4), resection margins <1 cm and being beyond the Milan criteria. HCC late recurrence at univariate analysis was associated with esophageal varices (hazard ratio [HR] 3.321, 95% CI 1.564-7.053), spleen length (HR 3.123, 95% CI 1.377-7.081), platelet/spleen length ratio if <909 (HR 2.170, 95% CI 1.026-4.587), LSM (HR 1.036, 95% CI 1.005-1.067), SSM (HR 1.046, 95% CI 1.020-1.073). HCC late recurrence at multivariate analysis was independently associated only with SSM (HR 1.046, CI 1.020-1.073). Late HCC recurrence-free survival was significantly different according to the SSM cut-off of 70 kPa (p = 0.0002)., Conclusions: SSM seems to be the only predictor of late HCC recurrence, since it is directly correlated with the degree of liver disease and portal hypertension, both of which are involved in carcinogenesis., Lay Summary: The main result of this study is that spleen stiffness measurement, evaluated by transient elastography, seems to be the only predictor of the late recurrence of hepatocellular carcinoma, defined as recurrence after 24 months from liver resection. Indeed, spleen stiffness measurement is directly correlated with the degree of liver disease and portal hypertension, which are both involved in carcinogenesis., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: Syncope is a common condition that affects individuals of all ages and is responsible for 1-3% of all emergency department (ED) visits. Prospective studies on syncope are often limited by the exiguous number of subjects enrolled. A possible alternative approach would be to use of hospital discharge diagnoses from administrative databases to identify syncope subjects in epidemiological observational studies. We assessed the accuracy of the International Classification of Diseases, Ninth Revision (ICD-9) code 780.2 "syncope and collapse" to identify patients with syncope., Methods: Patients in two teaching hospitals in Milan, Italy with a triage assessment for ED access that was possibly related to syncope were recruited in this study. We considered the index test to be the attribution of the ICD-9 code 780.2 at ED discharge and the reference standard to be the diagnosis of syncope by the ED physician., Results: The sensitivity, specificity, positive and negative predictive values of the ICD-9 code 780.2 to identify patients with syncope were 0.63 (95% confidence interval [CI] 0.58-0.67), 0.98 (95% CI 0.98-0.99), 0.83 (95% CI 0.79-0.87) and 0.95 (95% CI 0.94-0.95), respectively., Conclusions: The moderate sensitivity of ICD-9 code 780.2 should be considered when the code is used to identify patients with syncope through administrative databases.

Importance: Sparse data and conflicting evidence exist on the prevalence of pulmonary embolism (PE) in patients with syncope., Objective: To estimate the prevalence of PE among patients presenting to the emergency department (ED) for evaluation of syncope., Design, Setting, and Participants: This retrospective, observational study analyzed longitudinal administrative data from 5 databases in 4 different countries (Canada, Denmark, Italy, and the United States). Data from all adult patients (aged ≥18 years) who presented to the ED were screened to identify those with syncope codes at discharge. Data were collected from January 1, 2000, through September 30, 2016., Main Outcomes and Measures: The prevalence of PE at ED and hospital discharge, identified using codes from the International Classification of Diseases, was considered the primary outcome. Two sensitivity analyses considering prevalence of PE at 90 days of follow-up and prevalence of venous thromboembolism were performed., Results: A total of 1 671 944 unselected adults who presented to the ED for syncope were included. The prevalence of PE, according to administrative data, ranged from 0.06% (95% CI, 0.05%-0.06%) to 0.55% (95% CI, 0.50%-0.61%) for all patients and from 0.15% (95% CI, 0.14%-0.16%) to 2.10% (95% CI, 1.84%-2.39%) for hospitalized patients. The prevalence of PE at 90 days of follow-up ranged from 0.14% (95% CI, 0.13%-0.14%) to 0.83% (95% CI, 0.80%-0.86%) for all patients and from 0.35% (95% CI, 0.34%-0.37%) to 2.63% (95% CI, 2.34%-2.95%) for hospitalized patients. Finally, the prevalence of venous thromboembolism at 90 days ranged from 0.30% (95% CI, 0.29%-0.31%) to 1.37% (95% CI, 1.33%-1.41%) for all patients and from 0.75% (95% CI, 0.73%-0.78%) to 3.86% (95% CI, 3.51%-4.24%) for hospitalized patients., Conclusions and Relevance: Pulmonary embolism was rarely identified in patients with syncope. Although PE should be considered in every patient, not all patients should undergo evaluation for PE.

Chronic infection with the hepatitis delta virus (HDV) is a risk factor for cirrhosis and hepatocellular carcinoma (HCC), but little is known whether the outcome of hepatitis is predicted by serum markers of HDV and hepatitis B virus (HBV) infection. The aim of the study was to investigate these correlations in 193 patients with chronic HDV infection who had been followed up for a median of 9.5 years (4.8-19.3). HDV-RNA was first measured by qualitative in-house nested RT-PCR and quantified by in-house real-time PCR. HDV RNA levels only appeared significantly associated to HCC (univariate analysis: OR 1.32, 95% CI 1.02-1.71; p = 0.037; multivariate analysis: OR 1.42, 95% CI 1.04-1.95; p = 0.03). In non-cirrhotics at first presentation (n = 105), HDV RNA levels were associated with progression to cirrhosis (univariate analysis: OR = 1.57, 95% CI 1.20-2.05, p<0.001; multivariate analysis: OR = 1.60, 95% CI 1.20-2.12, p = 0.007) and development of HCC (univariate analysis: OR = 1.66, 95% CI 1.04-2.65, p = 0.033; multivariate analysis: OR = 1.88, 95% CI 1.11-3.19, p = 0.019). ROC analysis showed that approximately 600,000 HDV RNA copies/mL was the optimal cut-off value in our cohort of patients for discriminating the development of cirrhosis. High levels of HDV viremia in non-cirrhotic patients are associated with a considerable likelihood of progression to cirrhosis and the development of HCC. Once cirrhosis has developed, the role of HDV replication as a predictor of a negative outcome lessens.

Background & Aims: The hepatic vein pressure gradient (HVPG) is the standard used to determine the degree of portal hypertension (PH) and an important prognostic factor for patients with cirrhosis; HVPG values correlate with the presence of esophageal varices (EV). However, HVPG can only be accurately determined at specialized centers; noninvasive methods are needed to predict HVPG values and the presence of EV. We compared the diagnostic performance of spleen stiffness (SS) measurement by transient elastography with that of liver stiffness (LS) and of other recently proposed noninvasive tests., Methods: We measured SS and LS in 100 consecutive patients with hepatitis C virus-induced cirrhosis. Patients were also assessed by FibroScan, HVPG, esophagogastroduodenoscopy, and liver biopsy. We also analyzed LS-spleen diameter to platelet ratio score and platelet count to spleen diameter., Results: SS and LS were more accurate than other noninvasive parameters in identifying patients with EV and different degrees of PH. A linear model that included SS and LS accurately predicted HVPG values (R(2) = 0.85). The results were internally validated using bootstrap analysis., Conclusions: Measurement of SS can be used for noninvasive assessment and monitoring of PH and to detect EV in patients with hepatitis C virus-induced cirrhosis., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics were effective in preventing AAD and CDAD in several randomized controlled trials. This study was aimed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients., Methods: A single-center, randomized, double-blind, placebo-controlled, parallel-group trial was performed. Patients being prescribed antibiotics or on antibiotic therapy for <48 h were eligible. Exclusion criteria were ongoing diarrhea, recent assumption of probiotics, lack of informed consent, inability to ingest capsules, and severe pancreatitis. Patients received a capsule containing S. boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy, continued treatment for 7 days after antibiotic withdrawal, and were followed for 12 weeks after ending antibiotic treatment., Results: Of 562 consecutive eligible patients, 275 patients aged 79.2 ± 9.8 years (134 on placebo) were randomized and 204 aged 78.4 ± 10.0 years (98 on placebo) completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S. boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There was no difference in mortality rates (12.7% vs. 15.6%, P=0.60)., Conclusions: In elderly hospitalized patients, S. boulardii was not effective in preventing the development of AAD.

The objective of the study is to assess the prevalence of target organ damage (TOD) at carotid, cardiac, renal and peripheral vascular levels in a population at intermediate cardiovascular risk, with adjunctive major risk factors (AMRF). From March 2007 to July 2009 we examined 979 subjects at intermediate cardiovascular risk, as indicated by the Italian algorithm "Progetto Cuore"; the patients were aged 40-69 years, sensitized by one or more AMRF such as family history for cardiovascular disease (CVD), being overweight or obese, and smoking habit (more than 10 cigarettes/day). We measured common carotid intima-media thickness (cc-IMT) and plaque at any level, left ventricular mass index (LVMI), urine albumin/creatinine ratio (UACR), and ankle-brachial index (ABI). The prevalence of at least one TOD was 63% (617 subjects), cc-IMT was high in 48.2% (472), UACR abnormal in 14.1% (138), LVMI high in 12.6% (117) and ABI pathological in 9.1% (89). In those with carotid damage 423 had a plaque, amounting to 43.2% of the total population. Of note, carotid damage was present in all subjects with 3 TODs, and in 92% of subjects with 2 TODs. A multivariate logistic regression model including conventional factors and AMRF indicated that age 50-69 years, systolic blood pressure, relevant smoking and CV risk score ≥15 were independently and significantly associated with at least one TOD, and at least, with carotid damage. Among the AMRF, peripheral arterial disease was associated with relevant smoking, with an odds ratio (OR) of 3 [confidence interval (CI) 1.80-4.97, p < 0.0001]; overweight and obesity both had selective associations with cardiac damage with OR 2.75 (CI 1.2-6.3, p < 0.01) and OR 3.89 (CI 1.61-9.73, p < 0.01). A substantial proportion of people at intermediate risk, with at least one AMRF have at least one TOD, a major predictor of cardiovascular outcomes.

The mean incidence of cystic fibrosis (CF) among North Americans of European ancestry is 1 in 2,500. Studies carried out in different geographic areas report incidence values ranging from 1 in 1,800 to 1 in 8,500, suggesting that incidence has to be assessed specifically for any population. This paper represents the first attempt to evaluate the incidence of CF in Italy and its time-related changes following the discovery of the gene in 1989. Data recorded in the Italian National CF Registry for CF subjects born between 1988 and 2001 were evaluated. All CF patients (1,742) were diagnosed by 1 of 18 specialized CF centers and 7 support services (1-3 in each region) according to the consensus statement on CF diagnosis. The average CF incidence in Italy was found to be 1 in 4,238, which is lower than the values reported elsewhere. The incidence remained nearly constant from 1988 to 2001, although the percentage of subjects screened for CF increased by 44%. Molecular analysis (available for more than 80% of the patients) indicated that the most common mutation (DF508) in Italy occurs in only 49% of CF chromosomes; the other mutations differ from region to region. These differences appeared to be mildly related to differences in reason for diagnosis and type of mutation. Italian registry data supply an incidence of CF lower than that reported for populations of European descent. Part of this difference is probably due to the higher allelic heterogeneity of the CFTR gene in Italy with respect to Northern Europe or the U.S. population of European descent.