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Early prediction of COVID-19 in-hospital mortality relies usually on patients’ preexisting comorbidities and is rarely reproducible in independent cohorts. We wanted to compare the role of routinely measured biomarkers of immunity, inflammation, and cellular damage with preexisting comorbidities in eight different machine-learning models to predict mortality, and evaluate their performance in an independent population. We recruited and followed-up consecutive adult patients with SARS-Cov-2 infection in two different Italian hospitals. We predicted 60-day mortality in one cohort (development dataset, n = 299 patients, of which 80% was allocated to the development dataset and 20% to the training set) and retested the models in the second cohort (external validation dataset, n = 402).Demographic, clinical, and laboratory features at admission, treatments and disease outcomes were significantly different between the two cohorts. Notably, significant differences were observed for %lymphocytes (p

Primary lymphoma of bone (PLB) is a rare entity, defined as a lymphoma confined to the bone without evidence of systemic involvement. The disease commonly affects middle-aged to elderly population and it accounts for less than 1% of all malignant lymphomas. We present a case of a 10-year-old child affected by PLB of the forearm and the frontal bone. Characteristic imaging features of PLB and the main differential diagnosis were discussed. Keywords: Bone, Lymphoma, Paediatric

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, characterized by motor and non-motor symptoms due to the degeneration of the pars compacta of the substantia nigra (SNc) with dopaminergic denervation of the striatum. Although the diagnosis of PD is principally based on a clinical assessment, great efforts have been expended over the past two decades to evaluate reliable biomarkers for PD. Among these biomarkers, magnetic resonance imaging (MRI)-based biomarkers may play a key role. Conventional MRI sequences are considered by many in the field to have low sensitivity, while advanced pulse sequences and ultra-high-field MRI techniques have brought many advantages, particularly regarding the study of brainstem and subcortical structures. Nowadays, nigrosome imaging, neuromelanine-sensitive sequences, iron-sensitive sequences, and advanced diffusion weighted imaging techniques afford new insights to the non-invasive study of the SNc. The use of these imaging methods, alone or in combination, may also help to discriminate PD patients from control patients, in addition to discriminating atypical parkinsonian syndromes (PS). A total of 92 articles were identified from an extensive review of the literature on PubMed in order to ascertain the-state-of-the-art of MRI techniques, as applied to the study of SNc in PD patients, as well as their potential future applications as imaging biomarkers of disease. Whilst none of these MRI-imaging biomarkers could be successfully validated for routine clinical practice, in achieving high levels of accuracy and reproducibility in the diagnosis of PD, a multimodal MRI-PD protocol may assist neuroradiologists and clinicians in the early and differential diagnosis of a wide spectrum of neurodegenerative disorders.

BACKGROUND: Access to Directly Acting Antivirals (DAAs) for Hepatitis C Virus (HCV) treatment in Italy was initially restricted to severe patients. In 2017, AIFA expanded access to all patients, to achieve elimination by 2030. AIM: To investigate the impact of different hospitals’ organizational models on elimination timing, treatment capacity and direct costs. METHODS: Most Regional healthcare systems in Italy deploy a Center of Excellence (CoE) organizational model, where patients are referred to a single major hospital in the area, which is the only one that can prescribe and deliver DAAs. The study was conducted at Bergamo’s (Lombardy, Italy) Papa Giovanni XXIII hospital (PG-23), which deploys a Hub&Spoke model: the Hub (PG-23) prescribes and delivers DAAs while Spokes (four smaller hospitals) can only prescribe them. The study compares the two models (CoE vs. H&S). Patient journey and workloads were mapped and quantified through interviews with hospital stakeholders. Cost data were collected through the hospital’s IT system; the sample comprised 2,277 HCV patients, over one year. RESULTS: The study calculated the average cost to treat HCV patients (~ € 1,470 per patient). Key cost drivers are lab tests (60%) and specialist visits (30%). Over one year, H&S can treat 68% more patients than CoE. As deferred patients absorb up to 40% of total costs, the “Optimized” model was designed by streamlining specialists’ visits and involving general practitioners during follow-up. “Optimized” model increases treatment capacity and reduces costs of deferred patients by 72% vs CoE. CONCLUSION: The study demonstrates the importance of organizational models in efficiently achieving 2030 elimination.

We studied the stool samples of 151 school children in a district of the city of Portoviejo (Ecuador) in order to determine the prevalence and intensity of soil-transmitted helminthiasis (STH) and their relationships with anthropometric indices. The samples were analyzed with the semiquantitative Kato-Katz technique and the intensity of infections was categorized as light, moderate or high according to the thresholds set by the World Health Organization. Prevalence of soil transmitted helmintiasis was 65% (92 out of 141 collected samples), Ascaris lumbricoides was the most common STH (63%) followed by Trichuris trichiura (10%) and hookworm (1.4%). Heavy intensity infections were found in 8.5% of the stool samples, with T. trichiura showing higher worm burdens than A. lumbricoides. Sixteen percent of the children were below the third percentile for weight (wasted), while 27% were below the third percentile for height (stunted). A significant relationship was found between the worm burden and the degree of stunting. This study suggests that the periodic administration of an antihelminthic drug should be targeted to preschool and school children to allow a normal growth spurt and prevent stunting.

Abstract Background A consensus on the most reliable staging system for hepatocellular carcinoma (HCC) is still lacking but the most used is a revised Barcelona Clinic Liver Cancer (BCLC) system, adopted by the American Association for the Study of Liver Diseases (AASLD). We investigated how many patients are diagnosed in "very early" and "early" stage, follow the AASLD guidelines for treatment and whether their survival depends on treatment. Methods Data were collected in 530 "very early" and "early" HCC patients recruited by a multicentric Italian collaborative group (ITA.LI.CA). The Kaplan-Meier method was used to estimate overall survival and the log rank to test the statistical significance of difference between groups. Cox's multivariate stepwise regression analysis was used to pinpoint independent prognostic factors and the adjusted relative risks (hazard ratios) were calculated as well. A statistical analysis based on the chi-square test was used to identify significant differences in clinical or pathological features between patients. A P-value < 0.05 was considered statistically significant. Results "Very early" HCC were 3%; Cox multivariate analysis did not identify variables independently associated with survival. The patients following AASLD recommendations (20%) did not show longer survival. In "early" HCC patients (25%), treatment significantly modulated survival (p = 0.0001); the 28% patients treated according to the AASLD criteria survived longer (p = 0,004). The Cox analysis however identified only age, gender, number of lesions and Child class as independent predictors of survival. Conclusion patients with very early" HCC were very few in this analysis. In most instances they were not treated with the treatment suggested as the most appropriate by the AASLD guidelines and the type of treatment had no impact on survival, even though the number of patients was relatively low and part of the patients were diagnosed before the introduction of the guidelines: this analysis, therefore, might not be considered as conclusive and should be validated. The "early" stage group involved more patients, rarely treated according to the guidelines, both overall and also in those diagnosed after their publication; the survival was in part predicted by the type of treatment, with better results in those treated according to AASLD indications.

Sarcoidosis is a granulomatous disease that can potentially involve all body tissues, including the liver in about 10-20% of cases (1-4). High quality data on the management of hepatic sarcoidosis (HS) are scarce. In absence of national and international guidelines, management of HS is still experienced-based. This survey was carried out amongst Italian hepatologists to describe their practices in the management of patients with HS. 1985 questionnaires were forwarded, of which 37 were completed and returned. Thirty-three centers reported managing patients with HS, 17 (51%) of these reported managing more than one patient. Twenty-seven (81%) centers obtained the diagnosis by liver biopsy, the remaining centers by radiological techniques or biopsy in other sites. In coexistence with HS, the pulmonary sarcoidosis was reported from 18 (54%) centers, while patients with no other localization, except for the hepatic one, were followed up in 6 (18%) centers. Twenty-two (66%) centers treated such patients with first-line steroid therapy, the remainders reported using other drugs. Finally, 3 (9%) centers reported the presence of transplant patients, other 3 (9%) centers of deceased patients. HS is a rare entity in Italy and there is a wide variation in diagnostics and therapeutics. A multicentric, prospective, national cohort study is needed to study this disease. [ABSTRACT FROM AUTHOR]

Abstract: Background: In the Western world, hepatocellular carcinoma seldom develops in patients without cirrhosis, and reports describing the characteristics of non-cirrhotic patients with hepatocellular carcinoma are rather infrequent. Methods: We evaluated the main clinical characteristics, treatment options, and survival of patients with hepatocellular carcinoma developed in non-cirrhotic liver among the 3027 consecutive cases of hepatocellular carcinoma accrued in the Italian Liver Cancer database during the last 20 years. Results: We identified 52 patients with hepatocellular carcinoma in non-cirrhotic livers (1.7% of all hepatocellular carcinomas), 42 with (80.8%) and 10 without (19.2%) chronic liver disease. In patients without chronic liver disease, median tumour diameter was greater compared to patients with chronic liver disease (7.8 versus 4.0cm, P =0.046). Curative treatment was feasible in 20 patients (38.5%). Median overall survival was 26 months and 5-year survival rate was 23.7%. Detection of hepatocellular carcinoma outside surveillance (P =0.036), advanced hepatocellular carcinoma stage (P <0.0001), and non-curative treatment (P =0.007) were associated with worse prognosis, but tumour stage was the only independent predictor of survival. Conclusions: In Italy, less than 2% of hepatocellular carcinomas develop in a non-cirrhotic liver, and almost never in a normal liver. These patients frequently present with advanced tumours, have low eligibility rates for curative treatment, and have a dismal prognosis despite their preserved liver function. [Copyright &y& Elsevier]

Abstract: Background: The aetiological factors of hepatocellular carcinoma may vary over time. Aims: The study assessed the potential impact of the aetiological factors on the effectiveness of surveillance in real-world patients. Methods: Multicentre, cross-sectional study enrolling consecutive hepatocellular carcinoma cases during a six month period. Results: 1733 cases (1311 prevalent and 422 incident) were recruited (mean age 68.6 years; 46.1% cases over 70 years; 73.9% males; 95.3% with cirrhosis); 63.0% were hepatitis C virus positive and 23.7% were virus negative. Amongst incident HCCs, 34.5% were single ≤3cm and 54.4% met the Milan criteria; 61.6% were diagnosed during surveillance; virus negative patients showed the lowest rate of surveillance (51.0%). Surveillance was an independent predictor of detecting single HCCs ≤2cm (O.R.=5.4; 95% C.I.=2.4–12.4) or HCCs meeting the Milan criteria (O.R.=3.1; 95% C.I.=1.9–5.2). Compared with an earlier Italian survey, there was a higher proportion of elderly subjects (P <0.01), Child-Pugh class A cases (P <0.01), of virus-negative patients (P <0.01) and with single tumours ≤3cm (P <0.01) and a lower prevalence of hepatitis C virus positive individuals (P <0.01). Conclusion: HCC is characterised by a growing prevalence of elderly patients and cases unrelated to hepatitis virus infections. The application of surveillance must be implemented, particularly amongst non-viral patients. [Copyright &y& Elsevier]

Abstract: Background: Several studies in healthy populations have investigated normal liver stiffness on transient elastography, but none has excluded subjects with fatty liver. Aims: To define normal liver stiffness and its determinants in 923 healthy voluntary blood donors with and without fatty liver. Methods: Seven hundred and forty six subjects were analyzed with transient elastography according to the absence (602) or presence of fatty liver (144) at ultrasonography. The cut-off for significant fibrosis was a liver stiffness of 7.9kPa. Results: Normal subjects had significantly lower liver stiffness (median 4.4kPa) than fatty liver subjects (median 5.3, p <0.001). In normal livers male gender was significantly associated with increased liver stiffness at multiple linear regression analysis. Nine (1.4%) blood donors with normal liver and 9 with fatty liver (6.2%) had >7.9kPa. Subjects with verified liver stiffness >7.9kPa, were further investigated with liver biopsy or non-invasive fibrosis markers: only 1 patient with fatty liver had >F1 fibrosis. Conclusions: Liver stiffness in normal liver is lower than in fatty liver, and gender is the only influencing variable. Transient elastography has a very low false positive rate for significant fibrosis and may have a role in screening populations at risk for liver disease. [Copyright &y& Elsevier]

Background & Aims: It has been suggested that clinically relevant portal hypertension may affect the therapeutic management and prognosis of cirrhotic patients with hepatocellular carcinoma (HCC). Nevertheless, the importance of the presence of esophageal varices in these patients has not yet been addressed formally. In this study our aim was to evaluate the prevalence and prognostic relevance of the presence of esophageal varices in a large series of patients with HCC. Methods: The prevalence of esophageal varices was evaluated in 1153 HCC patients who were consecutively referred to 10 Italian centers (the Italian Liver Cancer group). Survival was calculated from the time of HCC diagnosis until death or until the most recent follow-up visit, and was evaluated according to the presence or absence of esophageal varices. The independent prognostic meaning of the presence of esophageal varices was evaluated further in a multivariate regression analysis. Results: Esophageal varices were found in 730 patients (63.3%). Patients with varices showed significantly shorter survival times (P < .0001) as compared with patients without varices. Death as a result of bleeding was more common in patients with varices (P = .0127). In multivariate analysis, the presence of esophageal varices was associated independently with poorer survival (adjusted relative risk, 1.25; 95% confidence interval, 1.06–1.48; P = .0095). Conclusions: More than half of the patients with HCC have esophageal varices. The presence of esophageal varices is associated with a higher risk of death from bleeding, and is an independent determinant of the patient’s prognosis. This variable should be taken into account in the diagnostic and therapeutic work-up of HCC patients. [Copyright &y& Elsevier]

Background & Aims Transient elastography (TE) is a noninvasive technique used to measure liver stiffness to estimate the severity of fibrosis. The range of liver stiffness measurements (LSMs) in healthy individuals is unclear. We performed a systematic review to determine the range of LSMs, examined by TE, in healthy individuals and individuals who are susceptible to fibrosis. Methods We collected data from 16,082 individuals, in 26 cohorts, identified from systematic searches of Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for studies of liver stiffness measurements. Studies analyzed included apparently healthy adults (normal levels of liver enzymes, low-risk alcohol use patterns, and negative for markers of viral hepatitis). The presence of diabetes, hypertension, dyslipidemia, or steatosis, based on ultrasound examination, was known for most participants. We performed a meta-analysis of data from individual participants. The cohort was divided into 4 groups; participants with a body mass index <30 kg/m2 were examined with the medium probe and those with a body mass index ≥30 kg/m2 were examined with the extra-large probe. Linear regression models were conducted after adjusting for potential confounding factors of LSMs. We performed several sensitivity analyses. Results We established LSM ranges for healthy individuals measured with both probes—these did not change significantly in sensitivity analyses of individuals with platelets ≥150,000/mm3 and levels of alanine aminotransferase ≤33 IU/L in men or ≤25 IU/L in women. In multivariate analysis, factors that modified LSMs with statistical significance included diabetes, dyslipidemia, waist circumference, level of aspartate aminotransferase, and systolic blood pressure at examination time. Significant increases in LSMs were associated with the metabolic syndrome in individuals examined by either probe. Diabetes in obese individuals increased the risk of LSMs in the range associated with advanced fibrosis. Conclusions In a systematic review and meta-analysis of data from individual participants, we established a comprehensive set of LSM ranges, measured by TE in large cohorts of healthy individuals and persons susceptible to hepatic fibrosis. Regression analyses identified factors associated with increased LSMs obtained by TE with the medium and extra-large probes. [ABSTRACT FROM AUTHOR]

Background & Aims Ultrasound surveillance does not detect early stage hepatocellular carcinomas (HCCs) in some patients with cirrhosis, although the reasons for this have not been well studied. We assessed the rate at which ultrasound fails to detect early stage HCCs and factors that affect its performance. Methods We collected information on 1170 consecutive patients included in the Italian Liver Cancer (ITA.LI.CA) database who had Child–Pugh A or B cirrhosis and were diagnosed with HCC during semiannual or annual ultrasound surveillance, from January 1987 through December 2008. Etiologies included hepatitis C virus infection (59.3%), alcohol abuse (11.3%), hepatitis B virus infection (9%), a combination of factors (15.6%), and other factors (4.7%). Surveillance was considered to be a failure when patients were diagnosed with HCC at a stage beyond the Milan criteria (1 nodule ≤5 cm or ≤3 nodules each ≤3 cm). Results HCC was found beyond Milan criteria in 34.3% of surveilled patients (32.2% during semi-annual surveillance and 41.3% during annual surveillance; P < .01). Nearly half of surveillance failures were associated with at least one indicator of aggressive HCC (levels of AFP >1000 ng/mL, infiltrating tumors, or vascular invasion and metastases). Semiannual surveillance, female sex, Child–Pugh class A, and α-fetoprotein levels of 200 ng/mL or less were associated independently with successful ultrasound screening for HCC. Conclusions Based on our analysis of surveillance for HCC in patients with cirrhosis, the efficacy of ultrasound-based screening is acceptable. Ultrasound was least effective in identifying aggressive HCC, and at surveillance intervals of more than 6 months. [ABSTRACT FROM AUTHOR]

Abstract: We describe the case of a 77-year-old woman with chronic hepatitis C and well compensated cirrhosis in whom a single encapsulated 5.5cm hepatocellular carcinoma was found in the right liver lobe. The patient was symptomatic with left upper quadrant pain and had elevated alfa-fetoprotein levels (3133ng/ml). While she was waiting for liver resection and 2 months after the initial diagnosis the pain improved and alfa-fetoprotein levels normalized. A computerized tomography scan showed reduction in size of the lesion to 2.5cm, with no central arterial enhancement, but with the demonstration of a peripheral rim enhancing in all dynamic phases. Follow up computerized tomography and magnetic resonance imaging examinations showed further reduction in size of the lesion to 1.3cm with persistence of the enhancing rim 20 months after the initial diagnosis. The spontaneous and durable regression of the HCC and the persistent peripheral enhancing rim could be explained by a strong and persistent activation of the immune system directed against the neoplastic cells. [Copyright &y& Elsevier]