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Introduction: Caring for the dying can generate anxiety and emotional distress, particularly in nursing students, and perceived competence could play a crucial role in enabling nurses to perform their duties with greater confidence. Unfortunately, few studies describe the relationship between students' nursing attitudes and perceived self-efficacy in palliative care (PC). To overcome this gap, this survey aimed to assess the attitudes towards dying patients and the perceived competence of nursing students in palliative care at different universities in the south of Italy. Methods: A cross-sectional study was conducted from September 2022 to March 2023 involving nursing students from the three major Sicilian universities (Italy). The study included a survey investigating socio-demographic characteristics, palliative care training, knowledge about pain management, and previous experience with dying. Moreover, the Professional Competence of the Core Curriculum in Palliative Care Nursing (CCPCN) questionnaire and the Frommelt Attitudes Toward Care of the Dying-B Italian version (FATCOD-B-I) assessed competencies and emotional attitudes. Results: A total of 1913 nursing students were recruited, of which 71.3% were females, and 53.9% were in the age range of 18 to 21 years. In the multivariable analysis, practical PC training was a substantial factor in enhancing competencies (Adj-OR 2.78 [95% CI = 2.12-3.65]). Male students had higher competence odds (Adj-OR 1.38 [95% CI = 1.14-1.66]), and perceived knowledge strongly correlated with self-assessed competence. Advancement in academic years also positively influenced competence self-assessment (Adj-OR 1.98 [95% CI = 1.75-2.24]). Regarding emotional attitudes, a per-quartile increase in competence score was found to improve the attitude score (Adj-OR 1.24 [95% CI = 1.13-1.35]). Conclusions: Nursing students gain valuable experience during clinical experience. PC training and perceived knowledge of PC significantly increase nurses' competencies, and the latter seem to be strongly associated with attitudes. Thus, introducing palliative care education into nurses' core curricula could be a way to reduce anxiety and emotional distress in young students.

Some data suggest the existence of intestinal inflammation in patients with non-celiac wheat sensitivity (NCWS). We aimed to verify whether fecal calprotectin (FCP), a marker of intestinal inflammation, could be used to confirm this inflammatory status and to test its diagnostic performance in differentiating NCWS from irritable bowel syndrome/functional dyspepsia (IBS/FD). We conducted a multicenter study, comparing NCWS patients, diagnosed by a double-blind placebo-controlled wheat challenge, with IBS/FD subjects. In the retrospective phase, FCP values were analyzed to define the prevalence of its positivity and its role as a NCWS diagnostic biomarker. In the prospective phase we tested the effects of a strict 6-month wheat-free diet (WFD) on FCP values. 31.3% (n = 63/201) of NCWS patients had above normal FCP values (NCWS FCP +), whereas all IBS/FD patients proved negative (P = 0.0001). FCP using a cut-off value > 41 µg/g showed a 58.6% sensitivity and a 98.0% specificity (AUC 0.755, 95% C.I. 0.702-0.837) in distinguishing NCWS from IBS/FD patients. Of the 63 NCWS FCP+, 65.1% had negative FCP values after ≥ 6 months of WFD, with a significant reduction in FCP values (P < 0.0001). All NCWS FCP- subjects still preserved negative FCP values after ≥ 6 months of WFD. Our study showed that FCP can be a useful but supplementary diagnostic marker for differentiating between NCWS and IBS/FD. Strict WFD adherence reduced FCP values, normalizing them in 65.1% of NCWS FCP + subjects. These data suggest the existence of two NCWS subgroups: NCWS FCP + characterized by a probable predominantly inflammatory/immunologic pattern and NCWS FCP- featuring non-immuno-mediated etiopathogenetic mechanisms. (Registration number NCT01762579)., (© 2024. The Author(s).)

Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in genetically predisposed individuals who adopt a sedentary lifestyle and consume an obesogenic diet progress through mitochondrial and endoplasmic reticulum dysfunction, which amplifies reactive oxygen species (ROS) production, lipid peroxidation, malondialdehyde (MDA) formation, and influence the release of chronic inflammation and liver damage biomarkers, such as pro-inflammatory cytokines. This close pathogenetic link has been a key stimulus in the search for therapeutic approaches targeting oxidative stress to treat steatosis, and a number of clinical trials have been conducted to date on subjects with NAFLD using drugs as well as supplements or nutraceutical products. Vitamin E, Vitamin D, and Silybin are the most studied substances, but several non-pharmacological approaches have also been explored, especially lifestyle and diet modifications. Among the dietary approaches, the Mediterranean Diet (MD) seems to be the most reliable for affecting liver steatosis, probably with the added value of the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations of phenols (oleocanthal) and phenolic alcohols, such as hydroxytyrosol (HT) and tyrosol (Tyr). In this review, we focus on non-pharmacological interventions in MAFLD treatment that target oxidative stress and, in particular, on the role of EVOO as one of the main antioxidant components of the MD.

Purpose: Ultrasound (US) surveillance is a cornerstone for early diagnosis of HCC, anyway US presentation has undergone significant changes. With the aim of evaluating the effects of US surveillance program in the real-world clinical practice, we wanted to evaluate US presentation of HCCs over the last 30 years and the differences of HCCs presentation according to etiology., Methods: 174 patients diagnosed between 1993 and 98 (G1), 96 between 2003 and 08 (G2), 102 between 2013 and 18 (G3), were compared. US patterns were: single, multiple or diffuse nodules. The echo-patterns: iso-, hypo-, hyper-echoic, or mixed. In G1, the HCC diagnosis was mainly histologic; in G2 by EASL 2001 and AASLD 2005, in G3 AASLD 2011, EASL 2012, and AISF 2013 guidelines., Results: HCV was the most frequent etiology, dropping between G1 (81%) and G3 (66%) (P < 0.01), metabolic increased between G1 (5%) and G3 (14%) (P < 0.01). Single HCC was more prevalent in G3 vs G1 (65.6% vs 40%) (P < 0.0001), multiple nodules in G1 (50%) vs G3 (33.3%) (P < 0.02) and diffuse in G1 (16%) vs G2 (2%) and vs G3 (1%) (P < 0.001). The most frequent echo-pattern was hypo-echoic G1 (50%) vs G2 (79%) and G1 vs G3 (65%) (P < 0.01). Iso-echoic pattern was the least frequent (7-12%). Mixed pattern decreased from G1 (28%) to G3 (12%) (P < 0.002). In G3 there were more multiple or diffuse HCCs in metabolic (P < 0.03)., Conclusion: US presentation became less severe due to surveillance programs. HCV remains the most frequent cause, an increase in metabolic etiology has been shown throughout the decades., (© 2024. The Author(s).)

The identification of biomarkers for predicting inter-individual sorafenib response variability could allow hepatocellular carcinoma (HCC) patient stratification. SNPs in angiogenesis- and drug absorption, distribution, metabolism, and excretion (ADME)-related genes were evaluated to identify new potential predictive biomarkers of sorafenib response in HCC patients. Five known SNPs in angiogenesis-related genes, including VEGF-A , VEGF-C , HIF-1a , ANGPT2 , and NOS3 , were investigated in 34 HCC patients (9 sorafenib responders and 25 non-responders). A subgroup of 23 patients was genotyped for SNPs in ADME genes. A machine learning classifier method was used to discover classification rules for our dataset. We found that only the VEGF-A (rs2010963) C allele and CC genotype were significantly associated with sorafenib response. ADME-related gene analysis identified 10 polymorphic variants in ADH1A (rs6811453), ADH6 (rs10008281), SULT1A2/CCDC101 (rs11401), CYP26A1 (rs7905939), DPYD (rs2297595 and rs1801265), FMO2 (rs2020863), and SLC22A14 (rs149738, rs171248, and rs183574) significantly associated with sorafenib response. We have identified a genetic signature of predictive response that could permit non-responder/responder patient stratification. Angiogenesis- and ADME-related genes correlation was confirmed by cumulative genetic risk score and network and pathway enrichment analysis. Our findings provide a proof of concept that needs further validation in follow-up studies for HCC patient stratification for sorafenib prescription.

Metabolic syndrome (MetS) is associated with cardiovascular risk factors, such as insulin resistance, dyslipidaemia, hypertension and abdominal obesity. Given the growing need to investigate food supplements with positive health effects, this study was aimed at testing the benefits of a specific supplement for people with MetS. Fifty-eight subjects with MetS and T2DM or impaired glucose tolerance assuming metformin, were randomly assigned to take a food supplement of glucomannan, D-chiro-inositol, Cinnamomum zeylanicum blume and inulin at a daily fixed dose of 4 g orally for four months. Body weight, waist circumference, plasma lipid profile (total cholesterol, LDL, HDL and triglyc-erides), plasma glycaemic profile and visceral adiposity index (VAI) were measured at baseline and after four months of supplementation. After 16 weeks, in subjects with T2DM or insulin resistance who took the supplement (+ metformin), there was a significant reduction in body weight and BMI ( p < 0.0001), serum insulin ( p < 0.05) and the HOMA index ( p < 0.01), as well as in the lipaemic pattern, with a significant improvement in total serum cholesterol ( p < 0.005), triglycerides ( p < 0.03) and LDL ( p < 0.02). Our study shows that the food supplement tested is a valid and safe alternative therapeutic approach in the management of MetS and all its resulting risk factors, as its efficacy has been demonstrated across anthropometric, glucose, lipid and hepatic parameters.

Background: Patients suffering from non-celiac wheat sensitivity (NCWS) frequently report extra-intestinal symptoms, such as anemia., Aims: We investigated the prevalence and associated clinical features of anemia in NCWS patients., Methods: Data from 244 NCWS patients, diagnosed by double-blind placebo-controlled wheat challenge, were retrospectively reviewed and compared with 2 control groups (celiac disease (CD) and irritable bowel syndrome (IBS)). Furthermore, 31 NCWS anemic patients were prospectively re-evaluated after at least 12 months on the "strict" wheat-free diet (WFD)., Results: Anemia prevalence in NCWS patients was 34.8% (mean hemoglobin 10.4 ± 1.4 g/dl), significantly higher than in IBS (17.4%, P = 0.03), but not in CD ones. The NCWS group, on the whole, had sideropenic-like features with low serum iron and altered iron deposits. Both anemia prevalence and sideropenic-like features were more evident in CD than in NCWS patients, whereas only a few IBS subjects showed such features. Significant differences were found in anemic vs non-anemic NCWS patients as regards to female sex, diagnostic delay, poly/hypermenorrhea, iron deficiency, and higher TSH values. A long-term WFD significantly reduced anemia and improved iron metabolism., Conclusion: Microcytic/hypochromic anemia and altered iron metabolism occur frequently in NCWS and can be treated with a long-term strict WFD. NCWS should be included in differential diagnosis of anemic patients with "functional gastrointestinal troubles"., Competing Interests: Conflict of interest Guarantor of the article: Antonio Carroccio, MD. The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: There is a scarcity of information in literature regarding the clinical differences and comorbidities of patients affected by Coronavirus disease 2019 (COVID-19), which could clarify the different prevalence of the outcomes (composite and only death) between several Italian regions., Objective: This study aimed to assess the heterogeneity of clinical features of patients with COVID-19 upon hospital admission and disease outcomes in the northern, central, and southern Italian regions., Methods: An observational cohort multicenter retrospective study including 1210 patients who were admitted for COVID-19 in Infectious diseases, Pulmonology, Endocrinology, Geriatrics and Internal Medicine Units in Italian cities stratified between north (263 patients); center (320 patients); and south (627 patients), during the first and second pandemic waves of SARS-CoV-2 (from February 1, 2020 to January 31, 2021). The data, obtained from clinical charts and collected in a single database, comprehended demographic characteristics, comorbidities, hospital and home pharmacological therapies, oxygen therapy, laboratory values, discharge, death and Intensive care Unit (ICU) transfer. Death or ICU transfer were defined as composite outcomes., Results: Male patients were more frequent in the northern Italian region than in the central and southern regions. Diabetes mellitus, arterial hypertension, chronic pulmonary and chronic kidney diseases were the comorbidities more frequent in the southern region; cancer, heart failure, stroke and atrial fibrillation were more frequent in the central region. The prevalence of the composite outcome was recorded more frequently in the southern region. Multivariable analysis showed a direct association between the combined event and age, ischemic cardiac disease, and chronic kidney disease, in addition to the geographical area., Conclusions: Statistically significant heterogeneity was observed in patients with COVID-19 characteristics at admission and outcomes from northern to southern Italy. The higher frequency of ICU transfer and death in the southern region may depend on the wider hospital admission of frail patients for the availability of more beds since the burden of COVID-19 on the healthcare system was less intense in southern region. In any case, predictive analysis of clinical outcomes should consider that the geographical differences that may reflect clinical differences in patient characteristics, are also related to access to health-care facilities and care modalities. Overall, the present results caution against generalizability of prognostic scores in COVID-19 patients derived from hospital cohorts in different settings., Competing Interests: Conflict of interest Authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The hypothesis is that inflammatory/allergic conditions should be considered in self-reported milk intolerance (SRMI) patients who test negative and/or are asymptomatic at Lactose Hydrogen Breath Test (LHBT). We analyzed fecal calprotectin (FCP) values in SRMI patients to investigate the frequency of a "positive" intestinal inflammation marker and its correlation with lactose tolerance/intolerance. Data from 329 SRMI patients were retrospectively analyzed; according to the positive/negative results (maldigester/digester) and the presence/absence of symptoms reported during LHBT (intolerant/tolerant), patients were divided into: 'lactose tolerants' (n. 104), 'maldigesters/intolerants' (n. 187), 'digesters/intolerants' (n. 38). FCP values were analyzed in all three subgroups. A percentage of SRMI patients complained of constipation (>15%), extraintestinal symptoms (>30% including anemia), multiple food hypersensitivity (7.6%) and had intraepithelial lymphocytic infiltration at duodenal biopsy (>50%). Over 50.0% showed FCP values above the normal limit. Lactose tolerants and maldigesters/intolerants had higher positivity frequencies ( p < 0.0001, for both) and absolute values ( p = 0.04, for maldigesters/intolerants) of FCP compared to digesters/intolerants. FCP was not useful to differentiate tolerant from intolerant subjects (AUC 0.58). Our data suggest the existence of an allergic/inflammatory pathogenetic mechanism in a subset of SRMI subjects. FCP results are in keeping with this hypothesis, even if they cannot differentiate lactose tolerant from intolerant patients.

The immune response to infection plays a crucial role in the pathogenesis of COVID-19, but several patients develop a wide range of persistent symptoms, which is becoming a major global health and economic burden. However, reliable indicators are not yet available to predict the persistence of symptoms typical of the so-called long COVID. Our study aims to explore an eventual role of IL-6 levels as a marker of long COVID. Altogether, 184 patients admitted to the COVID Medicine Unit of the University Hospital in Palermo, Italy, from the 1st of September 2020, were analyzed. Patients were divided into two groups according to the IL-6 serum levels (normal or elevated), considering the serum IL-6 levels measured during the first four days of hospitalization. In our study, higher serum IL-6 levels were associated with a doubled higher risk of long COVID (OR = 2.05; 95% CI: 1.04-4.50) and, in particular, they were associated with a higher incidence of mobility decline (OR = 2.55; 95% CI: 1.08-9.40) and PTSD (OR = 2.38; 95% CI: 1.06-8.61). The analysis of our case series confirmed the prominent role of IL-6 levels in response to SARS-CoV-2 infection, as predictors not only of COVID-19 disease severity and unfavorable outcomes, but also long COVID development trends.

Benign liver lesions are increasingly diagnosed in daily clinical practice due to the growing use of imaging techniques for the study of the abdomen in patients who have non-specific symptoms and do not have an increased risk of hepatic malignancy. They include simple or parasitic hepatic cysts and solid benign tumors which differ widely in terms of prevalence, clinical relevance, symptoms and natural history and often lead to significant clinical problems relating to diagnosis and clinical management. Following the need to have updated guidelines on the management of benign focal liver lesions, the Scientific Societies mainly involved in their management have promoted the drafting of a new dedicated document. This document was drawn up according to the present Italian rules and methodologies necessary to produce clinical, diagnostic, and therapeutic guidelines based on evidence. Here we present the second part of the guideline, concerning the diagnosis and clinical management of hemangioma, focal nodular hyperplasia, and hepatocellular adenoma., Competing Interests: Declaration of Competing Interest The Authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Benign liver lesions are increasingly diagnosed in daily clinical practice due to the growing use of imaging techniques for the study of the abdomen in patients who have non-specific symptoms and do not have an increased risk of hepatic malignancy. They include simple or parasitic cysts and solid benign tumors which differ widely in terms of prevalence, clinical relevance, symptoms and natural history and often lead to significant clinical problems relating to diagnosis and clinical management. Following the need to have updated guidelines on the management of benign focal liver lesions, the Scientific Societies mainly involved in their management have promoted the drafting of a new dedicated document. This document was drawn up according to the present Italian rules and methodologies necessary to produce clinical, diagnostic, and therapeutic guidelines based on evidence. Here we present the first part of the guideline, concerning the characterization of focal hepatic lesions detected by ultrasound, and the diagnosis and clinical management of simple and parasitic hepatic cysts, and of polycystic liver disease., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022. Published by Elsevier Ltd.)

Background and Aims: A wheat-free diet (WFD) represents the elective treatment for Non-celiac Wheat Sensitivity (NCWS) patients. Preliminary reports have shown a possible better tolerability of ancient grains in these subjects. The aim of this observational study was to evaluate the frequency of consumption of ancient grains and its correlation with clinical manifestations in NCWS patients., Methods: 223 NCWS patients were recruited, and their consumption of ancient grains was monitored. Participants were first administered a modified version of the Pavia/Biagi questionnaire to investigate their adherence to "modern WFD." The appearance/exacerbation of symptoms after ingestion of ancient grains was then assessed with WHO toxicity grading scale., Results: 50.2% of the recruited patients reported consuming ancient grains before NCWS diagnosis; the diagnostic delay in this group was significantly higher than in non-consumers [median (range) 72 (6-612) vs. 60 months (3-684), P = 0.03] and these patients reported lower frequency of constipation ( P = 0.04). Of the 107 patients with optimal adherence to modern WFD, 14 reported eating ancient wheat after NCWS diagnosis. Among them, 5 reported milder symptoms than those caused by modern wheat intake and 3 had an excellent tolerability without symptoms. Timilia/Tumminia variety was the most frequently used ancient grain., Conclusions: NCWS patients who consume ancient grains may receive a late diagnosis due to the possible clinical benefit (tolerability) obtained with these grains. Even after diagnosis, 10% of the patients still consumed ancient grains and had mild or no symptoms. Further studies are required to define the pathophysiological mechanism behind their putative greater tolerability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Seidita, Mansueto, Giuliano, Chiavetta, Mandreucci, Soresi, Pistone, Compagnoni, Castellucci, Bisso, Faraci, Maestri, Disclafani, Sapone, Fasano and Carroccio.)

Anemia is considered to be the most frequent extra-intestinal manifestation of Celiac Disease (CD). We assessed frequency, severity, morphologic features, and pathogenic factors of anemia in patients of the Sicilian Regional Network of Celiac Disease and attempted to identify putative pre-diet factors influencing anemia persistence. We retrospectively analyzed CD patients admitted to three centers between 2016-2020. 159 patients entered the study (129 females). More than half (54.7%) had mild-moderate, hypochromic and microcytic anemia, associated with below normal total serum iron and ferritin, indicative of iron deficiency anemia (IDA). One year after diagnosis, 134 patients were following 'strict' GFD. Hypochromic and microcytic anemia persisted in 46% of subjects who were anemic at diagnosis. Patients with persistent anemia had at diagnosis a higher prevalence of female gender ( p = 0.02), lower body mass index (BMI, p = 0.01), higher prevalence of poly/hypermenorrhea ( p = 0.02) and atopy ( p = 0.04), and lower ferritin levels ( p = 0.05) than the whole group of non-anemic ones. IDA is found in more than 50% of CD patients at diagnosis; nevertheless, in a lot of women IDA is not corrected by 'strict' GFD. Low BMI and poly/hypermenorrhea at diagnosis characterize this subgroup, suggesting that IDA might be due to iron loss rather than malabsorption, or to their coexistence/overlap.

Type 2 diabetes mellitus (T2DM) is a serious public health concern as it is one of the most common chronic diseases worldwide due to social and economic developments that have led to unhealthy lifestyles, with a considerable impact both in terms of morbidity and mortality. The management of T2DM, before starting specific therapies, includes cornerstones such as healthy eating, regular exercise and weight loss. Strict adherence to the Mediterranean diet (MedDiet) has been related to an inverse association with the risk of T2DM onset, as well as an improvement in glycaemic control; in particular, thanks to the consumption of extra virgin olive oil (EVOO). Agonists of gut-derived glucagon-like peptide-1 (GLP-1), gastrointestinal hormones able to increase insulin secretion in response to hyperglycaemia (incretins), have been recently introduced in T2DM therapy, quickly entering the international guidelines. Recent studies have linked the action of EVOO in reducing postprandial glycaemia to the increase in GLP-1 and the reduction of its inactivating protease, dipeptidyl peptidase-4 (DPP-4). In this review, we explore observations regarding the pathophysiological basis of the existence of an enhanced effect between the action of EVOO and incretins and, consequently, try to understand whether there is a rationale for their use in combination for T2DM therapy.

For years it has been established that the only truly effective treatment of metabolic syndrome (MS) is lifestyle modification to prevent its cardiovascular (e.g., coronary artery disease and atherosclerosis), metabolic (e.g., diabetes mellitus), and hepatic (e.g., steatosis and non-alcoholic steatohepatitis) complications. The focal points of this approach are to increase physical activity and intake of a diet characterized by high quantities of fruits, vegetables, grains, fish, and low-fat dairy products, the so called mediterranean diet (MD); however, the added value of MD is the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations (range 50-800 mg/kg) of phenols (oleuropein, ligstroside, and oleocanthal, and their derivatives, phenolic alcohols, such as hydroxytyrosol and tyrosol). Phenolic compounds not only determine EVOO's main organoleptic qualities (oxidative stability, specific flavor, and taste features) but, theoretically, make it a source of antioxidant, anti-inflammatory, insulin-sensitizing, cardioprotective, antiatherogenic, neuroprotective, immunomodulatory, and anticancer activity. Although many studies have been carried out on EVOO's clinical effects and attention toward this dietary approach (healthy and palatable food with strong nutraceutical activity) has become increasingly pressing, there are still many dark sides to be clarified, both in terms of actual clinical efficacy and biochemical and molecular activity. Thus, we reviewed the international literature, trying to show the state of the art about EVOO's clinical properties to treat MS (along with correlated complications) and the future prospective of its nutraceutical use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Seidita, Soresi, Giannitrapani, Di Stefano, Citarrella, Mirarchi, Cusimano, Augello, Carroccio, Iovanna and Cervello.)

Background: Celiac disease (CD) is still underestimated. To close this diagnostic gap, the Health Sicilian Authorities have constituted the "Sicilian Network for CD"., Aims: A) To verify the quality of the current diagnostic approach using the data sheet of the Network. B) To evaluate the clinical, serologic and histologic data of new diagnoses in the context of the Network METHODS: We retrospectively evaluated the data collection forms of 369 patients with CD from three Centers within the Sicilian Network. All the Centers used a standard data collection form., Results: A non-classical CD presentation was more frequent than the classical one, anemia being the most frequent symptom (50%). An IBS-like presentation was found in one third of the cases. A diagnostic delay of about 9 years following the onset of symptoms was observed. Almost half of the patients had not undergone multiple duodenal biopsies; unrecommended CD serology assays were prescribed in 59.9% of the cases., Conclusions: The regional data sheets allowed an assessment of the diagnostic delay. We recorded a frequent use of unrecommended tests prescribed before referring patients to the regional Centers. Updating the education of physicians regarding CD is necessary to avoid unwarranted health expenditure., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD), the most frequent liver disease in the Western world, is a common hepatic manifestation of metabolic syndrome (MetS). A specific cure has not yet been identified, and its treatment is currently based on risk factor therapy. Given that the initial accumulation of triglycerides in the liver parenchyma, in the presence of inflammatory processes, mitochondrial dysfunction, lipotoxicity, glucotoxicity, and oxidative stress, can evolve into non-alcoholic steatohepatitis (NASH). The main goal is to identify the factors contributing to this evolution because, once established, untreated NASH can progress through fibrosis to cirrhosis and, ultimately, be complicated by hepatocellular carcinoma (HCC). Several drugs have been tested in clinical trials for use as specific therapy for NAFLD; most of them are molecules used to cure type 2 diabetes mellitus (T2DM), which is one of the main risk factors for NAFLD. Among the most studied is pioglitazone, either alone or in combination with vitamin E, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors. Actually, the most promising category seems to be sodium-glucose cotransporter (SGLT2) inhibitors. Their action is carried out by inhibiting glucose reabsorption in the proximal renal tubule, leading to its increased excretion in urine and decreased levels in plasma. Experimental studies in animal models have suggested that SGLT2 inhibitors may have beneficial modulatory effects on NAFLD/NASH, and several trials in patients have proven their beneficial effects on liver enzymes, BMI, blood lipids, blood glucose, and insulin resistance in NAFLD patients, thus creating strong expectations for their possible use in preventing the evolution of liver damage in these patients. We will review the main pathogenetic mechanisms, diagnostic modalities, and recent therapies of NAFLD, with particular attention to the use of SGLT2 inhibitors.

Management for HCV has undergone a notable change using direct-acting antiviral drugs (DAAs), which are safe and effective even in elderly. Here, we define impact of comorbidities, concomitant medication and drug-drug interactions in elder patients with HCV related disease before starting DAAs regimen. We analyzed data of 814 patients prospectively enrolled at our Unit within the web based model HCV Sicily Network. Out of 814, 590 were treated with DAAs and 414 of them were older than 65 years. We divided those 414 in two groups, one including 215 patients, aged between 65 and 74 years, and another with 199 patients, aged of 75 years and over. Charlson Comorbidity Index (CCI) was assessed for each patient; drug-drug interactions (DDI) and de-prescribing process were carried out appropriately. Within 414 patients included, percentage rates of women treated was higher than males, BMI was lower and cirrhosis was frequently reported in patients older than 75 years. Hypertension, diabetes mellitus, dyslipidemia (p < 0.0001), prostatic pathologies, kidney disease, gastrointestinal disease (p < 0.0001), osteoporosis (p < 0.01) and depression were most common co-morbidities. CCI showed lower scores in the first group as compared with the second one (p < 0.0001). Among drugs, statins were frequently suspended and anti-hypertensive often replaced. DAAs are useful and effective regardless of disease severity, comorbidities, medications and age. De-prescribing allows a stable reduction of number of medications taken with real improvement of quality of life., (© 2021. The Author(s).)

Objective: 'Self-reported wheat sensitivity' (SRWS) is a self-reported condition caused by wheat ingestion in the absence of celiac disease or wheat allergy. The aim of the study was to investigate the frequency and characteristics of SRWS in outpatients referred for digestive endoscopy., Methods: The study, performed at the University of Palermo, enrolled 496 outpatients., Results: Seven individuals (1.4%) had an already established diagnosis of celiac disease. The questionnaire was administered to the other 489 individuals: 98 subjects (20%) were SRWS, the remaining 391 served as controls (i.e. not-SRWS). SRWS patients were younger (P < 0.001), with a higher percentage of females (P = 0.002) than not-SRWS. 'gastroesophageal reflux disease and ulcer-like dyspepsia' and 'chronic unexplained diarrhea' were more frequently the reasons for the endoscopy study in SRWS than in not-SRWS (P = 0.002, and P = 0.05, respectively). Food allergies/intolerances (P = 0.04), milk allergy/intolerance (P = 0.0001), GERD (P = 0.0001), IBS (0.0001), anxiety (P = 0.005) and depression (P = 0.04) were the previous medical diagnoses reported more frequently in SRWS patients than in not-SRWS. In the SRWS group, 38% of the patients had already undergone previous upper endoscopy and 24% colonoscopy. After these investigations, 58% of SRWS patients received no diagnosis, and the other 42% were informed that they 'were not suffering from celiac disease or wheat allergy'. Finally, 28.6% SRWS patients had followed a gluten-free diet (GFD), and 71.4% of them referred being asymptomatic on GFD., Conclusions: Our data showed a high frequency of SRWS in outpatients referred to a digestive endoscopy center and a lack of medical accuracy in identifying a possible gluten-related disease., Registration: The study was registered on Clinicaltrials.gov (registration number: NCT04154137), accessible at: https://clinicaltrials.gov/ct2/show/NCT04154137?term=non+celiac+wheat&draw=2&rank=1., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The COVID-19 pandemic has caused the relocation of huge financial resources to departments dedicated to infected patients, at the expense of those suffering from other pathologies., Aim: To compare clinical features and outcomes in COVID-19 pneumonia and non-COVID-19 pneumonia patients., Patients and Methods: 53 patients (35 males, mean age 61.5 years) with COVID-19 pneumonia and 50 patients (32 males, mean age 72.7 years) with non-COVID-19 pneumonia, consecutively admitted between March and May 2020 were included. Clinical, laboratory and radiological data at admission were analyzed. Duration of hospitalization and mortality rates were evaluated., Results: Among the non-COVID patients, mean age, presence of comorbidities (neurological diseases, chronic kidney disease and chronic obstructive pulmonary disease), Charlson Comorbidity Index and risk factors (tobacco use and protracted length of stay in geriatric healthcare facilities) were higher than in COVID patients. The non-COVID-19 pneumonia group showed a higher (24% vs. 17%), although not statistically significant in-hospital mortality rate; the average duration of hospitalization was longer for COVID patients (30 vs. 9 days, p  = .0001)., Conclusions: In the early stages of the COVID pandemic, our centre noted no statistical difference in unadjusted in-hospital mortality between COVID and non-COVID patients. Non-COVID patients had higher Charlson Comorbidity Scores, reflecting a greater disease burden in this population.Key MessagesIn March 2020, the COVID-19 disease was declared a pandemic, with enormous consequences for the organization of health systems and in terms of human lives; this has caused the relocation of huge financial resources to departments dedicated to infected patients, at the expense of those suffering from other pathologies.Few published reports have compared COVID-19 and non-COVID-19 pneumonia. In our study, performed in a geographic area with a low prevalence of SARS-CoV-2 infection, we found few statistically significant differences in terms of clinical characteristics between the two groups analyzed.In the early stages of the COVID pandemic, our centre noted no statistical difference in unadjusted in-hospital mortality between COVID and non-COVID patients. Non-COVID patients had higher Charlson Comorbidity Scores, reflecting a greater disease burden in this population.

Over the past few years, growing interest has been shown for the impact of dietary requirements and nutritional factors on chronic diseases. As a result, nutritional programs have been reinforced by public health policies. The precise role of micronutrients in chronic liver disease is currently receiving particular attention since abnormalities in vitamin levels are often detected. At present, treatment programs are focused on correcting vitamin deficiencies, which are frequently correlated to higher rates of comorbidities with poor outcomes. The literature reviewed here indicates that liver diseases are often related to vitamin disorders, due to both liver impairment and abnormal intake. More specific knowledge about the role of vitamins in liver disease is currently emerging from various results and recent evidence. The most significant benefits in this area may be observed when improved vitamin intake is combined with a pharmacological treatment that may also affect the progression of the liver disease, especially in the case of liver tumors. However, further studies are needed.

Background & Aims: Ancient wheat varieties are considered to be healthier than modern ones, but the data are not univocal. We investigated changes in hematochemical parameters and evaluated microbiota data before and after a set period on a diet containing a whole-meal ancient wheat mix., Patients and Methods: 29 cloistered nuns were recruited. The study comprised two consecutive 30-day periods; during the first one (T1), the nuns received wheat-based foods produced with refined "modern" flour ("Simeto"); during the second one (T2) received wheat-based foods produced with an unrefined flour mix composed of "ancient" cultivars. At entry to the study (T0) and at the end of T1 and T2 hematochemical parameters and fecal microbiota and metabolome were evaluated., Results: At the end of T2, there was a significant reduction in serum iron, ferritin, creatinine, sodium, potassium, magnesium, total cholesterol, LDL- and HDL-cholesterol and folic acid. Furthermore, increased the abundance of cultivable enterococci, lactic acid bacteria and total anaerobes. The ability of the gut microbiome to metabolize carbohydrates increased after the period of diet containing ancient grain products. Several volatile organic compounds increased after the one month on the diet enriched with ancient grain products., Conclusions: Our data showed the beneficial effects deriving from a diet including ancient whole-meal/unrefined wheat flours., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)