Quality of endoscopic screening for colorectal cancer in Italy: A national survey.

BACKGROUND: Colorectal cancer (CRC) is a major healthcare problem all over the world and screening is effective in reducing mortality and increasing survival. Since colonoscopy has a central role in faecal immunochemical test (FIT)-based CRC screening and surveillance, consistent quality measures are essential to ensure quality and outcomes. Nevertheless, screening modalities in clinical practice may differ according to the centers experience and the local availability of instrumentation and devices. AIMS: to assess the quality of endoscopic screening for CRC and adherence to international guidelines across Gastroenterology Departments in Italy. METHODS: All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a web-based survey. RESULTS: Data from 64 hospitals from 17 Italian regions were analyzed. 32/64 (50.0%) were from northern, 12/64 (18.75%) from central and 20/64 (31.25%) from southern Italy. Each center is equipped with a median of 5.0 (3.5-7.0) endoscopists involved in CRC screening, 71.4% of which are gastroenterologists. After a positive FIT, most centers (93.8%) schedule a colonoscopy within 3 months. High-definition video endoscopy is routinely performed in 68.8% and chromoendoscopy in 53.1% of centers. Withdrawal time is ≥6 min in 79.9% and cecal intubation rate is ≥90% in 94.4% of departments. Finally, in 92.7% of centers adenoma detection rate (ADR) overcome the minimum standard of 25%. Analyzing the data by regional areas, a significant higher number of median endoscopic examinations/year (6500 vs 4000 and 3000, respectively, p = 0.024) and of endoscopists per center (6.5 vs 5.0 and 3.5, respectively, p < 0.001) has been registered in the northern compared to central-southern centers. CONCLUSIONS: Data from this survey show adequacy and good quality of endoscopic screening for CRC in Italy, highlighting, at the same time, relevant deficiencies and a discrepancy in procedural attitudes between the different centers. These findings call for a urgent action to overcome the shortcomings, refine and homogenize the behaviour of all screening centers in the national territory and improve the outcomes.

The Apparent Asymmetrical Relationship Between Small Bowel Bacterial Overgrowth, Endotoxemia, and Liver Steatosis and Fibrosis in Cirrhotic and Non-Cirrhotic Patients: A Single-Center Pilot Study.

Introduction: Gut microbiota are a complex ecosystem harboring our intestine. They maintain human body equilibrium, while their derangement, namely, "dysbiosis", has been associated with several gastrointestinal diseases, such as liver steatosis (NAFLD) and liver cirrhosis. Small intestinal bacterial overgrowth (SIBO) is an example of dysbiosis of the upper gastrointestinal (GI) tract. Aim: The aim of this study is to evaluate the relationship between SIBO and levels of endotoxemia and grade of liver steatosis (LS) and liver fibrosis (LF) in hepatologic patients. Materials and Methods: Consecutive outpatients referred to our hepatology clinic were tested for SIBO by the lactulose breath test (LBT) and peripheral blood levels of endotoxemia; LS grading and LF were assessed by abdominal ultrasound and transient elastography, respectively. Results: Fifty-two consecutive patients (17 with alcohol abuse (4.5 ± 0.8 alcohol units per day), 4 with HCV and 2 with HBV infection, 24 of metabolic origin, 2 of autoimmune origin, and 3 with cholangiopathies; mean age 54.7 ± 8.3 years, 31 F, BMI 24.1 ± 1.1 Kg/m2) and 14 healthy volunteers (HV) (mean age 50.1 ± 4.3 years, 9 F, BMI 23.3 ± 1.1 Kg/m2) were enrolled. SIBO prevalence was significantly higher in cirrhotic (LC) vs. non-cirrhotic (LNC) patients and vs. HV (all, p < 0.05), with a significant positive trend according to Child-Pugh status (all, p < 0.05). SIBO prevalence was not correlated with LS stages (all, p = NS). Consensually, endotoxin levels were significantly higher in LC vs. LNC and vs. HV (all, p < 0.05) and significantly correlated with LF in patients with LC, according to Child-Pugh status (all, p < 0.05). Conclusion: This study shows that SIBO prevalence and relative endotoxin blood levels seem to be significantly associated with the grade of LF vs. LS in LC. SIBO is also present under pre-cirrhotic conditions, but its prevalence seems to correlate with liver disease irreversible derangement.

The role of gluten-free diet in nonalcoholic fatty liver disease development.

OBJECTIVE: Celiac Disease (CD) is an autoimmune disease involving the small bowel, generated by the ingestion of gluten-containing foods in genetically predisposed subjects. Currently, the unique therapy for CD is the absolute adherence to gluten-free diet, but this treatment has been related to the onset of non-alcoholic fatty liver disease (NAFLD). In this systematic review, we provide an update from the most recent studies on the risk of developing NAFLD patients adhering to GFD. MATERIALS AND METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria, we performed a systematic literature search on PubMed and Google Scholar from 2012 to 2021. RESULTS: In the present systematic review, eight studies investigated how GFD in CD patients may be a risk factor for the onset of NAFLD from a minimum of six months to the maximum follow-up period represented by a median of 10 years. CONCLUSIONS: Present systematic review evaluates how GFD plays a key role in NAFLD for consumption of products rich in saturated fats and carbohydrates that promotes accumulation of lipids and lead to hepatic steatosis and inflammation.

Multifaceted pathogenesis of liver steatosis in inflammatory bowel disease: a systematic review.

OBJECTIVE: Non-Alcoholic Fatty Liver Disease (NAFLD), as a hepatic manifestation of metabolic syndrome (MET)-related obesity, insulin resistance, dyslipidemia, and hypertension, is the main cause of chronic liver disease. Inflammatory Bowel Diseases (IBD), (Crohn's Disease (CD) and Ulcerative Colitis (UC)), are often associated with extraintestinal manifestations. Of these, NAFLD is one of the most frequently reported. To highlight the etiopathogenesis of NAFLD in IBD, we performed a systematic review emphasizing the relationship between NAFLD genetic alterations, metabolic syndrome, and drugs. MATERIALS AND METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria, we performed a systematic literature search on PubMed, Google Scholar, and Web of Science for literature updated from 2010 to 1 March 2021. Inclusion criteria for studies were observational design and Randomized Controlled Trials (RCTs); written in English; primary research only; based on adult patients, and human research only. RESULTS: We identified nine studies on the link between NAFLD and IBD. Among these, two described the genetic predisposition to NAFLD of patients with IBD. Four reported an association between MetS and NAFLD in IBD patients. Regarding medications, none of four studies included, detected a relationship between NAFLD onset and IBD treatment (corticosteroids, immunomodulators, methotrexate, or biologics).  However, a retrospective study showed a protective effect of anti-TNF alpha therapies against altered liver enzymes. CONCLUSIONS: In this interplay between genetic, metabolic, drug, and inflammatory factors, the underlying pathogenic mechanisms behind NAFLD in IBD are still far from clear. Further studies are needed to better clarify the role of individual components influencing the development of NAFLD in IBD.

Trends and characteristics associated with dietary triggers and psychological distress in patients with irritable bowel syndrome: a cross-sectional study.

OBJECTIVE: Diet, visceral sensitivity, and psychological distress play an important role in Irritable Bowel Syndrome (IBS). This study focused on the relation between IBS severity, foods, visceral sensitivity, and anxiety/depression. PATIENTS AND METHODS: Patients with IBS were investigated through (1) IBS-symptoms severity score (SSS), (2) self-reported food intolerance, (3) visceral sensitivity index (VSI), and (4) Hospital Anxiety and Depression Scale (HADS). Seventy-seven patients agreed to participate in the survey. Of them, 64 (83%) showed IBS according to Rome IV criteria and were included in the final analysis. Patients with IBS-D were 30 (47%), with IBS-C 27 (42%), and with IBS-M 7 (11%). RESULTS: Fifty-eight patients (90%) considered at least one foodstuff as IBS trigger. Amine-rich foods represented a symptom trigger for 77% of patients, those with lectin for 70%, IACs by 48%, and capsaicin by 37%. Overweight was significantly associated with amine-rich foods (p=0.015), age >45 years (p=0.001) and non-smoking condition (p=0.033) with lectin-rich foods, male gender (p=0.005) and overweight (p=0.027) with capsaicin-containing foods. A positive VSI score was found in 59% of patients, and non-smoking condition was significantly associated (OR 10.03; p=0.009). No factors were associated with a positive HADS score, shown by 80% of patients. Severe IBS was shown by 63% of patients, being amine-rich foods (p=0.024), overweight (p=0.020), and female gender (p=0.029) independent risk factors while marriage/cohabiting a protective one (p=0.038). Amine-rich foods are an independent risk factor for severe IBS, along with overweight and female gender. CONCLUSIONS: Clinicians should pay more attention to self-reported food intolerance in IBS patients. A personalized therapy including dietary advice as part of treatment could be of great benefit.

Real-life efficacy and safety of Ustekinumab as second- or third-line therapy in Crohn's disease: results from a large Italian cohort study.

OBJECTIVE: Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn's Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics. PATIENTS AND METHODS: 194 CD patients (108 males and 86 females, mean age 48 years (range 38-58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients. RESULTS: At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up. A logistic regression, UST therapy as third-line therapy (after both anti-TNFα and vedolizumab), FC >200 µg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment. CONCLUSIONS: UST seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.

Serum adipokine levels in overweight patients and their relationship with non-alcoholic fatty liver disease.

AIM: Non-alcoholic fatty liver disease (NAFLD) is a relevant public health matter in Western countries. The pathogenetic link between visceral fat, insulin resistance (IR) and NAFLD has been reported in literature. However, there are contradictions on the changes of adipokine levels in serum related to the presence of NAFLD. The aim of the present study was to evaluate the serum concentrations of a selected set of adipokines, that is, adiponectin, leptin, resistin and the pro-inflammatory cytokine interleukin-6 (IL-6) in overweight patients, and to clarify their relationship with NAFLD. METHODS: Fasting serum levels of adipokines were determined in 42 consecutive overweight patients and in 25 lean controls. The degree of ultrasound (US) liver steatosis was graded according to the Hamaguchi score. RESULTS: Liver steatosis was detected in 33 patients (78%) by US examination. Twelve patients with elevated transaminases levels showed significantly higher values of IR, leptin and resistin levels (P<0.05). Patients with steatosis presented a significantly higher leptin and a lower adiponectin levels (P<0.05) than controls. A significant inverse correlation was found between US steatosis progression and adiponectin and resistin levels (p<0.05). Considering the multiple logistic regression, adiponectin and leptin were good predictors to detect the presence of steatosis (p<0.05). CONCLUSION: Our data support the concept that adipokine level changes are closely linked with IR. In addition, serum adiponectin and leptin levels may be used as diagnostic markers to determine the presence of NAFLD in overweight patients.

Liver steatosis in celiac disease: the open door.

Non-alcoholic fatty liver disease (NAFLD) is a common disease of unknown origin characterized by histological features similar to alcoholic-like liver injury but in the absence of significant alcohol intake. Non-alcoholic fatty liver disease refers to a spectrum of diseases of the liver ranging from simple steatosis (i.e., fatty infiltration of the liver) to nonalcoholic steatohepatitis (i.e., steatosis with inflammation and hepatocyte necrosis) to cirrhosis. Non-alcoholic fatty liver disease is frequently associated with disorders such as insulin resistance, obesity, type 2 diabetes mellitus, hyperlipidemia and protein-calorie malnutrition. However, in a subgroup of NAFLD patients, the true relevant cause remains undetermined. Celiac disease (CD) is a common immune-mediated disorder and develops in genetically susceptible subjects after the ingestion of gluten proteins. Celiac disease has been found in about 10% of patients with unexplained abnormal liver tests, and in about 3.5% of patients with NAFLD as the only manifestation of the disease. The frequency of subclinical or silent presentations in older children and adults highlights the importance of CD screening in patients with unexplained chronic abnormal liver function tests and NAFLD without any specific etiology. The pathogenesis of liver steatosis in CD is uncertain. The aims of this review are to describe the possible mechanisms involved in the occurrence and progression of liver steatosis in CD patients.

Breath tests for the assessment of the orocecal transit time.

Orocecal transit time (OCTT) is one of the main determinant of the hunger ratings and gastrointestinal sensitivity. While marked-isotopes scintigraphy is the gold standard in its determination in the clinical frame, breath tests are cheap, well-tolerated and non-invasive alternatives. In fact C-13 and C-14 stable isotopes breath tests can be used to assess gastric emptying and OCTT in the clinical and research frames. Moreover, hydrogen (H2) lactulose breath test can be used to assess OCTT in the research frame only due to its laxative action; inulin breath test, devoid of this bias, could be replacing it. However, the main limitation in the use of breath tests in the OCTT determination is their low reproducibility.

Torsades de pointes in congenital long QT syndrome following low-dose orphenadrine.

We report the case of a woman, affected by congenital long QT syndrome (LQTS), who experienced three syncopal episodes shortly after the assumption of a low dose of orphenadrine. The ECG revealed a QT interval of 600 ms, and the corrected QT interval (QTc) was 537 ms. No structural cardiac disease was demonstrated by echocardiography. Orphenadrine treatment was discontinued. During the first 12 h of monitoring, three short-lasting, asymptomatic episodes of torsades de pointes occurred. No other sustained ventricular arrhythmia was revealed at Holter monitoring in the following days. During the ensuing 6 months, the patient remained asymptomatic, and the QTc did not change. Orphenadrine is an analogue of diphenhydramine, an antihistaminic drug that produces sodium channel blockade similar to that caused by quinidine and other Class Ia antiarrhythmic drugs. Our case rises the suspicion that orphenadrine could cause life-threatening arrhythmias in LQTS even at a low dose, and independently from concomitant assumption of potentially QT-prolonging drugs.

High seroprevalence of Helicobacter pylori infection in non-institutionalised children with mental retardation.

Eighty-four children with mental retardation (34 boys, 50 girls; age range 2-18 years, median 6 years) and 84 age- and gender-matched outpatient controls were studied. All children were living at home, had never stayed in an institution, and came from the same urban area. Seropositivity for Helicobacter pylori was found in 42 (50%) of 84 mentally retarded children and 16 (19%) of 84 controls (p < 0.01). Socio-economic factors did not differ between the two groups. The findings indicated that a higher prevalence of H. pylori infection occurs in children with mental retardation, regardless of whether they are institutionalised.

Prevalence of atrial septal aneurysm in patients with migraine: an echocardiographic study.

OBJECTIVE: To evaluate the prevalence of atrial septal aneurysm in patients with migraine. BACKGROUND: Migraine has long been considered a risk factor for stroke. Atrial septal aneurysm is often observed in young patients with ischemic stroke and is frequently associated with other conditions potentially leading to embolism. METHODS: We performed a transthoracic echocardiogram in 90 consecutive patients (65 women and 25 men; mean age, 35.3 years [standard deviation, 9]) with migraine but free from cerebral and cardiovascular disease and in 53 control subjects (37 women and 16 men; mean age, 34 years [standard deviation, 10]). The diagnosis of atrial septal aneurysm was performed according to Olivares-Reyes criteria. A transesophageal echocardiogram also was performed in 75 patients with migraine (83.3%). RESULTS: The prevalence of isolated atrial septal aneurysm was higher in patients with migraine with aura (28.5%) than in patients with migraine without aura (3.6%) (P <.005) or in control subjects (1.9%) (P <.005). CONCLUSIONS: Our data suggest a role of atrial septal aneurysm in the genesis of aura in patients with migraine.

Tilt-induced pseudosyncope.

Using the head-up tilt test (HUTT) we evaluated 986 consecutive patients affected by unexplained syncope. In 266 patients the test induced bradycardia and/or hypotension resulting in syncope or presyncope, thus allowing a diagnosis of neurally mediated syncope. In three other patients (0.3% of the entire population and 1% of the all positive tests) HUTT provoked loss of consciousness despite no significant change in heart rate and/or blood pressure. In all three cases unconsciousness was prolonged and no pathological finding was present except lack of response. This phenomenon has been defined as 'pseudosyncope' and related to psychiatric illness. Pseudosyncope induced by HUTT reproduced the clinical events, so the test outcome was considered a true positive response. Our experience suggests that HUTT may contribute to the recognition of psychiatric disorder in some patients affected by unexplained syncope.

[Thrombo-embolic risk evaluation in patients with atrial fibrillation. Role of echocardiography]. / Stratificazione del rischio tromboembolico nel paziente con fibrillazione atriale. Ruolo dell'ecocardiografia.

Atrial fibrillation (AF) is the most common observed cardiac arrhythmia and is the most frequent condition associated with thromboembolic events in patients with or without mitral valve disease. The source of cardiac emboli is the left atrium, the left atrial appendage or, less frequently, the left ventricle. Emboli may also originate from aortic atherosclerotic plaques. It is important to identify patients at risk in order to perform the appropriate therapy. Risk stratification is multiparametric, being based on clinical, laboratory, and echocardiographic data. Several trials have pointed out the role of echocardiography in the evaluation of anatomic and functional parameters associated with thromboembolic risk. Transthoracic echocardiography (TTE) does not provide sufficient information regarding posterior cardiac structures, being its sensitivity in detecting thrombi relatively low (33-72%). Transesophageal echocardiography (TEE) in contrast, has an almost 100% sensitivity; this technique is, therefore, mandatory in patients with AF for an adequate prevention of thromboembolism. The echocardiographic information joined with clinical features allow to stratify, in a proper way, the risk of every single patient.

[Pathophysiology of congestive heart failure]. / Attualità in tema di fisiopatologia dello scopenso cardiaco.

Pathophysiology of congestive heart failure (CHF) has undergone a remarkable evolution during the last two decades. CHF is now regarded especially as a neurohormonal disease and not only as a cardiocirculatory impairment. Many studies have emphasized that an abnormal neuroendocrine activation precedes the development of clinically recognized heart failure and plays an important pathogenetic role in progression of this disease. In patients with CHF, moreover, circulating levels of some neurohormonal factors have an independent negative prognostic value. More recently immunological and molecular biology studies have also demonstrated the negative effects exerted by some cytokines and by apoptosis. Correction of neurohormonal disorder is the rationale of therapeutical approach to patients with CHF and appears the only way to significantly decrease mortality. In this review the role of neuroendocrine activation in the pathophysiology of CHF is analyzed.

[Detection of left ventricular endocardial border with tissue harmonic imaging]. / Vantaggi della seconda armonica tissutale nella identificazione del bordo endocardico ventricolare sinistro.

BACKGROUND: Ultrasonic wave propagation in human tissues is not linear. As a consequence, harmonic waves, whose frequency is a multiple (harmonic) of the emitted frequency, are generated. Tissue Harmonic Imaging (THI) processes only the second harmonic frequency in order to improve the signal-to-noise ratio of the received signal. The study was aimed at investigating the impact of THI on the detection of the Left Ventricular (LV) endocardial border. Attention was paid to determine which LV walls were analysed more clearly with THI rather than with conventional Fundamental Frequency Imaging (FFI). METHODS: We compared the FFI and the THI visualization of the 16 LV segments and of the 6 LV walls in 30 consecutive patients by scoring the images as bad, sufficient or good. The equipment used was a GE Vingmed System Five (Orten, Norway). RESULTS: Images were good in 85% of segments explored with THI, whereas FFI provided good images in 47% of segments (p<0.001). From the apical window, visualization of the apex, lateral wall and anterior wall significantly improved with THI; using the parasternal approach, imaging of posterior wall was definitely better with THI than with FFI. CONCLUSIONS: THI enhances both endocardial visualization and global image quality. Tech-nical development, however, increases the diagnostic possibilities of echocardiography but does not substitute the operator's experience.

[The second tissue harmonic signal: from physics principles to clinical application]. / La seconda armonica tissutale: dai principi fisici all'applicazione clinica.

The second harmonic signals received from organs are due to the non linear properties of tissue which cause distortion of the transmitted signal and are not primarily caused by the transmission of a harmonic frequency. The velocity of ultrasound propagation depends on the density of the insonified material. During the compression phase, the tissue becomes denser, and the ultrasound waves travel faster through the tissue than during the rarefaction phase; the compression phase tends to overtake the rarefaction phase. The ultrasound waveform thus, undergoes a distortion that becomes greater as the distance from the transducer increases. Due to these effects, the tissue tends to generate harmonics and hence shifts energy from the fundamental to the harmonic bands. There are several reasons why harmonic tissue imaging increases the signal-to-noise ratio and facilitates interpretation. In technically difficult patients, there is often a diffuse haze due to distortion of the transmitted beam by shallow surface layers or to reverberations between the skin and ribs. These distortions and reverberations consist almost entirely of ultrasound energy at the fundamental frequency. When the returned signal is filtered at the harmonic so as to reject the fundamental frequency, the clutter and haze are removed and the image becomes more clear and defined. A further reason for the decrease in artifacts and clutter is the side-lobe level reduction in the second harmonic beam. Thus, harmonic beams are narrower and have lower side-lobe levels than fundamental ones. There are several clinical applications of harmonic tissue imaging. These include the correct definition of endocardial borders resulting in an improved assessment of left ventricular function at rest as well as during stress testing, the delineation of the left atrial appendage, the detection of atrial right to left shunting, and left atrial spontaneous echo contrast. Moreover, improved endocardial visualization leads to better endocardial tracking with acoustic quantification and to more segments being interpretable with the anatomic M-mode.