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Background: Both macroscopic and histological lesions are frequently detected at upper endoscopy in elderly patients. We assessed the prevalence of main endoscopic and histological alterations in elderly (> 65 years old) patients., Methods: In this study, clinical, endoscopic and histological features of patients referred for upper endoscopy in clinical practice were retrieved. Both univariate and multivariate analyses were executed. Comparisons with previous data were performed., Results: A total of 1336 underwent upper endoscopy in the 28 participating centres. At endoscopy, at least one macroscopic lesion was present in overall 420 (31.4%) patients. Erosive gastritis (13.3%) and erosive oesophagitis (9.8%) were the most prevalent lesions, whilst Barrett's oesophagus, gastric ulcer, duodenal ulcer and erosive duodenitis were observed in 1.8%, 2%, 1.4% and 3.1% patients, respectively. Nine (0.6%) cases of oesophageal, 25 (1.8%) gastric and 2 (0.1%) duodenal neoplasia were detected. At histology, Helicobacter pylori infection was diagnosed in 99 (15.9%) patients, and extensive precancerous lesions on gastric mucosa were detected in 80 (14.5%) patients. Endoscopic lesions were more frequent in males, at first endoscopy and in those with alarm symptoms and lower during PPI therapy. At multivariate analysis, PPI therapy significantly reduced the probability of finding endoscopic lesions (OR: 0.68, 95% CI: 0.46-0.99; P = 0.04), whilst neoplastic lesions were associated with presence of alarm symptoms (OR: 1.5, 95% CI: 1.1-2.1; P = 0.005)., Conclusions: We found that the frequency of erosive and neoplastic lesions remained high in elderly patients, whilst the prevalence of both H. pylori infection and peptic ulcer was decreased., Competing Interests: Declarations. Ethical approval: Since no identification of patients was allowed, no experimental drugs were administered, no additional costs or procedures for the patients were required, and no funds were received. The Investigational Review Boards of Nuovo Regina Margherita Hospital waived formal approval for this retrospective analysis. Consent to participate: Patients signed informed consent for both procedure and anonymous use of their data for scientific purposes. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Background/aims: Patients with diverticular disease (DD) frequently have abnormal bowel movements. However, it is unknown whether the entity of these alterations is associated with the severity of DD. We aimed to assess bowel habits and their relationship with the severity of DD according to Diverticular Inflammation and Complication Assessment (DICA) classification, Combined Overview on Diverticular Assessment (CODA) score, and fecal calprotectin (FC)., Methods: An international, multicenter, prospective cohort study was conducted in 43 centers. A 10-point visual analog scale (VAS) was used to assess the severity of constipation and diarrhea. The association of constipation and diarrhea with DICA classification, CODA score, and basal FC was tested using non-parametric tests. Survival methods for censored observations were applied to test the association of constipation and diarrhea with the incidence of acute diverticulitis over a 3-year follow-up., Results: Of 871 patients with DD were included in the study. Of these, 208 (23.9%) and 199 (22.9%) reported a VAS score for constipation and diarrhea at least 3 at baseline, respectively. Higher constipation and diarrhea scores were associated with increasing DICA classification, CODA score and basal FC (P< 0.001). Constipation and diarrhea scores were independently associated with an increased hazard of developing acute diverticulitis (hazard ratio [HR]constipation = 1.15 per 1-VAS point increase, 95% confidence interval [CI], 1.04-1.27; P=0.004; and HRdiarrhea =1.14; 95% CI, 1.03-1.26; P=0.014, respectively)., Conclusions: In newly diagnosed patients with DD, higher endoscopic and combined scores of DD severity were associated with higher scores of constipation and diarrhea at baseline. Both constipation and diarrhea were independent prognostic factors of acute diverticulitis.

The diagnostic work-up in iron deficiency anaemia (IDA) patients can be challenging when bleedings or malabsorption are not clinically manifest. Lesions on the small bowel mucosa may cause IDA. We evaluated the prevalence of lesions on the small bowel mucosa detected at Videocapsule Endoscopy (VCE) in IDA patients following negative upper and lower endoscopies. Clinical and endoscopic data collected in 5 centres were retrieved. Lesions with a high bleeding potential (P2) were computed, and predictive factors investigated at multivariate analysis. By considering data of 230 patients, the endoscopic examination detected a total of 96 (41.7%; 95% CI: 35.4-48.1) P2 lesions on the small bowel mucosa, including 4 (1.7%) cancers. The use of non-steroidal anti-inflammatory drugs was found to be the only associated factor at both univariate (OR: 5.7, 95% CI: 2.4-13.4; P <0.001) and multivariate (OR: 2.8; 95% CI: 1.7-3.9, P <0.01) analyses. Present study showed that evaluation of small bowel mucosa with VCE allows to disclose a potential cause of IDA in near half patients. The cooperation between haematologists and gastroenterologists in the diagnostic work-up may be useful., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: International guidelines advise improving esophagogastroduodenoscopy (EGD) quality in Western countries, where gastric cancer is still diagnosed in advanced stages. This nationwide study investigated some indicators for the quality of EGD performed in endoscopic centers in Italy., Methods: Clinical, endoscopic, and procedural data of consecutive EGDs performed in one month in the participating centers were reviewed and collected in a specific database. Some quality indicators before and during endoscopic procedures were evaluated., Results: A total of 3,219 EGDs performed by 172 endoscopists in 28 centers were reviewed. Data found that some relevant information (family history for GI cancer, smoking habit, use of proton pump inhibitors) were not collected before endoscopy in 58.5-80.7% of patients. Pre-endoscopic preparation for gastric cleaning was routinely performed in only 2 (7.1%) centers. Regarding the procedure, sedation was not performed in 17.6% of patients, and virtual chromoendoscopy was frequently (>75%) used in only one (3.6%) center. An adequate sampling of the gastric mucosa (i.e., antral and gastric body specimens) was heterogeneously performed, and it was routinely performed only by 23% of endoscopists, and in 14.3% centers., Conclusions: Our analysis showed that the quality of EGD performed in clinical practice in Italy deserves to be urgently improved in different aspects.

Introduction: We assessed the prevalence and clinical outcomes of segmental colitis associated with diverticulosis (SCAD) in patients with newly diagnosed diverticulosis., Methods: A 3-year international, multicenter, prospective cohort study was conducted involving 2,215 patients., Results: SCAD diagnosis was posed in 44 patients (30 male patients; median age: 64.5 years; prevalence of 1.99%, 95% confidence interval, 1.45%-2.66%). Patients with SCAD types D and B showed worse symptoms, higher fecal calprotectin values, needed more steroids, and reached less likely complete remission., Discussion: Although SCAD generally had a benign outcome, types B and D were associated with more severe symptoms and worse clinical course., (Copyright © 2023 by The American College of Gastroenterology.)

Background and Aims: The Diverticular Inflammation and Complication Assessment (DICA) classification and the Combined Overview on Diverticular Assessment (CODA) were found to be effective in predicting the outcomes of Diverticular Disease (DD). We ascertain whether fecal calprotectin (FC) can further aid in improving risk stratification., Methods: A three-year international, multicentre, prospective cohort study was conducted involving 43 Gastroenterology and Endoscopy centres. Survival methods for censored observations were used to estimate the risk of acute diverticulitis (AD) in newly diagnosed DD patients according to basal FC, DICA, and CODA. The net benefit of management strategies based on DICA, CODA and FC in addition to CODA was assessed with decision curve analysis, which incorporates the harms and benefits of using a prognostic model for clinical decisions., Results: At the first diagnosis of diverticulosis/DD, 871 participants underwent FC measurement. FC was associated with the risk of AD at 3 years (HR per each base 10 logarithm increase: 3.29; 95% confidence interval, 2.13-5.10) and showed moderate discrimination (c-statistic: 0.685; 0.614-0.756). DICA and CODA were more accurate predictors of AD than FC. However, FC showed high discrimination capacity to predict AD at 3 months, which was not maintained at longer follow-up times. The decision curve analysis comparing the combination of FC and CODA with CODA alone did not clearly indicate a larger net benefit of one strategy over the other., Conclusions: FC measurement could be used as a complementary tool to assess the immediate risk of AD. In all other cases, treatment strategies based on the CODA score alone should be recommended., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: The detection of subclinical/silent atrial fibrillation (SAF) in the general population is of the utmost importance, given its potential adverse consequences. Incident AF has been observed in 30% to 70% of patients with implanted devices, but its prevalence may indeed be lower in the general population. The prospective, multicentric, observational Silent Atrial Fibrillation ANCE Research Initiative (SAFARI) study aimed at assessing the SAF prevalence in a real-world outpatient setting by the means of a small, wearable, prolonged ECG Holter monitoring (>5 days) device (CGM HI 3-Lead ECG; CGM TELEMEDICINE, Piacenza, Italy)., Methods: Patients ≥ 55 years of age at risk for AF were screened according to the inclusion criteria to undergo prolonged 3-lead ECG Holter monitoring. SAF episodes were classified as follows: Class A, <30 s; Class B, 30 to 299 s; and Class C, ≥300 s., Results: In total, 119 patients were enrolled (64 men; median age 71 (IQR 55-85) years). At a median of 13.5 (IQR 5-21) days of monitoring, SAF episodes were found in 19 patients (16%). A total of 10,552 arrhythmic episodes were registered, 6901 in Class A (n = 7 patients), 2927 in Class B (n = 3), and 724 in Class C (n = 9), (Class A vs. B and C, p < 0.001). This latter group had multiple (all-class) episodes, and two patients had >1000 episodes. There were no clinical, echocardiographic, or laboratory findings able to discriminate patients with SAF from those in sinus rhythm in univariate and multivariable analyses; of note is that the Class C patients showed a higher diastolic blood pressure, resting heart rate, and indexed LA volume., Conclusions: Over a median of 13 days of Holter monitoring, the SAFARI study confirmed the usefulness of small wearable devices in detecting SAF episodes in real-world outpatients at risk for, but with no prior history of, AF.

Objective: To investigate the predictive value of the Diverticular Inflammation and Complication Assessment (DICA) classification and to develop and validate a combined endoscopic-clinical score predicting clinical outcomes of diverticulosis, named Combined Overview on Diverticular Assessment (CODA)., Design: A multicentre, prospective, international cohort study., Setting: 43 gastroenterology and endoscopy centres located in Europe and South America., Participants: 2215 patients (2198 completing the study) at the first diagnosis of diverticulosis/diverticular disease were enrolled. Patients were scored according to DICA classifications., Interventions: A 3-year follow-up was performed., Main Outcome Measures: To predict the acute diverticulitis and the surgery according to DICA classification. Survival methods for censored observation were used to develop and validate a novel combined endoscopic-clinical score for predicting diverticulitis and surgery (CODA score)., Results: The 3-year cumulative probability of diverticulitis and surgery was of 3.3% (95% CI 2.5% to 4.5%) in DICA 1, 11.6% (95% CI 9.2% to 14.5%) in DICA 2 and 22.0% (95% CI 17.2% to 28.0%) in DICA 3 (p<0.001), and 0.15% (95% CI 0.04% to 0.59%) in DICA 1, 3.0% (95% CI 1.9% to 4.7%) in DICA 2 and 11.0% (95% CI 7.5% to 16.0%) in DICA 3 (p<0.001), respectively. The 3-year cumulative probability of diverticulitis and surgery was ≤4%, and ≤0.7% in CODA A; <10% and <2.5% in CODA B; >10% and >2.5% in CODA C, respectively. The CODA score showed optimal discrimination capacity in predicting the risk of surgery in the development (c-statistic: 0.829; 95% CI 0.811 to 0.846) and validation cohort (c-statistic: 0.943; 95% CI 0.905 to 0.981)., Conclusions: DICA classification has a significant role in predicting the risk of diverticulitis and surgery in patients with diverticulosis, which is significantly enhanced by the CODA score., Trial Registration Number: NCT02758860., Competing Interests: Competing interests: SD served as speaker, consultant and/or advisory board member for AbbVie, Allergan, Alfa Wassermann, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Gilead, Hospira, Johnson and Johnson, Merck, MSD, Mundipharma, Pfizer, Sandoz, Takeda, Tigenix, UCB Pharma, Vifor. GM served as speaker and/or advisory board fees for AlfaSigma, Arena, Janssen, Gilead, Roche. GN received funding for target projects from Apharm and Sofar. APserved as lecturer for AlfaSigma and Polpharma. JR served as lecturer for AlfaSigma, Takeda, Ipsen and Servier. FS served as lecturer for Sanofi., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There are no evidence-based recommendations for performing upper gastrointestinal endoscopy (UGIE) in patients with extra-oesophageal symptoms of gastro-oesophageal reflux disease (GORD). However, UGIEs are often performed in clinical practice in these patients. We aimed to assess the prevalence of gastro-oesophageal lesions in patients with atypical GORD symptoms., Methods: Patients complaining of at least one extra-oesophageal GORD symptom and undergoing UGIE in seven centres were prospectively enrolled. Clinically relevant lesions (Barrett's oesophagus, erosive oesophagitis, gastric precancerous conditions, peptic ulcer, cancer, and H. pylori infection) were statistically compared between groups regarding GORD symptoms (atypical vs. both typical and atypical), type of atypical symptoms, age, and presence of hiatal hernia., Results: Two hundred eleven patients were enrolled (male/female: 74/137; mean age: 55.5 ± 14.7 years). Barrett's oesophagus was detected in 4 (1.9%), erosive oesophagitis in 12 (5.7%), gastric precancerous conditions in 22 (10.4%), and H. pylori infection in 38 (18%) patients. Prevalence of clinically relevant lesions was lower in patients with only atypical GORD symptoms (28.6 vs. 42.5%; p = 0.046; χ 2 test), in patients ≤50 years (20 vs. 44.8%; p = 0.004; χ 2 test), and in those in ongoing proton pump inhibitor (PPI) therapy (21.1 vs. 40.2%; p = 0.01; χ 2 test). No clinically relevant lesions were detected in patients ≤50 years, without alarm symptoms, and receiving PPI therapy. Hiatal hernia was diagnosed in only 6 patients with cardiologic and in 41 patients with ear-nose-throat symptoms (11.3 vs. 35.1%; p = 0.03; χ 2 test)., Conclusions: Clinically relevant lesions are uncommon among young (≤50 years) patients with extra-oesophageal GORD symptoms. Hiatal hernia is not more prevalent in patients with cardiologic symptoms and suspicion of GORD. The usefulness of UGIE in these patients is questionable., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)

An 86-year-old Caucasian man had prior episodes of fever (up to 38 °C), mild abdominal pain, tachycardia, and malaise in the last 3 months, lasting 2-3 days. He never suffered from abdominal or chest pain, rash, or arthralgia. Major causes of fever were excluded (pulmonary, urinary, abdomen, skin infections, neoplasms, and major rheumatologic disorders). The patient was native of Altamura with a family history of familial Mediterranean fever (FMF). The genetic testing confirmed the presence of MEFV gene variants c.442G>C (E148Q) on exon 2 and c.2282G>A (R761H) on exon 10, all in heterozygosity. Mildly elevated serum transaminases suggested an ongoing form of FMF hepatitis on nonalcoholic liver steatosis. The patient started colchicine 1 mg/day that induced symptom control and normalization of inflammatory markers, hyperbilirubinemia, and markers of cholestasis. Symptoms of FMF can appear at any age in life and our patient represents a very late-onset clinical case. The Apulian region has a consistent clustering of MEFV variants and FMF families with affected individuals in multiple consecutive generations. Families show unique clinical features and rare signs of secondary amyloidosis without kidney damage. Genetic and environmental bases of this phenotypic variant are under scrutiny. Colchicine lifetime remains the mainstay of treatment in FMF patients. KEY POINTS: • Familial Mediterranean fever (FMF) is the most frequent hereditary monogenic recurrent fever syndrome, and symptoms can appear at any age in life. • Late-onset FMF approaches 30% in late adulthood, but in general, onset of FMF after the age of 40 (late onset FMF) is rare, usually associated with M694V heterozygosity. • In a local cluster of FMF families (Altamura, Puglia, Southern Italy), we report a very late-onset FMF (variants E148Q, R761H) in an 86-year-old patient with a positive family history of FMF in two generations of descendants. • While lifetime colchicine remains the mainstay of treatment in FMF patients, prospective studies need to identify the characteristics of several phenotypic variants accounting for (very)-late onset FMF.

Background and Aims: 13 C-Urea Breath Test (UBT) is a non-invasive, highly accurate and recommended test to detect Helicobacter pylori (H. pylori) infection and to confirm post-therapy eradication. However, differences exist in terms of manufacturers, dose of labelled urea, addition of citric acid, solid vs. liquid formulation, and sampling times of breath samples. In this study, we compared the diagnostic accuracy of "short" (15 minutes) vs. "standard" (30 minutes) time for a single type of liquid UBT., Methods: We compared the performance of a single UBT type (BREATHQUALITY, AB Analitica, Padua, Italy, 10 mL of 75 mg 13 C-Urea and 1.4 g citric acid) during a "short" vs. "standard" breath sampling time. Enrolled were 151 subjects requiring UBT as naïve (N=92) or post-eradication (N=59) checks., Results: UBT at 15 and 30 minutes were highly comparable, showing optimal correlation in all subsets of patients (i.e. naïve vs. post eradication, negative vs. post eradication check). One discrepant result occurred at the borderline zone of the DOB 4‰, but proved to be true positive at a later confirmation by a second UBT and stool antigen test., Conclusions: By shortening the testing time of BREATHQUALITY to 15 minutes (-50%) comparable accuracy will be maintained and in addition, it will bring some benefits to patients' waiting lists, compliance, and hospital staff.

Objective: FMF is an inherited autoinflammatory syndrome, characterized by attacks of painful periodic fever caused by diffuse serositis and risk of secondary amyloidosis due to IL-1β-mediated inflammation. The disease appears to be transmitted through autosomal recessive mutations in the MEFV gene encoding the pyrin protein Although more than 300 variants have been reported worldwide so far, their association with symptom severity, the relative frequencies in different populations and the disease penetrance are far from being completely understood. We investigated genotype-phenotype correlations in two large nuclear families and verified whether commonly used web-based tools can usefully predict variant pathogenicity in FMF., Methods: Peripheral blood samples were obtained from 15 patients of two families who had been diagnosed with FMF according to international criteria. The entire MEFV coding region was sequenced in all subjects, and 179 MEFV variants were surveyed with five different pathogenicity predictors., Results: The inheritance of FMF could not be explained by traditional autosomal recessivity in both families. In silico tools demonstrated a significant association of variants' pathogenicity with their position along the coding sequence but not with variants' frequency., Conclusion: By describing two large families with paradigmatic complexity of FMF genetics, we conclude that established concepts in assessing the causative role of variants identified in mutation screening cannot be easily translated into appropriate genetic counselling in FMF. Furthermore, we demonstrate that variants frequently associated with severe disease are not predicted to significantly impact protein function using in silico algorithms., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cigarette smoke is the main source of indoor chemical and toxic elements. Cadmium (Cd), Thallium (Tl), Lead (Pb) and Antimony (Sb) are important contributors to smoke-related health risks. Data on the association between Rare Earth Elements (REE) Cerium (Ce) and Lanthanum (La) and domestic smoking are scanty. To evaluate the relationship between cigarette smoke, indoor levels of PM 2.5 and heavy metals, 73 children were investigated by parental questionnaire and skin prick tests. The houses of residence of 41 "cases" and 32 "controls" (children with and without respiratory symptoms, respectively) were evaluated by 48-h PM 2.5 indoor/outdoor monitoring. PM 2.5 mass concentration was determined by gravimetry; the extracted and mineralized fractions of elements (As, Cd, Ce, La, Mn, Pb, Sb, Sr, Tl) were evaluated by ICP-MS. PM 2.5 and Ce, La, Cd, and Tl indoor concentrations were higher in smoker dwellings. When corrected for confounding factors, PM 2.5 , Ce, La, Cd, and Tl were associated with more likely presence of respiratory symptoms in adolescents. We found that: i) indoor smoking is associated with increased levels of PM 2.5 , Ce, La, Cd, and Tl and ii) the latter with increased presence of respiratory symptoms in children., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Indoor allergens are risk factors for asthma: Thus, the characterization of indoor air quality is important for studying environment-health relationships in children. In particular, Dermatophagoides pteronyssinus is the dominant allergen for asthma. We cross-sectionally investigated the relationships among respiratory symptoms and function, airway inflammation, allergen sensitization, and indoor allergen concentration., Methods: One hundred and thirty-two children aging 10-14 years and living in a Southern Mediterranean area were evaluated by parental questionnaires. Spirometry, exhaled nitric oxide (FeNO), skin prick tests, total, and specific serum IgE analyses were performed along with the evaluation of home dust samples for the content in Der p 1 allergen. Three clusters were created on the basis of the presence/absence of wheeze in the last 12 months (Wh12m) and Der p 1-specific IgE level., Results: Cluster 1 (Wh12m+/high Der p 1 IgE) presented higher FeNO and poorer pulmonary function (lower FEV 1 and FEF 25%-75% ), while its symptom score was not different from Cluster 2 (Wh12m+/low Der p 1 IgE). Cluster 3 (Wh12m-/low IgE) showed the lowest FeNO values and pulmonary function similar to Cluster 2. Within Cluster 1, both Der p 1-specific IgE and FeNO were positively correlated with dust Der p 1., Conclusions: Similar asthma phenotypes may occur in children despite differences in their atopic state. In atopic children, sensitizing allergens in the indoor environment may increase airway inflammation worsening pulmonary function. Moreover, environmental exposures may contribute to the development of asthma-like symptoms also in the absence of atopic sensitization, thus contributing to asthma overdiagnosis., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder characterised by recurrent attacks of fever and serositis (peritonitis, pleuritic or synovitis) affecting mainly populations of Mediterranean origin., Aim: To describe a relatively new cluster of FMF subjects from Apulia and Basilicata regions (southern Italy)., Patients and Methods: Subjects were screened for FMF using the Tel-Hashomer criteria and genetic analysis. Demographic data were taken from patients' files and direct interviews. Patients were investigated about attack duration, intensity and site, body temperature, skin manifestations and overall quality of life before and after treatment with colchicine. Inflammatory parameters were also measured between these periods., Results: Forty-nine subjects had FMF (M : F = 26 : 23, age 38 years ± 2 SE) and followed-up up to 8 years. The age at disease onset was 22·1 years ± 1·2SE and the diagnostic delay was 15·5 years ± 1·9SE. The majority of patients (82%) suffered from abdominal pain, and 35% had undergone prior abdominal surgery or laparotomy. Severity score (ISSF) was mild in 43% of patients and intermediate in 57% of patients. Serum amyloid A (SAA) was increased in 20% of patients (16·9 ± 3·7, normal range < 6·4 mg/dL). In over 95% of patients, inflammation markers, duration and intensity of febrile painful attacks, quality of life and ISSF score improved dramatically following colchicine treatment., Conclusion: The Apulia region represents a new endemic area for FMF. Clinical presentation of FMF can be misleading and requires a complete and early workup to recognise the disease and avoid unjustified surgery. Colchicine remains the gold standard therapy to prevent FMF attacks and fatal long-term complications., (© 2017 Stichting European Society for Clinical Investigation Journal Foundation.)

Background and Aims: Helicobacter pylori (H. pylori) eradication in patients who failed one or more therapeutic attempts remains challenging. This study aimed to assess the efficacy of three-in-one capsules bismuth-based quadruple therapy (Pylera®) in these patients managed in clinical practice., Methods: This was a prospective, open-label, multicenter study enrolling consecutive, adult patients with persistent H. pylori infection following at least one standard therapy. All patients received a rescue quadruple therapy with Pylera (3 capsules four times daily) and esomeprazole 20 mg (1 tablet twice daily) for 10 days. H. pylori eradication was assessed by using Urea Breath Test 4-6 weeks following therapy ending. H. pylori eradication rates, compliance, and side-effects were calculated., Results: A total of 208 patients in the 9 participating centres were enrolled. Overall, 180 patients were successfully cured from the infection, accounting for 86.5% (95% CI 81.9-91.2) and 92.3% (95% CI 88.6-96.1) eradication rates at intention-to-treat analysis and at per protocol analysis, respectively. Cure rates were similar across patients who failed one to three previous therapy attempts, but the success rate fell to 67% after 4 or more therapy failures. Compliance to therapy was good in 198 (95.2%) patients, whilst in 7 (5.3%) cases the therapy was interrupted within 5 days due to side effects. A total of 97 (46.6%) patients complained of at least one side effect; nausea, diarrhea and vomiting were the most frequently reported., Conclusions: Our study found that this bismuth-based quadruple therapy is highly effective as second-line and rescue therapy for H. pylori eradication in clinical practice.

Background and Aims: H. pylori eradication is strongly affected by various factors, including the ongoing antibiotic resistance. We describe a "real life" scenario in patients managed for H. pylori-related conditions, living in a southern Italian region (Apulia), an area with clarithromycin resistance >15%., Methods: 2,224 subjects were studied in two tertiary referral centers in Apulia. Analyses included: reason for referral, H. pylori infection rates (13C-urea breath test - UBT or upper endoscopy), and eradication rates following distinct regimens previously prescribed or prospectively prescribed (such as the bismuth-based quadruple therapy Pylera®, recently marketed in Italy)., Results: Over 80% of the patients were referred by family physicians (60% naïve subjects). The overall infection rate was 32.5% and it was similar in asymptomatic patients (31.1%) or with H. pylori-related symptoms/clinical conditions (34.3%). In the 987 H. pylori+ve patients receiving therapy, the overall eradication rate was 80.2% (ITT). Observed eradication rate varied greatly across different regimens: 57.1% (2nd line levofloxacin), 59.6% (unconventional), 70.7% (7-day triple), 73.2% (7-day undefined), 89% (10-day sequential) and 96.9% (ITT, 10 day Pylera®, 1st to 5th line regimens given to 227 patients)., Conclusions: A heterogeneous "real life" scenario in Southern Europe shows that H. pylori+ve patients are put at risk of poor outcomes and points to the need of a susceptibility-based therapy according to guidelines and local microbial resistance. In the present setting (i.e. high clarithromycin resistance), despite the high observed eradication rate, sequential therapy should not be recommended (absent in guidelines, unneeded antibiotic). Bismuth-based quadruple treatment (1st, 2nd or subsequent lines) yields the highest eradication rates.

Goals: The goals of this study were to investigate the role of a new probiotic preparation (Lactobacillus reuteri DSM 17938 and L. reuteri ATCC PTA 6475) in Helicobacter pylori infection., Background: Specific probiotic strains play a role in H. pylori infection for their ability to decrease bacterial load and gastritis, prevent antibiotic-associated side effects, and increase the eradication rate., Study: This is a prospective, double-blind, randomized, placebo-controlled study in a tertiary care setting. A total of 100 H. pylori-positive naive patients received either L. reuteri combination (2×10 Colony Forming Units) or placebo during a 3-phase study (pre-eradication, eradication, and follow-up). All underwent C urea breath test (C-UBT), blood assessments of gastrin-17 (G17), endoscopy, and the Gastrointestinal Symptom Rating Scale. Eradication was confirmed by C-UBT 8 weeks after the completion of therapy., Results: Fifty patients were allocated in each group. During pre-eradication period, C-UBT δ decreased by 13% in L. reuteri combination as compared with a 4% increase in placebo (-13.2±34% vs. 4.3±27%; P<0.03). During eradication, GSRS increased significantly in placebo as compared with L. reuteri combination (6.8±2.9 vs. 4±3.1; P<0.01). Significantly less patients in L. reuteri combination as compared with placebo-reported side effects (40.9% vs. 62.8%; P<0.04). An abnormal G17 value was found in patients receiving placebo as compared with L. reuteri combination (28% vs. 12%; P<0.02). Eradication rate was 75% in L. reuteri combination and 65.9% in placebo (P=NS). L. reuteri combination increased eradication rate by 9.1% (odds ratio: 1.5)., Conclusions: L. reuteri combination alone is able to exert an inhibitory effect on H. pylori growth, and when administered with eradication therapy, it determines a significant reduction in antibiotic-associated side effects. Moreover, L. reuteri combination was able to decrease serum G17 levels and to (not significantly) increase the H. pylori-eradication rate.

Background: Familial Mediterranean fever (FMF) is a rare inherited autosomal recessive autoinflammatory disorder characterized by recurrent and self-limited episodes of fever and painful serositis, lasting 1-3 days. FMF occurs almost exclusively among ethnic groups of the Mediterranean basin, although cases have also been found in Japan and Korean populations. Diagnosis is based on clinical features, response to colchicine and genetic analysis. Novel drugs are emerging, allowing better management of colchicine-resistant/colchicine-intolerant patients. This review aims to attract the attention of the readers on differential diagnosis and management of patients with FMF., Methods: The current state-of-the-art on FMF is outlined, with respect to epidemiological, genetic, pathophysiological and therapeutic characteristics, based on critical analysis of solid scientific literature., Results: FMF is more frequent than it was thought before. The phenotypic expression of M694V is more severe than that of V726A. Patients with M694V/M694V homozygosity are exposed to a higher risk of developing renal amyloidosis, arthritis, dermatologic and oral lesions, higher fever and more frequent painful attacks. Life-long therapy with colchicine (1·0-2·4 mg/day) is effective and safe to prevent recurrent attacks and renal amyloidosis and to reverse proteinuria. In nonresponder patients, alternative novel approaches include interleukin-1 receptor antagonist anakinra and the interleukin-1 decoy receptor rilonacept., Conclusions: The prognosis of FMF is normal if AA amyloidosis is prevented. Colchicine remains the first-line therapy to treat pain and prevent amyloidosis. A follow-up should include clinical evaluation, therapeutic adjustments, measurement of serum amyloid A and proteinuria., (© 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background and Objective: Since the efficacy of the standard triple therapies for Helicobacter pylori eradication has decreased, novel antibiotic regimens have been introduced, including concomitant, sequential, and hybrid therapies. We aimed to compare the cure rates achieved by these new therapy regimens., Methods: This was a multicenter, open-label, pilot study enrolling consecutive non-ulcer dyspepsia patients with H. pylori infection never previously treated for the infection. Patients were randomized to receive one of the following treatments: (a) concomitant therapy: omeprazole 20mg, amoxicillin 1g, clarithromycin 500 mg, and tinidazole 500 mg for 5 days; (b) sequential therapy: omeprazole 20mg and amoxicillin 1g for 5 days followed by omeprazole 20mg, clarithromycin 500 mg, and tinidazole 500 mg for 5 days; (c) hybrid therapy: omeprazole 20mg, and amoxicillin 1g for 7 days followed by omeprazole 20mg, amoxicillin 1g, clarithromycin 500 mg, and tinidazole 500 mg, for 7 days. All drugs were administered twice daily. Bacterial eradication was checked 6 weeks after treatment by using a (13)C-urea breath test. A 10-day, second-line therapy with omeprazole 20mg, levofloxacin 250 mg, and amoxicillin 1g, all given twice daily, was offered to the eradication failure patients., Results: Overall, 270 patients were enrolled, but 13 patients early interrupted treatment due to side effects. At intention-to-treat (ITT) and per-protocol analysis (PP), the eradication rates were 85.5% and 91.6% with the concomitant regimen, 91.1% and 92.1% with the sequential therapy, and 80% and 85.7% with the hybrid regimen. Differences were not statistically significant. H. pylori infection was cured in 10 (55.6%) patients with the second-line regimen., Conclusion: In our study, both concomitant and sequential therapy, but not hybrid therapy, reached high eradication rates. The success rate of second-line levofloxacin-based triple therapy is decreasing., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background and Aims: A levofloxacin-based triple therapy and a rifabutin-based regimen are advised as second-line and rescue therapies in the current Italian guidelines for H. pylori eradication. However, no data are available for the efficacy of these treatments in clinical practice., Methods: A total of 86 consecutive patients who failed a standard, first-line, triple therapy for H. pylori infection were treated with a 10-day triple therapy including omeprazole 20 mg, amoxycillin 1 g, and levofloxacin 250 mg or 500 mg, each given twice daily. Eradication failure patients received a 10-day rescue therapy with omeprazole 20 mg, amoxycillin 1 g, and rifabutin 150 mg, each given twice daily. A further therapeutic attempt was performed with a 14-day, high-dose dual therapy (esomeprazole 40 mg and amoxicillin 1 g, each thrice daily)., Results: Following the second-line therapy, H. pylori infection was cured in 76.4% (95% CI = 67.8-85.0) and 79.5% (95% CI = 70.8-88.2) at intention-to-treat (ITT) and per-protocol (PP) analysis, respectively. After the rescue therapy, bacterial eradication was achieved in 84.6% (95% CI = 65-100). Two patients with persistent infection were successfully cured with the high-dose dual therapy., Conclusion: The efficacy of levofloxacin-based second-line therapy seems to be decreasing, whilst rescue therapy with rifabutin would appear a valid third-line therapy, and a high-dose dual therapy may be used as a further rescue therapy.

Background: Helicobacter pylori eradication rates achieved by standard seven-day triple therapies are decreasing in several countries, while a novel 10-day sequential regimen has achieved a very high success rate. A longer 10-day triple therapy, similar to the sequential regimen, was tested to see whether it could achieve a better infection cure rate., Methods: Patients with nonulcer dyspepsia and H pylori infection were randomly assigned to one of the following three therapies: esomeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1 g for seven days or 10 days, or a 10-day sequential regimen including esomeprazole 20 mg plus amoxycillin 1 g for five days and esomeprazole 20 mg, clarithromycin 500 mg and tinidazole 500 mg for the remaining five days. All drugs were given twice daily. H pylori eradication was checked four to six weeks after treatment by using a 13C-urea breath test., Results: Overall, 213 patients were enrolled. H pylori eradication was achieved in 75.7% and 77.9%, in 81.7% and 84.1%, and in 94.4% and 97.1% of patients following seven-day or 10-day triple therapy and the 10-day sequential regimen, at intention-to-treat and per protocol analyses, respectively. The eradication rate following the sequential regimen was higher than either seven-day (P=0.002) or 10-day triple therapy (P=0.02), while no significant difference emerged between the latter two regimens (P=0.6)., Conclusions: The 10-day sequential regimen was significantly more effective than both triple regimens, while 10-day triple therapy failed to significantly increase the H pylori eradication rate achieved by the standard seven-day regimen.

The aim of this study was to provide a further contribution to evaluate the alterations induced by age on a number of simple Doppler indexes of left ventricular diastolic function. A population of 48 healthy subjects aged between 15 and 78 years old was examined using pulsed Doppler analysis of the left ventricular refilling flow. Linear regression analysis revealed a significant inverse correlation between age and peak speed during rapid refilling (r = -0.80); between age and the ratio between peak speed during rapid refilling and peak during atrial systole (r = -0.92); between age and deceleration time of peak E wave speed, although on the contrary the peak speed of diastolic refilling flow during the atrial systole (r = 0.81) increased significantly with age. Variance analysis showed that indexes of left ventricular diastolic function and age continued on the contrary to be significant n the population as a whole and in both sexes. From these findings it is clear that in the different age groups (15-29, 30-49, 50-65, and over 65) the peak speed of rapid refilling flow was significantly lower in over-65-year-olds than in elderly, middle-aged and young subjects (55 +/- 0.8, 60 +/- 0.5, 65 +/- 0.7 and 75 +/- 0.6 respectively; p < 0.001). The ratio between the peak speed of rapid refilling and that during the atrial systole was lower in over-65-year-olds compared to elderly subjects, middle-aged subjects or the youngest age group (0.94 +/- 0.09, 1.05 +/- 0.13, 1.96 +/- 0.21 and 2.68 +/- 0.50 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy of amlodipine, a long half-life dihydropyridine calcium antagonist, at the dosage of 5-10 mg/day in a single daily administration, has been compared with that of nifedipine R, a short half-life dihydropyridine, at the dosage of 20-40 mg b.i.d. in 29 patients with chronic ischemic heart disease. After a one week placebo period, patients were assigned to the treatment with amlodipine or nifedipine R, according to a randomized sequence and a cross-over, single-blind design, for two control periods of four weeks and without a wash-out interval between these two phases. During the stress test, a significant increase from baseline in test duration and in time to onset of ischemia and of angina have been obtained with both treatments; moreover amlodipine increased significantly the time to onset of ST segment deviation (-1 mm) and the time to maximum ST segment deviation compared with nifedipine R changes. Also with Holter monitoring and in the angina diary there was a significant reduction of anginal episodes. As regards safety profile, amlodipine treatment was associated with a significantly lower incidence of side effects compared with nifedipine R. This is probably due to the particular pharmacokinetics of amlodipine which, besides the long half-life which allows a single daily administration, shows a retarded peak (between the 6th and the 12th hour) with consequent reduction of phenomena connected with fast and excessive peripheral vasodilatation. In conclusion, amlodipine was as effective in reducing the signs of ischemia as nifedipine R, but compliance was better due to the single daily administration and so was tolerability.

Ergometric tests were performed in 27 patients who had previously undergone coronarography following instrumental findings and/or symptoms which seemed highly indicative of ischemic cardiopathy. The aim of the study was to assess the diagnostic importance of the failure of systolic blood pressure to decrease during the third minute of the recovery phase of the test as an index of coronary disease. In particular, as reported by other studies, the ratio between systolic blood pressure at the third minute of recovery and maximum systolic blood pressure during the test was also assessed values above 0.7 were considered pathological. Sixteen out the 27 patients examined showed lesions which were hemodynamically significant, whereas 11 patients were free of lesions and 9 had previous myocardial necrosis. The level of the above ratio in subjects without significant coronary lesions was 0.66 +/- 0.05, whereas it was 0.85 +/- 0.04 (p less than 0.01) in patients with coronary disease. Sensitivity, specificity, and positive and negative prognostic values were respectively 91.6%, 62%, 64.7% and 90.9%. In patients with lesions to the three main arteries both the sensitivity and the specificity were 100%. In the same patients, the ST criteria were 85.7%, 50%, 81.8% and 74.3%.