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Ventilatory support is vital for the management of severe forms of COVID-19. Non-invasive ventilation is often used in patients who do not meet criteria for intubation or when invasive ventilation is not available, especially in a pandemic when resources are limited. Despite non-invasive ventilation providing effective respiratory support for some forms of acute respiratory failure, data about its effectiveness in patients with viral-related pneumonia are inconclusive. Acute respiratory distress syndrome caused by severe acute respiratory syndrome-coronavirus 2 infection causes life-threatening respiratory failure, weakening the lung parenchyma and increasing the risk of barotrauma. Pulmonary barotrauma results from positive pressure ventilation leading to elevated transalveolar pressure, and in turn to alveolar rupture and leakage of air into the extra-alveolar tissue. This article reviews the literature regarding the use of non-invasive ventilation in patients with acute respiratory failure associated with COVID-19 and other epidemic or pandemic viral infections and the related risk of barotrauma.

BACKGROUND/OBJECTIVES: Several scoring systems have been specifically developed for risk stratification in COVID-19 patients. DESIGN: We compared, in a cohort of confirmed COVID-19 older patients, three specifically developed scores with a previously established early warning score. Main endpoint was all causes in-hospital death. SETTING: This is a single-center, retrospective observational study, conducted in the Emergency Department (ED) of an urban teaching hospital, referral center for COVID-19. PARTICIPANTS: We reviewed the clinical records of the confirmed COVID-19 patients aged 60 years or more consecutively admitted to our ED over a 6-week period (March 1st to April 15th, 2020). A total of 210 patients, aged between 60 and 98 years were included in the study cohort. MEASUREMENTS: International Severe Acute Respiratory Infection Consortium Clinical Characterization Protocol-Coronavirus Clinical Characterization Consortium (ISARIC-4C) score, COVID-GRAM Critical Illness Risk Score (COVID-GRAM), quick COVID-19 Severity Index (qCSI), National Early Warning Score (NEWS). RESULTS: Median age was 74 (67-82) and 133 (63.3%) were males. Globally, 42 patients (20.0%) deceased. All the score evaluated showed a fairly good predictive value with respect to in-hospital death. The ISARIC-4C score had the highest area under ROC curve (AUROC) 0.799 (0.738-0.851), followed by the COVID-GRAM 0.785 (0.723-0.838), NEWS 0.764 (0.700-0.819), and qCSI 0.749 (0.685-0.806). However, these differences were not statistical significant. CONCLUSION: Among the evaluated scores, the ISARIC-4C and the COVID-GRAM, calculated at ED admission, had the best performance, although the qCSI had similar efficacy by evaluating only three items. However, the NEWS, already widely validated in clinical practice, had a similar performance and could be appropriate for older patients with COVID-19.

High incidence of thrombotic complications was observed in patients with Acute Respiratory Distress Syndrome (ARDS) related to Coronavirus Disease 2019 (COVID-19) [1]. The pathophysiology seems related to systemic thrombophilia by hyper-immune reaction, inducing a “cytokine storm” [1].

Celiac disease (CD) is a common gluten-related enteropathy that presents several extra-intestinal manifestations. Migraine is globally recognized as one of the most diffuse primary headaches. The present paper aims to review the current evidence on the possible association between CD and migraine. Both adults and children having CD exhibit a high prevalence of migraine. However, screening for CD in an unselected population of migraineurs demonstrated contrasting results. Brain imaging may reveal cerebral calcifications and/or white matter abnormalities in a small number of patients having migraine with underlying CD. Limited data are available on the effects of gluten-free diet (GDF) on migraine in the patients affected by CD, suggesting the efficacy of such intervention on the migraine symptoms in both adults and children. Nonetheless, this inference requires verification with high-quality trials conducted with larger sample sizes and longer follow-up periods.

Background and aims The COVID‐19 pandemic represents a source of stress and potential burnout for many physicians. This single‐site survey aimed at assessing perceived stress and risk to develop burnout syndrome among physicians operating in COVID wards. Methods This longitudinal survey evaluated stress and burnout in 51 physicians operating in the COVID team of Gemelli Hospital, Italy. Participants were asked to complete the Maslach Burnout Inventory (MBI) and the Perceived Stress Questionnaire on a short run (PSQs) (referring to the past 7 days) at baseline (T0) and then for four weeks (T1‐T4). Perceived Stress Questionnaire on a long run (PSQl) (referring to the past 2 years) was completed only at T0. Results Compared with physicians board‐certified in internal medicine, those board‐certified in other disciplines showed higher scores for the Emotional Exhaustion (EE) score of the MBI scale (P

Importance Interleukin-6 signal blockade has shown preliminary beneficial effects in treating aberrant host inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Objective to describe the effect of off-label intravenous use of Sarilumab in patients with severe SARS-CoV-2-related pneumonia. Design Observational clinical cohort study. Setting Fondazione Policlinico Universitario A. Gemelli IRCCS as Italian Covid reference center. Participants Patients with laboratory-confirmed SARS-CoV-2 infection and respiratory distress with PaO2/FiO2 ratio Main outcomes and measures We describe the clinical outcomes of 53 patients with SARS-CoV-2 severe pneumonia treated with intravenous Sarilumab in terms of pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards setting and of live discharge rate in ICU treated patients as well as in terms of safety. Each patient received Sarilumab 400 mg administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and was followed for at least 14 days, unless previously discharged or dead. No gluco-corticosteroids were used at baseline. Results Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39 (73.6%) were treated in medical wards (66.7% with a single infusion) while 14 (26.4%) in ICU (92.6% with a second infusion). The median PaO2/FiO2 of patients in the Medical Ward was 146(IQR:120-212) while the median PaO2/FiO2 of patients in ICU was 112(IQR:100-141.5), respectively. Within the medical wards, 7(17.9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89.7% of medical inpatients significantly improved (46.1% after 24 hours, 61.5% after 3 days), 70.6% were discharged from the hospital and 85.7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64.2% were discharged from ICU to the ward and 35.8% were still alive at the last follow-up. Overall mortality rate was 5.7% after Sarilumab administration: 1(2.5%) patient died in the Medical Ward whilst 2(14.2%) patients died in ICU, respectively. Conclusions and relevance IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical benefit and good safety. Key points Question SARS-CoV-2 infection remains a disease with many unknown aspects for which there are no therapies with proven efficacy. To date, it is recognized that COVID-19 disease may lead to the development of a cytokine storm for which drugs as IL-6R inhibitors may have beneficial effect. Findings In this observational clinical study, we reported the efficacy and safety of intravenous Sarilumab use in SARS-CoV-2 severe pneumonia with a global resolution rate of 83.0% (89.7% in medical wards and 64.3% in ICU) and an overall mortality rate of 5.7%. Meaning IL-6R-inhibition is an effective approach for severe SARS-CoV-2 pneumonia and intravenous Sarilumab is a promising treatment approach leading to an important clinical benefit and good safety in the short term.

Aims Although oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), they are often underused in this particularly high-risk population. The aim of the present study was to assess the appropriateness of OAC prescription and its associated factors in hospitalized patients aged 65 years or older. Methods Data were obtained from the retrospective phase of Simulation-based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients With Atrial Fibrillation (SIM-AF) study, held in 32 Italian internal medicine and geriatric wards. The appropriateness of OAC prescription was assessed, grouping patients in those who were and were not prescribed OACs at hospital discharge. Multivariable logistic regression was used to establish factors independently associated with the appropriateness of OAC prescription. Results A total of 328 patients were included in the retrospective phase of the study. Of these, almost 44% (N = 143) were inappropriately prescribed OACs, being mainly underprescribed or prescribed an inappropriate antithrombotic drug (N = 88). Among the patients prescribed OACs (N = 221), errors in the prescribed doses were the most frequent cause of inappropriate use (N = 55). Factors associated with a higher degree of patient frailty were inversely associated with the appropriateness of OAC prescription. Conclusions In hospitalized older patients with AF, there is still a high prevalence of inappropriate OAC prescribing. Characteristics usually related to frailty are associated with the inappropriate prescribing. These findings point to the need for targeted interventions designed for internists and geriatricians, aimed at improving the appropriate prescribing of OACs in this complex and high-risk population.

LINKED CONTENT This article is linked to Tian et al and Tian and Rong papers. To view these articles, visit https://doi.org/10.1111/apt.15731 and https://doi.org/10.1111/apt.15986

Background Previous studies showed that troponin blood levels may increase after exercise. In this study we assessed whether, among patients admitted with suspected unstable angina, the increase in high-sensitive troponin T (hs-TnT) levels after exercise stress test (EST) might help identify those with obstructive coronary artery disease (CAD) and predict symptom recurrence during short term follow-up. Methods Maximal treadmill EST was performed in 69 consecutive patients admitted to the emergency room with a suspicion of unstable angina (acute chest pain but confirmed normal serum levels of cardiac troponins) was measured before and 4 hours after EST. Coronary angiography was performed in 22 patients (32.8%). Results hs-TnT increased after EST compared to baseline in the whole population (from 0.84±0.65 to 1.17±0.87 ng/dL, p

Aims To assess the appropriateness of oral anticoagulant (OAC) prescription and its associated factors in acutely hospitalized elderly patients. Methods Data were obtained from the prospective phase of SIM-AF (SIMulation-based technologies to improve the appropriate use of oral anticoagulants in hospitalized elderly patients with Atrial Fibrillation) randomized controlled trial, aimed to test whether an educational intervention improved OAC prescription, compared to current clinical practice, in internal medicine wards. In this secondary analysis, appropriateness of OAC prescription was assessed at hospital admission and discharge. Results For 246 patients, no significant differences were found between arms (odds ratio 1.38, 95% confidence interval [CI] 0.84-2.28) in terms of appropriateness of OAC prescription. Globally, 92 patients (37.4%, 95% CI = 31.6-43.6%) were inappropriately prescribed or not prescribed at hospital discharge. Among 51 patients inappropriately prescribed, 82% showed errors on dosage, being mainly under-dosed (n = 29, 56.9%), and among 41 inappropriately not prescribed, 98% were taking an antiplatelet drug. Factors independently associated with a lower probability of appropriateness at discharge were those related to a higher risk of bleeding (older age, higher levels of aspartate aminotransferase, history of falls, alcohol consumption) and antiplatelet prescription at admission. The prescription of OACs at admission was the strongest predictor of appropriateness at discharge (odds ratio = 7.43, 95% CI = 4.04-13.73). Conclusions A high proportion of hospitalized older patients with AF remains inappropriately prescribed or nonprescribed with OACs. The management of these patients at hospital admission is the strongest predictor of prescription appropriateness at discharge.

Background & aims Diverticular Disease (DD) is a common clinical condition with a dramatic increasing of the prevalence among industrialized countries. Based on the most used classification, DD may be divided into asymptomatic diverticulosis, symptomatic uncomplicated diverticular disease and complicated diverticular disease. Since recent studies pointed out the role of GUT microbiota imbalance in promoting diverticular formation and inflammation, we have designed a systematic review focusing on the possible role of probiotics in the management of this condition. Methods According to PRISMA, we identified studies on DD patients treated with probiotics, by searching on Pubmed, Embase, Cochrane and ResearchGate. Results 13 studies were included in this review based on our selection criteria: 3 double-blind randomized placebo-controlled, 6 open randomized, and 4 non-randomized open studies. Conclusion This is the first systematic review providing an updated measure of evidence on the efficacy of probiotics in a different phase of DD. Even though the majority of studies are still preliminary, current data show a possible clinical application of certain probiotic strains in all stages of DD. Further investigation is then required to better understand when and how probiotics can be used in different phases of DD.

Background: Studies assessing the association between coeliac disease (CD) and psoriasis show conflicting results. Objective: To assess in the primary care setting the prevalence of CD in patients with psoriasis and the response to a gluten-free diet (GFD) in subjects with psoriasis and CD. Methods: We enrolled 218 patients with psoriasis and 264 controls. Coeliac screening was carried out in all subjects (Eurospital, Trieste, Italy). In subjects with a positive serology, the diagnosis of CD was confirmed histologically. Results: Nine (4.1%) psoriatic patients had positive anti-tissue transglutaminase antibodies compared to only 1 among controls (0.4%, p < 0.05; OR 2.03, 95% CI 1.42-90.11). The diagnosis of CD was confirmed histologically in all 10 subjects. At 6 months GFD was associated with a great improvement of skin lesions in 7 out of 8 patients with psoriasis. Conclusion: Our multicentre primary care study showed an high prevalence of CD in psoriasis and an improvement of skin lesions in CD under GFD.

Parkinson's disease is associated with gastrointestinal motility abnormalities favoring the occurrence of local infections. The aim of this study was to investigate whether small intestinal bacterial overgrowth contributes to the pathophysiology of motor fluctuations. Thirty-three patients and 30 controls underwent glucose, lactulose, and urea breath tests to detect small intestinal bacterial overgrowth and Helicobacter pylori infection. Patients also underwent ultrasonography to evaluate gastric emptying. The clinical status and plasma concentration of levodopa were assessed after an acute drug challenge with a standard dose of levodopa, and motor complications were assessed by Unified Parkinson's Disease Rating Scale-IV and by 1-week diaries of motor conditions. Patients with small intestinal bacterial overgrowth were treated with rifaximin and were clinically and instrumentally reevaluated 1 and 6 months later. The prevalence of small intestinal bacterial overgrowth was significantly higher in patients than in controls (54.5% vs. 20.0%; P = .01), whereas the prevalence of Helicobacter pylori infection was not (33.3% vs. 26.7%). Compared with patients without any infection, the prevalence of unpredictable fluctuations was significantly higher in patients with both infections (8.3% vs. 87.5%; P = .008). Gastric half-emptying time was significantly longer in patients than in healthy controls but did not differ in patients based on their infective status. Compared with patients without isolated small intestinal bacterial overgrowth, patients with isolated small intestinal bacterial overgrowth had longer off time daily and more episodes of delayed-on and no-on. The eradication of small intestinal bacterial overgrowth resulted in improvement in motor fluctuations without affecting the pharmacokinetics of levodopa. The relapse rate of small intestinal bacterial overgrowth at 6 months was 43%. © 2013 Movement Disorder Society.

Background: Parkinson's disease (PD) is associated with gastrointestinal motility abnormalities that could favor the occurrence of small intestinal bacterial overgrowth. The aim of the study was to assess the prevalence of small intestinal bacterial overgrowth in PD patients. Methods: Consecutive PD patients were enrolled. The controls were subjects without PD. All patients and controls underwent the glucose breath test to assess small intestinal bacterial overgrowth. Results: Forty-eight PD patients and 36 controls were enrolled. The prevalence of small intestinal bacterial overgrowth was significantly higher in PD patients than in controls (54.17% vs 8.33%; P < .0001; OR, 2.24; 95% CI, 3.50–48.24). Multivariate analysis showed Hoehn and Yahr stage (OR, 3.07; 95% CI, 1.14–8.27) and Unified PD Rating score (OR, 1.12; 95% CI, 1.02–1.23) were significantly associated with small intestinal bacterial overgrowth in PD patients. Conclusions: Small intestinal bacterial overgrowth is highly prevalent in PD. Gastrointestinal motility abnormalities might explain this association. © 2011 Movement Disorder Society

To assess the prevalence of small intestinal bacterial overgrowth (SIBO) in children affected by irritable bowel syndrome (IBS).Consecutive children affected by IBS according to Rome II criteria (n = 43) were enrolled at the Gemelli Hospital, Catholic University of Rome. The control population (n = 56) consisted of healthy subjects without IBS symptoms, similar to patients for age, sex, and social background. All subjects underwent lactulose/methane breath test (LBT) to assess small intestinal bacterial overgrowth.The prevalence of abnormal LBT result was significantly higher in patients with IBS (65%, 28/43) with respect to control subjects (7%, 4/56; OR 3.9, 95% CI 7.3-80.1, P.00001). Patients with abnormal LBT showed a trend toward a worse visual analog scale score with respect to children with IBS without SIBO, but a significant statistical difference was observed only for bloating.Results from this study suggest a significant epidemiologic association between SIBO and IBS in childhood. Placebo-controlled interventional studies with antibiotics used to treat bacterial overgrowth are warranted to clarify the real impact of the disease on IBS symptoms.

Background: Previous studies suggested an association between CagA-positive H. pylori strains and ischemic stroke. The aim of the present study was to assess the prevalence of Helicobacter pylori infection and CagA status in patients with atherosclerotic stroke in the primary care setting. Materials and methods: A total of 106 consecutive patients (age 76.6 ± 8 years; males 52%) with well-documented history of atherosclerotic stroke and 106 sex–age- (age 76.5 ± 9 years; males 52%) and social background-matched controls without relevant vascular diseases. Risk factors for ischemic stroke were recorded in all subjects. H. pylori infection was assessed by[13]C-urea breath test. A serologic assay for specific IgG against CagA was performed in infected subjects. Results: A trend toward a higher prevalence of H. pylori was observed in cases (63%) with respect to controls (54%) without reaching a statistical significance. CagA positivity was associated to a higher risk of atherosclerotic stroke (adjusted odds ratio 2.69, 95% confidence interval 1.37–5.30). Conclusions: Our findings suggest that CagA-positive strains of H. pylori are significantly associated to atherosclerotic stroke. This is not a merely confirmative study since it has been performed for the first time in the primary care setting and included only subjects with an active infection.

Introduction Short-chain fatty acids affect enterocyte metabolism and differentiation. Butyric acid in particular is already used in ulcerative rectal colitis, pouchitis and antibiotic-induced diarrhoea. Aims To assess the efficacy of butyrate in the treatment of irritable bowel syndrome (IBS). Patients Fifty patients with IBS were treated using enteric-coated sodium butyrate tablets at a dosage of 1 g/day for 30 days. Methods The patients were divided into two subgroups: constipation-predominant IBS and diarrhoea-predominant IBS. The IBS variant and symptom scores of patients were recorded before and after treatment. Results Treatment with butyric acid reduced in normalisation of status in 68% and 71% of patients in the diarrhoea-predominant IBS group vs. 14% and 16% of patients in the constipation-predominant IBS group (respectively for the intent-to-treat and per-protocol analyses) (p Conclusions Oral administration of butyrate may be effective in regulating status and improving gastrointestinal symptoms in patients with the diarrhoea-predominant irritable bowel syndrome.

ummary Background Rifaximin is a broad spectrum non-absorbable antibiotic used for treatment of small intestinal bacterial overgrowth. Doses of 1200 mg/day showed a decontamination rate of 60% with low side-effects incidence. Aims To assess efficacy, safety and tolerability of rifaximin 1600 mg with respect to 1200 mg/day for small intestinal bacterial overgrowth treatment. Methods Eighty consecutive small intestinal bacterial overgrowth patients were enrolled. Diagnosis of small intestinal bacterial overgrowth based the clinical history and positivity to H2/CH4 glucose breath test. Patients were randomized in two 7-day treatment groups: rifaximin 1600 mg (group 1); rifaximin 1200 mg (group 2). Glucose breath test was reassessed 1 month after. Compliance and side-effect incidence were also evaluated. Results One drop-out was observed in group 1 and two in group 2. Glucose breath test normalization rate was significantly higher in group 1 with respect to group 2 both in intention-to-treat (80% vs. 58%; P

Somatic pain is one of the most frequent symptoms reported by patients presenting to the emergency department (ED), but, in spite of this, it is very often underestimated and under-treated. Moreover, pain-killers prescriptions are usually related to the medical examination, leading to a delay in its administration, thus worsening the patient's quality of life. With our study, we want to define and validate a systematic and homogeneous approach to analgesic drugs administration, testing a new therapeutic algorithm in terms of earliness, safety, and efficacy. 442 consecutive patients who accessed our ED for any kind of somatic pain were enrolled, and then randomly divided into two groups: group A follow the normal process of access to pain-control drugs, and group B follow our SUPER algorithm for early administration of drugs to relieve pain directly from triage. We excluded from the study, patients with abdominal pain referred to the surgeon, patients with headache, recent history of trauma, history of drug allergies, and life-threatening conditions or lack of cooperation. Drugs used in the study were those available in our ED, such as paracetamol, paracetamol/codeine, ketorolac-tromethamine, and tramadol-hydrochloride. Pain level, risk factors, indication, and contraindication of each drug were taken into account in our SUPER algorithm for a rapid and safe administration of it. The Verbal Numeric Scale (VNS) and the Visual Analog Scale (VAS) were used to verify the patient's health and perception of it. Only 59 patient from group A (27.1 %) received analgesic therapy (at the time of the medical examination) compared to 181 patients (100 %) of group B (p < 0.001). Group B patients, received analgesic therapy 76 min before group A subjects (p < 0.01), resulting in a significant lower VNS (7.31 ± 1.68 vs 4.75 ± 2.3; p < 0.001), and a superior VAS after discharge (54.43 ± 22.16 vs 61.30 ± 19.13; p < 0.001) compared to group A subjects. No significant differences concerning side effects were observed between group A and group B patients. Early administration of a pain-control therapy directly from triage is safe and effective, and significantly improves patients perceptions of their own health.

Background: Triple therapy is the treatment of choice for Helicobacter pylori-infected patients with an eradication rate ranging from 70 to 85%. Poor compliance and antibiotic resistance are the main causes of treatment failure. The aim of the present study was to assess the efficacy of rifaximin, a poorly absorbed antibiotic, for H. pylori eradication. Methods: We enrolled 48 consecutive H. pylori-positive patients affected. They were randomized to receive two 7-day rifaximin-based triple therapies: rifaximin tablets 400 mg t.i.d., esomeprazole 40 mg o.d. and clarithromycin 500 mg b.i.d. (CRE) or levofloxacin 500 mg o.d. (LRE). H. pylori eradication was assessed using a 13C-urea breath test 4 weeks after the end of therapy. Treatment compliance and the incidence of side effects were also evaluated. Results: No dropouts were observed. The eradication rate both on intention-to-treat and per-protocol analysis did not show significant differences between groups: 58% (14/24 patients) in group 1 and 42% (10/24 patients) in group 2 (p = 0.24, OR 1.96, 95% CI 0.62–6.18). No significant differences in patients’ compliance and incidence of side effects were found between groups. Conclusions: Rifaximin-based therapy showed optimal compliance but a limited eradication rate compared to standard first-line treatment. Further investigations are needed to evaluate different dosages and combinations.

SUMMARY Background: Few controlled studies assessing choice and duration of antibiotic therapy for small intestinal bacterial overgrowth are available. Aim: To assess efficacy, safety and tolerability of different doses of rifaximin, a broad spectrum non-absorbable antibiotic, for intestinal bacterial overgrowth eradication. Methods: We enrolled 90 consecutive patients affected by small intestinal bacterial overgrowth. The presence of small intestinal bacterial overgrowth was based on the occurrence of a rise of H2 values >12 p.p.m. above the basal value after 50 g glucose ingestion. Patients were randomized in three 7-day treatment groups: rifaximin 600 mg/day (group 1); rifaximin 800 mg/day (group 2) and rifaximin 1200 mg/day (group 3). Glucose breath test was reassessed 1 month after the end of therapy. Compliance to the treatment and incidence of side-effects were also evaluated. Results: No drop-outs were observed in the three groups. Glucose breath test normalization rate was significantly higher in group 3 (60%) with respect to group 1 (17%; P < 0.001) and group 2 (27%, P < 0.01). No significant differences in patient compliance and incidence of side-effects were found among groups. Conclusions: Higher doses of rifaximin lead to a significant gain in terms of therapeutic efficacy in small intestinal bacterial overgrowth eradication without increasing the incidence of side-effects.

Small intestinal bacterial overgrowth and sugar malabsorption (lactose, fructose, sorbitol) may play a role in irritable bowel syndrome. The lactulose breath test is a reliable and non-invasive test for the diagnosis of small intestinal bacterial overgrowth. The lactose, fructose and sorbitol hydrogen breath tests are widely used to detect specific sugar malabsorption.To assess the extent to which small intestinal bacterial overgrowth may influence the results of hydrogen sugar breath tests in irritable bowel syndrome patients.We enrolled 98 consecutive irritable bowel syndrome patients. All subjects underwent hydrogen lactulose, lactose, fructose and sorbitol hydrogen breath tests. Small intestinal bacterial overgrowth patients were treated with 1-week course of antibiotics. All tests were repeated 1 month after the end of therapy.A positive lactulose breath test was found in 64 of 98 (65%) subjects; these small intestinal bacterial overgrowth patients showed a significantly higher prevalence of positivity to the lactose breath test (P0.05), fructose breath test (P0.01) and sorbitol breath test (P0.01) when compared with the small intestinal bacterial overgrowth-negatives. Small intestinal bacterial overgrowth eradication, as confirmed by negative lactulose breath test, caused a significant reduction in lactose, fructose and sorbitol breath tests positivity (17% vs. 100%, 3% vs. 62%, and 10% vs. 71% respectively: P0.0001).In irritable bowel syndrome patients with small intestinal bacterial overgrowth, sugar breath tests may be falsely abnormal. Eradication of small intestinal bacterial overgrowth normalizes sugar breath tests in the majority of patients. Testing for small intestinal bacterial overgrowth should be performed before other sugar breath tests tests to avoid sugar malabsorption misdiagnosis.

Background/Aims: Acquired lactase deficiency is a common cause of gastrointestinal symptoms but its etiology remains unclear. Celiac disease could lead to lactase deficiency and is much more common than previously suspected. Several studies have highlighted the prevalence of lactose intolerance in celiac disease, but studies assessing the prevalence of celiac disease in lactose intolerance are lacking. We evaluated the prevalence of celiac disease in patients with a positive H2-lactose breath test compared to a control group. Methods: This retrospective study included 54 patients (15 males/39 females; mean age 37.8 ± 7 years) from southern Italy, referred to the Gastroenterology Unit for bloating and diarrhea after the introduction of milk or dietary lactose. They had a positive H2-lactose breath test and a negative H2-glucose breath test. 50 blood donors were drawn from a similar population, matched for sex and age, and enrolled as a control group. All patients were screened for possible celiac disease by measuring the serum level of IgA antibodies to endomysium, anti-transglutaminase and total IgA. Patients positive for at least one of these markers were submitted to upper gastrointestinal endoscopy. Results: None of the patients had a IgA deficiency. 24% of the patients showed positivity of celiac disease antibodies compared to 2% in the control group (p < 0.001). Histologic samples of these patients showed villous atrophy (53.8% Marsh type IIIa, 38.4% Marsh IIIb, and 7.6% with Marsh type IIIc) confirming the celiac disease, while in the control subjects duodenal biopsies were normal. Conclusions: A high prevalence of celiac disease was observed in patients with a positive H2-lactose breath test compared to healthy controls. In these subjects lactase deficiency seems to be the only manifestation of celiac disease. We suggest serologic screening for celiac disease in all patients with a positive H2-lactose breath test before beginning a milk-exclusion diet.

Aims: There is contrasting evidence on the relevance of chronic infection by Helicobacter pylori ( H. pylori ) as a risk factor for stroke. We performed a meta-analysis of case-control studies to assess association of H. pylori infection and more virulent H. pylori strains, bearing the cytotoxin-associated gene-A (CagA) antigen, with different types of stroke. Methods: Outcome measures were: H. pylori and CagA seroprevalence in (1) patients with stroke versus controls, and (2) patients with stroke due to large vessel stroke versus patients with other types of stroke and controls. Results: Seven cross-sectional, case-control studies were included. Odds ratio for individual case-control studies and pooled OR for the association between H. pylori seropositivity and stroke was 1.49 (95% CI 1.24–1.81), for the association between stroke and anti-CagA positivity was 2.23 (95% CI 1.49–3.36). Patients with large vessel stroke had higher odds for H. pylori infection than patients with other types of stroke (odds ratio 1.65; 95% CI 1.12–2.45), and than controls (odds ratio 1.61; 95% CI 1.13–2.32). Conclusions: Association between H. pylori positivity, anti-CagA positivity and stroke is modest and seems higher with stroke due to large vessel disease. This meta-analysis suggests that the role of CagA positive H. pylori strains in different stroke etiologic subclasses should be the target of future prospective investigation.

Summary Background : Hyperhomocysteinaemia is an independent risk factor for atherosclerosis. It is often related to low levels of vitamin B12 and/or folate, enzymatic co-factors of methionine metabolism. Atrophic gastritis, often caused by Helicobacter pylori infection, may impair vitamin absorption. Aim : To assess whether the presence of atrophic gastritis is associated with hyperhomocysteinaemia via deficiency of its vitamin co-factors. Methods : Thirty-one patients with atrophic gastritis were recruited. The control group consisted of 28 patients with non-atrophic gastritis, matched with patients for sex, age and body mass index. The presence and degree of gastric atrophy were assessed by histology. H. pylori infection was assessed by histology/serology. Blood samples were collected for the measurement of homocysteine, vitamin B12 and folates. Results : Multiple logistic regression analysis showed that atrophic gastritis (odds ratio, 5.3; 95% confidence interval, 1.23–25.26; χ2 = 5.2; P = 0.01) and low vitamin B12 (odds ratio, 3.7; 95% confidence interval, 1.03–22.08; χ2 = 3.6; P

Subclinical celiac disease (CD) has been associated with various neurological disorders, the most common being neuropathy and cerebellar ataxia. The aims of the present study were to assess the following: 1) the prevalence of CD in patients affected by migraine; 2) whether there are regional cerebral blood flow abnormalities in migraine patients with CD compared to migraine patients without CD; and 3) the effects of a gluten free diet in migraine patients with CD.A total of 90 patients affected by idiopathic migraine were enrolled, and 236 blood donors were used as controls. Serum IgG antitransglutaminase (TgA) and IgA antiendomysial (EmA) were measured. In positive cases, diagnosis was confirmed endoscopically. A gluten free diet was started in the patients diagnosed with CD, who were followed for 6 months. A single photon emission CT brain study was performed before and after a gluten free diet.Four of 90 (4.4%; 95% CI = 1.2-11.0) migraine patients were found to have CD compared with 0.4% (95% CI = 0.01-2.3) blood donor controls (p0.05). During the 6 months of gluten free diet, one of the four patients had no migraine attacks, and the remaining three patients experienced an improvement in frequency, duration, and intensity of migraine. Single photon emission CT studies showed a regional baseline reduction in brain tracer uptake in all four patients. Such reduction in uptake completely resolved at follow-up.Our results suggest that a significant proportion of patients with migraine may have CD, and that a gluten free diet may lead to a improvement in the migraine in these patients.

Objectives Patients with Parkinson disease exhibit a highly increased prevalence of small intestinal bacterial overgrowth (SIBO), which has been also associated with the severity of motor fluctuations. Aim of this study was to test the efficacy of liquid levodopa with higher bioavailability in patients with SIBO. Methods Thirty-three patients with Parkinson disease underwent both lactulose and glucose breath tests to assess the presence of SIBO. A urea breath test was performed to assess the presence of a concomitant Helicobacter pylori infection. Patients were challenged with 250 mg of levodopa and 314 mg of levodopa methylester. Drug challenges were performed on different days and at baseline and 1 month after SIBO eradication. During the tests, the motor condition and the plasma levodopa concentrations were evaluated. Results At baseline, the onset of motor benefit was significantly shorter after melevodopa than after standard levodopa, as confirmed by the latency to motor on condition and t max (time to the on condition, 28.8±11.5 vs 55.5±40.2 minutes; P=0.0004; and t max, 28.2±9.7 vs 50.0±11.0 minutes; P=0.002). The duration of the on time or area under the curve was not significantly different. The underlying gastrointestinal condition did not influence these results. Conclusions The reduction of the latency to the on condition in the absence of a reduction of the on duration is a promising feature of melevodopa because this effect would increase the total daily on duration. Future studies that evaluate the usefulness of melevodopa beyond the acute challenge (eg, using motor diaries) in patients with gastrointestinal infections are warranted.

Helicobacter pylori (H. pylori) has been recently associated with some organic and functional vascular disorders. In particular, our group found a high prevalence of H. pylori in patients affected by migraine and a significant improvement of migraine symptoms after eradication of the bacterium, during a follow-up period of 6 months. However, seasonal variations may affect clinical manifestations of migraine, thus influencing our previous results. The present study evaluated the effect of H. pylori eradication during a 1-year follow-up period in a population of 148 consecutively enrolled migraine patients. H. pylori infection was assessed by 13C-urea breath test. Infected subjects underwent specific antibiotic treatment in order to eradiate the bactrium. Frequency, intensity and duration of attacks of migraine were assessed during a 1-year follow-up period. 42% of the patients showed H. pylori infection. 82% resulted eradicated. Interestingly, 28% of the patietns reported a disappearance of migraine during the follow-up period. Moreover, a significant decrease of intensity, frequency and duration of the migraine attacks evaluated 2, 4, 6 and 12 months from H. pylori eradication was observed in the remaining patients. The beneficial effects of H. pylori eradication on migraine seem to be confirmed by this prolonged 1-year follow-up study.

Recent studies have suggested an association between Helicobacter pylori infection and migraine. However, various strains of the bacterium are present, some endowed with greater pathogenicity. In particular, H. pylori type I CagA-positive strains induce a higher release of proinflammatory substances by the gastric mucosa that could trigger systemic vasospasms. The aim of the present study was to assess the prevalence of H. pylori CagA-positive strains in subjects with migraine. One hundred and seventy-five patients affected by migraine (49 with aura, 126 without aura) were consecutively enrolled and matched for sex, age, social background and geographical origin with 152 controls. Helicobacter pylori infection was assessed through 13C-urea breath test. Specific serological IgG against CagA were detected through ELISA. The prevalence of H. pylori infection was similar in migraine patients and in controls (40% vs. 39%, respectively). Among migraine patients, prevalence of infection was not related to presence or absence of aura (45% vs. 37%, respectively). However, among infected subjects, a significantly higher prevalence of CagA-positive strains was observed in patients affected by migraine with aura when compared with those affected by migraine without aura (41% vs. 19%, P < 0.01) and with controls (41% vs. 17%, P < 0.01). CagA-positive H. pylori strains were found to be strongly associated with migraine with aura. A higher inflammatory response of the gastric mucosa to more virulent strains could release substances that may act as triggers of vasospasm in peculiar cerebral arterial districts, probably implicated in the ‘aura’ phenomenon.

Migraine is the most frequent subtype of primary headache. It affects about 18% of females and 6% of males in the general population. Despite this high frequency the disease is substantially underdiagnosed and undertreated. Several hypotheses have been put forward to explain the pathogenesis of migraine; at present, a derangement of vascular tone is believed to be an essential component for the development of clinical attacks of the disease.

Background Patients with insulin-dependent diabetes mellitus (IDDM) are often affected by chronic infections; however, antibiotic absorption may be influenced by the disease. Helicobacter pylori, the most common gastric infection worldwide, is the main acquired factor in the pathogenesis of gastritis and peptic ulcer. The aim of the study was to compare the H. pylori eradication rate obtained with a standard 7-day antibiotic regimen in a group of IDDM H. pylori infected patients and in a control group of infected dyspeptic patients. Methods Thirty-one patients (18 male, 13 female, 39 ± 12 years) affected by IDDM and H. pylori infection, and 50 dyspeptic infected patients (23 male, 17 female, 37 ± 10 years) were evaluated. H. pylori infection was assessed through 13 C-urea breath test A triple therapy with amoxycillin (1 g b.i.d.), clarithromycin (250 mg ti.d.) and pantoprazole (40 mg b.i.d.) was given to both groups at the time of diagnosis for 7 days. Cure was defined as the absence of H. pylori infection, assessed by 13 C-urea breath test, 6 weeks after completing anti-microbial therapy. Effects of H. pylori eradication on gastrointestinal symptoms (pyrosis, epigastric pain, belching, bloating, halitosis and nausea) were also evaluated. Results All enrolled patients completed the study. When compared to dyspeptic patients, the eradication rate was significantly lower in IDDM patients: 92% (46/50) versus 65% (20/31), respectively (P < 0.002). IDDM patients infected by H. pylori showed a different prevalence of some of the gastrointestinal symptoms assessed when compared to the infected dyspeptic patients; in particular, pyrosis, epigastric pain and belching were significantly more prevalent in the infected dyspeptic group. After H. pylori eradication, both groups showed a significant reduction of the intensity of all the gastrointestinal symptoms evaluated, except for nausea. Conclusions IDDM patients showed a significantly lower H. pylori eradication rate when compared to that observed in dyspeptic subjects. The dosage and/or the duration of a standard eradication regimen does not appear to be sufficient to eradicate the infection in IDDM patients. The impairment of the gastrointestinal mucosa microvasculature with a reduction of antibiotic absorption, or the frequent use of antibiotics for other infections with development of resistant strains, may be the mechanisms underlying the observation.

The volume of human intestinal gas is about 200 ml, and it is derived from complex physiological processes including swallowed air, diffusion from bloodstream into the lumen, and particularly intraluminal production by chemical reactions and bacterial fermentation. Gas is continuously removed by eructation, anal evacuation, absorption through the intestinal mucosa, and bacterial consumption. More than 99% of it is composed of hydrogen, oxygen, carbon dioxide, nitrogen, and other odoriferous gases. Methane (CH4) production is detectable in about one third of healthy adult individuals. In the past years, several studies have been focused on CH4 metabolism at the intestinal level and on the putative association between this gas and the pathophysiology of organic and functional bowel disorders. An overview of the present knowledge about the physiology of CH4 metabolism and its role in intestinal diseases is provided in this report.

Rifaximin is a semisynthetic, rifamycin-based non-systemic antibiotic, with a low gastrointestinal absorption and a good antibacterial activity. The antibacterial action covers Gram-positive and Gram-negative organisms, both aerobes and anaerobes. Its antimicrobial action is based on its property to bind to the beta-subunit of bacterial DNA-dependent RNA polymerase inhibiting, thereby, the bacterial RNA synthesis. Rifaximin contributes to restore gut microflora imbalance, becoming an important therapeutic agent in several organic and functional gastrointestinal diseases such as hepatic encephalopathy, small intestine bacterial overgrowth, inflammatory bowel disease and colonic diverticular disease. This antibiotic has the advantage of low microbial resistance and few systemic adverse events and is safe in all patient populations, including young children.

OBJECTIVES: Current treatment for small intestinal bacterial overgrowth (SIBO) is based on courses of broad-spectrum antibiotics. No data concerning SIBO recurrence are available. The aims of the present study were to investigate SIBO recurrence as assessed by glucose breath test (GBT) after antibiotic treatment and conditions associated to SIBO recurrence. METHODS: Eighty consecutive patients affected by SIBO and decontaminated by rifaximin (1,200 mg per day for 1 wk) were enrolled. Diagnosis of SIBO was based on GBT. GBT was reassessed at 3, 6, and 9 months after evidence of GBT normalization. GBT positivity recurrence, predisposing conditions, and gastrointestinal symptoms were evaluated. RESULTS: Ten (10/80, 12.6%), 22 (22/80, 27.5%), and 35 (35/80, 43.7%) patients showed positivity to GBT at 3, 6, and 9 months after successful antibiotic treatment, respectively. At multivariate analysis, older age (OR 1.09, 95% CI 1.02-1.16), history of appendectomy (OR 5.9, 95% CI 1.45-24.19), and chronic use of proton pump inhibitors (PPIs) (OR 3.52, 95% CI 1.07-11.64) were significantly associated to GBT positivity recurrence. All gastrointestinal symptoms significantly increased at 3, 6, and 9 months in patients with evidence of GBT positivity recurrence. CONCLUSIONS: GBT positivity recurrence rate was high after antibiotic treatment. Older age, history of appendectomy, and chronic use of PPIs were associated with GBT positivity recurrence. Patients with evidence of GBT positivity recurrence showed gastrointestinal symptoms relapse thus suggesting SIBO recurrence.

There is a natural feeling between our intestinal flora and the gut. These microorganisms, living in the various tracts of human intestine, may affect the host homeostasis. Some of these bacteria can perhaps be a source of infection and sepsis when the bowel barrier is physically or functionally breached. The term ‘probiotic’ dates from the beginning of the last century and in the last years a market for probiotics worldwide, estimated to be worth billions of pounds, has developed. Although there is persuasive advertising for probiotics and there have been methodological advances in the study of the intestinal microbiota, much remains unproven, e.g. how probiotics work, which strains are effective, what can be expected to be achieved, and what dosage is required for effectiveness. This review of the literature is an evidence-based guide through the developing microbial universe affecting our life.

In a recent study by our group, it was shown that a large proportion of patients with lactose malabsorption and with no bacterial overgrowth are affected by silent coeliac disease (CD). Our aim was to evaluate the effect of a gluten-free diet on lactose malabsorption assessed using the hydrogen lactose breath test (LBT) and also the relationship with normalization of duodenal biopsies in coeliac patients.Fifteen patients (11 F, 4 M; mean age 35.8+/-6) affected by CD with a positive LBT and negative glucose breath test were enrolled. All were started on a gluten-free diet and were re-evaluated after 6 months by LBT and after 12 months by both LBT and upper gastrointestinal endoscopy with biopsies.LBT normalization was observed in 1 out of 15 patients (6.7%) after 6 months and in 9 of the remaining 14 (64.2%) after 12 months. Duodenal biopsies showed normal villi in 8 patients, partial villous atrophy in 5 and total atrophy in 2.The present study shows that a large proportion of CD patients experience a regression of lactose malabsorption after receiving a gluten-free diet. This may be related to normalization of the brush border with an improvement of lactase enzyme activity. LBT should be performed after 12 months in CD patients on a gluten-free diet in order to assess the persistence/disappearance of lactose malabsorption, thus avoiding an unnecessary lactose-free diet.

Small intestinal bacterial overgrowth is defined as an abnormally high bacterial population level in the small intestine. Intestinal motor dysfunction associated with hypothyroidism could predispose to bacterial overgrowth. Luminal bacteria could modulate gastrointestinal symptoms and interfere with levothyroxine absorption. The aims of the present study were to assess the prevalence and clinical pattern of bacterial overgrowth in patients with a history of overt hypothyroidism and the effects of bacterial overgrowth decontamination on thyroid hormone levels.A total of 50 consecutive patients with a history of overt hypothyroidism due to autoimmune thyroiditis was enrolled. Diagnosis of bacterial overgrowth was based on positivity to a hydrogen glucose breath test. Bacterial overgrowth positive patients were treated with 1,200 mg rifaximin each day for a week. A glucose breath test, gastrointestinal symptoms, and thyroid hormone plasma levels were reassessed 1 month after treatment.A total of 27 patients with a history of hypothyroidism demonstrated a positive result to the breath test (27 of 50, 54%), compared with two in the control group (two of 40, 5%). The difference was statistically significant (P0.001). Abdominal discomfort, flatulence, and bloating were significantly more prevalent in the bacterial overgrowth positive group. These symptoms significantly improved after antibiotic decontamination. Thyroid hormone plasma levels were not significantly affected by successful bacterial overgrowth decontamination.The history of overt hypothyroidism is associated with bacterial overgrowth development. Excess bacteria could influence clinical gastrointestinal manifestations. Bacterial overgrowth decontamination is associated with improved gastrointestinal symptoms. However, fermenting carbohydrate luminal bacteria do not interfere with thyroid hormone levels.

Small intestinal bacterial overgrowth (SIBO) is a clinical condition characterized by a malabsorption syndrome due to an increase in microorganisms within the small intestine. The main mechanisms restricting bacterial colonization in the upper gut are the gastric acid barrier, mucosal and systemic immunity and intestinal clearance. When these mechanisms fail, bacterial overgrowth develops. Diarrhea, steatorrhea, chronic abdominal pain, bloating and flatulence are common symptoms and are similar to those observed in irritable bowel syndrome. Breath tests (glucose and/or lactulose breath tests) have been proposed as a sensitive and simple tool for the diagnosis of bacterial overgrowth, being non-invasive and inexpensive compared to the gold standard represented by the culture of intestinal aspirates. Antibiotic therapy is the cornerstone of SIBO treatment. Current SIBO treatment is based on empirical courses of broad-spectrum antibiotics since few controlled studies concerning the choice and duration of antibiotic therapy are available at present.

Helicobacter pylori infection is the major agent of gastric damage. Coeliac disease may affect the morphology and function of the entire gastrointestinal tract from the stomach to the colon. The aim of this study was to assess the gastric histological pattern in patients with H. pylori and untreated coeliac disease.We retrospectively enrolled 183 H. pylori-positive patients with (85, group A) and without (98, group B) untreated coeliac disease. The groups were similar for age, gender and smoking habit, and all the patients came from the same geographical area. Histological evaluation of gastric pattern was performed on 4 biopsies (2 in the antrum, 2 in the corpus). Gastric damage was classified according to the modified Sydney System. Diagnosis of H. pylori infection was based on positivity to histology. The chi-square test was used to assess differences between groups. A p-value0.05 was considered significant.Group A showed a significantly higher prevalence of follicular gastritis than group B (23.5% versus 12.2%, p=0.045). A significantly lower prevalence of atrophic gastritis was observed in group A compared with that in group B (6% versus 22.5%, p=0.002). The prevalence of chronic superficial gastritis, activity degree and intestinal metaplasia was similar between the two groups.In patients with H. pylori infection, untreated coeliac disease could represent a risk factor for follicular gastritis and is associated with a lower prevalence of atrophic gastritis. The complex interaction between H. pylori and untreated coeliac disease on Th-1/Th-2 balance in the gastric mucosa could explain these results.

Summary Background: Studies assessing the prevalence of small intestinal bacterial overgrowth in irritable bowel syndrome gave contrasting results. Differences in criteria to define irritable bowel syndrome patients and methods to assess small intestinal bacterial overgrowth may explain different results. Moreover, no data exist on small intestinal bacterial overgrowth prevalence in a significant population of healthy non-irritable bowel syndrome subjects. Aim: To assess the prevalence of small intestinal bacterial overgrowth by glucose breath test in patients with irritable bowel syndrome symptoms with respect to a consistent control group. Methods: Consecutive patients with irritable bowel syndrome according to Rome II criteria were enrolled. The control population consisted of 102 sex- and age-matched healthy subjects without irritable bowel syndrome symptoms. All subjects underwent glucose breath test. A peak of H2 values >10 p.p.m above the basal value after 50 g of glucose ingestion was considered suggestive of small intestinal bacterial overgrowth. Results: A total of 65 irritable bowel syndrome patients and 102 healthy controls were enrolled. Positivity to glucose breath test was found in 31% of irritable bowel syndrome patients with respect to 4% in the control group, the difference between groups resulting statistically significant (OR: 2.65; 95% CI: 3.5–33.7, P

Idiopathic chronic urticaria (ICU) is a chronic relapsing cutaneous disease. Some case reports or studies on small series of celiac disease (CD) patients have suggested a possible association between CD and ICU. The aim of this study was to assess the prevalence of CD in a population of adults ICU patients with respect to healthy controls. We consecutively enrolled 80 patients affected by ICU and 264 blood donors as the control population without a history of ICU. Serum anti-transglutaminase IgG and anti-endomysium IgA antibodies were evaluated in all subjects. In the case of positivity to serology, diagnosis was confirmed by duodenal biopsy. One of 80 (1.25%) ICU patients were positive to both anti-transglutaminase and anti-endomysium antibodies. Duodenal biopsy showed partial villous atrophy. One control of 264 (0.38%) had CD. No statistical difference was found in the prevalence of CD between the two groups. ICU patients do not seem to bear a greater risk for CD compared to the general population.

Background. Hemodynamic, hemorheologic, and metabolic changes are main determinants in the genesis of ischemic leg ulcers. Because prostaglandin E1 (alprostadil) could successfully counteract these changes, it has been intravenously used in the treatment of this disease. Objective. The aim of this study was to evaluate the efficacy of alprostadil in the treatment of ischemic ulcers and to compare subcutaneous with intravenous administration. Methods. Eighty patients were enrolled. Twenty-five were treated by injecting low doses of alprostadil around ischemic ulcers of the leg and saline solution intravenously and 25 were treated with intravenous alprostadil and local injections of saline solution; the control group was composed of 30 patients who received saline solution around the ulcers and intravenously. Results. All patients showed a statistically significant improvement in ulcer diameter, pain, and transcutaneous oxygen pressure compared to the control group. No relevant differences in the clinical outcome in the two treated groups were found, but patients treated with subcutaneous alprostadil experienced no side effects and showed higher values of transcutaneous oxygen pressure. Conclusions. Both intravenous and local subcutaneous alprostadil are useful in the treatment of ischemic leg ulcers, but subcutaneous administration is less expensive and easier to perform.