Diagnosis and Treatment of Helicobacter pylori Infection.

The last 5 years have seen major shifts in defining whom to test and how to treat Helicobacter pylori infection. Peptic ulcer has changed from a chronic disease to a one-off condition, and countries with a high incidence of gastric cancer have begun implementing population-wide screening and treatment. A proactive approach to testing and treatment of H. pylori is now recommended, including outreach to family members of individuals diagnosed with active infection as well as high-risk local populations such as immigrants from high-risk countries. Increasing antimicrobial resistance has resulted in an overall decline in treatment success, causing a rethinking of the approach to development of treatment guidelines as well as the need to adopt the principles of antibiotic usage and antimicrobial stewardship. Required changes include abandoning empiric use of clarithromycin, metronidazole, and levofloxacin triple therapies. Here, we discuss these transformations and give guidance regarding testing and use of therapies that are effective when given empirically.

Self-Correcting Method for Highly Effective Office-Based Helicobacter pylori Therapy Using Cumulative Test of Cure Data.

BACKGROUND AND AIM: Helicobacter pylori infections have become resistant to many previously highly effective antimicrobial regimens resulting in clarithromycin, metronidazole, or fluoroquinolone-containing therapies becoming unsuccessful. Pretreatment susceptibility testing is only widely available in the United States but is still rarely done. Here, we propose a framework to monitor H. pylori eradication in small clinical settings by routinely assessing the effectiveness of therapy. METHODS: Because of the small sample size in individual practice's, we assume an acceptable cure rate of ≥80% (preferred cure rate ≥85%) in adherent patients, with a dichotomous outcome (cured vs. failed) and consecutive patient enrollment. To obtain results (feedback) in a timely manner, for individual practices, cure rates can be estimated after 10 patients. Large practices which acquire patients more rapidly can delay analysis until a total of 104 H. pylori-infected patients, assuming a baseline cure rate of at least 85% with the preferred regimen. RESULTS: We show how data from individual practices can be utilized to improve the effectiveness of H. pylori treatment decisions. The method consists of recording and accumulating the confirmation of cure data for successive small groups of patients. These data are then analyzed as binary outcomes (pass-fail) and serve as the basis for studying and improving the effectiveness of H. pylori treatment decisions. CONCLUSION: A simple actuarial method can serve outpatient clinics to ensure a reliable test-to-cure method and avoid futile Hp regimens.

Helicobacter pylori Infection Does Not Protect Against Allergic Diseases: Evidence From a Pediatric Cohort From Northern Sardinia, Italy.

BACKGROUND: The "hygiene hypothesis" states that reduced exposure to microbial antigens due to an excessively hygienic environment can increase the risk of developing autoimmune diseases, including atopic disorders and asthma. In recent decades, there has been a progressive decline in the prevalence of numerous microorganisms following improved hygienic-sanitary conditions. More specifically, several studies reported an inverse association between the reduction in Helicobacter pylori infection and the rise of asthma and allergic disorders. AIM: To evaluate the prevalence of atopic disorders in a pediatric population in relation to seropositivity against H. pylori. METHODS: Children from Northern Sardinia, Italy, referred to the local Children's Hospital for any reason, were investigated to identify risk factors, especially H. pylori infection, associated with atopic disorders. A validated questionnaire, including demographics, house size, history of breastfeeding, residence, school or daycare center attendance, exposure to animals, and a defined diagnosis of atopy-including asthma-was filled out by a trained pediatrician according to parents' answers and child records. A blood sample was collected from each participant and immunoglobulin G against H. pylori was assessed by a locally validated ELISA test. RESULTS: The seroprevalence of H. pylori infection was 11.7% among 492 children (240 females). Thirty-two children had a confirmed diagnosis of asthma and 12 of allergy. No one child showed both conditions. Statistically significant differences in H. pylori seropositivity were not detected between children with or without atopy (8.4% vs. 12.6; p = 0.233). Although atopic disorders were more frequent in children exposed to traditional atopic risk factors, none of them showed to be significant after adjusting for all covariates. CONCLUSIONS: Serologically assessed H. pylori infection was not significantly associated with a reduced risk of atopic diseases in children.

Is a plant-based diet effective to maintain a good psycho-affective status in old age? Results of a survey of a long-lived population from Sardinia.

BACKGROUND: Depression is common among the elderly, resulting in poor quality of life and elevated healthcare expenditure. Among other factors, dietary habits could also affect this condition, although the specific food patterns involved remain to be established. The present study aimed to assess the role of plant- versus animal-dominant foods consumption on the affective state of nonagenarians from a Sardinian population, Italy, well known for its longevity (Blue Zone). METHODS: Data, including demographic, education, anthropometric parameters, monthly income, and comorbidity were recorded and analyzed. Symptomatic depression was assessed using the Geriatric Depression Scale (GDS) during a comprehensive home geriatric assessment; nutritional status was evaluated by a validated food frequency questionnaire. RESULTS: A total of 200 elderly subjects living in the Sardinian Blue Zone (mean age 93.9 ± 3.9 years) participated in the study; symptomatic depression was present in 51% of the whole cohort and was more common among women. Multivariable logistic regression showed a significantly greater risk of depression in people consuming plantbased foods (OR = 1.42, 95% CI 1.04-1.93), whereas moderate animal-derived foods consumption was associated with a better affective state (OR = 0.79, 95% CI 0.62-0.98). CONCLUSIONS: These findings indicate that a more balanced diet, including animal-derived foods, instead of an exclusive plant-dominant diet, may be more appropriate in the elderly, and abstention from animal-based food intake should not be recommended in advanced age to prevent depression.

Trained Immunity and Trained Tolerance: The Case of Helicobacter pylori Infection.

Trained immunity is a concept in immunology in which innate immune cells, such as monocytes and macrophages, exhibit enhanced responsiveness and memory-like characteristics following initial contact with a pathogenic stimulus that may promote a more effective immune defense following subsequent contact with the same pathogen. Helicobacter pylori, a bacterium that colonizes the stomach lining, is etiologically associated with various gastrointestinal diseases, including gastritis, peptic ulcer, gastric adenocarcinoma, MALT lymphoma, and extra gastric disorders. It has been demonstrated that repeated exposure to H. pylori can induce trained immunity in the innate immune cells of the gastric mucosa, which become more responsive and better able to respond to subsequent H. pylori infections. However, interactions between H. pylori and trained immunity are intricate and produce both beneficial and detrimental effects. H. pylori infection is characterized histologically as the presence of both an acute and chronic inflammatory response called acute-on-chronic inflammation, or gastritis. The clinical outcomes of ongoing inflammation include intestinal metaplasia, gastric atrophy, and dysplasia. These same mechanisms may also reduce immunotolerance and trigger autoimmune pathologies in the host. This review focuses on the relationship between trained immunity and H. pylori and underscores the dynamic interplay between the immune system and the pathogen in the context of gastric colonization and inflammation.

Helicobacter pylori infection and rheumatoid arthritis as risk enhancers' factors for atherosclerotic cardiovascular diseases.

BACKGROUND: In addition to established risk factors for atherosclerotic cardiovascular diseases (aCVDs), infections and autoimmune diseases, such as Helicobacter pylori (H. pylori) and rheumatoid arthritis (RA), have been reported as risk-enhancer factors. In this retrospective single-center, case-control study, the relative weight of RA and H. pylori infection on aCVD was evaluated in a cohort of patients from Northern Sardinia, Italy, where both conditions are frequent. MATERIALS AND METHODS: Data were retrieved from records of subjects undergoing upper endoscopy and screened for H. pylori infection by at least four biopsies. The presence of H. pylori and chronic-active gastritis were labeled as a current infection or a long-lasting infection (LLHp) when atrophy and/or metaplasia and/or dysplasia were detected in at least one gastric specimen. Diagnosis of aCVD and RA was made by the cardiologist and the rheumatologist, respectively, according to guidelines. Odd ratios (ORs) for aCVD were evaluated, adjusting for age, sex, excess weight, cigarette smoking, blood hypertension, dyslipidemia, diabetes, H. pylori status, and RA. RESULTS: Among 4821 records (mean age 52.1 ± 16.7 years; 66.0% female), H. pylori infection was detected in 2262 patients, and more specifically, a LLHp infection was present in 1043 (21.6%). Three-hundred-three (6.3%) patients were diagnosed with aCVD, and 208 (4.3%) with RA. In patients with aCVD (cases), the LLHp infection (33.3% vs. 20.8%, p < 0.0001) and RA (12.2% vs. 3.8%, p < 0.0001) were more frequent in cases compared with controls (patients without aCVD). After adjusting for traditional aCVD risk factors, ORs significantly increased for LLHp infection (1.57; 95% CI 1.20-2.06) and RA (2.63; 95% CI 1.72-4.02). Interestingly, the LLHp infection in patients with RA showed an overall addictive effect on the risk for aCVD (7.89; 95% CI 4.29-14.53). CONCLUSIONS: According to our findings, patients with RA should benefit from being screened and eventually treated for H. pylori infection.

Persistence of Abdominal Pain: Did You Check for Mesenteric Vessels?

The incidence of abnormalities regarding the celiac-mesenteric trunk (CMT) has been reported to be between 1% and 2.7%, whereas for visceral aneurysms the incidence is between 0.1% and 0.2% of the general population. Anatomical variations in the CMT may be the result of abnormal embryogenesis of the primitive segmental splanchnic arteries that supply the bowel and several abdominal organs. The clinical presentation may range from vague abdominal symptoms to aneurysm rupture with a significant mortality risk. In this case, we describe the clinical history of a 37-year-old man with postprandial abdominal pain likely related to the celiac-mesenteric trunk enlargement, associated with high resistance flow in the proximal site. Postprandial symptoms improved by avoiding large meals and surveillance for the CMT anomalies was recommended by cross-imaging including the echo-color-Doppler to assess blood flow modification.

Impact of COVID-19 Pandemic and Associated Restrictions on Vitamin D Status in a Large Cohort of Italian Children and Adolescents.

Background and Objectives: Vitamin D is synthesized in the skin upon sunlight exposure, showing variations with season and latitude. We aimed to investigate the influence of age, sex, and season on vitamin D status in a large pediatric cohort during the COVID-19 pandemic period and the corresponding pre-pandemic period. Materials and Methods: Retrospective data concerning subjects aged < 18 years were extracted anonymously from the large database of a reference laboratory hospital (Sassari, Northern Sardinia, Italy). Serum 25-hydroxyvitamin D [25(OH)D] levels measured during the pre-pandemic period (1 March 2018 to 30 September 2019) were compared with those detected during the pandemic period (1 March 2020 to 30 September 2021). Results: A total of 2317 samples from subjects aged < 18 years were included in the analysis, 1303 (47.9% females) of which were collected in the pre-pandemic period and 1014 (51.3% females) in the pandemic period. No significant differences in 25(OH)D levels were found between the two periods, whereas, in children aged < 2 years, levels were higher than those in children aged 11-16 years (p < 0.05). Monthly levels of 25(OH)D between pre-pandemic and pandemic periods did not differ, although significant differences were detected across months (p < 0.0001). Similarly, 25(OH)D values did not differ significantly between males and females in both periods. Marked seasonal variations were observed in males and females across all age groups. Conclusions: Serum vitamin D levels and their season-related variations were not significantly affected by the COVID-19 pandemic and associated restrictions in a large cohort of Italian children and adolescents.

Clinically relevant thyroid disorders and inflammatory bowel disease are inversely related: a retrospective case-control study.

OBJECTIVES: The risk of thyroid disorders (TDs) in inflammatory bowel disease (IBD) is still controversial. The aim of this retrospective, single-center, case-control study was to explore the association between clinically relevant functional TDs and IBD. METHODS: Consecutive individuals for a total of 313 IBD patients [90 Crohn's disease (CD); 223 ulcerative colitis (UC)], and 833 individuals undergoing colonoscopy for screening without IBD were collected. In the study, subject's information on thyroid status were retrieved. Thyroid disorders were classified, according to the functional status, as hypothyroidism or hyperthyroidism. Patients with TDs (cases) were compared with 941 without (controls) according to IBD exposure. Unadjusted and adjusted odds ratios (ORs) and their 95% confidence interval (CI) were calculated. RESULTS: Clinically relevant TDs were detected in 205 (17,9%) patients and the prevalence was significantly lower in IBD patients compared with subjects without (8.3% vs 12.9%; p = 0.029). After adjusting for potential confounders, a higher TDs risk was confirmed in female (OR 2.72; 95%CI 1.88‒3.92) and older subjects (OR 1.01; 95%CI 1.00‒1.03), and a lower risk in IBD (OR 0.51; 95%CI 0.34‒0.76), especially for hypothyroidism (OR 0.33; 95%CI 0.17‒0.66) in UC. Among four thyroid cancers, only one was detected in IBD patients. CONCLUSIONS: Overall, in our study, the risk of TDs was lower in IBD patients. To assess routinely hormones and/or thyroid gland imaging in the absence of clinical signs or symptoms seems unnecessary in IBD patients, at least in our geographic area.

Probiotic-Induced Tolerogenic Dendritic Cells: A Novel Therapy for Inflammatory Bowel Disease?

Inflammatory bowel diseases (IBDs) are immune-mediated, chronic relapsing diseases with a rising prevalence worldwide in both adult and pediatric populations. Treatment options for immune-mediated diseases, including IBDs, are traditional steroids, immunomodulators, and biologics, none of which are capable of inducing long-lasting remission in all patients. Dendritic cells (DCs) play a fundamental role in inducing tolerance and regulating T cells and their tolerogenic functions. Hence, modulation of intestinal mucosal immunity by DCs could provide a novel, additional tool for the treatment of IBD. Recent evidence indicates that probiotic bacteria might impact immunomodulation both in vitro and in vivo by regulating DCs' maturation and producing tolerogenic DCs (tolDCs) which, in turn, might dampen inflammation. In this review, we will discuss this evidence and the mechanisms of action of probiotics and their metabolites in inducing tolDCs in IBDs and some conditions associated with them.

The impact of body weight on dysplasia of colonic adenomas: a case-control study.

OBJECTIVE: Colorectal cancer (CRC) is common across countries in males and females. Most cases originate from adenomas harboring high grade dysplasia. Among risk factors, weight excess has been suggested to positively influence dysplasia progression. In this study, the relationship between dysplasia grade of adenomas and body mass index (BMI) categories was analyzed. METHODS: This was a retrospective case-control study. A total of 4745 charts (59.8% females) from patients undergoing colonoscopy were collected. Data regarding age, sex, smoking habits, occupation, residence, personal history of CRC, personal history of polyps and BMI were retrieved. Adenomas with high-grade dysplasia were labeled as advanced. RESULTS: They were 970 (20.4%) subjects with adenomas (cases: mean age 64.67 ± 11.35 years) and 3775 without (controls: mean age 56.43 ± 16.56 years). As expected, adenomas were significantly associated with overweight or obesity. After adjusting for all covariates the presence of advanced adenoma was significantly associated with age, male sex, smoking habits, personal history of CRC, overweight (OR = 1.298, IC 95% 1.092-1.697) and obesity (OR = 1.780, IC 95% 1.260-2.515). CONCLUSIONS: Our findings support the protective effect a normal weight against advanced adenomas. Reduction of BMI value should be pursued in healthy programs.

Is mini-nutritional assessment a reliable tool in detecting malnutrition in elderly with body weight excess?

PURPOSE: The rising proportion of elderly population in high-income societies has resulted in increasing number of subjects with chronic disabling diseases and nutritional deficiency. Elderly's nutritional status is usually assessed through the mini-nutritional assessment (MNA®). However, its effectiveness may be influenced by weight excess or obesity. We tested the performance of MNA® questionnaire in subjects aged ≥ 65 years from Northern Sardinia, Italy, according to overweight/obesity, and we tried to identify the factors associated with malnutrition. METHODS: A modified version of MNA® (mMNA) test, not including BMI, was compared with the conventional MNA® (cMNA) test, and the overall test performance was assessed by calculating sensitivity, specificity and accuracy. In addition, indexes of cognitive health, disability, comorbidity and polypharmacy were compared between patients with concordant and discordant MNA tests. RESULTS: cMNA® sensitivity, specificity and accuracy were 67%, 99% and 84% compared with the mMNA test, due to malnourished patients misclassified as normal because of excess weight. Predictors of malnutrition were: depression (p < 0.0001), disability (p < 0.0001) and polypharmacy (p < 0.0001). Interestingly, the average scores of the "global", "subjective" and "dietary" components of the cMNA®, were significantly lower compared with the corresponding scores of the mMNA. CONCLUSIONS: Excess of weight, a condition progressively rising in the elderly population, may reduce the performance of cMNA® test in detecting malnutrition. LEVEL OF EVIDENCE: Level III, case‒control analytic study.

Relative potency of proton-pump inhibitors, Helicobacter pylori therapy cure rates, and meaning of double-dose PPI.

BACKGROUND: Helicobacter pylori treatment recommendations often recommend use of double-dose PPI or greater. This is confusing because PPIs very markedly in relative potency such that a double dose of one may not even be equivalent to the single dose of another. OBJECTIVE: To relate the concept of double-dose to specific amounts of the different PPIs METHODS: We used data standardizing PPI potency in terms of the duration of intragastric pH >4/24 hours (pH4-time) to rank PPIs. Relative potency varies from 4.5 mg omeprazole equivalents (20 mg pantoprazole) to 72 mg omeprazole equivalents (40 mg rabeprazole). RESULTS: We defined PPI dosing for H. pylori therapy as low dose (eg, approximately 20 mg omeprazole equivalents, b.i.d.), high or double dose as approximately 40 mg omeprazole equivalents, b.i.d.) and high dose as approximately 60 mg omeprazole equivalents, b.i.d.). For example, standard double dose PPI would thus be 40 mg of omeprazole, 20 mg of esomeprazole or rabeprazole, 45 mg of lansoprazole, or 120 mg of pantoprazole each given b.i.d. CONCLUSIONS: Simply doubling the dose of any PPI achieves markedly different effects on pH4-time. However, PPIs can be used interchangeably and cost effectively based on their omeprazole equivalency.

Twice-a-day PPI, tetracycline, metronidazole quadruple therapy with Pylera® or Lactobacillus reuteri for treatment naïve or for retreatment of Helicobacter pylori. Two randomized pilot studies.

BACKGROUND: Bismuth is no longer available in Europe except as part of combination therapy. Lactobacillus reuteri has also been used as an adjuvant for Helicobacter pylori therapy. We aimed to investigate the efficacy of a b.i.d. quadruple therapy containing Pylera® or L reuteri for H pylori infection. MATERIALS AND METHODS: We performed two open-label randomized pilot studies. Adult patients positive for H pylori were randomly assigned to b.i.d therapy with quadruple therapy containing bismuth (2 capsules of Pylera® plus 250 mg each of tetracycline and metronidazole for a total of 500 mg of each), or the same dose of antibiotics plus 2 × 108  CFU L reuteri DSM 17 938 plus 2 × 108  CFU L reuteri ATCC PTA 6475 (Gastrus®) once daily and pantoprazole 20 mg b.i.d. Regimens were given with meals for 10 days. Cure was defined by negative 13C-UBT or stool antigen test. RESULTS: A total of 99 subjects (29% men) were enrolled; 92 completed the study. In the Pylera® group, H pylori infection was cured in 95.7%; 95% CI = 85%-99% (44/46) PP and 88%; 95% CI = 75%-95% (44/50) ITT vs. 84.8%; 95% CI = 71%-95% (39/46) PP and 79.6%; 95% CI = 65%-89% (39/49) ITT in the Gastrus® group, respectively. Cure rates in naїve patients were 100%; 95% CI = 85%-100% (25/25) PP with Pylera®, and 89.7%; 95% CI = 72%-97% (26/29) with Gastrus®. Compliance was excellent and side effects mild with both regimens. CONCLUSIONS: B.i.d. bismuth quadruple therapy was highly effective for H pylori eradication in treatment of naïve patients in Sardinia. Replacement of bismuth with Gastrus® might be considered when bismuth is contraindicated or unavailable.

Clinical features and natural history of idiopathic peptic ulcers: a retrospective case-control study.

Objectives: Peptic ulcer disease (PUD) is still common worldwide and is characterized by high mortality and morbidity. Following the decline of Helicobacter pylori infection, the detection of idiopathic PUD (IPUD) has become more frequent, making diagnosis and treatment more difficult. In this study, the clinical features and natural history of IPUD were analyzed.Methods: This was a retrospective case‒control study conducted in a tertiary care setting (University of Sassari, Italy). Records of 9,212 patients undergoing upper endoscopy from 2002 to 2018 were analyzed. Following the exclusion of H. pylori, NSAIDs, and unusual PUD causes, the remaining were labelled as IPUD. Cases (IPUD) and controls (PUD negative) were compared, adjusting for several covariates through multivariate logistic regression models.Results: Among 380 PUD, 95 were considered IPUD. The proportion rose over the study period in contrast to the decline of H. pylori-PUD. Factors significantly associated with IPUD, after adjusting for all covariates, were age (OR, 3.520; 95% CI, 1.634 - 7.585), male sex (OR, 3.126; 95% CI, 1.888 - 5.176), hospitalization (OR, 2.968; 95% CI, 1.926 - 4.575), and number of medications (OR, 2.808; 95% CI, 1.178 - 6.735). A clinical history positive for PUD was the major risk associated with IPUD (OR, 3.729; 95% CI, 2.050 - 6.785). Patients with IPUD were treated with the highest proton pump inhibitor (PPI) dose for 40-60 days. Follow up endoscopy showed a cure rate of 97.6%.Conclusion: The relative proportion of IPUD is increasing in our population in contrast to the drop of H. pylori-PUD. Treatment with high-dose PPI, and for a long duration, heals IPUD and protects from recurrence.

Glucose-6-phosphate dehydrogenase deficiency reduces susceptibility to cancer of endodermal origin.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited enzyme defect worldwide. There is a growing scientific evidence for a protective role of G6PD deficiency against carcinogenesis. In this retrospective analysis, we tested the hypothesis that G6PD deficiency may reduce the risk of developing cancer in a tissue-specific manner. Material and methods: The study was conducted using data from 11,708 subjects undergoing gastrointestinal endoscopic procedures between 2002 and 2018 and tested for G6PD status in a teaching hospital of Northern Sardinia, Italy. Results: A 40% reduction of risk for cancer of endodermal origin was observed among G6PD-deficient patients compared with subjects with normal enzyme activity (relative risk (RR) 0.61, 95% confidence interval (CI) 0.47-0.80) in both genders, confirmed by multivariable generalized linear regression after adjusting for age, sex, smoking habits, body mass index, diabetes and socio-economic status. The 'protective' effect of G6PD deficiency was larger for gastric cancer (RR 0.41, 95% CI 0.18-0.99), hepatocellular carcinoma (RR 0.48, 95% CI 0.26-0.92) and colorectal cancer (RR 0.72, 95% CI 0.53-0.98), while a non-significant risk was observed for breast, prostate, lung, hematopoietic and metastases (primary site unknown). Conclusions: Our results suggest a reduced susceptibility to develop cancers, mostly of endodermal origin (stomach, colon and liver), but not of ectodermal/mesodermal origin, in carriers of G6PD deficiency. The effects of G6PD deficiency on carcinogenesis need further studies to better understand how cancer cells originating from different germ layers use pentose phosphate pathway to proliferate.

Italian Adagio: Every Law has Its Loophole.

The Italian law of December 2010 establishes new criteria and parameters for the evaluation of faculty members. The parameters are represented by the number of articles published in journals listed in the main international data banks, the total number of citations and the h index. Candidates with qualifications at least in two out of three parameters may access the national competitions for associate or full professor and apply for an academic appointment. This system developed with the aim to fight nepotism and promote meritocracy, progressively led to the deterioration of the Italian university system. Since promotion in academia is strictly dependent on publications the faculty members found the solution to get over this system by organizing themselves into large consortia or small groups with the purpose of sharing authorship in scientific publications. In this way parameter thresholds may be easily reached and even surpassed. An Italian adagio says: "Fatta la Legge, Trovato l'Inganno"; "Every law has its Loophole". However, there is no science without ethics and researchers must stay away from any kind of compromise.

Role of Probiotics in Helicobacter pylori Eradication: Lessons from a Study of Lactobacillus reuteri Strains DSM 17938 and ATCC PTA 6475 (Gastrus®) and a Proton-Pump Inhibitor.

BACKGROUND: Meta-analyses involving >4000 subjects with probiotics added to antimicrobial Helicobacter pylori eradication therapy have reported a mean increase in the eradication rate of 12 to 14%. It is unclear how to translate that result into clinical practice. AIM: To evaluate whether administration of Lactobacillus reuteri plus a PPI without antibiotics would eradicate H. pylori infections. METHODS: This was a double-blind placebo-controlled randomized 2-site study of L. reuteri (Gastrus®) at a dose of 2 × 108 CFU, 7 times per day, or matching placebo plus 20 mg pantoprazole b.i.d. for 4 weeks. Cure was defined by negative 13C-UBT, 4 weeks after therapy. Sample size required ≥50% cure rates for using probiotics as a clinically useful monotherapy. RESULTS: Recruitment was halted after 56 subjects because of the low cure rate; there were 8 dropouts; 48 subjects completed therapy (71% women, average age 49 years). The cure rates per protocol were 3/24 (12.5%; 95% CI 2.6-32%) with L. reuteri vs. 1/24 (4.1%) with placebo. Side effects (most often diarrhea) occurred infrequently (in 5/28 vs. 3/28; active vs. placebo therapy) (P=0.53). CONCLUSION: L. reuteri plus a PPI therapy was unable to provide a clinically important rate of H. pylori eradication. The cure rate albeit low (12.5%) was essentially identical to that achieved when probiotics were added to antibiotic therapy. The incremental improvement was additive and independent of antimicrobial resistance or antibiotics use. Probiotics can reliably increase the cure rate to ≥90% only in regimens achieving cure rates of ∼80%. This trial is registered with NCT03404440.

Constipation in the elderly from Northern Sardinia is positively associated with depression, malnutrition and female gender.

OBJECTIVES: Constipation is a common complaint in older adults. The rise in life expectancy may amplify the problem and increase social expenditure. We investigated the major risk factors associated with constipation in a large sample of elderly. METHODS: Outpatients from Northern Sardinia attending a Geriatric Unit between 2001 and 2014 were enrolled. Demographic and anthropometric data, income, education and self-reported bowel function were collected. The presence of constipation was adjusted for cognitive status, assessed by the Mini-Mental State Examination (MMSE) test; single and cumulative illness rating scale (CIRS); current or past symptomatic depression and anxiety measured by the Geriatric Depression Scale (GDS); nutritional status, evaluated using the Mini-Nutritional Assessment (MNA); type and number of different medications used. RESULTS: 1328 elderly patients (mean age 77.7 ± 7.2 years) were enrolled. Constipation was present in 32.1%, more commonly in women (35.4% vs 28.3%) and increased with age. The multivariate analysis showed a significantly greater risk of constipation in patients with a risk of malnutrition (OR = 1.745, 95% CI: 1.043-2.022; p = .034), female gender (OR = 1.735, 95% CI: 1.068-2.820; p = .026) and depression (OR = 1.079, 95% CI: 1.022-1.140; p = .006). Other potential predisposing factors assessed such as MMSE, CIRS, body mass index, marital status, smoking habit, education, income and number of taken drugs did not show a statistically significant association. Aging was a risk for constipation also in patients free of medications. CONCLUSIONS: Knowledge of risk factors associated with bowel alterations in elderly individuals may provide important clues for caregivers to prevent or reduce constipation.

Usefulness of Bisacodyl Testing on Therapeutic Outcomes in Refractory Constipation.

BACKGROUND: Although chronically constipated patients usually respond to medical treatment, there is a subgroup with scarce/no response, generally labeled as refractory or intractable. However, whether this lack of response is real or due to ancillary causes (suboptimal dosage, lack of compliance etc.) is unknown. AIMS: To see whether a pharmacologic test (bisacodyl colonic intraluminal infusion during manometric assessment) may predict the therapeutic outcome. METHODS: Data of patients undergoing 24/h colonic manometry for severe intractable constipation in whom the bisacodyl test (10 ml of drug dissolved into saline and injected through the more proximal recording port) had been carried out were retrieved and analysed, and correlations with the therapeutic outcome made. RESULTS: Overall, charts from 38 patients (5 men) were available; of these, only 21% displayed naive high-amplitude propagated contractions (average, less than 2/24 h), mostly meal-induced, during the recordings. A bisacodyl response was present in 31.6% patients, with a mean number of events of 1.8 per patient. After bisacodyl testing, 47.3% patients underwent intensive medical treatment, 44.7% surgery (medical failures), and 8% transanal irrigation, a procedure employed to treat refractory patients. The presence of naive propulsive contractions significantly correlated with the response to bisacodyl infusion (p < 0.0001), and with a favourable outcome to intensive medical treatment (p < 0.0001). CONCLUSIONS: The bisacodyl test may be clinically useful to better categorize constipated patients erroneously labelled as intractable and to exclude true colonic inertia, thus avoiding surgery in more than 30% of these subjects.