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.

Ustekinumab in the Treatment of Inflammatory Bowel Diseases: Evolving Paradigms.

Inflammatory bowel diseases, comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing, and remitting immune-mediated inflammatory diseases affecting the gastrointestinal tract. Ustekinumab (UST) is a monoclonal antibody that blocks the p40 subunit of the anti-interleukin (IL) 12/23. Pivotal trials (CERTIFI and UNITI-IM for CD, UNIFI for UC) established the efficacy of UST for the induction and maintenance of remission in both CD and UC, with the most favorable results in naïve patients to biologics. In recent years, a wealth of 'real-world' data has emerged supporting positive clinical, endoscopic, and histological outcomes in patients treated with UST, as well as reassuring safety data. More recently, the results of the first head-to-head trials of UST and tumor necrosis factor (TNF) antagonists were reported. Moreover, a number of studies exploring the role of UST in specific clinical settings, such as perianal CD, postoperative complications and recurrence, extraintestinal manifestations, chronic antibiotic-refractory pouchitis, and pregnancy, were reported. This review explores the results reported to date on UST, including those from pivotal trials, real-world data, and emerging studies regarding therapeutic drug monitoring and immunogenicity. The safety profile of UST was also reviewed.

Metaproteomic assessment of gut microbial and host functional perturbations in Helicobacter pylori-infected patients subjected to an antimicrobial protocol.

The impact of therapeutic interventions on the human gut microbiota (GM) is a clinical issue of paramount interest given the strong interconnection between microbial dynamics and human health. Orally administered antibiotics are known to reduce GM biomass and modify GM taxonomic profile. However, the impact of antimicrobial therapies on GM functions and biochemical pathways has scarcely been studied. Here, we characterized the fecal metaproteome of 10 Helicobacter pylori-infected patients before (T0) and after 10 days (T1) of a successful quadruple therapy (bismuth, tetracycline, metronidazole, and rabeprazole) and 30 days after therapy cessation (T2), to investigate how GM and host functions change during the eradication and healing processes. At T1, the abundance ratio between microbial and host proteins was reversed compared with that at T0 and T2. Several pathobionts (including Klebsiella, Proteus, Enterococcus, Muribaculum, and Enterocloster) were increased at T1. Therapy reshaped the relative contributions of the functions required to produce acetate, propionate, and butyrate. Proteins related to the uptake and processing of complex glycans were increased. Microbial cross-feeding with sialic acid, fucose, and rhamnose was enhanced, whereas hydrogen sulfide production was reduced. Finally, microbial proteins involved in antibiotic resistance and inflammation were more abundant after therapy. Moreover, a reduction in host proteins with known roles in inflammation and H. pylori-mediated carcinogenesis was observed. In conclusion, our results support the use of metaproteomics to monitor drug-induced remodeling of GM and host functions, opening the way for investigating new antimicrobial therapies aimed at preserving gut environmental homeostasis.

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.

Association of Helicobacter pylori Infection with Autoimmune Thyroid Disease in the Female Sex.

BACKGROUND: Helicobacter pylori infection has been associated with an increased risk of thyroid diseases (TDs), although scientific evidence is conflicting. In the present study the relationship between TDs, including both autoimmune (AI) and non-autoimmune TD, and H. pylori infection was investigated. METHODS: Data from records of patients undergoing upper endoscopy and histologically evaluated for H. pylori infection were retrieved. In addition to demographic information, the features of gastritis based on non-targeted biopsies collected from the antrum, angulus, and corpus were analyzed. The presence of H. pylori infection and atrophy and/or metaplasia and/or dysplasia in at least one gastric specimen was defined as a long-lasting H. pylori infection and the presence of a chronic-active gastritis as a current infection. Hashimoto's and Graves' diseases were included in the AITD group, and thyroid nodules, goiter, iatrogenic thyroid hypo/hyper function, and thyroidectomy in the non-autoimmune TD group. RESULTS: A total of 8322 records from adult patients from Northern Sardinia, characterized by a similar genetic background, was analyzed. Participants were aged 18-93 years (females 5339, 64.1%), and more specifically, 562 (6.7%) had a diagnosis of AITD and 448 (5.4%) of non-autoimmune TD. A significant association between long-lasting H. pylori and AITD (OR 1.34; 95%CI 1.13-1.60) was found, irrespective of age, sex, body mass index, and smoking status, while it was not associated with non-autoimmune TD. Current H. pylori infection did not show significant ORs for AITD (OR 0.99; 95%CI 0.64-1.57) and non-autoimmune TD (OR 0.86; 95%CI 0.66-1.15). The association with long-lasting H. pylori infection was confirmed to be significant for both Hashimoto's thyroiditis and Graves' disease by multivariable regression analysis. Stratification according to sex revealed a significant association only for females (OR 1.39; 95%CI 1.12-1.72). CONCLUSIONS: Our results indicate that long-lasting H. pylori infection is associated with AITD in the female adult population of Northern Sardinia.

Celiac Disease and Cardiovascular Risk: A Retrospective Case-Control Study.

BACKGROUND: The association of celiac disease (CD) with premature atherosclerosis, including increased carotid artery intima-media thickness and cardiovascular disease (CVD), is controversial. The aim of this study was to investigate this relationship. METHODS: Clinical records of patients from Northern Sardinia referred to the Gastroenterology section of the Department of Medicine, University of Sassari, Italy, were analyzed. Unadjusted and adjusted odds ratios (ORs) for CVD with their 95% confidence intervals (CIs) were calculated according to established risk factors, including age, sex, diabetes, dyslipidemia, overweight/obesity, blood hypertension, and cigarette smoking, as well as a possible risk factor such as H. pylori infection. RESULTS: In a total of 8495 patients (mean age 52.1 ± 17.3 years; 64.7% females), 2504 reported a diagnosis of CVD and 632 of CD. Logistic regression analysis showed a significantly reduced risk of CVD among patients with CD (OR 0.30, 95% CI 0.22-0.41). Moreover, the long duration of the gluten-free diet (GFD) was able to lower the risk of CVD in celiac patients. Finally, CD significantly decreased the frequency of carotid plaques (11.8% vs. 40.1%, p < 0.001). CONCLUSIONS: Our retrospective study demonstrated that CD reduces the risk of CVD in general and more specifically of carotid lesions after adjusting for potential confounders, especially in those on GFD for a long time.

Is Glucose-6-Phosphate Dehydrogenase Deficiency a Risk Factor for Autoimmune Thyroid Disease? A Retrospective Case-Control Study.

BACKGROUND: The risk of developing thyroid disorders (TDs) in subjects with inherited glucose-6-phosphate dehydrogenase (G6PD) deficiency is unknown. The aim of this study was to explore the association between autoimmune (AITD) and G6PD deficiency in Northern Sardinia, in a population with a high frequency of these two conditions. METHODS: In this retrospective single-center case-control study, demographic and clinical data were collected from patients examined in a tertiary referral Gastroenterology Section of a teaching hospital. RESULTS: In 8894 subjects examined (64.7% females), 1218 patients were diagnosed with TDs; more specifically, 767 were diagnosed with AITD and 451 were not (non-AITD). Overall, G6PD deficiency was more prevalent in TD patients compared with patients without TD (controls) (16.7% vs. 11.2%; p < 0.0001). Multivariable logistic regression analysis (after adjusting for age, sex, excess weight and smoking habits), confirmed a higher risk of AITD among G6PD deficient patients with an odds ratio (OR) of 1.36 and 95% confidence interval (CI) of 1.11-1.6, female patients (OR 1.33, 95% CI 1.07-1.65) and overweight patients (OR 1.22, 95% CI 1.03-1.44). CONCLUSIONS: The risk of AITD is increased in carriers of G6PD deficiency. A careful assessment of thyroid function is advisable in patients with inherited G6PD defects.

Clinical and epidemiological features of ulcerative colitis patients in Sardinia, Italy: Results from a multicenter study.

BACKGROUND: There are little data on the epidemiological and clinical features of adult patients with ulcerative colitis (UC) in the different Italian regions, mainly derived from the absence of a national registry. This prevents correct interpretation of the disease burden. AIM: To assess the main clinical and epidemiological features of adult patients diagnosed with UC in Sardinia, Italy. METHODS: We performed a multicenter, observational, cross-sectional study that included adult patients with UC enrolled in seven gastroenterology unit centers in Sardinia. Data were obtained from the patients' medical records and from a questionnaire administered at the inclusion visit. RESULTS: Four hundred and forty-two patients with UC were included. The median age at diagnosis was 39 years (interquartile range 28-48). After a median disease duration of 10 years, 53 patients experienced proximal extension of proctitis or left-sided colitis. Seventy-five patients developed extraintestinal manifestations. Nineteen patients (4.3%) developed cancer: two with colorectal cancer and seventeen with extracolonic cancers. Mesalazine (5-ASA) remains the mainstay of treatment for UC. Overall, 95 patients (21.5%) were treated with one or more biologic agents, whereas 15 patients (3.4%) underwent surgery, mostly colectomy. CONCLUSION: Our results provide important insights into the clinical and epidemiological features of patients with UC, and while waiting for a national Italian registry, present eligible data on the UC population in Sardinia.

Autoimmune Thyroid Disorders Are More Prevalent in Patients with Celiac Disease: A Retrospective Case-Control Study.

Background. Among patients with celiac disease (CD), there is an increased incidence of autoimmune thyroid disorders (AITDs), with hypothyroidism being more frequent than hyperthyroidism. This retrospective case-control study aimed to explore the prevalence of TDs in a population of adult celiac patients from Northern Sardinia, a geographic area with a high prevalence of autoimmune disorders. Methods. Data were collected from consecutive patients with CD (cases) and without CD (controls) who were undergoing upper endoscopy and referred to a tertiary gastroenterology section of a teaching hospital (University of Sassari, Italy). Thyroid disorders were stratified as (i) autoimmune: including Hashimoto's disease in euthyroidism or with hypofunction, and Graves' disease; or (ii) non-autoimmune: thyroid nodules/goiter, iatrogenic thyroid hypo/hyperfunction, and thyroidectomy for any reason, including cancer. Results. Among a total of 8489 participants (females 5839, 64.7%) enrolled, there were 623 (7.3%) celiac patients and 7866 controls (92.7%). The overall frequency of TDs was 1177 (13.9%) and was higher (26.0%) in celiac patients than in controls (12.9%) (p < 0.001). The difference between AITDs (15.4% vs. 7.5%) and no-AITDs (2.7% vs. 1.1%) was statistically significant in CD patients compared with controls, respectively, and prevailed in the fifth and sixth decades. Hashimoto's thyroiditis was more commonly associated with gland hypofunction. Odds ratios with their 95% confidence intervals (CIs) for the presence of AITDs were calculated, adjusting for sex, age, body mass index, smoking habits, occupation, and residence, and they were 2.387 (95% CI 1.857−3.068, p < 0.001) in CD patients, 5.855 (95% CI 4.434−7.731, p < 0.001) for female sex, and 1.012 (95% CI, 1.007−1.017, p < 0.001) for age. Conclusion. These results suggest the need for surveillance for TDs in patients with CD at onset and during follow-up.

Increased Risk to Develop Hypertension and Carotid Plaques in Patients with Long-Lasting Helicobacter pylori Gastritis.

Helicobacter pylori infection has been reported to be positively associated with hypertension, although with conflicting results. In this study, the relationship between H. pylori infection and hypertension, as well as atherosclerotic carotid lesions, was analyzed. METHODS: Clinical records of patients referred to undergo upper endoscopy and gastric biopsy were retrieved. Information regarding the presence of H. pylori infection with atrophy/metaplasia/dysplasia (interpreted as a long-lasting infection), and current or past H. pylori infection was collected, as well as demographic variables, smoking habits, body mass index (BMI), dyslipidemia, diabetes, hypertension, presence of carotid lesions, and current treatment, and analyzed by multivariable regression models. RESULTS: A total of 7152 clinical records from patients older than 30 years (63.4% women) were available for the study. Hypertension was present in 2039 (28.5%) patients and the risk was significantly increased in those with long-lasting H. pylori infection after adjusting for age decades, sex, BMI, cigarette smoking, diabetes, and dyslipidemia (OR 1.17, 95% CI 1.02-1.35). In addition, the long-lasting H. pylori infection was an independent risk for carotid plaques (OR 2.15, 95% CI 1.14-4.09). CONCLUSIONS: Our retrospective study demonstrated that long-lasting H. pylori infection is an independent risk factor for hypertension and the presence of carotid lesions after adjusting for potential confounders, although further validation our findings is needed from prospective studies.

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.

Association between Glucose-6-Phosphate Dehydrogenase Deficiency and Asthma.

BACKGROUND: Among the determinants contributing to the pathogenesis of asthma, antioxidant genetic factors play a leading role. Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that is competent to detoxify free radicals. Although a relationship between G6PD deficiency and asthma has been previously reported, the literature is still scanty. In this study, we test this hypothesis in a large cohort of patients from Sardinia, Italy. METHODS: A retrospective case-control study was performed using data from 11,829 clinical records of outpatients referred to a teaching hospital for a medical visit. In total, 455 cases (asthma-positive) and 11,374 controls (asthma-negative) were compared for G6PD status using multivariable analysis, adjusting for all covariates. RESULTS: Overall, G6PD deficiency was detected in 11.2% of study participants and was associated with an increased risk of asthma (odds ratio (OR) 1.63; 95% confidence interval (CI) 1.27-2.10). Additional variables significantly associated with asthma were female sex (OR 1.66; 95% CI 1.34-2.06), overweight/obesity (OR 1.56; 95% CI 1.27-1.92), smoking (OR 1.44; 95% CI 1.449-3.963), and high socioeconomic status (OR 1.40; 95% CI 1.16-1.70), whereas age was inversely related with asthma (OR 0.49; 95% CI 0.39-0.61). CONCLUSIONS: Our study shows that G6PD deficiency is an independent risk for asthma. These findings suggest that G6PD should be assessed in asthmatic patients for better risk stratification.

What Is New in Helicobacter pylori Diagnosis. An Overview.

Helicobacter pylori infection remains one of the most prevalent infections worldwide, especially in low-resource countries, and the major risk factor for peptic ulcer and gastric cancer. The "test-and-treat" strategy is recommended by several guidelines and consensus. The choice of testing method is based on patient age, presence of alarm signs and/or symptoms, use of non-steroidal anti-inflammatory drugs, as well as local availability, test reliability, and cost. Culture is the gold standard to detect H. pylori and, possibly, to perform susceptibility testing, however, it requires upper endoscopy and dedicated labs. Recent advances in molecular biology have provided new strategies in detecting infection and antimicrobial resistance without invasive tests. In this review we attempt to offer a comprehensive panorama on the new diagnostic tools and their potential use in clinical settings, in order to accomplish specific recommendations.

The Controversial Role of Glucose-6-Phosphate Dehydrogenase Deficiency on Cardiovascular Disease: A Narrative Review.

Cardiovascular disorders (CVD) are highly prevalent and the leading cause of death worldwide. Atherosclerosis is responsible for most cases of CVD. The plaque formation and subsequent thrombosis in atherosclerosis constitute an ongoing process that is influenced by numerous risk factors such as hypertension, diabetes, dyslipidemia, obesity, smoking, inflammation, and sedentary lifestyle. Among the various risk and protective factors, the role of glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common inborn enzyme disorder across populations, is still debated. For decades, it has been considered a protective factor against the development of CVD. However, in the recent years, growing scientific evidence has suggested that this inherited condition may act as a CVD risk factor. The role of G6PD deficiency in the atherogenic process has been investigated using in vitro or ex vivo cellular models, animal models, and epidemiological studies in human cohorts of variable size and across different ethnic groups, with conflicting results. In this review, the impact of G6PD deficiency on CVD was critically reconsidered, taking into account the most recent acquisitions on molecular and biochemical mechanisms, namely, antioxidative mechanisms, glutathione recycling, and nitric oxide production, as well as their mutual interactions, which may be impaired by the enzyme defect in the context of the pentose phosphate pathway. Overall, current evidence supports the notion that G6PD downregulation may favor the onset and evolution of atheroma in subjects at risk of CVD. Given the relatively high frequency of this enzyme deficiency in several regions of the world, this finding might be of practical importance to tailor surveillance guidelines and facilitate risk stratification.

Spatial Association between Gastric Cancer Mortality and Goiter in Sardinia.

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer mortality worldwide. The incidence of GC varies between countries according to exposure to different risk factors. Hypothyroidism has been suggested as a potential GC risk factor. In Sardinia, Italy, the prevalence of endemic goiter is high and GC mortality is unevenly distributed. This ecological study aimed to investigate GC mortality and its relationship with hypothyroidism, adjusting for potential confounders. METHODS: The spatial association between GC mortality and goiter (a proxy of hypothyroidism), diet, stature and pastoralism (a proxy of Helicobacter pylori infection), available at the aggregated level, was modelled in the island's 377 municipalities, separately by sex, using geographically weighted regression (GWR). RESULTS: The GC standardized mortality ratio ranged from 0.0 to 10.4 across municipalities. A hotspot of GC mortality was detected in the central mountainous area of Sardinia among males, positively associated with goiter (GWR estimate 0.213 ± 0.122), and the practice of sheep‒rearing (GWR estimate 0.127 ± 0.080), whereas a negative association with the diet score (GWR estimate 0.032 ± 0.034), and null for stature were found. No significant associations were found in females. CONCLUSION: Within the limitations of ecological studies goiter prevalence was an independent predictor of GC mortality in males.

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.

The Elderly with Glucose-6-Phosphate Dehydrogenase Deficiency are More Susceptible to Cardiovascular Disease.

AIM: Recent studies suggest that glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetically inherited condition causing hemolytic anemia, may be a risk factor for cardiovascular disease (CVD). We aimed to perform a retrospective case-control study in Sardinia taking advantage from clinical records of patients undergoing upper digestive endoscopy and screened for H. pylori infection. METHODS: A total of 9,604 patients with a known G6PD status and a complete clinical history, encompassing CVD, and leading CVD risk factors, including H. pylori infection, undergoing upper endoscopy between 2002 and 2017 were enrolled in this study. RESULTS: Multivariate logistic regression analysis confirmed an increased CVD risk in subjects with G6PD deficiency [odd ratio (OR), 3.24; 95% confidence interval (CI) 2.44-4.30] after adjusting for potential confounders and effect modifiers, including H. pylori infection. Cardiovascular risk was similar in subjects with and without G6PD deficiency before age 60 (OR, 1.26; 95% CI 0.78-2.04, P=0.562), whereas it increased after age 60 in the former group (OR, 3.05; 95% CI 2.22-4.19, P＜0.0001) especially in males (OR 3.67; 95% CI 2.19-6.14) compared with females (OR, 2.96; 95% CI 1.89-4.64) by sex-specific logistic regression analysis. CONCLUSION: The risk of CVD was greater in G6PD-deficient subjects after age 60, both in males and females, than those with normal enzyme activity, after adjusting for conventional CVD risk factors and H. pylori infection. The reduction of important protective mechanisms against oxidative stress in the elderly might explain the study findings.

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.

Male Predominance of Gastric Cancer among Patients with Hypothyroidism from a Defined Geographic Area.

In the past, hypothyroidism has been associated with an increased susceptibility to gastric cancer (GC). Although several epidemiological studies have corroborated this association, a precise mechanistic explanation remains elusive. In this study, this hypothesis was tested by using a large database of subjects who underwent upper endoscopy for various reasons. This was a retrospective, case-control, single-center study. Subjects with GC (cases) were compared with subjects without (controls), according to hypothyroidism status. Overall, the prevalence of GC was 0.73% in the total cohort and was significantly higher in males compared to females (1.4% versus 0.4%, p < 0.0001). Multivariate logistic regression analysis confirmed an increased risk in males with hypothyroidism (OR 5.10; p < 0.0001) after adjusting for potential confounders, especially H. pylori infection. Interestingly, only hypothyroidism and not treatment with levothyroxine was a significant predictor of GC, ruling out a possible direct carcinogenic effect of the replacement therapy. The present study suggests a male-restricted association of gastric carcinogenesis with a hypothyroid state. If the results of this study are confirmed by longitudinal studies, an attractive perspective could open up for the better management of males with concomitant hypothyroidism and a higher risk of GC.

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.